Prevalence of human papillomavirus in cervical cancer: a multicenter study in China

A large-scale epidemiologic survey on the prevalence of different types of human papillomavirus (HPV) in cervical cancer in China is indicated because of the implications for the development of diagnostic probes and vaccines against cervical cancer. A total of 809 cervical cancer specimens were collected from 5 regions in China including Shanghai, Guangzhou, Sichuan, Beijing and Hong Kong. HPV DNA was detected in 83.7% of the specimens. HPV-16 was present in 79.6%, HPV-18 in 7.5%, HPV-52 in 2.6% and HPV-58 in 3.8% of all HPV-positive specimens. The prevalences of HPV-16 and HPV-18 in Hong Kong were 61.7 and 14.8%, respectively, representing a lower HPV-16 and a higher HPV-18 proportion compared with the other regions. HPV-16 remained the most common HPV infection in both squamous cell carcinoma (SCC) and adenocarcinoma (AC). The proportion of HPV-18 infection was significantly higher in AC than in SCC.     

Selected Risk Factors,Human Papillomavirus Infection and the P53 Codon 72 Polymorphism in Patients with Squamous Intraepithelial Lesions in Northeastern Thailand

Risk factors for cervical squamous intraepithelial lesions (SIL) including human papillomavirus (HPV) infection ‍and the p53 codon 72 polymorphism were investigated in a case-control study with 103 cases and 105 controls in ‍Northeastern Thailand. Increased risk for SIL was observed for age at menarche (odds ratio (OR) = 2.2; p<0.005), ‍age at the first sexual intercourse (OR=2.4; p<0.05), number of sexual partners (OR=2.7; p<0.005) and partners’ ‍smoking history (OR=2.3-3.2; p<0.01). Prevalence of malignant type of HPV infection in the control and SIL groups ‍was 18.1% and 60.2%, respectively. HPV infection significantly increased risk for SIL 6.8-fold (p<0.001). HPV-16 ‍infection was the commonest (31 out of 62 carriers) in SIL patients and highly associated with risk. The p53 codon 72 ‍polymorphism was not identified as a genetic risk for SIL in this study, as demonstrated in Thai cervical cancer. ‍Therefore, to prevent cervical neoplasia or HPV infection, inclusion of knowledge on sexual behavior and effects of ‍smoking into public health programs is important and, at the same time, a nation-wide screening scheme for cervical ‍abnormalities including HPV-typing is a high priority in Thailand.     

Integration of human papillomavirus vaccination, cytology, and human papillomavirus testing

There is justifiable excitement about the recent introduction of prophylactic vaccines against human papillomavirus (HPV) types 16 (HPV-16) and HPV-18. Preventing these infections theoretically could avert approximately 70% of cervical cancer cases worldwide. In the U.S., numerous influential advocates are calling for universal vaccination of adolescent females. Given the promise of the vaccines, perhaps it is inevitable that vaccine introduction is proceeding before full consideration of how universal vaccination would affect existing, successful cervical cancer prevention programs. Determining the impact and cost effectiveness of the vaccines unavoidably will require time. Nevertheless, it is worth describing in broad terms for the readers of Cancer Cytopathology how successful, broad HPV vaccination of adolescent girls may affect cytology and HPV testing.     

Cervical Cancer : Is Vaccination Necessary in India?

In India, cervical cancer is the most common woman-related cancer, followed by breast cancer. The rateof cervical cancer in India is fourth worldwide. Two vaccines, Gardasil and Cervarix, both targeting HPV-16and 18 which account for 70% of invasive cervical carcinomas, are licensed in the United States and numerouscountries worldwide. Both vaccine formulations have shown excellent efficacy with minimal toxicity in activefemale population but numerous questions arise in vaccinating like cost effectiveness, lack of proven efficacyagainst other HPV strains, social acceptance of HPV vaccination and other ethical issues. The main objective ofthis study is to emphasis the advantages and disadvantages of the vaccination in India.     

