Vaccine-related HPV genotypes in women with and without cervical cancer in Mozambique: burden and potential for prevention

Knowledge about the burden of Human Papillomavirus (HPV) infections in Sub-Saharan Africa is very limited. We collected cervical samples from 262 women from the general population and 241 tumor samples from women with invasive cervical cancer in Mozambique and tested them for HPV genotyping by the SPF(10)-LiPA(25) PCR system. Among the 195 women without cervical abnormalities by cytology HPV prevalence was 75.9%. In this group of women, the most frequently identified HPV types among HPV-positive women were in descending order of frequency: HPV51 (23.6%), HPV35 (19.6%), HPV18 (14.2%), HPV31 (13.5%) and HPV52 (12.8%). In women with cervical cancer HPV DNA detection was 100%. The type-specific distribution of the most frequent types in descending order of frequency was: HPV16 (47.0%), HPV18 (31.3%), HPV51 (14.8%), HPV52 (14.3%), HPV45 (12.6%), HPV35 (10.4%), HPV33 (4.8%) and HPV31 (2.6%). HPVs 16/18 and HPVs 16/18/31/45 were detected in 71.7% and 80.9% of cervical cancer tissue, respectively. While HPVs 51 and 35 were the two most common types in cytologically normal women in Mozambique, HPVs 16 and 18 remained the two most frequently identified types in cervical cancer. The introduction of an efficacious HPV 16/18 vaccine could potentially prevent the occurrence of 72% of cervical cancer cases and up to 81% of the cases if full cross-protection against HPVs 31 and 45 is assumed.     

Human papillomavirus genotype in cervical intraepithelial neoplasia grades 2 and 3 of Taiwanese women

We aimed to assess the distribution of human papillomavirus (HPV) genotypes in high‐grade cervical lesions in Taiwan. The study included 1,086 paraffin‐embedded, formaldehyde‐fixed cervical intraepithelial neoplasia (CIN) 2/3 specimens. HPV genotyping was performed using polymerase chain reaction (PCR)‐based methods. Multiple HPV types were validated by E6 type‐specific PCR, direct sequencing and/or real‐time PCR. HPV DNA was detected in 995 (91.6%) specimens, and multiple HPV types were identified in 192 (19.3%) samples. The leading HPV types were HPV16 (24%), HPV52 (20%), HPV58 (20%), HPV33 (13%), HPV31 (8%) and HPV18 (4.6%). Although the leading six types consisted of 87.6%, HPV16 or 18 comprised only 30.9%. The prevalence of different HPV types showed a significant association with age. In women older than 50 yr, HPV16 and 18 comprised 21.3% (83/389), while HPV52, 58 and 33 represented 55.5% (216/389). In women aged less than 50 yr, HPV16 and 18 comprised 32.1% (224/697, p < 0.0001), while HPV 52, 58 and 33 represented 47.9% (334/697, p = 0.02). The distribution of HPV genotypes was compared with previously reported findings for Taiwanese women with cervical cancer (CC). The overall HPV16 positivity rate was significantly higher in CC than in CIN 2/3 (odds ratio: 2.14, 95% CI: 1.91–2.40). In addition, HPV18, 39 and 45 were significantly overrepresented in CC, whereas HPV52, 58, 33, 31, 35, 51 and 53 were underrepresented. We concluded that an effective vaccine against the most common HPV types could prevent a significant proportion of cervical cancer cases that occur in Taiwan.     

Baseline prevalence and type distribution of human papillomavirus in healthy Chinese women aged 18–25 years enrolled in a clinical trial

