EDITORIAL ESPANOL:

====================

Hola amigos de la red, DERMAGIC en su edición 69. El tema el bien conocido y famoso VIRUS DEL PAPILOMA HUMANO (VPH). Días atrás me puse a pensar cómo se comporta este VIRUS en las poblaciones de nuestro MUNDO y cuántos realmente existen, hice una investigación en la red y encontré muchas cosas interesantes, entre ellas: 

Los estudios fueron hechos en estos países: 

Croacia, Francia, Eslovenia, Amsterdam, Méjico, Brasil, Londres, Filipinas, Alemania, Suecia, Estados Unidos, China, Japón, Italia, Colombia, Irlanda, Singapur, Canadá, Checoslovaquia, España, Australia, Finlandia, Noruega, Groenlandia, Dinamarca, Hungría, Finlandia, Jamaica, Malasia, Kenya, India, Grecia, Alaska, Turquía, Rusia, Venezuela, Ecuador, Perú, Guatemala, Panamá, Israel, Sudáfrica, Las antillas Neerlandesas. 

1.) Para Julio de 1.999 hay 82 tipos reportados. 

2.) Los más asociados con neoplasias son los tipos: 6,11,16,18, 31 y 33, y entre estos el 16 y 18 son los más frecuentes. 

3.) Existen estudios que demuestran una asociación HLA y susceptibilidad a neoplasia cervical intraepitelial (NIC) por VPH.. 

4.) Su distribución es mundial. 

5.) No respetan Razas ni condiciones sociales. 

6.) Las nuevas técnicas han permitido detectar los tipos mas exactamente 

7.) A pesar de las campañas de educación sexual, continúan diseminandose en nuestro mundo. 

8.) En la población China los tipos 52 y 58 también están asociados a neoplasia intraepitelial cervical. 

9. ) Se han detectado oncoproteinas, denominadas E6 y E7 que le confieren al VPH su capacidad de malignidad. 

10.) Se ha encontrado virus VPH en lesiones malignas o premalignas tales como: queratosis actínica, epitelioma basocelular, espinocelular, enfermedad de Bowen, queratoacantomas, condiloma acuminado, adenocarcinoma del útero, lesiones premalignas de la cavidad oral y otras. 

Saquen ustedes otras conclusiones... 

Bienvenidos a DERMAGIC/EXPRESS: dr Ganda H. (Indonesia), R Jerajani (India) 

Saludos,,,

Dr. José Lapenta R.,,,

 EDITORIAL ENGLISH:

===================

Hello friends of the net, DERMAGIC in their edition 69. The topic the very well-known and famous the HUMAN PAPILLOMA VIRUS (HPV). Days behind I began to think about the behavior of this VIRUS in the populations of our WORLD and how many they really exist. I made an investigation in the net and I found many interesting things, among them: 

The studies were made in these countries: 

Croatia, France, Slovenia, Amsterdam, Mexico, Brazil, London, Philippines, Germany, Sweden, USA, China, Japan, Italy, Colombia, Ireland, Singapure, Canada, Czech Republic, Spain, Australia, Thailand, Norway, Greenland, Denmark, Hungria, Finland, Jamaica, Malaysia, Kenya, The India, Greek, Alaska, Turkey, Russia, Venezuela, Ecuador, Perú, Guatemala, Panamá, Israel, South Africa, The Netherlands . 

1.) For July 1.999 there are 82 reported types. 

2.) The most common types associated with carcinoma are the: 6,11,16,18, 31 y 33, and among these, the 16 and 18 are the most frequent. 

3.) Studies that demonstrate an association HLA and susceptibility to cervical intraepithelial neoplasia CIN) and HPV exist. 

4.) Their distribution is world-wide. 

5.) They don't respect Races neither social conditions. 

6.) The new techniques have allowed to detect the types but exactly 

7.) Despite of the campaigns of sexual education, they continue being disseminated in our world 

8.) In the Chinese population the types 52 and 58 are also associated in cervical intraepithelial neoplasia. 

9.) Oncoproteins has been detected, denominated E6 and E7 that confer the VPH its capacity to produce malignancies. 

10.) Investigators has been found in malignant and premalignant lesions, HPV virus: actinic keratosis, basal cell carcinoma, squamous cell carcinoma, keratoacanthomas, Bowens's disease, condilomata acuminated, cervix uterine adenocarcinoma, premalignant mucosal lesions of the oral cavity, and others. 

You can make other conclusions... 

Welcome to DERMAGIC/EXPRESS: dr Ganda H. (Indonesia), R Jerajani (India) 

Greetings,,,

Dr. José Lapenta R. 

============================E-MAIL- CORREO ======================== 

From: Altanisia Ramunno 

Subject: Hola Jose / hello jose 

English: I congratulate YOU, your DERMAGIC ARTICLE: THE GOOD, THE BAD, AND THE UGLY OF THE MINOCYCLINE it was published in the Magazine Chilean of Dermatology. 

Your friend Altanisia 

=================================================================== 

REFERENCIAS BIBLIOGRÁFICAS / BIBLIOGRAPHICAL REFERENCES 

=================================================================== 

A.- Human Papillomaviruses: Diversity, Infection and Host Interactions.

B.- The International Human Papillomavirus Reference Center: Standardization, Collaboration, and Quality Assurance in HPV Research and Diagnostics.

C.- International Standardization and Classification of Human Papillomavirus Types.

D.- The Low-Risk Papillomaviruses.

E.- The Biology and Life-Cycle of Human Papillomaviruses.

F.- The Occasional Role of Low-Risk Human Papillomaviruses 6, 11, 42, 44, and 70 in Anogenital Carcinoma Defined by Laser Capture Microdissection/­PCR Methodology: Results From a Global Study.

G.- High-Risk and Low-Risk Human Papillomavirus and the Absolute Risk of Cervical Intraepithelial Neoplasia or Cancer.

H.- Human Papillomavirus Type Specific Risk of Progression and Remission During Long-Term Follow-Up of Equivocal and Low-Grade HPV-positive Cervical Smears.

I.- Human Papillomavirus Genotype-Specific Risks for Cervical Intraepithelial Lesions.

J.- Are 20 Human Papillomavirus Types Causing Cervical Cancer?.

K.- The Biology and Life-Cycle of Human Papillomaviruses.

L.- Sexually Transmitted Infections Treatment Guidelines, 2021.

1.) Detection and typing of human papillomaviruses by polymerase chain reaction in cervical scrapes of Croatian women with abnormal cytology. (CROATIA) 

2.) Risk factors for HPV DNA detection in middle-aged women. (FRANCE) 

3.) Human papillomavirus 16 and 18 infection of the uterine cervix in women 

with different grades of cervical intraepithelial neoplasia (CIN). (SLOVENIA) 

4.) HPV 16 infection and progression of cervical intra-epithelial 

neoplasia: analysis of HLA polymorphism and HPV 16 E6 sequence variants. (AMSTERDAM) 

5.) HPV prevalence among Mexican women with neoplastic and normal 

cervixes. (MEXICO) 

6.) Cigarette smoking and high-risk HPV DNA as predisposing factors for 

high-grade cervical intraepithelial neoplasia (CIN) in young Brazilian women. (BRAZIL) 

7.) Prevalence of human papillomavirus infection in premalignant and 

malignant lesions of the oral cavity in U.K. subjects: a novel method of detection. (LONDON) 

8.) Causes of cervical cancer in the Philippines: a case-control study. (PHILLIPINES) 

9.) Novel HPV types present in oral papillomatous lesions from patients 

with HIV infection. (GERMANY) 

10.) HPV-types, cytological and histopathological findings in three groups of women with possible HPV-related disease. (SWEDEN) 

11.) A general primer GP5+/GP6(+)-mediated PCR-enzyme immunoassay method for rapid detection of 14 high-risk and 6 low-risk human papillomavirus genotypes in cervical scrapings. (AMSTERDAM) 

12.) Prevalence of antibodies to human papillomavirus (HPV) type 16 virus-like particles in relation to cervical HPV infection among college women. (USA) 

13.) Detection of human papillomavirus mRNA and cervical cancer cells in peripheral blood of cervical cancer patients with metastasis. (TAIWAN) 

14.) Human papillomavirus in tissue of bladder and bladder carcinoma specimens. A preliminary study. (GERMANY) 

15.) Detection of human papillomavirus (HPV) type 47 DNA in malignant lesions from epidermodysplasia verruciformis by protocols for precise typing of related HPV DNAs. (JAPAN) 

16.) HLA and susceptibility to cervical neoplasia. (NETHERLANDS) 

17.) Non-isotopic in situ hybridization of HPV types in cervical intraepithelial lesions in patients with AIDS. (BRAZIL) 

18.) HLA-A2-restricted peripheral blood cytolytic T lymphocyte response to HPV type 16 proteins E6 and E7 from patients with neoplastic cervical lesions. (GERMANY) 

19.) Human papilloma virus 16-18 infection and cervical cancer in Mexico: a case-control study. (MEXICO) 

20.) Detection of human papillomavirus (HPV) type 6, 16 and 18 in head and neck squamous cell carcinomas by in situ hybridization. (CROATIA) 

21.) Prevalence of human papillomavirus infection in women attending a sexually transmitted disease clinic. (JAPAN) 

22.) Demonstration of multiple HPV types in laryngeal premalignant lesions using polymerase chain reaction and immunohistochemistry. (ITALY) 

23.) Adenocarcinoma of the uterine cervix in Ireland and Sweden: human papillomavirus infection and biologic alterations. (IRELAND AND SWEDEN) 

24.) Risk factors for high-risk type human papillomavirus infection among Mexican-American women. (USA-MEXICO) 

25.) Many different papillomaviruses have low transcriptional activity in spite of strong epithelial specific enhancers. (SINGAPORE) 

26.) Low frequency of human papillomavirus infection in initial papillary bladder tumors. (CANADA) 

27.) Human papillomavirus genotype spectrum in Czech women: correlation of HPV DNA presence with antibodies against HPV-16, 18, and 33 virus-like particles. (CZECH REPUBLIC) 

28.) Mucosal oncogenic human papillomaviruses and extragenital Bowen disease. (FRANCE) 29.) High prevalence of a variety of epidermodysplasia verruciformis-associated human papillomaviruses in psoriatic skin of patients treated or not treated with PUVA. (GERMANY) 

30.) Human papillomavirus type 31 oncoproteins E6 and E7 are required for the maintenance of episomes during the viral life cycle in normal human keratinocytes. (USA) 

31.) Clinical, histopathologic, and molecular aspects of cutaneous human papillomavirus infections. (USA) 

32.) Screening for genital human papillomavirus: results from an international validation study on human papillomavirus sampling techniques. (SPAIN) 

33.) Use of the same archival papanicolanou smears for detection of human papillomavirus by cytology and polymerase chain reaction. (AUSTRALIA) 

34.) Detection and typing of human papillomavirus in cervical cancer in the Thai. (THAILAND) 

35.) Correlation between polymerase chain reaction and cervical cytology for detection of human papillomavirus infection in women with and without dysplasia. (NORWAY) 

36.) Detection and quantitation of human papillomavirus by using the fluorescent 5' exonuclease assay. (SWEDEN) 

37.) Risk factors for HPV detection in archival Pap smears. A population-based study from Greenland and Denmark. (GREENLAND AND DENMARK) 

38.) [Human papillomavirus infection in women with and without abnormal cervical cytology]. (MEXICO) 

39.) Follow-up of human papillomavirus (HPV) DNA and local anti-HPVantibodies in cytologically normal pregnant women. (HUNGARY) 

40.) Relatively low prevalence of human papillomavirus 16, 18 and 33 DNA inthe normal cervices of Japanese women shown by polymerase chain reaction. (JAPAN) 

41.) Comparison of a one-step and a two-step polymerase chain reaction with degenerate general primers in a population-based study of human papillomavirus infection in young Swedish women. (SWEDEN) 

42.) Human papillomavirus DNA in unselected pregnant and non-pregnant women. (FINLAND) 

43.) Prevalence of HPV cervical infection in a family planning clinic determined by polymerase chain reaction and dot blot hybridisation. (LONDON) 

44.) Type-specific prevalence of human papillomavirus DNA among Jamaican colposcopy patients. (JAMAICA) 

45.) Polymerase chain reaction detection and restriction enzyme typing of human papillomavirus in cervical carcinoma. (MALAYSIA) 

46.) Human papillomavirus (HPV) cervical lesions: results from 300 Italian women studied with DNA hybridization techniques and morphology. (ITALY) 

47.) Detection of human papillomavirus (HPV) DNA in human prostatic tissues by polymerase chain reaction (PCR). (USA) 

48.) High-risk human papillomavirus types in cytologically normal cervical scrapes from Kenya. (KENYA) 

49.) Detection of type specific human papillomavirus (HPV) DNA in cervical cancers of Indian women. (INDIA) 

50.) Natural history of cervical human papillomavirus lesions. (JAPAN) 

51.) Detection of human papillomavirus types in cervical lesions of patients from Taiwan by the polymerase chain reaction. (TAIWAN) 

52.) Human papillomaviruses in cervical cancer I. HPV-16 and 18 predominate in the Greek population. (TAIWAN-CHINA) 

53.) The prevalence of cervical infection with human papillomaviruses and cervical dysplasia in Alaska Native women. (ALASKA) 

54.) Detection of human papillomaviruses in exfoliated cervicovaginal cells by in situ DNA hybridization analysis. (TAIWAN) 

55.) Detection and typing of human papillomavirus in cervical specimens of Turkish women. (TURKEY) 

56.) Prevalence of human papillomavirus DNA in cervical tissue. Retrospective analysis of 855 cervical biopsies. (GERMANY) 

57.) Prevalence of human papillomavirus DNA in female cervical lesions from Rio de Janeiro, Brazil. (BRAZIL) 

58.) Prevalence of human papilloma virus 16 or 18 in cervical cancer in Hualien, eastern Taiwan. (TAIWAN) 

59.) Human papillomavirus types 52 and 58 are prevalent in cervical cancers from Chinese women. (CHINA) 

60.) Human papillomavirus infection and risk determinants for squamous intraepithelial lesion and cervical cancer in Japan. (JAPAN) 

61.) Detection and typing of human papillomavirus in cervical carcinomas in Russian women: a prognostic study. (RUSSIA) 

62.) Serologic response to human papillomavirus type 16 (HPV-16) virus-like particles in HPV-16 DNA-positive invasive cervical cancer and cervical intraepithelial neoplasia grade III patients and controls from Colombia and Spain. (COLOMBIA, SPAIN) 

63.) Detection of human papillomavirus-related oral verruca vulgaris among Venezuelans. (VENEZUELA) 

64.) Oncogenic association of specific human papillomavirus types with cervical neoplasia. (USA, PERU and BRAZIL) 

65.) Chromosome fragility in lymphocytes of women with cervical uterine lesions produced by human papillomavirus. (ECUADOR) 

66.) Multifocal papilloma virus epithelial hyperplasia [see comments] (GUATEMALA) 

67.) Genital human papillomavirus infection in Panama City prostitutes. (PANAMA) 

68.) Risk factors for genital papillomavirus infection in populations at high and low risk for cervical cancer. (PANAMA) 

69.) Demonstration of multiple HPV types in normal cervix and in cervical squamous cell carcinoma using the polymerase chain reaction on paraffin wax embedded material. (ENGLAND) 

70.) Morphological correlation of human papillomavirus infection of matched cervical smears and biopsies from patients with persistent mild cervical cytological abnormalities. (ENGLAND) 

71.) Epidermodysplasia verruciformis in Africans. (SOUTH AFRICA) 

72.) Transmissibility and treatment failures of different types of human papillomavirus. (ISRAEL) 

73.) High frequency of detection of epidermodysplasia verruciformis-associated human papillomavirus DNA in biopsies from malignant and premalignant skin lesions from renal transplant recipients. (THE NETHERLANDS) 

=================================================================== 

=================================================================== 

1.) Detection and typing of human papillomaviruses by polymerase chain reaction in cervical scrapes of Croatian women with abnormal cytology. (CROATIA) 

=================================================================== 

Author 

Grce M; Husnjak K; Magdi´c L; Ilijas M; Zlacki M; Lepusi´c D; Lukac J; 

Hodek B; Grizelj V; Kurjak A; Kusi´c Z; Paveli´c K 

Address 

Ruder Boskovi´c Institute, Division of Molecular Medicine, Zagreb, Croatia. 

grce@olimp.irb.hr 

Source 

Eur J Epidemiol, 13(6):645-51 1997 Sep 

Abstract 

The association between certain human papillomaviruses (HPV) and cervical 

intraepithelial neoplasia (CIN) is well documented, but still unknown among 

Croatian women. In 1995, women between the age of 17 and 64 with 

cytomorphologically abnormal smears (CIN I-IV) were tested for the presence 

of HPV. Consensus and specific primers were used in the polymerase chain 

reaction (PCR) to detect the most common types: 6, 11, 16, 18, 31 and 33, 

as well as the unknown-risk HPV types (HPV X). Out of 379 specimens, 163 

(43%) contained one or more HPV types. Coinfection with different HPV types 

in the same sample was observed in 16 cases. Beside low-risk HPV 6/11 (25.8%) 

the most frequently observed types were high-risk HPV types 16 (20.2%) and 

31 (17.8%). Globally, the HPV positivity rate declines with age. The 

presence of HPV DNA significantly increased from 35.5 to 61.1% along with 

the severity of the cervical intraepithelial neoplasia (CIN I-IV). HPV type 

6/11 was strongly associated with CIN I (33.8%), HPV type 31 with CIN II 

(22.9%), and HPV type 16 with CIN III (50%). 

=================================================================== 

2.) Risk factors for HPV DNA detection in middle-aged women. (FRANCE) 

=================================================================== 

Author 

Mu~noz N; Kato I; Bosch FX; Eluf-Neto J; De Sanjos´e S; Ascunce N; Gili M; 

Izarzugaza I; Viladiu P; Tormo MJ; Moreo P; Gonzalez LC; Tafur L; 

Walboomers JM; Shah KV 

Address 

Unit of Field and Intervention Studies, International Agency for Research 

on Cancer, Lyon, France. 