Prophylactic HPV vaccines: prospects for eliminating ano-genital cancer

Virtually all cases of cervical cancer and its precursor intra-epithelial lesions are a result of infection with one or other of a subset of genital human papillomaviruses (HPVs), suggesting that prevention of HPV infection by prophylactic vaccination would be a highly effective anticancer strategy. Two HPV L1 virus-like particle vaccines have been developed, a quadrivalent HPV16/18/6/11 product and a bivalent HPV16/18 product; both have been shown to be highly immunogenic with a good safety profile and 100% efficacy against HPV16/18-related high-grade cervical intra-epithelial neoplasia (CIN2/3), implying that they will be effective at preventing HPV16/18-related cervical cancer.     

Social Responsibility in Cancer Prevention Research: IARC as a 'Global Science Force'

Ten million new cancer patients are diagnosed each year worldwide. Many specific causes of cancer are known, ‍ranging from factors related to lifestyle, diet and chronic infections to occupational exposures. Primary and secondary ‍prevention continue to be of major importance in cancer control globally. The global burden of cancer, especially the ‍part attributable to infectious diseases, disproportionally affects populations in developing countries. Inadequate ‍access to treatment (pharmaceuticals and other modern technology) plays a role in perpetuating this disparity. ‍Drugs and vaccines may not be accessible because of excessive cost or because development of the required products ‍has been neglected. The remarkable advances in molecular understanding of the carcinogenesis process over the ‍past 25 years have transformed the approaches to cancer control. Promising new tools in preventive oncology, such ‍as immunization (vaccines) and chemoprevention, have emerged. Vaccines are currently being tested in trials e.g., ‍against hepatitis B virus and human papillomaviruses. Chemoprevention has been successfully achieved in animal ‍experiments, and has been validated in several clinical trials. The current agents and strategies should not be ‍regarded as a panacea; more effective and safer vaccines and chemopreventive agents are needed. Future enhanced ‍efforts on an international basis are needed to coordinate the prevention and intervention research efforts in a costefficient ‍and affordable manner. Cancer prevention deserves continuing high priority in terms of both research and ‍application, also in the developing countries. New ventures may be built on possible expansion of IARC’s role in ‍prevention and intervention research into a “Global Science Force” by following the examples of e.g., the Gambia ‍Hepatitis Intervention Study and the cervix cancer screening trials in India. WHO’s support with its regional offices ‍would be beneficial, together with further national funding and support, and research collaboration and funding ‍from more wealthy countries.     

Characterization of HPV genotype profile in squamous cervical lesions in Portugal, a southern European population at high risk of cervical cancer.

A different prevalence of human papillomavirus (HPV) types has been reported in distinct populations. Although Portugal has a relatively high incidence of cervical cancer within the European Union, no studies have been reported in the Portuguese population. Recently, a clinical trial using a vaccine targeted against HPV-16 demonstrated a high efficacy in preventing HPV-16 cervical lesions. The aim of the present study was the characterization of HPV genotype profile in squamous intraepithelial lesions (SIL) and invasive cervical cancer (ICC) from 608 patients using polymerase chain reaction (PCR) methodology. We frequently detected HPV-6/11 and HPV-16 in low-grade SIL (HPV-6/11, 18.9%; HPV-16, 44.2%). In high-grade SIL, HPV-16 was demonstrated in 74.2% of those lesions and in 80.0% of the cases with ICC. HPV-18 was found in 3.1%, 0.8% and in 15.0% of low, high SIL and ICC, respectively. The overall prevalence of multiple infections with high-risk HPV was 7.2%. Other types of HPV were detected in 7.0% of all cases. Our results demonstrate a high prevalence of HPV-16 in SIL and ICC in Portuguese women. Therefore, a prophylactic HPV-16/18 vaccine may be effective in the prevention of cervical cancer in a significant number of women from this southern European population.     

HLA-DQB1*02-restricted HPV-16 E7 peptide-specific CD4+ T-cell immune responses correlate with regression of HPV-16-associated high-grade squamous intraepithelial lesions.