Baseline human papillomavirus (HPV) prevalence and type distribution were evaluated in young Chinese women enrolled in a clinical trial of an HPV vaccine ( ClinicalTrials.gov registration NCT00779766). Cervical specimens and blood samples were collected at baseline from women aged 18–25 years (n = 6,051) from four sites across Jiangsu province. Cervical specimens were tested for HPV DNA by SPF₁₀ PCR‐DEIA‐LiPA₂₅ version 1, and HPV‐16/18 type‐specific polymerase chain reaction. Anti‐HPV‐16 and anti‐HPV‐18 antibody titres were quantified by enzyme‐linked immunosorbent assay. At baseline, 15.3% of women were DNA positive for any of 14 HPV high‐risk (hr) types (HPV‐16/18/31/33/35/39/45/51/52/56/58/59/66/68). The most commonly detected hrHPV types in cervical specimens were HPV‐52 (4.0%) and HPV‐16 (3.7%). High‐risk HPV DNA‐positivity increased with severity of cytological abnormalities: 39.3% in atypical squamous cells of undetermined significance, 85.0% in low‐grade squamous intraepithelial lesions and 97.8% in high‐grade squamous intraepithelial lesions (HSIL). The hrHPV types most frequently detected in HSIL were HPV‐16 (63.0%), HPV‐18 (17.4%), HPV‐52 (17.4%), HPV‐58 (15.2%) and HPV‐33 (15.2%). The hrHPV types most frequently detected in cervical intraepithelial neoplasia 2+ were HPV‐16 (66.1%), HPV‐33 (16.1%), HPV‐52 (16.1%), HPV‐58 (14.5%) and HPV‐51 (11.3%). Multiple hrHPV infections were reported for 24.4% of hrHPV DNA positive women. Regardless of baseline HPV DNA status, 30.5% and 16.0% of subjects were initially seropositive for anti‐HPV‐16 and anti‐HPV‐18, respectively. In conclusion, the high baseline seropositivity rate and intermediate prevalence of cervical hrHPV types in Chinese women aged 18–25 years underlines the importance of early HPV vaccination in this population.     

Incidence risk of cervical intraepithelial neoplasia 3 or more severe lesions is a function of human papillomavirus genotypes and severity of cytological and histological abnormalities in adult Japanese women

We examined incidence probabilities of cervical intraepithelial neoplasia 3 (CIN3) or more severe lesions (CIN3+) in 1,467 adult Japanese women with abnormal cytology in relation to seven common human papillomavirus (HPV) infections (16/18/31/33/35/52/58) between April 2000 and March 2008. Sixty‐seven patients with multiple HPV infection were excluded from the risk factor analysis. Incidence of CIN3+ in 1,400 patients including 68 with ASCUS, 969 with low grade squamous intraepithelial lesion (LSIL), 132 with HSIL without histology‐proven CIN2 (HSIL/CIN2(?)) and 231 with HSIL with histology‐proven CIN2 (HSIL/CIN2(+)) was investigated. In both high grade squamous intraepithelial lesion (HSIL)/CIN2(?) and HSIL/CIN2(+), HPV16/18/33 was associated with a significantly earlier and higher incidence of CIN3+ than HPV31/35/52/58 (p = 0.049 and p = 0.0060, respectively). This association was also observed in LSIL (p = 0.0002). The 1‐year cumulative incidence rate (CIR) of CIN3+ in HSIL/CIN2(?) and HSIL/CIN2(+) according to HPV genotypes (16/18/33 vs. 31/35/52/58) were 27.1% vs. 7.5% and 46.6% vs. 19.2%, respectively. In contrast, progression of HSIL/CIN2(+) to CIN3+ was infrequent when HPV DNA was undetected: 0% of 1‐year CIR and 8.1% of 5‐year CIR. All cervical cancer occurred in HSIL cases of seven high‐risk HPVs (11/198) but not in cases of other HPV or undetectable/negative‐HPV (0/165) (p = 0.0013). In conclusion, incidence of CIN3+ depends on HPV genotypes, severity of cytological abnormalities and histology of CIN2. HSIL/CIN2(+) associated with HPV16/18/33 may justify early therapeutic intervention, while HSIL/CIN2(?) harboring these HPV genotypes needs close observation to detect incidence of CIN3+. A therapeutic intervention is not indicated for CIN2 without HPV DNA.     