Source 

Sex Transm Dis, 23(6):504-10 1996 Nov-Dec 

Abstract 

BACKGROUND AND OBJECTIVES: Strong epidemiologic evidence indicates that 

human papillomavirus (HPV) is the main etiologic factor of cervical cancer. 

A few cohort studies suggest that most HPV infections are transient in 

young women and that persistent HPV infections are more common in older 

women. Little is known about the determinants of persistent HPV infections. 

The present study was aimed at increasing our knowledge about these 

determinants. GOALS: To identify risk factors for genital HPV DNA detection 

among cytologically normal middle-aged women. STUDY DESIGN: Eight hundred 

ten women who participated as control subjects in three case-control 

studies on cervical cancer in Spain, Colombia, and Brazil were included in 

this study. After an interview, women underwent a gynecologic examination 

with collection of exfoliated cells for a Papanicolaou smear and HPV DNA 

detection. Human papilloma virus DNA was detected by polymerase chain 

reaction (PCR)-based hybridization techniques. RESULTS: The HPV positivity 

rate was 10.5% in the whole population, but was higher in the areas with 

high incidence of cervical cancer (17% in Brazil and 13% in Colombia) than 

in Spain (4.9%), which is a low-risk area for cervical cancer. Age was 

related to the prevalence of HPV DNA in Brazil, but not in Spain and 

Colombia. In univariate analyses in all three countries, the prevalence of 

HPV DNA was positively associated with the number of lifetime sexual 

partners and inversely associated with the levels of family income and with 

age at first sexual intercourse. There was four times increase in the odds 

ratio (OR) of HPV infection in women who had six or more lifetime sexual 

partners compared with those with one or less. The use of any kind of 

contraceptive tended to decrease the OR for HPV detection. Their ORs ranged 

from 0.44 (barrier methods) to 0.48 (oral contraceptives). In Spain and 

Colombia, antibodies against Chlamydia trachomatis were positively 

associated with the prevalence of HPV DNA. In a final multivariate model, 

the positive associations with lifetime number of sexual partners, 

socioeconomic status, and C. trachomatis persisted. CONCLUSIONS: These 

results support the sexual transmission of HPV and suggest that 

socioeconomic status and antibodies to C. trachomatis are independent 

predictors of HPV detection in middle-aged cytologically normal women. 

=================================================================== 

3.) Human papillomavirus 16 and 18 infection of the uterine cervix in women 

with different grades of cervical intraepithelial neoplasia (CIN). (SLOVENIA) 

=================================================================== 

Author 

Takac I; Marin J; Gorisek B 

Address 

Gynecology and Perinatology Clinic, Maribor Teaching Hospital, Slovenia. 

Source 

Int J Gynaecol Obstet, 61(3):269-73 1998 Jun 

Abstract 

OBJECTIVE: To evaluate the frequency of human papillomavirus (HPV) 16 and 

18 infection in patients with different grades of cervical intraepithelial 

neoplasia (CIN). METHOD: Five-hundred and five patients with CIN, referred 

for conization, were included in this study. Before conization, cytological 

material for in situ hybridization was obtained from the uterine cervix to 

detect the presence of HPV 16 and 18 infection. RESULT: Among all patients 

with CIN, 82 (16.2%) were solely HPV 16 and 51 (10.1%) were solely HPV 18 

positive. There were 133 patients (26.3%) positive for HPV 16 or HPV 18 and 

31 patients (6.1%) were positive for both viral types, giving an overall 

HPV 16/18 infection rate of 32.4%. There were 15 (55.5%) HPV 16 or HPV 18 

positive patients with CIN 1, 45 (33.8%) HPV 16 or HPV 18 positive patients 

with CIN 2 and 104 (30.2%) HPV 16 or HPV 18 positive patients with CIN 3. 

CONCLUSION: In patients with CIN 1, HPV 16 and 18 infection was more 

frequent than in patients with CIN 2, but the difference was not 

significant. Patients with CIN 2 were infected slightly more frequently, 

but not significantly, than patients with CIN 3. On the other hand, 

patients with CIN 1 were significantly more frequently infected than 

patients with CIN 3. 

=================================================================== 

4.) HPV 16 infection and progression of cervical intra-epithelial 

neoplasia: analysis of HLA polymorphism and HPV 16 E6 sequence variants. (AMSTERDAM) 

=================================================================== 

Author 

Bontkes HJ; van Duin M; de Gruijl TD; Duggan-Keen MF; Walboomers JM; 

Stukart MJ; Verheijen RH; Helmerhorst TJ; Meijer CJ; Scheper RJ; Stevens 

FR; Dyer PA; Sinnott P; Stern PL 

Address 

Department of Pathology, Free University Hospital, Amsterdam, The 

Netherlands. 

Source 

Int J Cancer, 78(2):166-71 1998 Oct 5 

Abstract 

High-risk human papillomavirus (HPV) infection plays an important role in 

cervical intra-epithelial neoplasia (CIN), but HPV infection alone is not 

sufficient for progression to cervical cancer. Several lines of evidence 

suggest that cellular immune surveillance is important in the control of 

HPV infection and the development of CIN. The presentation to T cells of 

target viral peptides in the context of HLA molecules is influenced by the 

genetic polymorphisms of both HPV and HLA and thereby influences the host 

immune response and clinical outcome of HPV infection. HLA class I and II 

polymorphism in susceptibility for HPV 16 infection, development and 

progression of CIN was analyzed in a group of 118 patients participating in 

a prospective study of women with initial abnormal cytology. Patients were 

stratified according to HPV status and course of the disease. HLA-B*44 

frequency was increased in the small group of patients with a lesion that 

showed clinical progression during follow-up [OR = 9.0 (4.6-17.5), p = 

0.007]. HLA-DRB1*07 frequency was increased among HPV 16-positive patients 

compared with patients who were negative for all HPV types [OR = 5.9 

(3.0-11.3), p = 0.02]. Our results are consistent with the immunogenetic 

factors associated with disease progression being different from those 

associated with susceptibility to HPV 16 infection. Sequencing of the HPV 

16 E6 and E7 open reading frames of a subset of these patients (n = 40) 

showed the frequency of HPV 16 variants to be similar to other studies. 

However, there was no significant correlation between variant incidence and 

disease progression or viral persistence and no significant correlation 

with any HLA allele. It appears that multiple HLA types can influence HPV 

16-associated cervical dysplasia but the role of HPV 16 variants in disease 

progression and susceptibility in relation to HLA polymorphism remains 

unclear. 

=================================================================== 

5.) HPV prevalence among Mexican women with neoplastic and normal 

cervixes. (MEXICO) 

=================================================================== 

Author 

Torroella-Kouri M; Morsberger S; Carrillo A; Mohar A; Meneses A; Ibarra M; 

Daniel RW; Ghaffari AM; Solorza G; Shah KV 

Address 

Instituto Nacional de Cancerologia, San Fernando, Tlalpan, Mexico, DF. 

Source 

Gynecol Oncol, 70(1):115-20 1998 Jul 

Abstract 

Genital human papillomavirus (HPV) infection is causally linked to cervical 

cancer, yet little is known regarding HPV prevalence in cancerous and 

normal women in Mexico, a country with a high cervical cancer incidence. We 

studied 185 Mexican women among the patients attending gynecological 

outpatient clinics in four hospitals in Mexico City. Each woman had a Pap 

smear, a colposcopy, and, when necessary, a biopsy. HPVs were identified by 

a consensus-primer-based polymerase chain reaction (PCR) assay. HPV was 

detected in 87% of 69 cancers, 83% of 24 high-grade squamous 

intraepithelial lesions (HGSILs), 33% of 21 low-grade squamous 

intraepithelial lesions (LGSILs), and 17% of 71 normals. Twenty-one of the 

32 HPV types tested were detected at least once. The ratio of 

high-risk:low-risk types was 87:6 in HGSILs and cancers, compared to 11:8 

for LGSILs and normals. In invasive cancers, HPV types found at the highest 

frequency were, in descending order: HPV-16, -18, and -45, followed by -39, 

-59, and -58 with the same frequency. HPV-16 and related types were present 

in 52% of the cancer cases, as well as in 79% of HGSILs, and HPV-18 and 

related types were present in 36% of the cancers but in only 12.5% of the 

HGSILs. HPV-16 was predominant in squamous carcinomas, and HPV-18 and 

related types were predominant in adenosquamous carcinoma. Both biopsies 

and scrapes were tested for HPVs in 63 women, all of them with cervical 

neoplasia. Identical HPV results were obtained in 89% of the samples, but 

additional types were often identified in scrapes. HPV prevalence and type 

distribution in cervical cancer in Mexico was similar to the reported 

worldwide, as well as in other Latin American countries. 

=================================================================== 

6.) Cigarette smoking and high-risk HPV DNA as predisposing factors for 

high-grade cervical intraepithelial neoplasia (CIN) in young Brazilian women. (BRAZIL) 

=================================================================== 

Author 

Roteli-Martins CM; Panetta K; Alves VA; Siqueira SA; Syrj¨anen KJ; Derchain 

SF 

Address 

Department of Obstetrics and Gynecology, Campinas State University 

(UNICAMP), Brazil. 

Source 

Acta Obstet Gynecol Scand, 77(6):678-82 1998 Jul 

Abstract 

BACKGROUND: This cross-sectional study was designed to evaluate the role of 

cigarette smoking and high-risk HPV types as risk factors of CIN 2 and 3 in 

young, sexually active Brazilian women. MATERIALS AND METHOD: A series of 

100 consecutive women with abnormal Pap smears were recruited, subjected to 

colposcopy, punch biopsy, and questionnaire for their social, sexual and 

reproductive factors. Of these, 77 women between 20 and 35 years of age 

(median 26.5 years) with biopsy-confirmed CIN 1 or CIN 2 and 3, were 

enrolled in this study. Representative samples from the exocervix and 

endocervix were obtained for HPV testing with the Hybrid Capture HPV-DNA 

assay, including the probes for the oncogenic HPV types (16, 18, 31, 33, 

35, 45, 51, 52 and 56). RESULTS: The overall rate of CIN 2 and 3 was 23/77 

(29.8%). The women with CIN 1, 2 and 3 did not differ from each other with 

regard to their age, race, schooling, marital status, lifetime number of 

sexual partners, age at first intercourse, use of oral contraceptives, or 

parity. However, current cigarette smoking was strongly associated with CIN 

2 and 3 (p<0.001), and among smokers, the risk of high-grade CIN increased 

in parallel with the time of exposure (years of smoking) (p=0.07). HPV-DNA 

of the oncogenic types was detected in 43 (56%) women, the risk of being 

HPV DNA-positive was significantly higher in CIN 2 and 3 as compared with 

CIN 1 (p=0.037). Importantly, the prevalence of high-risk HPV types was 

significantly higher in cigarette smokers than in non-smokers (p=0.046). 

CONCLUSIONS: The results indicate that the severity of CIN lesions was 

clearly related to two fundamental risk factors: 1) high-risk HPV types, 

and 2) current cigarette smoking. These two risk factors were closely 

interrelated in that the high-risk HPV types were significantly more 

frequent in current smokers than in non-smokers, suggesting the possibility 

of a synergistic action between these two risk factors in cervical 

carcinogenesis. 

=================================================================== 

7.) Prevalence of human papillomavirus infection in premalignant and 

malignant lesions of the oral cavity in U.K. subjects: a novel method of 

detection. (LONDON) 

=================================================================== 

Author 

Elamin F; Steingrimsdottir H; Wanakulasuriya S; Johnson N; Tavassoli M 

Address 

RCS Department of Dental Sciences, King's College School of Medicine and 

Dentistry, Rayne Institute, London, U.K. 

Source 

Oral Oncol, 34(3):191-7 1998 May 

Abstract 

To evaluate the possible role of human papillomavirus (HPV) in oral 

neoplasms, 28 oral squamous cell carcinomas (SCC) and 12 potentially 

malignant lesions were analysed for the presence of HPV DNA. A nested 

polymerase chain reaction (PCR) approach, using two sets of HPV consensus 

primers to the L1 region, was used, which was able to detect a broad 

spectrum of HPV types. HPV DNA was detected in 14/28 (50%) carcinomas and 

4/12 (33%) precancerous lesions. A novel approach based on labelling the 

PCR products with 32P and the separation of radioactively labelled products 

on an 8% polyacrylamide gel increased the sensitivity of the detection and 

enabled the identification of the HPV types. The typing of HPV was 

subsequently confirmed by direct DNA sequencing. HPV 6 and HPV 16 were the 

only HPV types detected and seven tumours harboured both types. Our results 

suggest that HPVs may be an important aetiological factor in the 

development of oral cancer. The detection procedure ensured sensitivity and 

consistency of the detection of low copy numbers of the virus DNA. The 

presence of HPV in 33% of premalignant tissues suggests that HPV infection 

may be an early event in the malignant transformation of oral SCC. There 

was no statistically significant association between viral infection and 

tumour grade or stage. 

=================================================================== 

8.) Causes of cervical cancer in the Philippines: a case-control study. (PHILLIPINES) 

=================================================================== 

Author 

Ngelangel C; Mu~noz N; Bosch FX; Limson GM; Festin MR; Deacon J; Jacobs MV; 

Santamaria M; Meijer CJ; Walboomers JM 

Address 

Department of Medicine, Philippine General Hospital, University of the 

Philippines, Manila. 

Source 

J Natl Cancer Inst, 90(1):43-9 1998 Jan 7 

Abstract 

BACKGROUND: Among the numerous human papillomavirus (HPV) types, only types 

16 and 18 have been formally classified as human carcinogens. To evaluate 

the associations of 33 HPV types and other risk factors with squamous cell 

carcinoma and adenocarcinoma of the cervix, we performed a hospital-based, 

case-control study in the Philippines. METHODS: The study included 356 case 

subjects who had histologically confirmed cervical cancer (323 incident 

cases of squamous cell carcinoma and 33 incident cases of 

adenocarcinoma/adenosquamous carcinoma) and 381 control subjects. 

Information on risk factors was obtained by personal interview. HPV DNA was 

detected in exfoliated cervical cells and biopsy specimens by use of a 

polymerase chain reaction assay. RESULTS: HPV DNA was detected in 93.8% of 

case subjects with squamous cell carcinoma and in 90.9% of case subjects 

with adenocarcinoma/adenosquamous carcinoma compared with 9.2% of control 

subjects, giving age-adjusted odds ratios of 156 (95% confidence interval 

[CI] = 87-280) for squamous cell carcinoma and 111 (95% CI = 31-392) for 

adenocarcinoma/adenosquamous carcinoma. Fifteen different HPV types were 

detected in squamous cell carcinoma, and six different HPV types were 

detected in adenocarcinoma/adenosquamous carcinoma. Among HPV types other 

than types 16 and 18, the associations of HPV with risk of squamous cell 

carcinoma were strongest for HPV45. In addition to HPV, high parity, low 

socioeconomic status, and smoking were also associated with both types of 

cervical cancer. CONCLUSIONS: As has been shown for squamous cell 

carcinoma, HPV is the central cause of adenocarcinoma/adenosquamous 

carcinoma of the uterine cervix. The observed associations of less 

prevalent HPV types with cervical cancer have important implications for 

cervical cancer prevention strategies. 

=================================================================== 

9.) Novel HPV types present in oral papillomatous lesions from patients 

with HIV infection. (GERMANY) 

=================================================================== 

Author 

V&uml;olter C; He Y; Delius H; Roy-Burman A; Greenspan JS; Greenspan D; de 

Villiers EM 

Address 

Division for Tumorvirus Characterizatiom, Deutsches Krebsforschungszentrum, 

Heidelberg, Germany. 

Source 

Int J Cancer, 66(4):453-6 1996 May 16 

Abstract 

Patients infected with the human immunodeficiency virus (HIV) often develop 

multiple papillomatous lesions of the oral cavity. In the present study, a 

total of 67 biopsies from benign oral lesions were analyzed for the 

presence of human papillomavirus (HPV) DNA using Southern-blot 

hybridization in combination with a polymerase chain reaction designed to 

detect all known HPV types, as well as unidentified types. These samples, 

collected at random from a high-risk population, were subsequently divided 

into 57 biopsies originating from patients with confirmed HIV infection and 

10 biopsies from patients with unknown HIV status. Each sample was 

amplified with 7 different combinations of degenerate primers. All 

amplified products were sequenced. HPV DNA sequences were detected in 67% 

(45/67) of the samples. HPV 7 (19%) and HPV 32 (28%) were the predominant 

HPV types. HPV 32 was present in 2/4 fibromas tested. Two new HPV types, 

HPV 72 and HPV 73, were identified in oral warts with atypia. The complete 

genomes of these viruses were cloned and sequenced. Other HPV types 

detected were HPV 2a, HPV 6b, HPV 13, HPV 16, HPV 18, HPV 55, HPV 59 and 

HPV 69. 

=================================================================== 

10.) HPV-types, cytological and histopathological findings in three groups 

of women with possible HPV-related disease. (SWEDEN) 

=================================================================== 

Author 

Frederiksson A; Larson B; Persson E; Auer G; Johansson B; Kalantari M; von 

Krogh G; Silfversw&uml;ard C 

Address 

Department of Obstetrics and Gynaecology, Karolinska Hospital, Stockholm, 

Sweden. 

Source 

Acta Obstet Gynecol Scand, 75(6):556-62 1996 Jul 

Abstract 

OBJECTIVE. The aim of this investigation was to study three groups of women 

presenting with possible HPV-infection with regard to HPV-types and 

cervical dysplasia. METHODS. Eighty women were included. Eighteen of them 

were present partners to men with condylomas, 20 had clinical vulvar 

HPV-lesions and 42 were referred due to an abnormal PAP-smear. Samples for 

HPV-analysis by PCR-technique were taken from the vulva, the portio and the 

cervical canal. A universal HPV-primer as well as specific primers for HPV 

6/11, 16, 18, 31, and 33 were utilized. PAP-smears were taken as well as 

biopsies from cervix/portio. RESULTS. Seventy-eight percent had HPV-DNA 

identified. Sixty-seven percent of those with HPV 16 and/or 18 had 

dysplasia verified by histopathology and 50% of those with 31 and/or 33. 