PURPOSE: The fact that up to 30% of established high-grade squamous intraepithelial lesions (HSIL) of the cervix regress spontaneously presents the opportunity to identify clinically relevant human papillomavirus (HPV) viral epitopes associated with disease outcome. Two human HPV antigens, E6 and E7, are functionally required for initiation and maintenance of cervical cancer precursor lesions and invasive cervical cancer. The identification and characterization of endogenously processed HPV antigenic epitopes in closely characterized patient cohorts will provide insight into the reasons for success or failure of therapeutic approaches. EXPERIMENTAL DESIGN: We characterized the HPV-16 E6/E7-specific T-cell epitopes using E6/E7 overlapping peptide pools with peripheral blood lymphocytes obtained from normal healthy donors. We then analyzed the difference in the HPV-16 T-cell immune responses in HPV-16+ HSIL patients with or without spontaneous regression of lesions using the statistical methods. RESULTS: We have identified an HPV-16 E7-specific CD4+ T-cell epitope [amino acids (aa) 71-85] that was restricted by HLA-DQB1*0201. Analysis of peripheral blood lymphocytes obtained from 14 HLA-DQB1*02 patients with HPV-16+ HSILs showed that the HPV-16+ E7 peptide (aa 71-85)-specific CD4+ T-cell immune response was significantly higher in the group of patients with regression compared with the patients without regression (P value <0.05). CONCLUSIONS: The HPV-16 E7 peptide-specific CD4+ T-cell immune response correlates with spontaneous regression of established HPV16+ HSILs. Thus, this E7 epitope may be useful for the characterization of HPV-specific immune responses in patients infected with HPV-16 or immunized with HPV vaccines.     

宫颈高级别病变与HPV感染型别分析

目的探讨HPV在宫颈高级别病变中的感染率及感染型别。方法采用导流杂交法分别检测CINII～Ⅲ30例和宫颈癌患者160例HPV基因型别,比较HPV感染与宫颈病变的关系。结果CINⅡ～III和宫颈癌患者HPV感染率均为90％,且以单型别感染为主,分别为70．37％（19／27）、81．94％（118／144）;在CIN II～Ⅲ中HPV58型、52型感染居多,宫颈癌则以HPV16型、18型感染最常见;无论宫颈鳞癌还是宫颈腺癌,以HPV16型检出率最高。结论HPV16型、18型是宫颈癌的主要致病型,不同病理类型并无HPV型别上的差异;宫颈上皮高级别内瘤变则以HPV58型、52型感染为主;对HPV58型、52型感染者应重视随访。     

Nested Multiplex PCR Based Detection of Human Papillomavirusin Cervical Carcinoma Patients of North- East India

Background: Persistent infection of one or more of about 15 high-risk human papillomaviruses (HR-HPVs),most commonly HPV types 16/18, has a significant role in cervical cancer initiation and progression. There arelimited data available from north-east India about HPV prevalence though this region has high incidence ratesof cervical cancer. The aim of this study was to investigate the HPV genotypes prevalent in cervical cancerpatients of north-east India. Materials and Methods: We analyzed 107 cervical cancer patient samples. Nestedmultiplex PCR assays were employed for detection of 13 high risk and 5 low risk HPV types. Results: HPV wasconfirmed in 105 samples. The presence of 6 ‘carcinogenic’ HPV types, HPV-16 (88%), -18 (15%), -31(4%) ,-45(3%), -59 (4%), -58(1%), and one non carcinogenic, HPV-6/11 (6%), was recorded. Among various demographicand clinical factors only tumour stage showed a statistically significant association with HPV type infection(P=0.019). Conclusions: We suggest that the most prevalent genotype is HPV-16 followed by HPV-18 in cervicalcarcinoma patients of the north-eastern region of India. Advanced tumour stage may be associated with increasedpossibility of harbouring multiple HPV genotypes.     