Identification of genital human papillomaviruses in cervical biopsy specimens: Segregation of specific virus types in specific clinicopathologic lesions

We have established a critical identification method for the full spectrum of genital human papillomaviruses (HPVs) in clinical specimens. It was based on the recognition of Pstl, Banl and Mspl cleavage patterns of HPV DNA detected by blot hybridization with HPV 58 DNA probe at Tm—40°C. By this method, we identified 24 different types of genital HPV including 5 novel types (HPV 59, 61, 62, 64 and 67) in the specimens collected at one hospital and found almost all the HPVs with the authentic cleavage patterns of their respective prototypes. In 235 cervical biopsy specimens, HPV 6 or 11 was found in exophytic condyloma acuminatum (15/15) but not in any cervical intraepithelial neoplasia (CIN) specimens. In contrast, HPV 18, 30, 43, 54, 56, 59, 62, 66 and 67 were identified in CIN I (28/71) or II (4/56) but not in CIN III, while HPV 16, 31, 33, 35, 39, 51, 52 and 58 were identified in CIN III (83/93) as well as in CIN I (34/71) and II (47/56). The result indicates that heterogeneous genital HPVs prevail all over the world. In addition, HPV 6 and 11 are etiologic agents only of exophytic condyloma, whereas the other HPVs are etiologic agents of CIN with the segregation of specific HPVs in CIN III. We propose a new clinicopathologic grouping of genital HPVs founded on nucleotide homology of the HPV genome. © 1995 Wiley-Liss, Inc.     

The distribution and prevalence of human papillomavirus in women in mainland China

We conducted a systematic review of the epidemiology of high-risk human papillomavirus (HPV) infections in mainland Chinese women to provide a general profile for the application and subsequent effectiveness evaluation of HPV vaccines. The PubMed, Web of Science, Medline (Ovid), China National Knowledge Infrastructure, and Wanfang databases were used for the literature search. The epidemiological studies published from January 2000 to June 2018 on high-risk HPVs in mainland Chinese women were investigated to systematically evaluate their epidemiological status. A total of 198 eligible studies were included. The results of meta-analysis showed that the overall infection rate of high-risk HPVs in mainland Chinese women was 19.0% (95% confidence interval [CI], 17.1%-20.9%), and the top 5 subtypes with the highest infection rates were 16, 52, 58, 53, and 18. The overall infection rates of cervical intraepithelial neoplasia I (CINI), CINII+, and cervical cancer patients were 59.6% (95% CI, 52.7%-66.4%), 84.8% (95% CI, 81.2%-88.5%), and 89.9% (95% CI, 86.6%-93.1%), respectively. The high-risk HPV infections and common subtypes in women of various ages in various regions were different, and the high-risk HPVs and subtypes in cervical cancer patients in various regions were also different. In conclusion, we systematically analyzed the HPV infections in women who live on the Chinese mainland. The epidemiology of high-risk HPVs in mainland Chinese women is basically consistent with that for the rest of the world. The HPV vaccines currently licensed in China could cover the major prevalent high-risk HPV subtypes in China, providing a basis for the development of a cervical cancer screening strategy and vaccine implementation in China.     

Distinct geographic clustering of oncogenic human papillomaviruses multiple infections in cervical cancers: Results from a worldwide cross-sectional study

Coinfections by multiple Human Papillomaviruses (HPVs) are observed in approximately 6–8% of invasive cervical cancer (ICC) cases worldwide. But neither the presence of persistent HPVs coinfections nor their etiological role in the development of ICC is well understood. Cervical HPVs coinfections have been observed randomly, mostly in women with preneoplastic lesions, and only few studies have globally analyzed ICC cases. Here we explored the HPVs multiple infection patterns in a large worldwide sample of cross-sectional ICC cases. Paraffin-embedded ICC biopsy samples were tested using stringent HPV genotyping. Logistic regression models were used to identify the most likely pairwise HPV types in multiple infections. Multivariate analysis was applied to detect significant HPV coinfection patterns beyond pairwise HPVs comparison. Among 8780 HPV DNA-positive ICC cases worldwide, 6.7% (N = 587) contained multiple HPVs. Pairwise analysis revealed that HPV16|74, HPV31|33, HPV31|44, HPV33|44 and HPV45|70 pairs were significantly more frequently found together in multiple infections compared to any other HPV type combination, which supports the occasional role of Alpha-10 LR-HPVs in cervical cancers. In contrast, HPV16|31, HPV16|45, HPV16|51 and HPV18|HPV45 pairs were significantly less frequently found together than with any other HPV pair combination. Multivariate analysis sustained the results and revealed for the first time a distinct coinfection pattern in African ICCs stemming from the clustering of oncogenic HPV51/35/18/52 coinfections in African women. We suggest that the differential geographic HPVs coinfections clustering observed might be compatible with a specific modulation of the natural history/oncogenic potential of particular HPVs multiple infections and warrant monitoring for post-vaccinated.     