Twenty of 21 women with dysplasia had HPV 16, 18, 31 and/or 33 identified. 

One woman with dysplasia was HPV-negative. Histopathologically verified CIN 

were diagnosed in all groups investigated. Women referred for suspicion of 

CIN significantly more often had HPV detected at the cervix/portio. HPV 

6/11 was mostly found in women with condylomas. Apart from this the 

occurrence of the different HPV types were alike in the three groups. 

CONCLUSION. Infection with HPV is a process and the usefulness of different 

diagnostic methods seems to depend on when during the course of the disease 

they are used. HPV-findings in women with dysplasia were all associated 

with oncogenic virus-types. High-risk virus was often found simultaneously 

with low-risk virus indicating a covariation in the acquisition of the 

different HPV-types. 

=================================================================== 

11.) A general primer GP5+/GP6(+)-mediated PCR-enzyme immunoassay method 

for rapid detection of 14 high-risk and 6 low-risk human papillomavirus 

genotypes in cervical scrapings. (AMSTERDAM) 

=================================================================== 

Author 

Jacobs MV; Snijders PJ; van den Brule AJ; Helmerhorst TJ; Meijer CJ; 

Walboomers JM 

Address 

Department of Pathology, University Hospital Vrije Universiteit, Amsterdam, 

The Netherlands. 

Source 

J Clin Microbiol, 35(3):791-5 1997 Mar 

Abstract 

Two cocktails of digoxigenin-labeled human papillomavirus (HPV) 

type-specific oligonucleotide probes and an enzyme immunoassay (EIA) were 

used as a basis to developed a group-specific detection method for 14 

high-risk (types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 

68) and 6 low-risk (types 6, 11, 40, 42, 43, and 44) HPVs, following a 

general primer GP5+/bioGP6(+)-mediated PCR. The sensitivity of this 

high-risk/low-risk (HR/LR) HPV PCR-EIA ranged from 10 to 200 HPV copies, 

depending on the HPV type. Comparison of HR/LR HPV PCR-EIA with radioactive 

Southern blot hybridization using a general probe on the same PCR products 

derived from 417 cytomorphologically abnormal cervical scrapings resulted 

in an overall agreement of 96% between the two methods. Complete 

concordance between group-specific HR/LR detection and individual typing 

results for both single and multiple infections indicate the strong 

specificity of this HR/LR HPV PCR-EIA. Multiple infections could be 

predicted by comparing PCR-EIA optical density values of the cocktail 

probes with one of the individual oligonucleotide probes. This novel HR/LR 

PCR-EIA allows accurate and rapid identification of high-risk and low-risk 

HPV types in cervical scrapings and will facilitate HPV detection in HPV 

mass-screening programs. 

=================================================================== 

12.) Prevalence of antibodies to human papillomavirus (HPV) type 16 

virus-like particles in relation to cervical HPV infection among college 

women. (USA) 

=================================================================== 

Author 

Viscidi RP; Kotloff KL; Clayman B; Russ K; Shapiro S; Shah KV 

Address 

Eudowood Division of Infectious Diseases, Department of Pediatrics, Johns 

Hopkins University School of Medicine, Baltimore, Maryland, USA. 

rviscidi@welchlink.welch.jhu.edu 

Source 

Clin Diagn Lab Immunol, 4(2):122-6 1997 Mar 

Abstract 

A human papillomavirus type 16 (HPV-16) virus-like particle (VLP)-based 

enzyme-linked immunosorbent assay (ELISA) was used to measure serum 

antibody to capsid proteins in 376 sexually active college women who were 

also screened for the presence of genital HPVs by PCR and interviewed for 

demographic and behavioral risk factors for HPV infection. The 

seroprevalence was 46% in women with HPV-16 DNA in the genital tract. The 

corresponding values for women who harbored other HPV types or no HPV in 

the genital tract were 30 and 19%, respectively (HPV-16 group versus no-HPV 

group; odds ratio [OR], 3.7; 95% confidence interval [CI], 1.5 to 8.9). The 

antibody response was significantly higher among women with a high viral 

load than among those with a low viral load (median optical density value, 

0.838 versus 0.137, P = 0.009). Comparable levels of seroreactivity were 

observed among women infected with HPV types distantly or closely related 

genetically to HPV-16. Seroreactivity was significantly associated with an 

age of 25 to 30 years (OR, 2.3; 95% CI, 1.2 to 4.4), three or more lifetime 

sexual partners (OR, 2.9; 95% CI, 1.1 to 10), and history of a sexually 

transmitted disease other than HPV (OR, 3.1; 95% CI, 1.5 to 6.3). The 

percent seropositivity increased linearly with number of lifetime sexual 

partners until reaching a plateau at 35% for women with more than six 

partners (chi for linear trend, P < 0.001). The low sensitivity of HPV-16 

VLP-based ELISA may limit the usefulness of the assay as a diagnostic test 

for HPV-16 infection. However, the assay appears to have adequate 

specificity and should be useful as an epidemiological marker of HPV-16 

infection and sexual behavior. 

=================================================================== 

13.) Detection of human papillomavirus mRNA and cervical cancer cells in 

peripheral blood of cervical cancer patients with metastasis. (TAIWAN) 

=================================================================== 

Author 

Pao CC; Hor JJ; Yang FP; Lin CY; Tseng CJ 

Address 

Department of Biochemistry, Chang Gung College of Medicine and Technology, 

Taipei, Taiwan. ccpao@cguaplo.cgu.edu.tw 

Source 

J Clin Oncol, 15(3):1008-12 1997 Mar 

Abstract 

PURPOSE: To determine the presence of cervical cancer cells in circulating 

peripheral blood of stage IVb cervical cancer patients with metastasis to 

distant organs. PATIENTS AND METHODS: Cervical cancer tissue from 15 stage 

IVb cervical cancer patients with metastasis were analyzed for the presence 

of human papillomavirus (HPV) type 16 DNA by nested polymerase chain 

reaction (PCR). The presence of transcriptional products of the HPV type 16 

E6-transforming gene in the peripheral blood of the same 15 cancer patients 

was analyzed by reverse transcription and PCR. Cervical tissues and 

peripheral-blood specimens from 12 normal healthy individuals served as 

controls. RESULTS: Thirteen of 15 (86.7%) cervical cancer tissues from same 

number of patients were found to contain HPV type 16 DNA. Peripheral-blood 

specimens from 12 of 13 (92.3%) cervical HPV DNA-positive patients were 

found to contain HPV-specific mRNA detectable by reverse transcription (RT) 

and PCR. Cervical tissues from all 12 normal controls were HPV-free. None 

of the peripheral-blood specimens from two cervical HPV-negative cancer 

patients and 12 normal controls contained detectable amounts of mRNA of HPV 

type 16 E6-transforming gene. CONCLUSION: The most likely source of the 

HPV-specific mRNA detected in the peripheral blood of cervical cancer 

patients with metastasis is the cervical cancer cells derived from or shed 

from the cervix. The presence of HPV E6 mRNAs in peripheral blood may be a 

sensitive indicator of circulating cervical cancer cells. If PCR positivity 

is proven to be able to predict disease progression reliably, these 

findings may have clinical applications in the treatment of cervical and 

many other cancers. 

=================================================================== 

14.) Human papillomavirus in tissue of bladder and bladder carcinoma 

specimens. A preliminary study. (GERMANY) 

=================================================================== 

Author 

Ludwig M; K&uml;ochel HG; Fischer C; Ringert RH; Weidner W 

Address 

Department of Urology, Justus-Liebig-Universit&uml;at, Giessen, Germany. 

Source 

Eur Urol, 30(1):96-102 1996 

Abstract 

OBJECTIVE: To evaluate the significance of HPV type 6b, 11, 16 and 18 

together with type-specific antibodies in the serum of bladder carcinoma. 

METHODS: The prevalence of HPV type 6b, 11, 16 and 18 in bladder tumor, 

normal bladder and urethra together with type-specific antibodies in serum 

was investigated in 23 patients with bladder cancer and 9 patients with 

chronic cystitis. HPV DNA analysis was done by polymerase chain reaction 

(PCR). Open reading frames of HPV were expressed in Escherichia coli as 

beta-galactosidase fusion proteins. RESULTS: HPV 6b was demonstrated in the 

tumor tissue of 6 patients (19%), and in the nonmalignant specimens of 6 

further patients (19%). HPV 16/18 was only found in the urethral swabs of 2 

patients (6%). Anti-HPV antibodies were positive in 7 patients (22%). There 

was no association between the demonstration of HPV 6b and the occurrence 

of bladder tumor in this study. CONCLUSION: Though, in this study, HPV was 

not associated with bladder cancer, further investigation is necessary to 

elucidate the role of HPV 6b in bladder tissue possibly by a 

semiquantitative PCR in tissue samples and of anti-HPV antibodies in serum. 

=================================================================== 

15.) Detection of human papillomavirus (HPV) type 47 DNA in malignant 

lesions from epidermodysplasia verruciformis by protocols for precise 

typing of related HPV DNAs. (JAPAN) 

=================================================================== 

Author 

Adachi A; Kiyono T; Hayashi Y; Ohashi M; Ishibashi M 

Address 

Laboratory of Viral Oncology, Research Institute, Nagoya, Japan. 

Source 

J Clin Microbiol, 34(2):369-75 1996 Feb 

Abstract 

Our discovery of human papillomavirus type 47 (HPV47) in benign lesions 

from a patient suffering from epidermodysplasia verruciformis prompted us 

to examine whether the viral DNA also resided in malignant lesions from the 

same patient. By using newly devised protocols for amplifying a group of 

epidermodysplasia verruciformis-associated HPV DNAs by PCR and 

differentially identifying them by reverse-phase dot blot hybridization, we 

demonstrated that HPV47 DNA, but not other HPV DNAs of the group, was 

abundant (about 10(3) copies per diploid amount of cell DNA) in DNAs 

prepared from three carcinomas. Using DNA from one of these carcinomas, we 

also confirmed that DNA of HPV5, HPV14, or HPV21, detected in significant 

amounts in DNAs from benign lesions from the patient, were present only in 

negligible amounts or not at all. The results suggest the involvement of 

HPV47 DNA in tumorigenesis. Furthermore, we demonstrated by the Southern 

technique that most, if not all, of the HPV47 DNA consists of either a unit 

(or a nongrossly deleted unit) length of the viral genome carrying no (or 

no gross) internal rearrangements or tandem repeats. This and other results 

obtained by this technique indicated that a considerable amount of the 

viral DNA resides as a circular monomer a unit length of the viral genome 

in carcinoma cells, while the remainder reside as catenanes, concatemers, 

or both. The concatemers were considered more likely to be replicated 

without integration into cellular DNA than to be integrated, because no 

bands for the corresponding fragments including integration sites were 

detected by treatment with restriction enzymes that would have produced 

such fragments. 

=================================================================== 

16.) HLA and susceptibility to cervical neoplasia. (NETHERLANDS) 

=================================================================== 

Author 

Krul EJ; Schipper RF; Schreuder GM; Fleuren GJ; Kenter GG; Melief CJ 

Address 

Department of Pathology, Leiden University Medical Center, The Netherlands. 

Source 

Hum Immunol, 60(4):337-42 1999 Apr 

Abstract 

The association between cervical neoplasia and certain HLA phenotypes 

observed in different studies has not been consistent. By serological 

typing, the association between HLA antigens, cervical carcinoma and 

cervical intraepithelial neoplasia (CIN) was studied in a group of 172 and 

116 patients, respectively. We demonstrated an increased frequency of B63 

in patients with HPV types other than HPV 16 or 18, and B55 in patients 

that were negative for all HPV types. The association between cervical 

carcinoma and DQ3, described in various populations, was not observed in 

the present study. However, we confirmed other previously observed 

associations between cervical cancer and class II antigens, i.e., a 

positive correlation with DR15 irrespective of the HPV status, with DR3 in 

patients harboring HPV types other than HPV 16 or 18, and with DR11 among 

HPV 16 positive patients. In contrast, a negative correlation between DR13 

and HPV positive cervical cancer was observed which suggests protection of 

this antigen against HPV-associated cervical cancer. A slight increase of 

DR15 and DQ4 antigens was observed in CIN patients, suggesting that these 

specific HLA antigens may be important in determining the risk of CIN. 

=================================================================== 

17.) Non-isotopic in situ hybridization of HPV types in cervical 

intraepithelial lesions in patients with AIDS. (BRAZIL) 

=================================================================== 

Author 

Calore EE; Calore NM; Cavaliere MJ 

Address 

Department of Pathology, Faculty of Medicine, University of S~ao Paulo, 

Brazil. calore@uol.com.br 

Source 

Arch Gynecol Obstet, 262(1-2):75-9 1998 

Abstract 

Human papilloma viruses (HPVs), particularly types 16 and 18 have a key 

role in the development of preneoplastic and neoplastic lesions of the 

uterine cervix. We studied, by non isotopic in situ hybridization using 

probes to HPV 6, 11, 16 and 18, cervical biopsies from AIDS patients with 

condilomata or cervical intraepithelial neoplasia. There were 32 biopsies 

which showed low-grade cervical intraepithelial neoplasia (Lo-CIN); 5 

biopsies showed high-grade cervical intraepithelial neoplasia (Hi-CIN). Of 

32 Lo-CIN biopsies, 18 (56.3%) were positive for HPV; 7 for HPV 6 and/or 11 

(21.9%), 11 for HPV 16 and/or 18 (34.4%) and one for HPV 6 and 18. Of 5 

Hi-CIN biopsies 3 were positive for HPV: one for HPV 6 and 2 for HPV 16 or 

18. The total positivity was 56.8% (21/37). This result was similar to 

those obtained by various other authors studying the general population. 

=================================================================== 

18.) HLA-A2-restricted peripheral blood cytolytic T lymphocyte response to HPV type 16 proteins E6 and E7 from patients with neoplastic cervical 

lesions. (GERMANY) 

=================================================================== 

Author 

Evans C; Bauer S; Grubert T; Brucker C; Baur S; Heeg K; Wagner H; Lipford GB 

Address 

Institute for Medical Microbiology, Technical University of Munich, Germany. 

Source 

Cancer Immunol Immunother, 42(3):151-60 1996 Mar 

Abstract 

The DNA from human papillomavirus (HPV) can be detected in 90% of cervical 

carcinomas. To address whether patients infected with HPV can mount 

efficient T cell responses to this pathogen we examined the cytotoxic T 

lymphocyte (CTL) response of peripheral blood mononuclear cells (PBMC) from 

patients with abnormal genital epithelial cells. PBMC from 11 HLA-A2+ 

patients were stimulated with CaSki, a cervical carcinoma cell line that is 

HPV 16+ and HLA-A2+. The CTL were screened for reactivity to the cervical 

carcinoma cell line C33A (HPV-, HLA-A2+) transfected with the HPV 16 E6 or 

E7 genes or the plasmid without insert. The CTL of 1 patient showed 

particularly strong CaSki and HPV E6 or E7 protein-specific cytotoxicity in 

a HLA-A2+-restricted fashion. In contrast, these CTL lysed neither a 

vector-only transfectant, the natural killer cell (NK) target, K562 nor the 

lymphokine-activated killer cell (LAK) target, Daudi. HLA-A2 restriction 

was demonstrated by the lack of recognition of a HLA-A2- CaSki cell line 

developed in our laboratory. The CTL line was cloned and 99 clones were 

harvested and screened; 51 clones lysed CaSki, of which 17 did not lyse the 

A2- CaSki. Of these HLA-A2- restricted clones, 8 did not lyse C33A 

transfectants, 6 lysed all C33A transfectants, 3 lysed C33A-E7 only and 

none lysed C33A-E6 only. These data imply that, within the bulk CTL line, 

HLA-A2-restricted recognition of antigens was restricted to CaSki antigens, 

antigens common to cervical carcinoma (CaSki plus C33A), or 

HPV-16-E7-derived antigen on the clonal level. The E7-restricted clones 

were negative for recognition of known HLA-A2-binding peptides from E7. 

=================================================================== 

19.) Human papilloma virus 16-18 infection and cervical cancer in Mexico: a 

case-control study. (MEXICO) 

=================================================================== 

Author 

Hern&acute;andez-Avila M; Lazcano-Ponce EC; Berumen-Campos J; Cruz-Vald&acute;ez A; 

Alonso de Ru&acute;iz PP; Gon&acute;zalez-Lira G 

Address 

Centro de Investigaci&acute;on en Salud Poblacional, Instituto Nacional de Salud 

P&acute;ublica, Cuernavaca, Morelos, M&acute;exico. 

Source 

Arch Med Res, 28(2):265-71 1997 Summer 

Abstract 

Cervical cancer (CC) is one of the principal public health problems in 

Mexico. The national mortality rate due to CC was estimated at 21.8 per 

100,000 among women over 15 years old during 1994. Despite this high 

incidence little is known in Mexico about the risk factors for CC. The 

objectives of the study were to evaluate the association between CC and HPV 

types 16 and 18 in women living in Mexico City. From August, 1990 to 

December, 1992, a case-control study was carried out in the metropolitan 

area of Mexico City. HPV 16-18 types were determined in a sample of 148 CC 

cases and 204 controls randomly selected from a sample frame representative 

of the metropolitan area of Mexico City. Sixty cases corresponded to in 

situ CC and 88 cases to the invasive phase. Determination of HPV 16 and 18 

types was done by polymerase chain reaction using primers specific to 

E6/E7. Results showed that 48.3% of in situ CC cases and 48.8% of invasive 

CC cases were positive for HPV 16 while only 13.2% were positive among the 

204 controls. Association between HPV 16 infection in the in situ cancer 

cases had an estimated odds ratio (OR) of 5.17 (95% CI 2.60-10.51). In the 

invasive cervical cancer cases, association between HPV 16 infection and 

invasive CC in this sample had an OR of 3.84 (95% CI 2.04-7.22). For the 

total sample, the estimated OR was 5.48 (95% CI 3.07-9.62). In the total 

sample, those women with a strong positive reaction to PCR were associated 

with a large increase in the risk, OR of 38.0 (95% CI 8.66-167.1). The 

prevalence the HPV 18 was 6.7%, only observed in the invasive cervical 

cancer cases. At present there is general consensus that HPV is the 

principal causal agent in C C etiology. This study intends to contribute to 

the knowledge concerning the etiology of cervical cancer. However, it is 

necessary to consider that the single most effective tool in the reduction 

of mortality due to cervical cancer has been the Pap test. Secondary 

prevention has proven to be highly effective in other populations, and this 

should be viewed as a priority activity for all at-risk populations. 