Human papillomavirus vaccines versus cervical cancer screening

Prophylactic vaccination with human papillomavirus (HPV) virus-like particle (VLP) vaccines against HPV 16 and HPV 18, which are the cause of 70% or more of cervical cancers in women, has transformed our prospects for reducing the incidence of this disease on a global scale. HPV VLP vaccines are immunogenic, well tolerated and show remarkable efficacy, achieving >98% protection in randomised clinical trials against the obligate precursor lesions cervical intraepithelial neoplasia grade 2/3 (CIN2/3) and adenocarcinoma in situ. The implementation of these vaccines as a public health intervention is, however, complex. Cervical cancer screening can be a highly effective secondary intervention, but in the developing world these programmes are either not available or are ineffective. HPV vaccination represents the most effective intervention in that scenario. In countries with successful well-organised cervical cancer screening programmes, such as the UK, the cost-effectiveness of vaccination as opposed to screening is a major factor. Screening will have to continue, as only two of the 15 oncogenic HPV types are in the vaccines and for two to three decades at least unvaccinated sexually active women will remain at risk for the disease. However, if both vaccination and screening are combined then the virtual elimination of cervical cancer and the other HPV 16 and 18-associated cancers is possible.     

A comprehensive natural history model of HPV infection and cervical cancer to estimate the clinical impact of a prophylactic HPV-16/18 vaccine

The object of our study is to project the impact of a prophylactic vaccine against persistent human papillomavirus (HPV)-16/18 infection on age-specific incidence of invasive cervical cancer. We developed a computer-based mathematical model of the natural history of cervical carcinogenesis to incorporate the underlying type-specific HPV distribution within precancerous lesions and invasive cancer. After defining plausible ranges for each parameter based on a comprehensive literature review, the model was calibrated to the best available population-based data. We projected the age-specific reduction in cervical cancer that would occur with a vaccine that reduced the probability of acquiring persistent infection with HPV 16/18, and explored the impact of alternative assumptions about vaccine efficacy and coverage, waning immunity and competing risks associated with non-16/18 HPV types in vaccinated women. The model predicted a peak age-specific cancer incidence of 90 per 100,000 in the 6th decade, a lifetime cancer risk of 3.7% and a reproducible representation of type-specific HPV within low and high-grade cervical precancerous lesions and cervical cancer. A vaccine that prevented 98% of persistent HPV 16/18 was associated with an approximate equivalent reduction in 16/18-associated cancer and a 51% reduction in total cervical cancer; the effect on total cancer was attenuated due to the competing risks associated with other oncogenic non-16/18 types. A vaccine that prevented 75% of persistent HPV 16/18 was associated with a 70% to 83% reduction in HPV-16/18 cancer cases. Similar effects were observed with high-grade squamous intraepithelial lesions (HSIL) although the impact of vaccination on the overall prevalence of HPV and low-grade squamous intraepithelial lesions (LSIL) was minimal. In conclusion, a prophylactic vaccine that prevents persistent HPV-16/18 infection can be expected to significantly reduce HPV-16/18-associated LSIL, HSIL and cervical cancer. The impact on overall prevalence of HPV or LSIL, however, may be minimal. Based on the relative importance of different parameters in the model, several priorities for future research were identified. These include a better understanding of the heterogeneity of vaccine response, the effect of type-specific vaccination on other HPV types and the degree to which vaccination effect persists over time.     