Use of Universal and Type-specific Primers in the Polymerase Chain Reaction for the Detection and Typing of Genital Human Papillomaviruses

By using polymerase chain reaction (PCR), we have developed a system for type-specific as well as universal detection of genital human papillomaviruses (HPVs). Primers and probes for specific detection of HPV-16, -18 and -33 were synthesized from the E7 open reading frame (ORF). They were capable of detecting corresponding HPV types with high specificity and sensitivity. Primers for detection of a broad spectrum of HPV (universal primers) were synthesized from the LI ORF. The universal primers were shown to be capable of amplifying HPV-6b, -11, -16, -18, -33, -52b and -58. The system was applied to various cervical tissue specimens from Japanese patients. They consisted of 26 normal specimens, 18 from cervical dysplasias and 29 from cervical carcinomas. HPV was detected in none of the normal specimens. On the other hand, many of the specimens from cervical dysplasias and carcinomas were found to be positive for HPV, especially HPV-16. Except for one, all the specimens which were positive with the type-specific PCRs were also positive with the universal PCR. Furthermore, substantial numbers of specimens were found to be positive only with the universal PCR. Cloning and sequencing of DNA segments amplified by the universal primers were undertaken to characterize some of the unknown HPVs. Our PCR system may thus be useful for the specific detection of the three major types of oncogenic HPVs and also for the detection of a broad spectrum of HPVs including possibly novel HPV types.     

Use of universal and type-specific primers in the polymerase chain reaction for the detection and typing of genital human papillomaviruses.

By using polymerase chain reaction (PCR), we have developed a system for type-specific as well as universal detection of genital human papillomaviruses (HPVs). Primers and probes for specific detection of HPV-16, -18 and -33 were synthesized from the E7 open reading frame (ORF). They were capable of detecting corresponding HPV types with high specificity and sensitivity. Primers for detection of a broad spectrum of HPV (universal primers) were synthesized from the L1 ORF. The universal primers were shown to be capable of amplifying HPV-6b, -11, -16, -18, -33, -52b and -58. The system was applied to various cervical tissue specimens from Japanese patients. They consisted of 26 normal specimens, 18 from cervical dysplasias and 29 from cervical carcinomas. HPV was detected in none of the normal specimens. On the other hand, many of the specimens from cervical dysplasias and carcinomas were found to be positive for HPV, especially HPV-16. Except for one, all the specimens which were positive with the type-specific PCRs were also positive with the universal PCR. Furthermore, substantial numbers of specimens were found to be positive only with the universal PCR. Cloning and sequencing of DNA segments amplified by the universal primers were undertaken to characterize some of the unknown HPVs. Our PCR system may thus be useful for the specific detection of the three major types of oncogenic HPVs and also for the detection of a broad spectrum of HPVs including possibly novel HPV types.     

Temporal trends over 3 decades and intrafamilial clustering of HPV types in Swedish patients with cervical cancer in situ

Information on HPV type distribution in cervical cancer in situ in different populations is needed for evaluation of prophylactic vaccination programs targeting HPV 16 and 18. In our study, the HPV type prevalence in 1,079 Swedish women from multicase families diagnosed with cervical cancer in situ 1965–1993 was investigated using real‐time PCR and archival tissue material. HPV type information was obtained for 974 samples. Among these, HPV 16 (61%) was the dominant type followed by HPV 33/52/58 (24%), HPV 31 (13%) and HPV 18/45 (12%). The detected prevalence of HPV 16 among cancer in situ decreased by 13% over the study period while the group of low frequency high‐risk types increased. Related women were not prone to infection by the same type. These data suggest that the prevalence of individual HPV types has changed over time in Swedish patients with cervical cancer in situ. Large‐scale studies of pathology biobank materials will enable further insight into the temporal changes of individual HPV types, as baseline information to properly evaluate the effect of vaccine programs. The findings also indicate that genetic susceptibility to cervical cancer operates through general and not type specific susceptibility to HPV infection. © 2009 UICC     

Prevalence of genotype‐specific human papillomavirus infection and cervical neoplasia in Taiwan: A community‐based survey of 10,602 women