Although a vaccine for HPV may be available in the near future its efficacy 

in primary prevention has yet to be demonstrated. 

=================================================================== 

20.) Detection of human papillomavirus (HPV) type 6, 16 and 18 in head and 

neck squamous cell carcinomas by in situ hybridization. (CROATIA) 

=================================================================== 

Author 

Cerovac Z; Sar&uml;cevi&acute;c B; Kralj Z; Ban J 

Address 

Ruder Bo&uml;skovic Institute, Department of Molecular Genetics, Zagreb, Croatia. 

Source 

Neoplasma, 43(3):185-94 1996 

Abstract 

Seventy seven squamous cell carcinomas (10 oral cavity, 15 tongue, 26 

pharynx and 26 larynx), with different grading, were analyzed for the 

presence of HPV DNA by in situ hybridization. Positive signals were found 

on the nuclei of cancer cells in 25 (32.5%), in the epithelia adjacent to 

squamous cell carcinomas in 2 (8.7%), and in the resected margins in 1 

(4.3%) case. HPV DNA positive signals were obtained in 42% of laryngeal, 

34% of pharyngeal, in 20% of oral, and 20% of tongue carcinomas. Out of 25 

HPV positive carcinomas a single HPV type was detected in at least 11 

(44%), and double or multiple infection in 9 (36%) cases; altogether, HPV 6 

DNA was determined in 15 (60%), and HPV 16 and/or 18 DNA in 17 (68%) head 

and neck tumors. The detection rate of HPV 6 was lower than of HPV 16 

and/or 18 for tumors in oral cavity, tongue and larynx. Out of 25 HPV DNA 

positive carcinomas 21% were graded as G1, 27% as G2, and 44% were G3. The 

results indicate that HPV may be involved in the pathogenesis of head and 

neck squamous cell carcinomas. 

=================================================================== 

21.) Prevalence of human papillomavirus infection in women attending a 

sexually transmitted disease clinic. (JAPAN) 

=================================================================== 

Author 

Kubota T; Ishi K; Suzuki M; Utsuno S; Igari J 

Address 

Department of Obstetrics and Gynecology, Juntendo University, Juntendo 

Urayasu Hospital, Chiba, Japan. 

Source 

Kansenshogaku Zasshi, 73(3):233-8 1999 Mar 

Abstract 

The purpose of this study was to determine the prevalence of infection due 

to human papillomavirus (HPV) types of high and intermediate oncogenic 

risk, which was most frequently associated with uterine cervical neoplasia. 

The subjects were 236 prostitutes who visited a sexually transmitted 

diseases (STD) clinic in a metropolitan area in 1998. Another 95 women who 

visited a university hospital were selected as a normal control group. A 

swab sample collected from the uterine cervix and external os was subjected 

to hybrid capture assays for low-oncogenic-risk HPV types (HPV A; including 

types 6, 11, 42, 43 and 44) and high- and intermediate-oncogenic-risk HPV 

types (HPV B; including 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 

68). Chlamydia trachomatis and Neisseria gonorrhoeae. Fisher's exact test 

was used for statistical analyses. Among the microorganisms tested, the 

positive rate for HPV B was the highest both in the women attending the STD 

clinic (STD group) and in the control group. The positive rate for HPV B in 

the STD group was 47.5% (112 of 236), and this was significantly higher 

than the 5.3% (5 of 95) in the control group (p < 0.0001). These findings 

suggest that HPV examination is recommended for women who visit an STD 

clinic to assess the future risk of cervical neoplasia. 

=================================================================== 

22.) Demonstration of multiple HPV types in laryngeal premalignant lesions 

using polymerase chain reaction and immunohistochemistry. (ITALY) 

=================================================================== 

J Med Virol 1999 Sep;59(1):110-116 

Azzimonti B, Hertel L, Aluffi P, Pia F, Monga G, Zocchi M, Landolfo S, 

Gariglio M 

Department of Medical Sciences, Medical School of Novara, University of 

Piemonte Orientale "A. Avogadro," Novara, Italy. 

Recent evidence has shown that human papillomavirus (HPV) is involved in 

both the development of carcinoma and in premalignant mucosal lesions of 

the oral cavity. This study examined the relationship of HPV infection to 

some pathological features in precancerous lesions of the larynx, not 

examined extensively so far. Fifty formalin-fixed paraffin-embedded tissue 

sections containing human laryngeal precancerous lesions were screened for 

the presence of HPV infection by polymerase chain reaction, and for capsid 

protein expression by immunohistochemistry with polyclonal antibody 

directed against the L1 protein. The presence of HPV DNA was detected in 28 

of 50 specimens (56%), including 9/12 cases with mild dysplasia (75%), 3/6 

cases with moderate dysplasia (50%), and 7/11 cases with severe dysplasia 

(64%). Multiple HPV infections, containing two or three types, were 

detected in 17 of the 28 HPV-positive lesions (60%). Of 21 cases with 

keratosis and no dysplasia, 11 were positive for HPV DNA (52%) and 4 showed 

L1 staining (36%). By contrast, L1 positivity was revealed only in two 

lesions with moderate dysplasia, confirming that fully productive HPV 

infection is strictly dependent on epithelial differentiation and surface 

keratinization. The probability that HPV is a cofactor in the malignant 

progression of these lesions is suggested by the fact that 3/4 patients who 

developed cancer within 50 months were positive for HPV DNA. Copyright 1999 

Wiley-Liss, Inc. 

=================================================================== 

23.) Adenocarcinoma of the uterine cervix in Ireland and Sweden: human 

papillomavirus infection and biologic alterations. (IRELAND AND SWEDEN) 

=================================================================== 

Mod Pathol 1999 Jul;12(7):675-82 

Skyldberg BM, Murray E, Lambkin H, Kelehan P, Auer GU 

Department of Oncology-Pathology, Cancer Center Karolinska, Huddinge 

Hospital, Karolinska Institute, Stockholm, Sweden. Barbro.Skyldberg@cck.ki.se 

Paraffin-embedded samples from cervical adenocarcinomas, 19 cases from 

Irish patients and 19 cases from Swedish patients, were analyzed by 

polymerase chain reaction for the presence of infection with human 

papillomavirus (HPV). The results were compared with DNA ploidy, 

proliferation activity, and p53 and p21/WAF1 expression. The studies were 

performed to discover whether high-risk HPV infection in adenocarcinomas of 

the uterine cervix is associated with an increased proliferative activity 

and genomic instability. The results show that the majority (84.6%) of 

patients 59 years of age or younger showed HPV infection. The overall 

prevalence of HPV DNA was 60.5%, with the high-risk types, 16 and 18, the 

most frequent. HPV-16 had a prevalence of 23.7% (9 of 38), and HPV-18 had a 

prevalence of 26.3% (10 of 38). The HPV-positive tumors predominantly 

showed a tetraploid DNA distribution pattern, whereas HPV-negative tumors 

more frequently showed highly scattered aneuploid DNA profiles. Both 

HPV-positive and HPV-negative cases displayed high proliferative activity, 

as indicated by high Ki-67 and cyclin A immunoreactivity. Tumor suppressor 

gene analysis detected low p53 expression and high p21/WAF1 expression in 

HPV-positive patients and high p53 expression without simultaneously 

increased p21/WAF1 (indicative of mutated p53) in HPV-negative cases in the 

groups of women older than 59 years of age. 

=================================================================== 

24.) Risk factors for high-risk type human papillomavirus infection among 

Mexican-American women. (USA-MEXICO) 

=================================================================== 

Cancer Epidemiol Biomarkers Prev 1999 Jul;8(7):615-20 

Giuliano AR, Papenfuss M, Schneider A, Nour M, Hatch K 

Arizona Cancer Center, University of Arizona, Tucson 85724, USA. 

agiuliano@azcc.arizona.edu 

Minority women in the United States experience a disproportionately high 

burden of the more than 2 million yearly cases of squamous intraepithelial 

lesions of the cervix. Risk factors for squamous intraepithelial lesions of 

the cervix are infection with the sexually acquired human papillomavirus 

(HPV), an early age at first intercourse, history of multiple sexual 

partners, oral contraceptive use, high parity, lower socioeconomic status, 

poor diet, immunosuppression, and promiscuous male sexual partners. 

Although Hispanics are the largest growing minority population in the 

United States, few HPV risk factor studies have either included or focused 

on Hispanics in the United States. To determine risk factors for HPV 

infection among Mexican-American women, we conducted a cross-sectional 

study from 1992-1995. Nine hundred and seventy-one women, 18-47 years of 

age, with cytology results were included in this analysis. Overall, 13.2% 

of participants were HPV positive by the Hybrid Capture tube method for 

high-risk types 16, 18, 31, 33, 35, 45, 51, 52, or 56. Age [adjusted odds 

ratio (AOR) = 0.3 for ages >36 years compared with ages 18-20] and duration 

of oral contraceptive use (AOR = 0.4 for > or =4 years relative to 

nonusers) were inversely associated with these high-risk types of HPV 

infection. Marital status (AOR = 1.9 among single women compared with 

married) and lifetime number of sexual partners (AOR = 2.3 for women > or 

=5 partners relative to monogamous women) were positively associated with 

an increased risk. Participants born in Mexico were significantly (P < 

0.05) older, had fewer sex partners, and older age at first intercourse. 

Despite this lower behavioral risk profile, women born in Mexico were 

significantly more likely (AOR = 1.9; CI = 1.2-3.2) to have an HPV 

infection compared with United States-born, Mexican-American women after 

adjustment for potential confounders. Collectively, these results suggest 

that an unmeasured factor, such as the sexual behavior of the male partner, 

may be influencing HPV risk. Further research is needed to define this 

factor and to assess cultural norms of sexual behavior. 

=================================================================== 

25.) Many different papillomaviruses have low transcriptional activity in 

spite of strong epithelial specific enhancers. (SINGAPORE) 

=================================================================== 

J Gen Virol 1999 Jul;80 ( Pt 7):1715-24 

Sailaja G, Watts RM, Bernard HU 

Institute of Molecular and Cell Biology, National University of Singapore, 

Republic of Singapore. 

Transcription of the E6-E7 genes of human papillomavirus type 11 (HPV-11), 

HPV-16 and HPV-18 is specific to epithelial cells. This mechanism 

originates from synergism between different transcription factors such as 

AP-1, NFI and Sp1, which occur in many different cell types, but whose 

activity is biased in favour of epithelial cells. In this study, the 

transcriptional regulation of 14 different papillomavirus types in the 

absence of the viral E2 transcription factor was compared. Genital HPV 

types, including high-risk, low-risk and common wart-associated HPVs, were 

found to have strong epithelial specific enhancers, irrespective of mucosal 

or skin target cell and pathology. Skin specific non-genital HPVs, like 

HPV-1 and HPV-8, as well as bovine papillomavirus type 4 (BPV-4), had much 

lower enhancer activity. Contiguous genomic segments including the enhancer 

and the E6 promoter of genital as well as non-genital papillomaviruses 

generally had very low transcriptional activities, presumably due to 

silencers between enhancer and promoter sequences. This generalization 

applies to all cell types tested in spite of significant quantitative 

differences between the cervical carcinoma-derived cell line HeLa, the 

skin-derived cell line HaCat, undifferentiated and differentiated primary 

keratinocytes. The only enhancer with activity in fibroblasts was 

identified in BPV-1, apparently a reflection of the broader target cell 

specificity of this virus. The low transcriptional activity of 

papillomaviruses most likely reflects the low gene expression required 

during most or even all parts of the life-cycle of these viruses. 

=================================================================== 

26.) Low frequency of human papillomavirus infection in initial papillary 

bladder tumors. (CANADA) 

=================================================================== 

Urol Res 1999 Jun;27(3):180-4 

Simoneau M, LaRue H, Fradet Y 

Centre de recherche en cancerologie de l'Universite Laval, Centre 

Hospitalier Universitaire de Quebec, Canada. 

The involvement of human papillomavirus (HPV) in bladder cancer remains 

controversial. We previously reported detection of L1-HPV DNA in 39% of 

bladder cancers of mixed grade and stage. To clarify the possible etiologic 

role of HPV we studied, using the same technique, a more homogeneous group 

of initial low-stage tumors. We investigated a total of 187 newly diagnosed 

superficial papillary bladder tumors for the presence of L1-HPV DNA by the 

polymerase chain reaction method and hybridization with specific probes for 

HPV 6, 11, 16, 18, 33. HPV DNA was detected in 16 (8.5%) of the 187 

specimens tested, although in a low copy number compared with SiHa cervical 

cancer cells used as control. HPV type 16 was observed in eight tumors 

while HPV type 6 and type 11 were each observed in three tumors. Two tumor 

specimens contained two types of HPV: one tumor hybridized with type 6 and 

16 and the other with type 11 and 18. This low rate of HPV detection (8.5%) 

in initial tumors does not favor a prominent role for HPV in bladder 

carcinogenesis. 

=================================================================== 

27.) Human papillomavirus genotype spectrum in Czech women: correlation of 

HPV DNA presence with antibodies against HPV-16, 18, and 33 virus-like 

particles. (CZECH REPUBLIC) 

=================================================================== 

J Med Virol 1999 Aug;58(4):378-86 

Tachezy R, Hamsikova E, Hajek T, Mikyskova I, Smahel M, Van Ranst M, Kanka 

J, Havrankova A, Rob L, Guttner V, Slavik V, Anton M, Kratochvil B, 

Kotrsova L, Vonka V 

Department of Experimental Virology, Institute of Hematology and Blood 

Transfusion, Prague, Czech Republic. rutach@uhkt.cz 

Because the biological spectrum of human papillomavirus (HPV) genotypes 

present in cervical cancer lesions varies according to the geographical 

region studied, and because little genotype information is available for 

Central and Eastern European countries, we studied the endemic HPV-genotype 

spectrum in cervical samples collected from women visiting gynaecological 

departments of selected hospitals in the Czech Republic. In a series of 389 

samples, 171 (44.0%) were positive for HPV DNA using a consensus-primer 

polymerase chain reaction (PCR). Genotyping of the HPV PCR products was 

done using dot-blot hybridisation with type-specific oligonucleotide probes 

and thermocycle DNA sequencing. Twenty-two different HPV types were 

detected, HPV-16 being the most prevalent type irrespective of severity of 

the lesions (55.0%). Multiple HPV types were found in 16.4% of our 

HPV-DNA-positive samples. The prevalence of HPV infection was 23.0% in 

women with normal findings and 59.4% in patients with cervical neoplasia, 

and increased significantly with the severity of the disease: 52.9% in 

low-grade lesions, 58.0% in high-grade lesions, and 73.5% in cervical 

carcinomas (P for trend < .00001). In the sera of 191 subjects, 89 with 

normal findings and 102 with different forms of cervical neoplasia, the 

prevalence of HPV-specific IgG antibodies was tested by an enzyme-linked 

immunosorbent assay (ELISA) using virus-like particles (VLPs) of HPV-16, 

-18, and -33. Antibodies were significantly more prevalent in 

HPV-DNA-positive than in HPV-DNA-negative women and there was no 

association with age. In agreement with the results of HPV genotyping, 

antibodies reactive with HPV-16 VLPs were the most frequent and, moreover, 

their prevalence increased with the cervical lesion severity. About half of 

the subjects with smears in which either HPV-16 or HPV-33 DNA had been 

detected possessed antibodies reactive with homotypic VLPs. With 

HPV-18-DNA-positive subjects, however, fewer than 25% displayed homotypic 

antibodies. In general, subjects older than 30 years of age had antibodies 

reactive to HPV-specific VLPs more often than subjects younger than 30 

years of age. In women with benign findings, the seropositivity to HPV-16, 

-18, and -33 VLPs increased with age, whereas in women with cervical 

neoplasia the seropositivity decreased with age. 

=================================================================== 

28.) Mucosal oncogenic human papillomaviruses and extragenital Bowen disease. (FRANCE) 

=================================================================== 

Cancer 1999 Jul 15;86(2):282-7 

Clavel CE, Huu VP, Durlach AP, Birembaut PL, Bernard PM, Derancourt CG 

Department of Pathology, Laboratoire Pol Bouin, Cell Biology Unit, CHU de 

Reims, France. 

BACKGROUND: Genital Bowen disease is known to have a strong association 

with human papillomavirus (HPV) type 16. On the other hand, previous 

studies of extragenital Bowen disease (EBD) that have used different 

hybridization techniques have produced discordant results in the detection 

of mucosal oncogenic HPV. METHODS: Ninety-four samples of EBD from 78 

patients were investigated clinicopathologically. DNA extracted from fixed 

and embedded tissues was analyzed for the presence of the main mucosal 

oncogenic HPV types 16, 18, 31, and 33 using polymerase chain reaction 

(PCR) with specific primers described in 1996 by Baay et al., which are 

particularly well adapted to fixed tissues and give small amplimers. 

Moreover, 11 EBD of the hands were investigated by in situ hybridization 

(ISH). RESULTS: Of the 94 extragenital BD obtained from 78 patients, HPV 

DNA type 16 was detected in 78 cases (83%) from 65 patients (83.3%) by PCR. 