Accuracy of Visual Inspection with Acetic Acid (VIA) for Early Detection of Cervical Dysplasia in Tehran,Iran

Objective: To evaluate the accuracy of visual inspection with 5% acetic acid (VIA) when used to detect cervical ‍cancer and its precursors. ‍Methods: The study population included women attended Family Planning and Gynecological Clinic in Bagher ‍Abad Health Center and Mirza Koochak Khan Hospital for regular cervical screening tests. After obtaining informed ‍consent from each woman, VIA was performed. One hundred with a positive VIA test and 100 women with a ‍negative VIA test were randomly selected for this study. Cytology and colposcopy examination were performed for ‍all 200 cases and cervical biopsies were conducted for those individuals showing abnormal colposcopic findings. ‍Results: Nine cases in VIA-positive group and two cases in VIA-negative group had an abnormal cytology. Ninety ‍five women in the VIA-positive group and 25 in the VIA-negative group had abnormal colposcopic findings. From ‍biopsy examination, 67 (71%) of cases in the VIA-positive group and 3 (12%) cases in the VIA-negative group had ‍a final diagnosis of dysplasia. Among biopsied samples, only 7 cases of VIA-positive group showed abnormal result ‍and the remaining were normal. Based on these results, VIA test sensitivity and specificity were 95.7% and 44.0% ‍respectively, while they were 10% and 92% for cytology tests. ‍Conclusions: The results of this study indicate that although VIA is a sensitive screening test for detection of ‍cervical dysplasia, it can not be used by itself. Applying VIA along with Pap smears helps to detect a higher number ‍of cases with cancer precursor lesions.     

Incidence of cervical intraepithelial neoplasia in women infected with human immunodeficiency virus (HIV) with no evidence of disease at baseline: Results of a prospective cohort study with up to 6.4 years of follow-up from India

We report the incidence of cervical intraepithelial neoplasia (CIN) among HIV-infected women who did not have any colposcopic or histopathological evidence of CIN at baseline. Of the 1,023 women without any CIN at baseline, 855 (83.6%) have been followed up to a maximum of 6.4 years contributing 2,875 person years of observation (PYO). Among these 855 women, 54 cases of any CIN were observed resulting in incidence rate of any CIN of 1.9 per 100 PYO. The median time for follow-up for women with any CIN was 3.0 (IQR 1.6–3.7) years. The cumulative incidence rate per 100 PYO of CIN 2 or worse lesion in women with HPV-18 infection at baseline was 13.3% (95% CI 5.1–26.8); in women with HPV-16 infection was 10.8% (95% CI 4.4–20.9); in women with HPV-31 infection was 4.2% (95% CI 0.9–11.7); and in women with other high-risk HPV infections was 5.4% (95% CI 2.6–9.7). HPV-18 infection at baseline contributed highest frequency of incident CIN 2 or worse lesions followed by HPV-16 infection; however, other high-risk HPV types were also responsible for substantial number of incident CIN. The elevated risk of CIN2+ disease in the study cohort was non-significant in women with CD4 count <200, possibly because of the small number of cases. Our results emphasize the need for regular cervical cancer screening of HIV-infected women and urgent implementation of cervical cancer screening services in HIV programs in India and other low and middle-income countries.     

Cervical cancers require the continuous expression of the human papillomavirus type 16 e7 oncoprotein even in the presence of the viral e6 oncoprotein

High-risk human papillomaviruses (HPV), such as HPV-16, are etiologic agents of a variety of anogenital and oral malignancies, including nearly all cases of cervical cancer. Cervical cancers arising in transgenic mice that express HPV-16 E7 in an inducible manner require the continuous expression of E7 for their maintenance. However, in HPV-associated cancers in vivo, E6 and E7 invariably are coexpressed. In this study, we investigated whether cervical cancers rely on the continuous expression of E7 in the context of constitutively expressed E6. We placed the inducible HPV-16 E7 transgene onto a background in which HPV-16 E6 was constitutively expressed. In transgenic mice with high-grade cervical dysplastic lesions and cervical cancer, repressing the expression of E7 led to the regression of all cancers and the vast majority of high-grade dysplastic lesions. In addition, cervical cancers were occasionally observed in transgenic mice in which E7 was repressed and then reexpressed. Our findings indicate that even in the presence of constitutively expressed E6, the continuous expression of E7 is required for the maintenance of cervical cancers and most precancerous lesions. These data have important implications for the potential clinical use of drugs designed to inhibit the expression and/or function of E7 to treat HPV-associated cancers. Cancer Res; 72(16); 4008-16. ?2012 AACR.     