Human papillomavirus (HPV) causes cervical neoplasia; but limited data are available from Asia. We conducted a large‐scale community‐based cohort study in Taiwan to estimate prevalence of genotype‐specific HPV infection and cervical neoplasia. Following written informed consent, cervical cells for cytology and HPV testing were collected from 11,923 participants (aged 30–65 years old, mean 46.3) in 1991–1992. Genotyping was performed using MY11/GP6+ PCR‐based HPV Blot (EasyChip) for 39 HPV types. The overall HPV prevalence was 16.2% for 10,602 eligible participants, and 13.8% for 10,190 cytologically normal participants. The most common carcinogenic types were HPV52 (2.5%), HPV16 (2.0%), HPV56 (1.8%), HPV18 (1.6%), HPV33 (1.2%), HPV58 (1.3%) and HPV39 (1.0%). Among the 56 prevalent invasive and in situ cases, HPV16 (48.2%) was most common, followed by HPV58 (25.0%), HPV52 (19.6%), HPV31 (8.9%), HPV33 (8.9%) and HPV18 (3.6%). HPV16 and HPV58 caused cytological HSIL+ at younger ages than HPV52. Approximately half of the cervical cancer cases and high‐grade precursors in Taiwan could be prevented by prophylactic vaccines against HPV16 and HPV18 infection. Up to 40% more could be prevented by targeting HPV58, HPV52, HPV33 and HPV31, arguing for the introduction of vaccines including more types.     

Association between Prestored Smartphone Monitored Physical Activity and the Risk of HPV Infection and Cervical Cancer

Objective: This study was to determine the prevalence of HPV in non-vaccinated women from East China, and the association between prestored smartphone monitored physical activity and the risk of human papillomaviruses (HPV) infection and cervical cancer. Methods: We retrospectively reviewed medical records of unvaccinated women received first-time cervical HPV screening in the Affiliated Cancer Hospital of University of Chinese Academy of Sciences between March 2018 and December 2019. HPV genotyping was examined by the GenoArray. Physical activity defined by any movements at speeds of 0.5-2 m/s was obtained from smartphones. We collected prestored physical activity data for 6 months prior to the HPV screening. Logistic regression models were applied to determine the association between physical activity and the risk of HPV infection and cervical cancer. Results: A total of 11,730 women were initially included. Women with cervical cancer had significantly higher prevalence of infection with any high-risk (HR) HPV, or with individual HPV16, 18, 31, 33, 45, 52 and 58. Among them, 896 controls and 289 cervical cancer women had information of smartphone monitored physical activity. Multivariate logistic regression analysis showed that more daily physical activity time (or distance) was a protective factor for infection with any HR HPV, or infection with HPV16, but not other individual HPVs. Increased age, less physical activity time (or distance), and infection with any HR HPV (16, 18, 31, 52 and 58) were associated with a significantly increased risk of cervical cancer. In contrast, obesity was not associated with risk of HPV infection and cervical cancer. Conclusion: The high prevalence of HPV infection in unvaccinated women highlights the importance of prevention. More daily physical activity time (or distance) may help to reduce the risk of HPV infection and cervical cancer. Smartphone monitoring is an effective tool for recording physical activity.     

Analysis of cytomorphologically abnormal cervical scrapes for the presence of 27 mucosotropic human papillomavirus genotypes,using polymerase chain reaction