Nine patients with EBD of the hands (90%) had HPV type 16, and ISH 

displayed a diffuse hybridization pattern that corresponded to the episomal 

viral form of HPV DNA. CONCLUSIONS: The current retrospective study of 94 

samples clearly demonstrates the high prevalence of HPV type 16 infection 

in EBD, especially in EBD of the hands. In this study, no specific 

clinical, topographic, or histopathologic features of any lesions were 

found to be indicative of the presence or absence of HPV. 

=================================================================== 

29.) High prevalence of a variety of epidermodysplasia 

verruciformis-associated human papillomaviruses in psoriatic skin of 

patients treated or not treated with PUVA. (GERMANY) 

=================================================================== 

J Invest Dermatol 1999 Jul;113(1):122-6 

Weissenborn SJ, Hopfl R, Weber F, Smola H, Pfister HJ, Fuchs PG 

Institut for Virology, University of Cologne, Germany. 

Epidermodysplasia verruciformis-associated human papillomaviruses and in 

particular human papillomavirus type 5 were recently shown to be highly 

prevalent in psoriatic skin. We have analyzed lesional skin from 54 

psoriasis patients for infections with genital-specific and 

epidermodysplasia verruciformis-specific human papillomaviruses to define 

the spectrum of involved human papillomavirus types and to test if it is 

influenced by psoralen ultraviolet A therapy. Using polymerase chain 

reaction analysis we could detect human papillomavirus sequences in skin 

lesions of 83% of the tested patients. In contrast, human 

papillomavirus-DNA was only demonstrated in 19% of skin samples from 42 

dermatologically healthy, immunocompetent individuals. Sequence analysis of 

the polymerase chain reaction amplimers revealed 14 human papillomavirus 

types, all belonging to the epidermodysplasia verruciformis or 

epidermodysplasia verruciformis-related papillomaviruses. Only in one case 

we identified sequences related to those of genital viruses, which, 

however, represented a putatively new human papillomavirus type. The most 

prevalent human papillomavirus type in our patient series was human 

papillomavirus type 36, found in 62% of the patients positive for human 

papillomavirus-DNA, followed by human papillomavirus type 5 (38%) and human 

papillomavirus type 38 (24%). Multiple infections with two to five 

different human papillomavirus types could be detected in skin samples of 

63% of the analyzed patients. The overall human papillomavirus detection 

rate did not differ significantly between patients which have been 

subjected to psoralen ultraviolet A photochemotherapy or solely treated 

with topical preparations (77 vs 89%). Human papillomavirus type 5, 

however, could be detected significantly more frequent in lesions of 

psoralen ultraviolet A-treated patients (p < 0.001). Our data strongly 

argue for infections with epidermodysplasia verruciformis-specific 

papillomaviruses being an almost consistent feature of the lesional 

psoriatic skin and substantiate the importance of further studies to 

elucidate a possible involvement of human papillomaviruses in psoriasis 

pathology. 

=================================================================== 

30.) Human papillomavirus type 31 oncoproteins E6 and E7 are required for 

the maintenance of episomes during the viral life cycle in normal human 

keratinocytes. (USA) 

=================================================================== 

Proc Natl Acad Sci U S A 1999 Jul 20;96(15):8449-54 

Thomas JT, Hubert WG, Ruesch MN, Laimins LA 

Department of Microbiology-Immunology, Northwestern University Medical 

School, 303 East Chicago Avenue, Chicago, IL 60611, USA. 

The E6 and E7 oncoproteins of the high-risk human papillomavirus (HPV) 

types are able to immortalize human keratinocytes in vitro and likely 

contribute to the development of anogenital malignancies in vivo. The role 

of these oncoproteins in the productive viral life cycle, however, is not 

known. To begin to examine these possible roles, mutations in E6 were 

introduced in the context of the complete HPV 31 genome. Although 

transfected wild-type HPV 31 genomes, as well as genomes containing an E6 

translation termination linker, an E6 frameshift mutation, and a point 

mutation in the p53 interacting domain were able to replicate in transient 

assays, only the wild-type genome was stably maintained as an episome. 

Interestingly, mutant genomes in either the E6 splice-donor site or 

splice-acceptor site were reduced in replication ability in transient 

assays; however, cotransfection of E1 and E2 expression vectors restored 

this function. In a similar fashion, genomes containing mutant HPV 31 E7 

genes, including a translation termination mutant, two Rb-binding site 

mutants, a casein kinase II phosphorylation site mutant, and a 

transformation deficient mutant, were constructed. Although transient 

replication was similar to wild type in all of the E7 mutants, only the 

casein kinase II mutant had the ability to maintain high copies of episomal 

genomes. These findings suggest a role for E6 and E7 in the viral life 

cycle beyond their ability to extend the life span of infected cells. 

=================================================================== 

31.) Clinical, histopathologic, and molecular aspects of cutaneous human 

papillomavirus infections. (USA) 

=================================================================== 

Dermatol Clin 1999 Jul;17(3):521-36, viii 

Fazel N, Wilczynski S, Lowe L, Su LD 

Department of Pathology and Dermatology, University of Michigan School of 

Medicine, Ann Arbor, USA. 

Human papillomaviruses comprise a large family of double stranded DNA 

viruses that are the etiologic agents of benign warts and anogenital 

cancers. At least 82 different human papillomavirus types have been 

identified and many remain yet uncharacterized. The development of new 

molecular techniques in recent years has led to an increased understanding 

of human papillomaviruses and their roles in carcinogenesis. Several 

clinicopathologic entities arising from human papillomavirus infection 

encountered by the dermatologist are the subject of the article. The 

epidemiology, molecular biology, clinical presentation, histologic 

findings, and treatment of each disorder, where applicable, is discussed. 

=================================================================== 

32.) Screening for genital human papillomavirus: results from an 

international validation study on human papillomavirus sampling techniques. (SPAIN) 

=================================================================== 

Diagn Mol Pathol 1999 Mar;8(1):26-31 

de Sanjose S, Bosch XF, Munoz N, Chichareon S, Ngelangel C, Balaguero L, 

Jacobs MV, Meijer CJ, Walboomers JM 

Servei d'Epidemiologia i Registre del Cancer, Institut Catala d'Oncologia, 

Barcelona, Spain. 

The objective of this study was to determine the validity of human 

papillomavirus (HPV) detection using exfoliated cervical cells compared 

with cervical biopsy specimens in women with normal cervix and to assess 

whether HPV detection rates using exfoliated cells is dependent on the 

number and order in which cervical scrapes are taken. Women undergoing 

hysterectomy for reasons other than cervical cancer were recruited in three 

hospitals in countries with varying risks of cervical cancer. After 

informed consent and at the time of surgery, three consecutive cervical 

scrapes were taken as well as four biopsy specimens, one in each of the 

quadrants around the cervical os. In this study, 331 women were recruited 

and provided 992 cell samples and 1324 biopsy samples. All scrapes and a 

sample of biopsy specimens (n = 103) were tested by polymerase chain 

reaction enzyme immunoassay using a general primer (GP5+/ bio6+). 

Type-specific tests were performed for 14 HPV types at the subpicogram 

level in one test and individually. Positive samples were verified using 

Southern blot hybridization. The prevalence of HPV DNA was 6.3% in cervical 

cells. Of 19 HPV positive samples in the scrapes, 17 were confirmed in the 

biopsy specimens. The agreement, as measured by the Kappa statistic, was 

0.90 (P < 0.0001). The concordance in detecting HPV infection between 

scrapes and biopsy specimens was 97.5%, and the concordance in categorizing 

the samples as negatives was 94.4%. These values were unchanged when the 

order in which scrapes were taken was compared. Among women without 

cervical cancer, HPV DNA detection rates do not vary if exfoliated cells or 

random biopsy specimens are taken as the primary testing specimen. 

Screening programs based on highly sensitive HPV DNA detection technology 

in cell scrapes should expect a minimal underdetection. 

=================================================================== 

33.) Use of the same archival papanicolanou smears for detection of human 

papillomavirus by cytology and polymerase chain reaction. (AUSTRALIA) 

=================================================================== 

Diagn Mol Pathol 1999 Mar;8(1):20-5 

McDonald RL, Rose BR, Gibbins J, Baird PJ 

Cytology Department, Baird Pathology, Toongabbie, New South Wales, Australia. 

An optimal method for the processing of archival cervical Papanicolaou 

(pap)-stained smears for the amplification of human papillomavirus (HPV) 

DNA by polymerase chain reaction (PCR) was developed. This methodology was 

then applied to a series of 44 pap smears designated as HPV positive or 

negative (on the basis of both major and minor cytological criteria) or 

cervical intraepithelial neoplasia (CIN)-cancer. For the detection of HPV 

DNA, each sample was tested with the consensus GP5/6 primers, and when 

negative, with CPI-IIG primers. The HPV DNA was detected in 100% (8 of 8) 

of CIN-cancer smears using the GP5/6 primers. In smears with cytological 

evidence of HPV without CIN. the use of both sets of primers yielded 

positive results in 100% (19 of 19) of the samples. Direct sequence 

analysis of PCR products showed that 16 of the 27 HPV-positive samples 

contained more recently described HPV types. When tested with both primer 

combinations, all 17 cytologically negative smears were positive for 

beta-globin but negative for HPV DNA. The findings show the value of using 

archival pap smears for further investigations to address issues such as 

latency, but they indicate that cytological criteria and DNA technology 

will be critical factors in the reliability of the results. 

=================================================================== 

34.) Detection and typing of human papillomavirus in cervical cancer in the 

Thai. (THAILAND) 

=================================================================== 

J Med Assoc Thai 1996 Dec;79 Suppl 1:S56-64 

Bhattarakosol P, Poonnaniti A, Niruthisard S 

Department of Microbiology, Faculty of Medicine, Chulalongkorn University, 

Bangkok, Thailand. 

One hundred formalin-fixed paraffin embedded tissues with histopathologic 

diagnosed invasive cervical cancer (squamous cell carcinoma) were examined 

for the presence of HPV-DNA by polymerase chain reaction (PCR) using 

L1-consensus primers. The results indicated that 82 out of 100 (82%) 

samples were positive for HPV-DNA. Among the positive samples, 50 samples 

(61%) were typed by dot hybridization technique (DH). HPV-16 was the 

dominant type (42.68%), followed by HPV-18 (20.73%) and HPV-33 (3.66%). 

There were double infection of HPV-16 and 18 in 5 (6.1%) samples. None of 

HPV-6 and 11 were detected in this study. This finding suggests that HPV 

infection is an important etiologic factor for the development of cervical 

cancer especially the infection with high risk types, i.e., HPV-16 and 18. 

=================================================================== 

35.) Correlation between polymerase chain reaction and cervical cytology 

for detection of human papillomavirus infection in women with and without 

dysplasia. (NORWAY) 

=================================================================== 

APMIS 1997 Jan;105(1):71-5 

Gjoen K, Sauer T, Olsen AO, Orstavik I 

Department of Virology, National Institute of Public Health, Oslo, Norway. 

The aim of this study was to compare the ability of two methods, the 

polymerase chain reaction (PCR) and cervical cytology, to detect HPV 

infection. The study population included 222 randomly selected women 

without dysplasia (controls) and 91 women with histologically confirmed 

dysplasia (CIN II-III) (cases). In women without dysplasia, 8.6% had 

cytological signs of HPV infection, whereas 15.3% were HPV DNA positive by 

PCR. In women with dysplasia, 72.5% had cytological signs of HPV infection, 

whereas 90.1% were HPV PCR positive. The statistical agreement between the 

two diagnostic methods was low (controls: kappa = 0.26, cases: kappa = 

-0.03). In total, PCR failed to detect 17 of 85 women with cytological 

signs of HPV infection, whereas cervical cytology failed to detect 48 of 

116 HPV PCR-positive women. In women with dysplasia, but not in women 

without dysplasia, the oncogenic HPV types were associated with cytological 

signs of HPV infection. 

=================================================================== 

36.) Detection and quantitation of human papillomavirus by using the 

fluorescent 5' exonuclease assay. (SWEDEN) 

=================================================================== 

J Clin Microbiol 1999 Mar;37(3):490-6 

Josefsson A, Livak K, Gyllensten U 

Department of Genetics and Pathology, Unit of Medical Genetics, University 

of Uppsala, S-751 23 Uppsala, Sweden. 

A method for the detection and quantitation of oncogenic human 

papillomavirus (HPV) was developed by using the fluorescent 5' exonuclease 

assay. The method is based on the amplification of a 180-bp fragment from 

the 3' part of the E1 open reading frame in a single PCR with type-specific 

probes for HPV types 16, 18, 31, 33, and 35. The probes can be used 

separately or in combinations of up to three probes per assay. Quantitation 

over a range of 10(1) to 10(6) initial HPV copies was possible by using 

real-time detection of the accumulation of fluorescence with cycle number. 

Reconstitution experiments, performed to mimic mixed infections, showed 

that individual HPV types can be detected down to a ratio of about 1% in a 

mixture. The performance of the assay depends on DNA quality, the presence 

of PCR inhibitors, and the number of different probes used simultaneously. 

This homogeneous assay provides a fast and sensitive way of screening for 

oncogenic HPV types in biopsy specimens as well as cervical smear samples. 

The closed-tube nature of the assay and the inclusion of uracil 

N'-glycosylase reduces cross contamination of PCR products to a minimum. A 

similar assay for beta-actin was used in parallel for quantitation of 

genomic DNA. After normalizing the samples for genomic DNA content, the 

mean number of HPV copies per cell could be calculated. 

=================================================================== 

37.) Risk factors for HPV detection in archival Pap smears. A 

population-based study from Greenland and Denmark. (GREENLAND AND DENMARK) 

=================================================================== 

Eur J Cancer 1998 Jul;34(8):1230-4 

Svare EI, Kjaer SK, Smits HL, Poll P, Tjong-A-Hung SP, ter Schegget J 

Danish Cancer Society, Institute of Cancer Epidemiology, Copenhagen, Denmark. 

The most important risk factor for cervical cancer is genital infection 

with certain types of human papillomavirus (HPV). The presence of HPV was 

studied in archival smears from a random sample of women living in 

Greenland (GW) and Denmark (DW) having, respectively, a high risk and an 

intermediate risk for cervical cancer. Risk factors were also examined of 

the original 126 Danish and 129 Greenlandic archived smears collected 

during October and November 1988. 125 were located from each country 

including all abnormal smears. HPV DNA was isolated from the smears and 

detected by means of a consensus polymerase chain reaction (PCR) detecting 

a broad spectrum of genital HPV types. HPV was detected in all the abnormal 

smears and in 22 and 33% respectively of the cytological normal smears from 

DW and GW. Risk of HPV was significantly higher in smears from women who 

started sexual life relatively recently (respectively, < or = 4 and < or = 

6 years ago in DW and GW) compared with > or = 10 years ago (adjusted 

prevalence-OR: 9.3; 95% CI: 2.2-39.2 in DW and 5.9; 95% CI: 1.4-25.3 in 

GW). Among other important risk factors were age in both areas, lifetime 

number of sex partners and current smoking in DW and ever and gonorrhoea in 

GW. This study confirms the usefulness of the method as all abnormal smears 

were positive and, furthermore, the predictors for HPV presence in the 

normal smears corroborate with those found in recent studies of HPV in 

fresh cervical swabs. Thus, this method can be useful for large-scale 

epidemiological studies of HPV DNA in already sampled material. 

=================================================================== 

38.) [Human papillomavirus infection in women with and without abnormal 

cervical cytology]. (MEXICO) 

=================================================================== 

Ginecol Obstet Mex 1993 Feb;61:27-34 

Tamayo Legorreta EM, Echaniz Aviles G, Cruz Valdez A, Camacho Alcantara G, 

Calderon Jaimes E 

Centro de Investigaciones sobre Enfermedades Infecciosas, Instituto 

Nacional de Salud Publica, Cuernavaca, Mor. 

This study sought to define the prevalence rates of human papillomavirus 

(HPV) infection and cytologic abnormalities in 3,257 sexually active 

females 13 to 45 years of age, undergoing routine cervical cytologic 

screening in the outpatient clinic of an urban hospital. One hundred and 

fifty patients (4.6%) showed cytologic evidence of cervical human 

papillomavirus infection (abnormal Pap). We selected a control group (n = 

150) with negative cervical cytologic smears. Cells collected were analysed 

for HPV-DNA by PCR amplification method with probes for HPV types 6.11, 

16.18 and 33. The HPV-DNA was detected in 21/300 (7.0%). The prevalence of 

cervical HPV-DNA types among women with negative cytology was 5.3% (8/150) 

and 8.6% (13/150) among women with abnormal Pap. The risk of HPV infection 

seems to be related with age at first intercourse, younger age and number 

of sexual partners. We did not find relation with the use of oral 

contraceptives smoking and history of prior sexually transmitted disease. 

=================================================================== 

39.) Follow-up of human papillomavirus (HPV) DNA and local anti-HPV antibodies in cytologically normal pregnant women. (HUNGARY) 

=================================================================== 

Med Microbiol Immunol (Berl) 1996 Nov;185(3):139-44 

Veress G, Csiky-Meszaros T, Konya J, Czegledy J, Gergely L 

Department of Microbiology, University Medical School of Debrecen, Hungary. 

The high level of progesterone during pregnancy may enhance the 

transcription and replication of genital human papillomaviruses (HPV) 

through the glucocorticoid/progesterone response element found in the long 

control region of the viral genome. In this study, cytologically and 

colposcopically healthy pregnant women were subjected to a follow-up 

examination. Samples from the uterine cervix were collected during early 

pregnancy (n = 39), in the third trimester (n = 31), and a few weeks after 

birth (n = 30). The presence of HPV DNA was detected by polymerase chain 

reaction (PCR), while local secretory anti-viral IgA antibodies were 

demonstrated by enzyme-linked immunosorbent assay using synthetic peptide 

antigens. Follow-up examination by PCR revealed HPV DNA persistence in 5 

women. In 5 other cases, HPV positivity changed from negative to positive 

during the follow-up. There was 1 case which changed from positive to 

negative and 1 in which the HPV type changed during the study. Altogether, 

12 of 39 women (31%) were shown to harbor HPV DNA at some time during 

follow-up. HPV DNA positivity increased from 18% during early pregnancy to 

27% after birth (difference not significant). On the other hand, there was 

a significant rise in the level of local antibodies against HPV antigens 

(E2, E7, and L2) between samples collected in early pregnancy and those 

collected after birth (P < 0.0001). This may indicate the reactivation of 

genital HPV infections during late pregnancy. 