The Present Scenario of Cervical Cancer Control and HPV Epidemiology in India: an Outline

Objective: To give a clear picture with epidemiological evidence about the present scenario of cervical cancercontrol and HPV in India. Design: Review of published studies, concentrating on recent systematic reviews,meta-analyses and large prospective studies. Conclusions and recommendations: Cervical cancer is unique amongcancers in that it can largely be prevented through screening and removal of precursor lesions. It is the secondmost common cancer among women worldwide and is the most common malignancy in developing countries,particularly in India. Nowadays, cervical screening for women is necessary because there are no signs andsymptoms of cervical precancers. The establishment of a prevention program is urgently required consideringboth screening and vaccination. But most women in India do not have access to effective screening programmes.It has been estimated that in India, even with a major effort to expand cytology services, it will not be possibleto screen even one-fourth of the population once in a lifetime in the near future. New HPV vaccines will alsohelp prevent HPV infection and the precancerous changes that lead to cervical cancer. The focus on detectionand prevention of cervical cancer must be emphasized in a highly populated country like India to prevent itsextensive spread.     

Occurrence of antibodies to L1, L2, E4 and E7 gene products of human papillomavirus types 6b, 16 and 18 among cervical cancer patients and controls.

Sera from 118 women of 33 to over 90 years of age, with or without a history of cervical squamous-cell carcinoma, were examined for the presence of antibodies to HPV-6b, HPV-16 and HPV-18, L1, L2, E4, and E7 gene products by the use of bacterially derived beta-Gal fusion proteins and Western-blot analysis. Among the cervical cancer patients, 29/46 (63.0%) were positive for antibodies to E4 and/or E7 of HPV-16 and/or E7 of HPV-18. In contrast, only 2 of 31 (6.5%) non-genital cancer patients and 4 of 41 (9.8%) healthy individuals were antibody-positive for HPV-16 E4 or E7, while antibodies to the homologous proteins of HPV-18 could not be detected. Prevalence rates of antibodies to the HPV-16/18 late proteins were 25/46 (54.3%) in the cervical carcinoma group, 13/31 (41.9%) among women with non-genital cancer types, and 18/41 (43.9%) among normal, healthy individuals. Antibodies to HPV-6b late gene products ranged between 6.5% and 12.2% in the different patient groups. Antibodies to HPV-6b E4 and E7 were detected only once. By studying an additional control group of 207 women with a different age distribution, age-dependence of antibodies to HPV gene products could be ruled out. Whereas antibodies to late proteins may indicate that, regardless of clinical stage, HPV infections are wide-spread among the female population, the striking difference between the prevalence rates of antibodies to early proteins of HPV-16 and HPV-18 among cervical cancer patients and controls (p less than 0.001) supports the idea of the involvement of these virus types in carcinogenesis of the cervix.     

Cervical human papillomavirus infection and squamous intraepithelial lesions in rural Gambia, West Africa: viral sequence analysis and epidemiology

The development of effective strategies against cervical cancer in Africa requires accurate type specific data on human papillomavirus (HPV) prevalence, including determination of DNA sequences in order to maximise local vaccine efficacy. We have investigated cervical HPV infection and squamous intraepithelial lesions (SIL) in an unselected cohort of 1061 women in a rural Gambian community. Squamous intraepithelial lesions was diagnosed using cytology and histology, HPV was typed by PCR-ELISA of DNA extracts, which were also DNA sequenced. The prevalence of cervical HPV infection was 13% and SIL were observed in 7% of subjects. Human papillomavirus-16 was most prevalent and most strongly associated with SIL. Also common were HPV-18, -33, -58 and, notably, -35. Human papillomavirus DNA sequencing revealed HPV-16 samples to be exclusively African type 1 (Af1). Subjects of the Wolof ethnic group had a lower prevalence of HPV infection while subjects aged 25-44 years had a higher prevalence of cervical precancer than older or younger subjects. This first report of HPV prevalence in an unselected, unscreened rural population confirms high rates of SIL and HPV infection in West Africa. This study has implications for the vaccination of Gambian and other African populations in the prevention of cervical cancer.     