The aim of this study was to investigate the distribution of 27 mucosotropic human papillomavirus (HPV) genotypes (HPV 6, 11, 13, 16, 18, 30, 31, 32, 33, 35, 39,4 0, 42, 43, 44, 45, 51, 52, 53, 54, 55, 56, 57, 58, 59, 61 and 66) in cytomorphologically abnormal cervical scrapes (Pap IIIa-Pap IV; n = 1, 373) using the polymerase chain reaction (PCR) method on crude cell suspensions. The scrapes were analyzed for the presence of HPV DNA by HPV general-primer-mediated PCR (GP-PCR), which allows the detection of a broad spectrum of HPV types at the subpicogram level. Subsequently, 2 HPV typing procedures based on either type-specific PCR (for HPV 6, 11, 16, 18, 31 and 33) or characterization of GP-PCR products by hybridization (for HPV 13, 30, 32, 35, 39, 40, 42, 43, 44, 45, 51, 52, 53, 54, 55, 56, 57, 58, 59, 61 and 66) were applied. Increasing total HPV prevalence was found with increasing severity of dysplasia from 71% in Pap IIIa to 100% in Pap IV scrapes (carcinoma in situ). The scrapes which were positive by type-specific PCR included 47% cases of Pap IIIa, 71% cases of Pap IIIb and 90% cases of Pap IV. Moreover, 12% of Pap IIIa scrapes, 6% of Pap IIIb scrapes and 8% of Pap IV scrapes revealed positivity for one or more of the remaining HPV types, as determined by successive hybridizations of the GP-PCR products. Taking the typing data together, we noted that the level of HPV heterogeneity decreased from 22 different HPV types (HPV 6, 11, 16, 18, 31, 33, 35, 39, 40, 42, 43, 44, 45, 51, 52, 54, 55, 56, 58, 59, 61 and 66) detected in the group of Pap IIIa scrapes to 13 (HPV 6, 11, 16, 18, 31, 33, 35, 45, 51, 52, 58, 59 and 61) and 10 HPV genotypes (HPV 6, 16, 18, 31, 33,45, 51, 52, 54 and 58) in the Pap IIIb and Pap IV classes, respectively. An increasing prevalence rate from Pap IIIa to Pap IV was found for HPV 16, 18, 31, 33, 45 and 54. The prevalence rate of identified HPV genotypes increased from 59% in Pap IIIa to 98% in Pap IV, indicating that almost all high-risk HPV genotypes related to cervical cancer in The Netherlands have been characterized.     

Human papillomavirus type 52 polymorphism and high‐grade lesions of the uterine cervix

The association between polymorphism of human papillomavirus type 52 (HPV52) and high‐grade cervical intraepithelial neoplasia (CIN2,3) was investigated in Canadian women. HPV‐52‐positive endocervical specimens collected from 216 women selected from a total of 3,614 participants recruited in two case‐control and two cohort studies conducted in Canada, were further analyzed by PCR‐sequencing of the LCR and E6 gene. Overall, the HPV52 LCR prototype was detected more frequently in Caucasian women (69 of 132, 52.3%, 95% confidence interval (CI): 43.8%–60.6%) than in non‐Caucasian women (15 of 48, 31.3%, 95% CI 19.9%–45.4%). In two cohort studies, HPV52 prototype was detected in seven of 15 (46.7%, 95% CI 24.8–69.9) HPV52 persistent infections and 14 of 35 (40.0%, 95% CI 25.5–56.5) transient infections (p = 0.76). In two case‐control studies, 30 participants did not have CIN, 18 had low‐grade CIN (CIN1), 64 had CIN2,3, seven had cervical cancer and the diagnosis was undefined for 27 women. Variant MTL‐52‐LCR‐02 was detected more frequently in women with cancer (28.6%, 95% CI 7.6%–64.8%) than in women without cancer or CIN2,3 (0%, 95% CI 0.0%–9.2%; p = 0.015). CIN2,3 risk was significantly associated with a deletion at nucleotide position 7695 in the LCR (OR 4.9, 95% CI 1.2–20.8), the T7744C variation in the LCR (OR 5.7, 95% CI 1.1–32.0), and the K93R variation in E6 (OR 6.9, 95% CI 1.3–36.8), after adjusting for age, detection of HPV16 or 18 and study site. These findings indicate that HPV52 polymorphism influences risk of CIN‐2,3 and possibly invasive cancer.     

Identification of human papillomavirus DNA gene sequences in human breast cancer

Human papilloma viruses (HPVs) are accepted as being carcinogenic in human cervical and anogenital cancers. The suspicion that HPVs may also have a role in human breast cancer is based on the identification of HPVs in human breast tumours and the immortalisation of normal human breast cells by HPV types 16 and 18. For this investigation, DNA that had been previously extracted and fresh frozen at -70 degrees C from 50 unselected invasive ductal breast cancer specimens were screened by polymerase chain reaction (PCR) for HPV type 16, 18 and 33 gene sequences. We show that HPV 18 gene sequences are present in DNA extracted from breast tumours in Australian women. Overall, 24 (48%) of the 50 samples were HPV positive. Overall no correlations with tumour grade, patient survival, steroid receptor status, ERB-2, p53 expression and mutation were observed. Human papilloma viruses may have a role in human breast cancer. We speculate that HPVs may be transmitted by hand from the female perineum to the breast.     