=================================================================== 

40.) Relatively low prevalence of human papillomavirus 16, 18 and 33 DNA in 

the normal cervices of Japanese women shown by polymerase chain reaction. (JAPAN) 

=================================================================== 

Jpn J Cancer Res 1991 May;82(5):532-8 

Nishikawa A, Fukushima M, Shimada M, Yamakawa Y, Shimano S, Kato I, Fujinaga K 

Department of Obstetrics and Gynecology, Cancer Research Institute, Sapporo 

Medical College. 

Ninety-two cervical scrapes and tissues, obtained from cytologically or 

histologically normal cervices of Japanese women, were examined for the 

presence of human papillomavirus (HPV) 16, 18 and 33 DNA by the polymerase 

chain reaction (PCR) method. Five out of 92 cases were HPV 16 DNA-positive, 

but neither HPV 18 nor 33 DNA was detected. The HPV (type 16, 18 and 33) 

prevalence rate in pregnant women, including postpartum, was 10% (3/31), 

which was higher than that in non-pregnant women. In two HPV 16-positive 

cases, we detected HPV 16 DNA again 2 months later. HPV (type 16, 18 and 

33) prevalence in normal cervices was shown to be relatively low. However, 

it is very important to follow up the HPV-positive cases in cytologically 

normal cervices in order to elucidate the relation between HPV infection 

and the progression of cervical cancer. 

=================================================================== 

41.) Comparison of a one-step and a two-step polymerase chain reaction with 

degenerate general primers in a population-based study of human papillomavirus infection in young Swedish women. (SWEDEN) 

=================================================================== 

J Clin Microbiol 1992 Apr;30(4):987-92 

Evander M, Edlund K, Boden E, Gustafsson A, Jonsson M, Karlsson R, Rylander 

E, Wadell G 

Department of Virology, University of Umea, Sweden. 

The prevalence of human papillomavirus (HPV) infection in cervical cell 

scrapes from young women was determined by polymerase chain reaction (PCR) 

by using general primer pairs localized within the L1 region. With a 

one-step general PCR, 5.9% (35 of 590) of young women in a population-based 

study were found to contain HPV DNA. The proportion of HPV-positive women 

increased with age, from 1.4% (1 of 69) among women aged 19 years to 9.2% 

(13 of 142) among women aged 25 years. Among the cervical scrapes from 

women with normal cytology, 5.6% (30 of 539) harbored HPV DNA. A total of 5 

of 19 (26.3%) of the women with pathological signs were positive for HPV 

DNA. By a two-step PCR, using nested general primers, 20.3% (118 of 581) of 

all women were shown to contain HPV DNA. The proportion of HPV-positive 

women also increased with age, from 17.4% (12 of 69) among women aged 19 

years to 31.9% (43 of 135) among women aged 25 years, when the two-step PCR 

was used. Some 19.2% (102 of 530) of cervical scrapes from women with 

normal cytology contained HPV DNA. Among the women with pathological signs, 

16 of 19 (84.2%) were positive for HPV DNA. The HPV DNA-positive specimens 

were demonstrated to contain HPV type 6, 11, 16, 18, 31, 33, 35, 39, 40, 

45, 55, or 56. The most prevalent HPV types were 6 (2.0%) and 16 (2.7%). 

More than one type was found in 16 specimens. Sixty HPV-positive samples 

could not be typed. 

=================================================================== 

42.) Human papillomavirus DNA in unselected pregnant and non-pregnant women. (FINLAND) 

=================================================================== 

Int J STD AIDS 1990 Jul;1(4):276-8 

Soares VR, Nieminen P, Aho M, Vesterinen E, Vaheri A, Paavonen J 

Department of Obstetrics and Gynecology, University Central Hospital, 

Helsinki, Finland. 

Human papillomavirus (HPV) DNA is associated with genital squamous cell 

neoplasia, especially types 16, 18, and 31. Several studies, using 

histopathology and DNA hybridization, have shown an increased prevalence of 

cervical HPV DNA in pregnant women. We determined the prevalence of HPV DNA 

and the distribution of specific HPV DNA types in exfoliated cervical cells 

from 748 randomly selected pregnant and 503 non-pregnant women, using a dot 

blot DNA hybridization technique. The prevalence of HPV DNA was 9.6% in 

pregnant women and 8.9% in non-pregnant women. Thus, we found no evidence 

of higher prevalence of HPV DNA in pregnant women. HPV DNA types 16/18 and 

31/33/35 were more common than types 6/11. The prevalence of HPV DNA was 

highest (15%) in the youngest age groups suggesting an association between 

young age and the prevalence of HPV DNA. 

=================================================================== 

43.) Prevalence of HPV cervical infection in a family planning clinic determined by polymerase chain reaction and dot blot hybridisation. (LONDON) 

=================================================================== 

J Med Virol 1991 Jul;34(3):154-8 

Hallam N, Green J, Gibson P, Powis J, Bibby J 

Virus Reference Laboratory, Central Public Health Laboratory, London. 

The overall prevalence of human papillomavirus (HPV) cervical infection in 

131 women attending a family planning clinic was 7% (HPV 6/11, 16, 18, 31) 

by dot blot hybridisation, 53% (HPV 11, 16, 31) by polymerase chain 

reaction (PCR), and 56% by the two methods combined. HPV 16 and 18 were the 

commonest types (4% each) by dot blot, HPV 16 (39%) by PCR. Fifteen percent 

of subjects had mildly abnormal cervical cytology (grades 1A, 2A, or 3). 

There was no significant correlation between cytological abnormality and 

HPV positivity, or between cytological or HPV status and other postulated 

risk factors for cervical neoplasia. It is concluded that PCR is 

considerably more sensitive than dot blot DNA hybridisation in detecting 

HPV cervical infection in such a "low risk" setting, where HPV copy number 

may be low. Firm conclusions cannot be drawn from our results regarding a 

causal role for HPV or other factors in the development of cervical 

neoplasia. 

=================================================================== 

44.) Type-specific prevalence of human papillomavirus DNA among Jamaican colposcopy patients. (JAMAICA) 

=================================================================== 

J Infect Dis 1996 Mar;173(3):718-21 

Rattray C, Strickler HD, Escoffery C, Cranston B, Brown C, Manns A, 

Schiffman MH, Palefsky JM, Hanchard B, Blattner WA 

Department of Obsterics/Gynecology, University Hospital of the West Indies, 

Kingston, Jamaica. 

Human papillomavirus (HPV) types differ in their association with cervical 

cancer. Therefore, the types of HPV in precancerous lesions are important. 

In many regions with high cancer incidence, the HPV types in precancerous 

lesions have not been well studied. In Jamaica, a country that has high 

cervical cancer incidence, 174 colposcopy patients were tested for HPV DNA 

using polymerase chain reaction. HPV DNA detection was strongly related to 

presence and grade of cervical neoplasia (P<.001). Furthermore, severe 

neoplastic change was most highly associated with HPV DNA types also 

considered high-risk for severe neoplasia in other populations. HPV-45 DNA, 

a high-risk type uncommon in most previously tested countries, was detected 

in 12% of patients who had neoplasia. Thus, cervical neoplasia in Jamaica, 

as elsewhere, is linked to HPV. The high prevalence of HPV-45 was notable, 

and its relation to high cervical cancer incidence in Jamaica must be 

assessed. 

=================================================================== 

45.) Polymerase chain reaction detection and restriction enzyme typing of human papillomavirus in cervical carcinoma. (MALAYA) 

=================================================================== 

Med J Malaysia 1995 Mar;50(1):64-71 

Yadav M, Nurhayati ZA, Padmanathan A, Abdul Aziz Y, Norhanom AW 

Department of Genetics & Cellular Biology, University of Malaya, Kuala 

Lumpur. 

Specific human papillomavirus (HPV) types have been implicated in the 

development of cervical carcinoma worldwide. Novel molecular techniques 

have facilitated the detection and typing of HPV in cervical lesions. DNA 

preparations from a series of 23 histopathologically confirmed cervical 

carcinoma patients were analyzed by polymerase chain reaction (PCR) using 

degenerate primers for the presence of HPV DNA sequences. A total of 22 of 

23 cases studied (95.7%) were found positive for HPV DNA sequences. Further 

studies by DNA hybridization with viral specific probe and restriction 

enzyme analysis demonstrated the presence of HPV 16 in 73.9% (17/23) and 

HPV 18 in 65.2% (15/23) of the cases examined. Interestingly, the uncommon 

HPV 31 and 33 were also found but with a lower percentage (16.9%). It was 

noted that HPV 16 frequency in the carcinoma increased with age but HPV 18 

was evenly present at all ages investigated. We found that HPV was 

frequently associated with the majority of the cervical carcinomas, and in 

all but one case, oncogenic high risk HPV genotypes were present. We 

conclude that HPV infection of the genital tract has an important role in 

the development of the disease in Malaysia. 

=================================================================== 

46.) Human papillomavirus (HPV) cervical lesions: results from 300 Italian 

women studied with DNA hybridization techniques and morphology. (ITALY) 

=================================================================== 

Tumori 1988 Dec 31;74(6):745-9 

Nuzzo F, Tison V, Castagnoli A, Tiboni M, De Villiers EM 

Dipartimento di Patologia, Osp. M. Bufalini, Cesena, Italia. 

Human papillomavirus cervical infection was investigated in a series of 300 

unselected women by comparing morphological diagnoses (cytology and 

histology) with results of DNA hybridization techniques (filter in situ 

hybridization of DNA from exfoliated cervical cells and Southern blot 

analysis of HPV-DNA in cervical biopsy specimens). The prevalence of HPV 

cervical infection diagnosed by PAP smears was 11.6%. Despite 

disadvantages, filter in situ hybridization was confirmed to be 

particularly useful for screening purposes to detect HPV in cervical 

scrapings. In 3 cases it was the only applicable method for diagnosing 

"high-risk" HPV infection. Southern blot hybridization of tissue DNA with 

HPV 16-DNA revealed the presence of this virus in 8 cases, and HPV 31-DNA 

and HPV 42-DNA in 1 case each. 

=================================================================== 

47.) Detection of human papillomavirus (HPV) DNA in human prostatic tissues by polymerase chain reaction (PCR). (USA) 

=================================================================== 

Prostate 1993;22(2):171-80 

Sarkar FH, Sakr WA, Li YW, Sreepathi P, Crissman JD 

Department of Pathology, Wayne State University School of Medicine, 

Detroit, Michigan 48201. 

Human papillomavirus (HPV) infections are strongly linked to the 

pathogenesis of uterine cervical neoplasms, and have been implicated in 

other cancers of the female genital tract. In contrast, the association of 

HPV with the cancers of the male urogenital tract is less evident, except 

in anal and penile cancers. However, recent studies reporting the 

prevalence of HPV infections in human prostate cancers (60-100% HPV 16 

positive vs. no infection of HPV) have raised controversies regarding the 

prevalence of HPV in benign and neoplastic human prostate. We investigated 

the prevalence of HPV infections in prostatic intraepithelial neoplasia 

(PIN) and prostatic adenocarcinomas in 23 surgically resected prostates. 

Polymerase chain reaction (PCR) was used to amplify HPV 6b/11, 16, and 18 

specific DNA sequences, using type specific HPV primers selected from the 

transforming gene E6-E7. The areas of PIN and cancer in 6 microns H&E 

stained tissue sections were identified, and respective areas of PIN and 

cancer were isolated from the adjacent serial sections and used for DNA 

amplification and HPV detection (Fig. 1). Our results demonstrated the 

presence of HPV 16 in three carcinomas (13%), using type specific primers 

in PCR amplified samples. We were not able to demonstrate the presence of 

other HPV types (HPV 6b/11 or HPV 18) in any of the samples using specific 

primers. Two of these prostates showed relatively strong positive signals 

by dot blot analysis, when hybridized with a 32P-labeled HPV 16 type 

specific oligonucleotide probe. One more sample showed weak positivity, 

when hybridized with a 32P-labeled HPV 16 type specific oligonucleotide 

probe. Subsequently, we have confirmed these results by Southern 

hybridization of the samples transferred to nylon membrane after agarose 

gel electrophoresis and detected by HPV 16 type specific oligonucleotide 

probe, using chemiluminescent assay. We, therefore, conclude that HPV 

infections of the prostate in general are not as common as has been 

previously claimed by other investigators. 

=================================================================== 

48.) High-risk human papillomavirus types in cytologically normal cervical scrapes from Kenya. (KENYA) 

=================================================================== 

Med Microbiol Immunol (Berl) 1992;180(6):321-6 

Czegledy J, Rogo KO, Evander M, Wadell G 

Institute of Microbiology, University Medical School of Debrecen, Hungary. 

Seventy-seven women with normal cervical cytology on routine visit to a 

family planning clinic in Nairobi, Kenya, were analysed for genital human 

papillomavirus (HPV) types by polymerase chain reaction (PCR). We applied a 

general primer pair (GP60/GP124) recognising sequences conserved among HPV 

types 6, 11, 16, 18, 31 and 33. Of the 77 specimens tested 15 (19.5%) 

proved to be positive for genital HPV. Amplification products were examined 

for the presence of high-risk HPV types by Slot-blot hybridization. Out of 

the 15 PCR-positive samples, 4 were positive for HPV 16.3 for HPV 18, while 

1 contained both HPV 16 and 33. HPV DNA prevalence in this group of women 

from a "high-risk" area is similar to that in "low-risk" Swedish women but 

much lower than in cervical cancer samples from the same region. 

=================================================================== 

49.) Detection of type specific human papillomavirus (HPV) DNA in cervical cancers of Indian women. (INDIA) 

=================================================================== 

Indian J Pathol Microbiol 1995 Jan;38(1):33-42 

Chatterjee R, Roy A, Basu S 

Department of Tumor Virology, Chittaranjan National Cancer Institute, 

Calcutta, India. 

Commercial Vira Pap and Vira Type kits of Life Technologies Inc., U.S.A., 

were used to determine prevalence and type specific distribution of human 

papilloma viruses (HPV) in 18 biopsy samples of cervical carcinomas and 26 

specimens of exfoliated cervical cells (swabs). The women were either 

attending out-patient's department of a suburban hospital or a cancer 

hospital in Calcutta, India. HPV DNA was detected in 9 biopsy specimens but 

not in any of the cervical swabs. Five of the 9 HPV positive biopsies had 

HPV DNA type 16/18. Neither HPV 6/11 nor HPV 31/33/35 DNAs were detected in 

any of these 9 specimens. Results indicated possible presence of HPV DNAs 

of types other than the above in at least 4 specimens. 

=================================================================== 

50.) Natural history of cervical human papillomavirus lesions. (JAPAN) 

=================================================================== 

Intervirology 1995;38(3-4):192-4 

Katase K, Teshima H, Hirai Y, Hasumi K 

Department of Gynecology, Cancer Institute Hospital, Tokyo, Japan. 

A total of 87 HPV-positive patients with grade I and II cervical 

intraepithelial neoplasia (CIN I and II) were followed up by cytology and 

colposcopy every 3 months for more than 5 years following the first biopsy. 

These patients were classified into three groups (progressive, persistent, 

and regressive disease) according to the results. The human papillomavirus 

(HPV) genome and viral types were identified by Southern blot hybridization 

at Tm-40 degrees and Tm-20 degrees with DNA extracted from exfoliated 

cervical cells. The lesion progressed to CIN III in 4/87 patients (4.6%), 

persisted in 39 patients (44.8%), and regressed in 44 patients (50.6%). In 

the progressive disease group, HPV 16 was detected in 2 patients, HPV 33 in 

1 patient, and HPV 52 in 1 patient. In the persistent disease group, HPV 58 

was predominant (28%), whereas in the regressive disease group, there was 

no predominant HPV type. In 10/39 patients from the persistent disease 

group, cytological examination transiently revealed severe dysplasia and/or 

findings similar to carcinoma in situ. These patients showed severe 

cytological abnormalities only once or twice during the follow-up. These 

results suggest that the natural history of CIN possibly depends upon the 

type of HPV that infects the cervix, and the relative risk of progression 

was similar to that shown by previous cross-sectional studies. 

=================================================================== 

51.) Detection of human papillomavirus types in cervical lesions of patients from Taiwan by the polymerase chain reaction. (TAIWAN) 

=================================================================== 

Sex Transm Dis 1994 Nov-Dec;21(6):309-14 

Wu CH, Lee MF, Chang MC, Ho SC 

Department of Medical Research, Taichung Veterans General Hospital, Taiwan, 

Republic of China. 

BACKGROUND AND OBJECTIVES: The association of human papillomavirus (HPV) 

infection with cervical carcinoma is well documented. The HPV types in 

cervical lesions of patients from Taiwan are analyzed by the polymerase 

chain reaction (PCR). STUDY DESIGN: DNA was extracted from 

paraffin-embedded, formalin-fixed tissues using a sonication method. PCR 

was performed using type-specific primers for the presence of HPV types 6, 

11, 16, 18, 31, and 33 DNA. Amplified product was subjected to gel 

electrophoresis and Southern blot hybridization analysis. RESULTS: A total 

of 129 cervical lesions and normal cervical biopsies were examined. 