Safety and immunogenicity of human papillomavirus-16/18 AS04-adjuvanted vaccine in healthy Chinese females aged 15 to 45 years: a phase I trial

Globally, about 70% of cervical cancers are associated with human papillomavirus (HPV)-16 or HPV-18 infection. A meta-analysis of epidemiologic studies in China showed that HPV was present in 98% of cervical cancer samples. The HPV-16/18 AS04-adjuvanted vaccine Cervarix has shown a high level of protection against HPV-16/18 infections and associated cervical lesions. This phase I trial (NCT00549900) assessed the safety, tolerability, and immunogenicity of the vaccine in Chinese. Thirty healthy Chinese females, aged 15 to 45 years with a median age of 29.5 years, received three doses of Cervarix in Months 0, 1, and 6. Safety was assessed via recording solicited local and systemic symptoms within 7 days and unsolicited symptoms within 30 days after each vaccination. Serious adverse events, new onset of chronic diseases, and other medically significant conditions were recorded throughout this trial. As an exploratory objective, HPV-16/18 antibody titers were determined by enzyme-linked immunosorbent assay in serum samples collected in Months 0 and 7. Pain at the injection site was the most frequently reported local symptom. Two subjects reported medically significant adverse events. Both cases were assessed as unrelated to vaccination by the investigator. In Month 7, 100% seroconversion was observed for both anti-HPV-16 and anti-HPV-18 with high geometric mean antibody titers. HPV-16/18 AS04-adjuvanted vaccine, evaluated for the first time in Chinese females, was generally well tolerated and immunogenic, as previously shown in global studies.     

High-risk and multiple human papillomavirus infections associated with cervical abnormalities in Japanese women.

To estimate the risk of human papillomavirus (HPV) infection for cervical malignancies, we conducted a case-control study in Japan. Abnormal cervical cell (366) and normal cell samples (1562) were tested for the presence of HPV DNA using a new PCR-based test (LCR-E7 PCR). When single HPV infections were considered, 26 different HPV types were identified in normal cervices and in low-grade squamous intraepithelial lesions (LSIL); whereas HPV-16, -18, -31, -33, -35, -45, -51, -52, -56, -58 and -67 were detected in high-grade squamous intraepithelial lesions (HSIL) and in squamous cell carcinoma (SCC) of the cervix, and HPV-16 and -18 were detected in cervical adenocarcinoma. HPV-6 and -11 were detected in condyloma acuminatum tissue. In HSIL and SCC, HPV-16 was the most prevalent type and HPV-51, -52, and -58 were the next most prevalent; whereas HPV-39, -59, and -68 were not detected. Analysis by odds ratio (OR) revealed that HPV-11, -39, -42, -44, -53, -59, -62, and -66 (HPV-66: OR,139; 95% confidence interval (CI) = 6.7-168) were associated with LSIL; HPV-16, -18, -31, -51, -52 and -58 (HPV-16: OR, 69; 95%CI = 36-131) were associated with SCC; and HPV-16 and -18 (OR, 94; 95% CI = 28-317) were associated with adenocarcinoma. Multiple HPV infection was associated with LSIL (OR, 24; 95%CI = 13-44), HSIL (OR, 16; 95%CI = 8.4-32), and SCC (OR, 8.3; 95%CI = 3.2-22), although the prevalence decreased with the grade of the lesions. All results suggest that HPV-6 and -11 are condyloma types, HPV-16, -18, -31, -51, -52, -58, and perhaps -33, -35, -45, -56, and -67, are the high-risk HPV types, and many other types are LSIL-associated types in Japan. HPV typing and detection of multiple HPV infections in clinical samples may be useful as surrogate markers for cervical cell abnormalities.