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.     

HPV infection in cervical-cancer cases in Russia

The presence of human papillomavirus (HPV) sequences in 21 biopsies from cervical carcinomas, II specimens of tissues adjacent to tumours, 2 specimens of cervical tissues with radiation fibrosis from patients after radiation therapy of cervical cancer and 7 normal epithelial tissues from the patients with other genital tumours were examined by polymerase chain reaction (PCR) and Southern-blot analysis. All tumours were HPV-positive by type-specific PCR and 86% by Southern-blot analysis. In normal epithelial and adjacent tissues, HPV sequences were detected in 20% of samples by Southern-blot analysis and in 70% of samples by PCR, including 2 cases of tissues after radiation therapy. HPV 16 was the most prevalent type in tumours (18/21) as well as in normal epithelial tissues (5/7). One HPV-positive tumour contained HPV18 DNA and 2 were doubly infected with HPVs 16 and 18 (2/21). The persistence of exclusively episomal HPV16 DNA was observed in 5 out of 11 tumours examined: 3 cases of squamous-cell carcinomas on the early stage of tumour progression and 2 advanced tumours (squamous-cell carcinoma and adenocarcinoma). The integration of HPV16 genome was detected in 6 out of 11 tumours, but most of them contained episomal forms of viral DNA simultaneously (5 out of 6). The integrative HPV18 genome was found in 2 tumours examined, and the persistence of episomal forms was also observed in one of them. Our data demonstrate that cervical tumours are associated invariably with high-risk types of HPV in Russia. © 1995 Wiley-Liss, Inc.     

Analysis of E6 variants of human papillomavirus type 33, 52 and 58 in Japanese women with cervical intraepithelial neoplasia/cervical cancer in relation to their oncogenic potential.

The variation of the E6 region of human papillomavirus type 16 (HPV16) is associated with a high risk for cervical carcinogenesis. To see whether the same is the case with HPV33, 52 and 58, known to have high homology with HPV16, we analyzed the E6 sequence variation of these HPVs in 107 Japanese women with cervical intraepithelial neoplasia (CIN) or invasive cervical cancer (ICC): 20 HPV33-positive, 46 HPV52-positive and 41 HPV58-positive cases. HPV33 variants were more frequently observed in CINs I/II than in CIN III/ICCs (71% (5/7) versus 15% (2/13), P=0.02). In HPV52-positive cases, a single E6 variant was detected in 98% of the cases, whereas the prototype accounted for 98% of HPV58-positive cases. In summary, the distribution of E6 variants is different among HPV types tested, suggesting a link between E6 variation and oncogenic potential being type-specific.     

Distinct manifestations of human papillomaviruses in the vagina

To clarify the pathogenic relationships between human papillomavirus (HPV) and vaginal intraepithelial neoplasia (VAIN), we examined 71 vaginal biopsy specimens by histopathology and immunohistochemistry and analyzed the presence of HPV DNA by blot hybridization at Tm − 40°C using an HPV 58 probe (PBM-58 method). We found 27 cases of VAIN in patients with previous hysterectomy or antecedent or concomitant cervical intraepithelial neoplasia (CIN) and 44 cases of VAIN in patients without any abnormal findings on the cervix and the vulva. Histopathologically, 53 of 71 cases were graded as VAIN I and 15 and 3 cases were VAIN II and III, respectively, while 59 cases showed positivity for HPV capsid antigen by immunohistochemistry. Using the PBM-58 method, all 71 VAIN cases harbored a single HPV type at more than 1,000 viral copies per cell. We identified 15 different types (HPV 16, 18, 30, 31, 35, 40, 42, 43, 51, 52, 53, 54, 56, 58 and 66). Furthermore, we molecularly cloned 7 novel prototypes (HPV 59, 61, 62, 64, 67, 69 and 71) from VAIN I. Our results are strongly indicative that HPVs are etiologic agents of VAIN, like in the case of CIN. The distinct manifestations of HPV infection in the vagina are discussed in comparison with those in the cervix. Int. J. Cancer 72:412–415, 1997. © 1997 Wiley-Liss, Inc.