Histologic examination revealed a spectrum of lesions, which were 

classified as condyloma acuminata (AC), condyloma (CL), koilocytosis (KL), 

various grades of cervical intraepithelial neoplasia (CIN I, II, and III), 

carcinoma in situ (CIS), and invasive carcinoma (ICa). Of 114 cervical 

lesions, 65% (26 of 40) of AC; 61% (11 of 18) of CL; 20% (2 of 10) of KL; 

25% (1 of 4) of CIN I; 69% (9 of 13) of CIN II; 80% (12 of 15) of CIN III; 

83% (5 of 6) of CIS; and 100% (8 of 8) of ICa were positive for at least 

one type of HPV by the PCR. Among the 74 HPV-positive specimens, 19 (26%) 

were detected with multiple types. HPV DNA was detected in the cervical 

biopsies of 1 of 15 (6.7%) normal individuals. CONCLUSION: Excluding AC, 

HPV 6 and/or 11 (HPV 6/11), HPV 16 and/or 18 (HPV 16/18), and HPV 31 and/or 

33 (HPV 31/33) were detected in 40% (19 of 48), 71% (34 of 48), and 12% (6 

of 48) of neoplastic lesions of patients from Taiwan respectively. These 

findings are compatible with those reported by others worldwide. 

=================================================================== 

52.) Human papillomaviruses in cervical cancer I. HPV-16 and 18 predominate in the Greek population. (GREEK) 

=================================================================== 

Anticancer Res 1997 Jan-Feb;17(1A):117-20 

Vassilandonopoulou G, Panotopoulou E, Fotiou S, Tserkezoglou A, Machera E, 

Kottaridis S 

St. Savas Hospital, Papanikolaou Research Center, Athens, Greece. 

Human papillomaviruses (HPV) and their role in carcinogenesis have been the 

subject of extensive investigation Specific types of HPV have been 

associated with cervical carcinoma HPV 16 and 18 are mainly associated with 

malignant progression and considered "high risk" viruses Using Southern 

blot analysis and in situ hybridization we investigated the presence of 

papilloma viruses in cervical carcinoma patients as well as appropriate 

controls. The results presented here support the aetiological role of HPV 

16 and 18 in cervical carcinoma and demonstrate the prevalence of these 

viruses in Greek women. The role of viruses in carcinogenesis in well 

established in almost all species from fishes, to birds, to mammals. 

Although not well circumstantiated, viruses probably play as-great a role 

in human cancer as in other species. The role of human papillomaviruses 

(HPV) not only in benign proliferations, but also in a number of 

malignancies has long been postulated (1,2). Presently over 20 HPV types 

have been identified and there is evidence now associating specific types 

with certain human anogenital cancers, notably cervical cancer (3,4). 

Advance neoplasias such as squamous cell carcinomas are associated with 

types, 16,18 and 31, with type 16 prevailing in these lesions (5,6). In 

this paper we shall present evidence which extends and confirms that 

previously reported on the prevalence of HPV 16 and 18 in Greek women. 

=================================================================== 

53.) The prevalence of cervical infection with human papillomaviruses and cervical dysplasia in Alaska Native women. (ALASKA) 

=================================================================== 

J Infect Dis 1994 Apr;169(4):792-800 

Davidson M, Schnitzer PG, Bulkow LR, Parkinson AJ, Schloss ML, Fitzgerald 

MA, Knight JA, Murphy CM, Kiviat NB, Toomey KE, et al 

National Center for Infectious Diseases, Centers for Disease Control and 

Prevention, Anchorage, Alaska. 

Alaska Native women historically have high rates of sexually transmitted 

diseases (STDs) and invasive cervical cancer. Their prevalence of cervical 

infections with human papillomavirus (HPV) in relation to cervical 

dysplasia was determined with a commercial dot hybridization test for seven 

HPV genotypes. Type-specific HPV DNA, similarly distributed between 

genotype groups 16/18 and 31/33/35, was detected in 234 cervical specimens 

(21%) from 1126 Alaska Native women seeking routine care and colposcopy or 

from population-based lists. The prevalence of HPV DNA declined with age 

and increased with sexual activity and cigarette smoking. It was unrelated 

to use of oral contraceptives or condoms or to STDs. Relative risks 

associating HPV with increasing severe grades of cervical dysplasia 

increased markedly with HPV infection, up to 7.1 for high-risk genotypes 

16/18 and 14.4 for coinfection with 31/33/35. These genotypes were detected 

in 8% of women without dysplasia seeking routine care. Screening for 

strain-specific HPV DNA may identify women at highest risk for cervical 

neoplasia. 

=================================================================== 

54.) Detection of human papillomaviruses in exfoliated cervicovaginal cells by in situ DNA hybridization analysis. (TAIWAN-CHINA) 

=================================================================== 

J Clin Microbiol 1989 Jan;27(1):168-73 

Pao CC, Lai CH, Wu SY, Young KC, Chang PL, Soong YK 

Department of Biochemistry, Chang Gung Medical College, Taipei, Taiwan, 

Republic of China. 

A total of 851 specimens of exfoliated cervicovaginal cells and 27 

specimens of male urethral smears obtained from 706 individuals with 

various clinical findings were examined for the presence of human 

papillomavirus (HPV) types 6, 11, 16, 18, 31, and 33 by in situ DNA 

hybridization analysis. The nonradioactive DNA in situ hybridization method 

used in this study showed no detectable cross-hybridization either among 

different types of HPV (except between types 6 and 11) or between HPV DNA 

and human cellular DNA. Furthermore, this system was found to be more 

sensitive than the Southern blotting method in detecting HPV. HPV was found 

in 233 of 276 (84.4%) and in 34 of 47 (72.3%) samples of cervicovaginal 

cells from patients with urogenital condylomata and cervical dysplasia, 

respectively. HPV was also detected in 6 of 39 (15.4%) women with normal 

cytological findings who were also symptom-free. Young women who were at 

low risk but were infected with HPV showed significantly reduced ratios of 

helper-inducer T lymphocytes to suppressor-cytotoxic T lymphocytes compared 

with those of uninfected normal controls (1.28 +/- 0.31 versus 2.47 +/- 

0.64; P less than 0.001). This in situ DNA hybridization method can have 

broad application to the screening of HPV in early lesions and in 

normal-looking tissues and may be used to identify patients at risk of more 

serious or possibly malignant progression. 

=================================================================== 

55.) Detection and typing of human papillomavirus in cervical specimens of Turkish women. (TURKEY) 

=================================================================== 

Eur J Gynaecol Oncol 1997;18(6):546-50 

Guney AI, Ince U, Kullu S, Pekin S, Cirakoglu B 

Department of Medical Biology and Genetics, Faculty of Medicine, University 

of Marmara, Istanbul, Turkey. 

The DNA in situ hybridization (DISH) and conventional solution phase 

polymerase chain reaction (PCR) were applied to identify human 

papillomavirus (HPV) DNA in cervical specimens of Turkish women. Samples 

consisted of 21 cervical brushings from pregnant women and 20 

paraffin-embedded biopsies from women with condylomatous or dysplasic 

lesions. It was found that two out of 21 (9.5%) pregnant women were 

harbouring HPV-DNA detected by PCR. One woman was infected with HPV 16/30's 

and the other with an unidentified type. As for the biopsy specimens, the 

rate of HPV-DNA positivity was 30% and 45% by DISH and PCR, respectively. A 

double infection was observed in more than 50% of the positive cases. 

Moreover, HPV 18 was never detected. The results indicated that HPV-DNA is 

rarely present in cytomorphologically normal smears from pregnant women. 

The PCR method was successfully adapted for HPV typing in clinical lesions 

which simultaneously contained different HPV sequences. 

=================================================================== 

56.) Prevalence of human papillomavirus DNA in cervical tissue. Retrospective analysis of 855 cervical biopsies. (GERMANY) 

=================================================================== 

Arch Gynecol Obstet 1997;259(2):69-77 

Backe J, Roos T, Mulfinger L, Martius J 

Department of Obstetrics and Gynecology, University of Wurzburg, Germany. 

The histopathologic features of 855 cervical biopsies were correlated with 

the presence of human papillomavirus DNA using in situ hybridization (ISH) 

with biotin labeled type specific probes for Human Papilloma Virus (HPV) 

types 6, 11, 16, 18, 31, 33 and 51. HPV-DNA was found in 18% (13/72) of 

cervical intraepithelial neoplasia I (CIN I), 30% (35/115) of CIN II, 28% 

(57(206) of CIN III, in 84% (21/25) of flat condyloma and in 13% (15/112) 

of normal cervical tissue. HPV DNA was detectable in 11% (5/46) of cervical 

adenocarcinoma and in 21% (59/279) of squamous cell carcinoma (SCC) of the 

cervix. High risk HPV types were identified more often than low risk HPV 

types in CIN I, CIN II, CIN III and SCC. HPV type 16/18 predominates over 

HPV types 31/33/51 in CIN I, flat condyloma and in SCC. The prevalence of 

HPV was strongly associated with the grade of differentiation of SCC. It 

was identified in 59% (23/39) of well differentiated SCC, in 18% (25/142) 

of moderately differentiated and in 11% (11/98) of poorly differentiated SCC. 

=================================================================== 

57.) Prevalence of human papillomavirus DNA in female cervical lesions from Rio de Janeiro, Brazil. (BRAZIL) 

=================================================================== 

Mem Inst Oswaldo Cruz 1994 Oct-Dec;89(4):575-80 

Cavalcanti SM, Frugulhetti IC, Passos MR, Fonseca ME, Oliveira LH 

Departamento de Microbiologia e Parasitologia, Universidade Federal 

Fluminense, Niteroi, RJ, Brasil. 

A hundred-sixty paraffin-embedded specimens from female cervical lesions 

were examined for human papillomavirus (HPV) types 6, 11, 16 and 18 

infections by non-isotopic in situ hybridization. The data were compared 

with histologic diagnosis. Eighty-eight (55%) biopsies contained HPV DNA 

sequences. In low grade cervical intraepithelial neoplasias (CIN I), HPV 

infection was detected in 78.7% of the cases, the benign HPV 6 was the most 

prevalent type. HPV DNA was detected in 58% of CIN II and CIN III cases and 

in 41.8% of squamous cell carcinomas (SCC). Histologically normal women 

presented 20% of HPV infection. Oncogenic HPV was found in 10% of these 

cases, what may indicate a higher risk of developing CINs and cancer. 

Twenty-five percent of the infected tissues contained mixed infections. HPV 

16 was the most common type infecting the cervix and its prevalence raised 

significantly with the severity of the lesions, pointing its role in cancer 

pathogenesis. White women presented twice the cervical lesions of mulatto 

and African origin women, although HPV infection rates were nearly the same 

for the three groups (approximately 50%). Our results showed that HPV 

typing by in situ hybridization is a useful tool for distinguishing between 

low and high risk cervical lesions. Further studies are required to 

elucidate risk factors associated with HPV infection and progression to 

malignancy in Brazilian population. 

=================================================================== 

58.) Prevalence of human papilloma virus 16 or 18 in cervical cancer in Hualien, eastern Taiwan. (TAIWAN) 

=================================================================== 

Kao Hsiung I Hsueh Ko Hsueh Tsa Chih 1997 May;13(5):315-9 

Hsu YH, Wei TC, Horng IJ, Jan WC, Su IJ 

Department of Pathology, Tzu-Chi General Hospital, Hualien, Taiwan, 

Republic of China. 

In order to determine the association of human papilloma virus (HPV) with 

cervical cancer of patients in the Hualien area, we analyzed 40 cervical 

cancer specimens using polymerase chain reaction (PCR) to detect the 

presence of HPV type 16 (HPV-16) and type 18 (HPV-18) genomes. The results 

showed that at least 70% (28/40) of the specimens had HPV DNA. Of the 37 

squamous cell carcinomas of the cervix, HPV-16 was present in 25 cases 

(68%) and HPV-18 in 2 (5.4%). HPV-16 DNA was detected in one of 2 

adenocarcinomas and HPV-18 in a case of small cell carcinoma. Seven (87.5%) 

of 8 specimens from aborigines were HPV-positive. These findings support a 

role for HPV in the development of cervical cancer in the Hualien population 

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59.) Human papillomavirus types 52 and 58 are prevalent in cervical cancers from Chinese women. (CHINA) 

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Int J Cancer 1997 Feb 7;70(4):408-11 

Huang S, Afonina I, Miller BA, Beckmann AM 

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 

Seattle, WA, USA. 

A substantial body of evidence has confirmed human papillomavirus (HPV) 

infection as an etiologic agent in human cervical cancer. To evaluate the 

association between HPV and cervical cancer in Chinese women, we examined 

tumor specimens from women who lived in Shanghai, People's Republic of 

China. Biopsies from 40 women, diagnosed with either squamous-cell 

carcinoma (n = 35) or adenocarcinoma (n = 5) were tested for HPV DNA by 

PCR. The HPV types present in tumors were determined either by 

hybridization of PCR products with HPV type-specific probes or by PCR-based 

sequencing. A total of 35 of the 40 cervical cancer specimens (87.5%) 

contained HPV DNA. The following distribution and types were detected: 7.5% 

HPV 16, 10% HPV 18, 20% HPVs 16 and 18, 15% HPV 52, 15% HPV 58, 12.5% HPVs 

52 and 58 and 7.5% unclassified HPVs. In this population of Chinese women 

with cervical cancer, HPV 52 and 58 were as prevalent as the "high-risk" 

(for cervical cancer) viruses HPVs 16 and 18. 

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60.) Human papillomavirus infection and risk determinants for squamous intraepithelial lesion and cervical cancer in Japan. (JAPAN) 

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Jpn J Cancer Res 1997 Apr;88(4):376-84 

Sasagawa T, Dong Y, Saijoh K, Satake S, Tateno M, Inoue M 

Department of Obstetrics and Gynecology, School of Medicine, Kanazawa 

University, Takara-machi. 

A case control design was used to investigate human papillomavirus (HPV) 

prevalence and risk factors associated with development of cervical 

squamous intraepithelial lesion (SIL) and cervical cancer (CC) in Japan. 

One hundred and twenty-three women with histologically confirmed SIL or CC 

were compared to a control group of 778 cytologically normal women. With 

the use of a polymerase chain reaction (PCR)-based method for detection of 

low-risk (types 6 and 11) and high-risk (types 16, 18, 31, 33, 35, 52 and 

58) HPVs, a high prevalence of HPV infection was observed in smokers among 

the controls. Logistic regression analysis demonstrated that high-risk HPV 

infection was the most significant risk determinant for LSIL (OR=9.4, 95% 

CI=4.5-19), HSIL (OR=77, 95% CI=28-217) and CC (OR=97, 95% CI=35-269). It 

also showed that unmarried women, women married for 5 to 19 years and 

smokers represented high risk groups for SIL, while smokers and women with 

a history of many pregnancies/parities had increased risk for CC. Smoking 

was the only HPV infection-independent factor for CC, suggesting that 

smoking may have a carcinogenic effect on the cervix. Since neither history 

of other cancer nor family cancer history was associated with SIL or CC, 

genetic factors appear to play little role in cervical carcinogenesis. The 

risk for cervical neoplasia due to HPV infection increased after marriage 

in Japan, suggesting a role for husbands as carriers of HPV transmission. 

Protection from high-risk HPV infection may be of greatest importance for 

prevention of cervical cancer. 

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61.) Detection and typing of human papillomavirus in cervical carcinomas in Russian women: a prognostic study. (RUSSIA) 

=================================================================== 

Cancer 1999 May 1;85(9):2011-6 

van Muyden RC, ter Harmsel BW, Smedts FM, Hermans J, Kuijpers JC, Raikhlin 

NT, Petrov S, Lebedev A, Ramaekers FC, Trimbos JB, Kleter B, Quint WG 

Department of Gynecology, Reinier de Graaf Gasthuis, Delft, The Netherlands. 

BACKGROUND: The correlation between human papillomavirus (HPV) infection 

and tumor prognosis in 159 Russian women with cervical carcinoma was 

investigated. The presence of various HPV types was correlated with the 

histologic parameters of the carcinomas and with their immunoreactivity 

with antibodies to p53, Ki-67-Ag, and bcl-2. METHODS: Formalin fixed, 

paraffin embedded tissue specimens representing 159 cases of International 

Federation of Gynecology and Obstetrics Stage I and II were used. HPV DNA 

was detected by polymerase chain reaction (PCR) using a general primer set 

that targets the L1 region and synthesizes a product of only 65 base pairs. 

The HPV types were determined by direct sequencing and compared with known 

HPV types. RESULTS: All 159 carcinomas were positive for HPV. HPV 16 

(64.8%) was most frequently found, followed by HPV 18 (10.7%) and HPV 45 

(8.2%). In 6 patients (3.8%), HPV types could not been further classified, 

and these cases were therefore categorized as HPV X. Although a trend was 

noted toward poorer prognosis for women with carcinomas harboring HPV types 

16, 18, and 45 than for patients with carcinomas harboring HPV types 31, 

33, 35, 52, 56, 58, and 68, the differences were not statistically 

significant. The prevalence of adenocarcinoma and adenosquamous carcinoma 

was higher among HPV 18 positive patients than among patients with the 

other known HPV types (P=0.0002). CONCLUSIONS: The rate of HPV positivity 

in these 159 cervical carcinomas was 100%. These findings challenge the 

assumption that HPV negative cervical carcinomas exist. This high rate 

might be attributed to the use of a new broad-spectrum HPV PCR test. HPV 

typing in cervical carcinoma was not significantly related to clinical 

outcome. HPV 18 was significantly more frequently found in adenocarcinoma 

and adenosquamous carcinoma. The possibility of classifying HPV 45 as an 

oncogenic high risk type should be considered. 

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62.) Serologic response to human papillomavirus type 16 (HPV-16) virus-like particles in HPV-16 DNA-positive invasive cervical cancer and cervical intraepithelial neoplasia grade III patients and controls from Colombia and Spain. (COLOMBIA AND SPAIN) 

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ARTICLE SOURCE: J Infect Dis (United States), Jul 1995, 172(1) p19-24 

AUTHOR(S): Nonnenmacher B; Hubbert NL; Kirnbauer R; Shah KV; Munoz N; Bosch FX; de 

Sanjose S; Viscidi R; Lowy DR; Schiller JT 

ABSTRACT: A human papillomavirus (HPV) type 16 virus-like particle-based ELISA was used to 

assess antivirion immune responses in 300 women participating in cervical cancer case-control 

studies in Colombia and Spain. Virion IgG antibodies were detected in the sera of 51% and 59% of 

women with HPV-16 DNA-positive invasive cervical cancer and 81% and 73% of women with 

HPV-16 DNA-positive cervical intraepithelial neoplasia grade III (CIN III) in Colombia and Spain, 

respectively. Capsid antibodies were detected in 22% and 3% of cancer controls (P .001) and in 

43% and 10% of CIN III controls (P = .010) from Colombia and Spain, respectively. Since 

Colombia has an 8-fold higher incidence of cervical cancer, these results demonstrate an association 

between ELISA positivity and cancer risk. Capsid antibody responses did not correlate with 

humoral responses of the same women to HPV-16 E6 and E7 oncoproteins. 

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63.) Detection of human papillomavirus-related oral verruca vulgaris among Venezuelans. (VENEZUELA) 

=================================================================== 

ARTICLE SOURCE: J Oral Pathol Med (Denmark), Mar 1993, 22(3) p113-6 

AUTHOR(S): Premoli-de-Percoco G; Galindo I; Ramirez JL; Perrone M; Rivera H 

AUTHOR'S ADDRESS: Instituto de Investigaciones Raul Vicentelli, Facultad de Odontologia, 

Universidad Central de Venezuela, Caracas. 

ABSTRACT: A sensitive in situ hybridization test under low stringency conditions (LCS) with a set 

of digoxigenin-labeled human papillomavirus mixed probes (D-L HPV MP) revealed a positive 

reaction in 8 of 10 cases of oral verruca vulgaris (OVV). Ages ranged from 5 to 37 years with a 

mean of 14.5 years. 50% of all cases were located intraorally on the hard palate, followed in 

frequency by the commissures. These preliminary findings provide evidence of the role of HPV in 

OVV from a sample of the Venezuelan population. We show that in situ hybridization conducted 

under LSC is useful in HPV detection (regardless of the type) and the digoxigenin-labeling system is 

a rapid, relatively easy and specific method. In addition, this technique permits the retrospective 

evaluation of routinely processed material, thus widening the investigative spectrum for HPV. 

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64.) Oncogenic association of specific human papillomavirus types with cervical neoplasia. (USA, PERU, BRAZIL) 

=================================================================== 

ARTICLE SOURCE: J Natl Cancer Inst (United States), Oct 1987, 79(4) p671-7 

AUTHOR(S): Lorincz AT; Temple GF; Kurman RJ; Jenson AB; Lancaster WD 

ABSTRACT: Molecular hybridization analysis of human papillomavirus (HPV) DNA from 190 

cervical biopsy specimens from women in the United States, Brazil, and Peru revealed viral 

sequences in 2 (9%) of 23 biopsy specimens of normal mature squamous epithelium, 7 (44%) of 16 

biopsy specimens of metaplastic squamous epithelia, 60 (77%) of 78 cervical intraepithelial 

neoplasia (CIN), 57 (89%) of 64 invasive squamous carcinomas, and 8 (89%) of 9 endocervical 

adenocarcinomas. HPV typing by DNA hybridization revealed HPV 6 and HPV 11 sequences in 

metaplastic squamous epithelia, CIN I, and CIN II, but not in CIN III lesions or invasive 

carcinomas. HPV 16 was detected in metaplastic epithelium and in nearly half of the invasive 

squamous carcinomas and adenocarcinomas. It was present in 31% of CIN lesions, increasing in 

frequency with the severity of CIN from 20% of CIN I to 50% of CIN III. HPV 16 showed a 

striking difference in geographic distribution, being detected in 36% of the carcinomas from the 

United States compared to 64% of the carcinomas from Brazil and Peru. HPV 18 was found in 

metaplastic epithelia and in 17% of carcinomas but in only 1% of CIN lesions. HPV 31 was not 

found in metaplastic epithelium but was present in 6% of carcinomas and in 18% of CIN lesions. In 

addition, a group of uncharacterized HPVs, not corresponding to any of the probes used, was found 

in 5% of normal and metaplastic epithelia and in 18% of CIN and 19% of invasive cancers. These 

results suggest that individual HPV types that infect the cervix have varying degrees of oncogenic 

association. HPV 6 and HPV 11 appear to have very little oncogenic association, HPV 31 has low 

oncogenic association, and HPV 16 and HPV 18 have high oncogenic association. 

=================================================================== 

65.) Chromosome fragility in lymphocytes of women with cervical uterine lesions produced by human papillomavirus. (ECUADOR) 

=================================================================== 

ARTICLE SOURCE: Cancer Genet Cytogenet (United States), Apr 1992, 59(2) p173-6 

AUTHOR(S): Paz-y-Mino C; Ocampo L; Narvaez R; Narvaez L 

AUTHOR'S ADDRESS: Departamento de Ciencias Biologicas, Facultad de Ciencias Exactas y 

Naturales, P. Universidad Catolica del Ecuador, Quito. 

ABSTRACT: We studied 30 women with cervical lesions that showed human papillomavirus 

infection (HPV). Cervical HPV infection was diagnosed by cytology, histology, 

immunohistochemistry, and electron microscopy, as well as by DNA viral hybridization in situ with 6, 

11, 16, and 18 HPV types. Three groups of patients were studied: 15 women infected by HPV of 6 

and 11 types with koilocytic lesions and benign evolution, 15 women infected by HPV of 16 and 18 

types with koilocytic lesions and malignant evolution, and 15 normal women without cervical lesions 

who served as controls. For each group, chromosome fragility was studied in peripheral blood 

lymphocytes. Aphidicolin (AP) was used as a clastogenic agent at a concentration of 0.12 microM. 

There were significant differences (p less than 0.001) between the control population and the 

patients affected by HPV. There were also significant differences (p less than 0.001) between the 

two groups infected with HPV. Our findings support the concept that chromosome fragility could 

serve as a cytogenetic marker to measure evolution, prognosis, and treatment of cervical lesion 

associated with HPV. 

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66.) Multifocal papilloma virus epithelial hyperplasia [see comments] (GUATEMALA) 

=================================================================== 

COMMENTS: Comment in: Oral Surg Oral Med Oral Pathol 1994 Dec; 78(6):680 

ARTICLE SOURCE: Oral Surg Oral Med Oral Pathol (United States), Jun 1994, 77(6) p631-5 

AUTHOR(S): Carlos R; Sedano HO 

ABSTRACT: Multifocal papilloma virus epithelial hyperplasia is an infection of the oral mucosa 

produced by human papilloma virus types 13 and 32, which primarily bilaterally affects lips, lateral 

borders of tongue, and buccal mucosa. The attached oral mucosa, floor of mouth, soft palate, and 

oropharynx are sites that appear not to be affected. This study comprises 110 patients with 

multifocal papilloma virus epithelial hyperplasia identified over a period of 3 years in Guatemala City 

and neighboring rural areas. All but four patients were younger than 18 years of age. More than one 

affected patient was observed in several families. All but three cases occurred in patients living in 

extreme poverty (annual family income less than $1,200 in U.S. dollars). Biopsies of 60 lesions 

demonstrated acanthosis and nuclear degeneration within the epithelium. We suggest that the 

eponym Heck's disease be abandoned because this disease was described in the Latin-American 

literature before the initial description in the American literature. We propose the term multifocal 

papilloma virus epithelial hyperplasia, which best describes the nature and multifocality of this 

disease. 

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67.) Genital human papillomavirus infection in Panama City prostitutes. (PANAMA) 

=================================================================== 

ARTICLE SOURCE: J Infect Dis (United States), Oct 1989, 160(4) p599-603 

AUTHOR(S): Reeves WC; Arosemena JR; Garcia M; de Lao SL; Cuevas M; Quiroz E; Caussy 

D; Rawls WE 

ABSTRACT: Little is known of the natural history of genital human papillomavirus (HPV) infections 

in women from high-risk populations. Samples were collected from 183 Panama City prostitutes and 

assessed for HPV (filter in situ DNA hybridization) and for sexually transmitted agents. The cohort 

was followed for 8 mo; 51% of subjects completed four monthly return visits and 16% were 

sampled eight times. The proportion of women found infected with HPV increased significantly with 

increasing numbers of consecutive samples tested; 38 (21%) of 183 women were positive after one 

visit and 46 (82%) of 56 who completed six visits were infected. The pattern of viral detection over 

time was not random, which implied that most prostitutes were persistently infected with genital 

HPVs and that either scattered foci of infection or periodic reactivation of latent virus occurred. Our 

findings suggest that multiple sampling is necessary to accurately estimate HPV infection rates and to 

define whether patterns of DNA expression are present. 

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68.) Risk factors for genital papillomavirus infection in populations at high and low risk for cervical cancer. (PANAMA) 

=================================================================== 

ARTICLE SOURCE: J Infect Dis (United States), Oct 1994, 170(4) p753-8 

AUTHOR(S): Reeves WC; Gary HE Jr; Johnson PR; Icenogle JP; Brenes MM; de Britton RM; 

Dobbins JG; Schmid DS 

ABSTRACT: This study sought to determine risk factors for genital infection with papillomavirus 

(HPV) in Panamanian women 20-49 years old. Subjects were randomly selected from Herrera and 

Panama provinces (cervical cancer incidence 79 and 25/100,000, respectively). Participants were 

interviewed to determine sexual behavior. Cervicovaginal lavage specimens were obtained to test for 

HPV DNA by commercial dot blot hybridization. HPV-16/18 DNA was detected significantly more 

frequently (5%) in Panama than Herrera (2%) samples (P = .002). Clearly, infection with high-risk 

HPV types alone cannot account for the differences in cervical cancer incidence between the two 

populations. HPV-16/18 detection decreased with increasing years of sexual experience among all 

women in Panama and among women with multiple partners in Herrera. However, HPV-16/18 

detection did not change with sexual experience among monogamous women in Herrera. Thus, the 

epidemiology of HPV is complex and reflects both virus- and population-specific factors. 

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69.) Demonstration of multiple HPV types in normal cervix and in cervical squamous cell carcinoma using the polymerase chain reaction on paraffin wax embedded material. (ENGLAND) 

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ARTICLE SOURCE: J Clin Pathol (England), Jan 1990, 43(1) p52-6 

AUTHOR(S): Griffin NR; Bevan IS; Lewis FA; Wells M; Young LS 

AUTHOR'S ADDRESS: Department of Pathology, University of Leeds, England. 

ABSTRACT: The prevalence of human papilloma virus (HPV) types 6, 11, 16 and 18 was 

investigated using the polymerase chain reaction on formalin fixed, paraffin wax embedded material 

in 19 cases of cervical squamous cell carcinoma and in 10 normal cervices. HPV DNA was 

detected in 16 of 19 carcinomas, with multiple types present in 11 of these. HPV 16 or 18, or both, 

were present in all cases in which HPV was shown. Six of 10 cases of normal cervix contained 

HPV; five of these contained two or more HPV types, including HPV 16 or 18, or both. This study 

shows the feasibility of using the PCR on paraffin wax embedded material and indicates a high rate 

of carriage of multiple HPV types in both normal and neoplastic cervix. 

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70.) Morphological correlation of human papillomavirus infection of matched cervical smears and biopsies from patients with persistent mild cervical cytological abnormalities. (ENGLAND) 

=================================================================== 

ARTICLE SOURCE: Hum Pathol (United States), Sep 1995, 26(9) p951-5 

AUTHOR(S): Herrington CS; Evans MF; Gray W; McGee JO 

ABSTRACT: Human papillomavirus (HPV) analysis of cytological material has been advocated for 

determining those patients with low-grade cervical cytological abnormalities who have current 

high-grade squamous intraepithelial lesions (SILs). In this study, we analyzed concurrent cervical 

smears and biopsies from 167 patients with Papanicolaou (Pap) smears showing persistent atypical 

squamous cells of uncertain significance (ASCUS) or low grade SILs (1) to compare the detection 

of HPV by nonisotopic in situ hybridization (NISH) on matched smears and biopsies; (2) to analyze 

the type and distribution of NISH signal within lesions; and (3) to define further the ability of NISH 

techniques to distinguish between patients with low- and high-grade SIL. Whether present in cervical 

smears or biopsies, high-risk HPV types (16, 18, 31, 33, and related types) were significantly 

associated with high-grade SILs (P .001) but were found in 15% of low-grade SILs. Ninety percent 

of high grade lesions were directly infected by these HPV types, and good concordance (92.2%) 

was found between NISH analysis of matched cervical smears and biopsies, indicating accurate 

colposcopic targetting of biopsies and excision specimens. Punctate signal morphology, which 

correlates with viral integration, was associated with high-grade SILs but was also observed in two 

low-grade SILs. Although the presence of high-risk HPV types in low-grade SILs limits the 

predictive ability of HPV testing by this means in this group of patients, those patients with high-risk 

HPV infection of low-grade SILs may be a greater risk of progression to high-grade SIL or invasive 

carcinoma. If this were the case, HPV testing would be of potential value in the management of 

patients with low-grade cytological abnormalities. 

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71.) Epidermodysplasia verruciformis in Africans. (SOUTH AFRICA) 

=================================================================== 

ARTICLE SOURCE: Int J Dermatol (United States), Nov 1993, 32(11) p806-10 

AUTHOR(S): Jacyk WK; De Villiers EM 

ABSTRACT: BACKGROUND. Epidermodysplasia verruciformis (EV) is a rare cutaneous 

disorder characterised by persistent, refractory infection with human papillomaviruses (HPV). 

Although EV does not seem to have racial or geographic preference, there is a scarcity of reports on 

its occurrence in Africans. METHODS. Twenty Africans with EV were studied, and the literature on 

this condition in Africans was reviewed. Virologic studies were performed on 10 patients. 

RESULTS. Three types of lesions were observed: flat warts, pityriasis versicolor-like macules, and 

seborrheic keratosis-like changes. Malignant transformation occurred in only one patient. HPV-3 

was isolated only from flat warts, HPV-5 and HPV-17 were isolated only from PV-like lesions, 

whereas an HPV-5-related type was found in all three types of changes. HPV-5-related type 

revealed DNA that was related but not identical to any of the viruses in the HPV-5 group. This 

particular type was isolated from all five South African patients with EV in whom virologic studies 

were performed. CONCLUSIONS. The benign nature of EV in dark-skinned Africans has been 

confirmed. Four HPV types have been isolated, of which HPV-related type was found in all South 

African patients with EV and in all types of skin changes, regardless of their morphology. African 

patients with EV frequently present seborrheic keratosis-like changes. 

=================================================================== 

72.) Transmissibility and treatment failures of different types of human papillomavirus. (ISRAEL) 

=================================================================== 

ARTICLE SOURCE: Obstet Gynecol (United States), Mar 1989, 73(3 Pt 1) p308-11 

AUTHOR(S): Gal D; Friedman M; Mitrani-Rosenbaum S 

ABSTRACT: In order to evaluate the transmissibility and treatment failures of different types of 

human papillomavirus (HPV), we obtained biopsy specimens from genital lesions related to HPV in 

113 women prior to laser therapy. Sixty-eight had condylomata acuminata, 14 had flat condyloma, 

and 31 had cervical intraepithelial neoplasia with or without condylomata. Of 76 male sexual 

partners examined colposcopically, 58 (76%) had HPV-related lesions. All biopsy specimens were 

analyzed for specific type of HPV DNA by Southern blot hybridization with probes for HPVs 6, 11, 

16, and 18. Sixty-one women had HPV 6 or 11 (6/11), 40 had HPV 16 or 18 (16/18), and in 12 

the analysis was negative for these types of viral DNA. Deoxyribonucleic acid analysis of biopsy 

specimens from recurrent lesions showed the same type of viral DNA as in the primary lesion. 

Significantly more male partners (28 of 47) with the same HPV type were found among women with 

HPV 6/11 than among women with HPV 16/18 (P less than .005). Patients with HPV 16/18 had 

significantly more recurrences (14 of 40) after laser therapy than patients with HPV 6/11 (six of 60) 

(P less than .001). 

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73.) High frequency of detection of epidermodysplasia verruciformis-associated human papillomavirus DNA in biopsies from malignant and premalignant skin lesions from renal transplant recipients. (THE NETHERLANDS) 

=================================================================== 

ARTICLE SOURCE: J Invest Dermatol (United States), Sep 1995, 105(3) p367-71 

AUTHOR(S): de Jong-Tieben LM; Berkhout RJ; Smits HL; Bouwes Bavinck JN; Vermeer BJ; van der Woude FJ; ter Schegget J 

AUTHOR'S ADDRESS: Department of Dermatology, University Hospital Leiden, The Netherlands. 

PUBLICATION TYPE: JOURNAL ARTICLE 

ABSTRACT: Based on immunologic and epidemiologic data, it is plausible that skin cancer in renal transplant recipients is associated with human papillomaviruses (HPV). At present, conflicting evidence exists concerning the presence of HPV DNA in these cancers. We recently described a nested polymerase chain reaction method that enables the detection of all previously isolated epidermodysplasia verruciformis (EV)-associated HPVs. We now describe the detection of EV-associated HPV DNA in 49 (80%) of 61 biopsies from squamous cell carcinomas, in four (50%) of eight basal cell carcinomas, in 14 (93%) of 15 actinic keratoses, in two (40%) of five cases of Bowen's disease, and in four (57%) of seven keratoacanthomas. HPV DNA typing revealed that all detected HPV types belonged to the EV-associated HPV types. A wide spectrum of EV-associated HPVs was found, including six putative new HPV types. In a high percentage of the lesions more than one HPV type was detected. We often found the same HPV types in different skin biopsies from both malignant and premalignant lesions from the same patient. The high frequency of detection of EV-associated HPV types in biopsies from malignant and premalignant lesions is in agreement with the hypothesis that EV-associated HPVs are involved in the pathogenesis of skin cancer in renal transplant recipients. 

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DATA-MÉDICOS/DERMAGIC-EXPRESS No (69) 18/08/99 DR. JOSE LAPENTA R. 

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Produced by Dr. José Lapenta R. Dermatologist
Venezuela 1.998-2.024

Producido por Dr. José Lapenta R. Dermatólogo Venezuela 1.998-2.0024

Tlf: 0414-2976087 - 04127766810