Effectiveness of high-risk human papillomavirus genotyping for cervical cancer screening. A multicentre screening cohort study in rural China.

BACKGROUND: This study aimed to assess the effectiveness of high-risk human papillomavirus (HR-HPV) primary testing for cervical cancer screening in China's rural areas. METHODS: Women aged 21-64 years were recruited. Cervical cytology was diagnosed following the Bethesda 2001 classification system, HPV infection (HR-HPV, HPV-16, HPV-18, and other 12 genotypes) identified by Cobas-4800, and colposcopy and biopsy performed when required. Primary outcomes were defined as the cumulative incidence of cervical intraepithelial neoplasia grade 2/3/higher (CIN2/3+) and its relative risk at baseline and at the 36-month follow-up. RESULTS: The study included 9,218 women; mean age was 45.15 years (SD: 8.74); 81% completed the follow-up. The most frequent type of cytological lesions (12.4% ) were ASCUS (8.4%) and LSIL (2.2%). HR-HPV infection (16.3%) was more prevalent in HPV-16 than in HPV-18 (3 vs 1.5%); a positive relationship with the severity of the lesions, from 29.8% in ASCUS to 89.6% in HSIL was found. At baseline, 3.5% of the patients underwent colposcopy; 20% had a positive diagnosis. At the 36-month follow-up, the cumulative incidences of CIN2+ and CIN3+ were higher in women with HR-HPV infection (16.9 vs 0.5% and 8.2 vs 0.2%). The relative risk of CIN2/3+ was lower in HR-HPV-negative women compared to those with a negative cytology at baseline (0.4; 95%CI: 0.3-0.4). CONCLUSIONS: High-risk HPV-based screening may significantly reduce the risk of CIN2/3+ compared with cytology testing. This may be a new resource for public health demands in China's rural areas.

Changes in High-Risk HPV Infection Prevalence and Associated Factors in Selected Rural Areas of China: A Multicenter Population-Based Study.

Background: The Chinese government has taken action to prevent cervical cancer by implementing the National Cervical Cancer Screening Programme in Rural Areas (NACCSPRA), which was launched in 2009. Numerous studies have demonstrated that long-term cervical cancer screening alters human papillomavirus (HPV) infection rates and cervical disease detection. Nearly 80 million women have been screened over 10 years, representing <30% of the target population; however, in some rural areas, such as Ordos City of Inner Mongolia Autonomous Region, Xiangyuan County of Shanxi Province, and Jinyun County, and Jingning County of Zhejiang Province, programs for prevention and treatment of cervical cancer have been implemented. Numerous studies have demonstrated that long-term cervical cancer screening alters rates of human papillomavirus (HPV) infection and cervical disease detection. In this study, we aimed to determine the infection rates of high-risk HPV (hrHPV) and the detection rate of cervical lesions; and changes in factors associated with cervical cancer, to provide scientific data to inform efforts to eliminate cervical cancer in rural areas. Methods: This was a cross-sectional, population-based, and multi-center survey. Populations from three rural areas of China (Ordos City of Inner Mongolia Autonomous Region, Xiangyuan County of Shanxi Province, and Jinyun County and Jingning County of Zhejiang Province) were selected and 9,332 women aged 20-64 years old were invited to participate in cervical cancer screening by both cytology and HPV testing. The outcomes assessed were: infection rates with hrHPV, HPV16, 18, 16/18, and other 12 hrHPV types (HPV 31,33,35,39,45,51,52,56,58,59,66 and 68); detection rates of cytological and histological lesions; and factors associated with HPV infection. Results: A total of 9,217 women aged 45.62 ± 8.02 years were included in this study. Infection rates with hrHPV, HPV 16, 18, 16/18, and other 12 hrHPV types were 16.3%, 3.0%, 1.5%, 4.3%, and 13.6%, respectively. There were significant differences among the age-specific HPV infection rates (P < 0.05). Infection rates with hrHPV, 16, 18, 16/18, and the other 12 hrHPV types showed a single peak infection mode, with a peak age of 56-65 years old. Age, marital status, number of live births, education level, reproductive disease history, and a history of alcohol consumption were risk factors for hrHPV infection. The detection rate of cytological abnormalities was 12.98% in the study and was higher in women older than 56 years old. The detection rates of cervical intraepithelial neoplasia CIN2+ and CIN3+ in the population were 1.45% and 0.77%, respectively. The highest incidence rates of CIN2+ and CIN3+ were 32.12% and 17.51%, respectively, in the 41-45 years old group. Conclusion: Infection rates with hrHPV, HPV16, and cervical lesions among our screening population were lower than the mean level in rural areas of China. Infection rates with hrHPV, HPV16, 18, and 16/18 showed a single-peak infection pattern, with the peak age of infection being 56-65 years old. Risk factors for hrHPV infection were age, history of alcohol consumption, marital status, reproductive diseases, education level, and the number of live births. Based on these data, we recommend that cervical cancer screening be offered to women older than 30 years in rural areas, particularly those aged 41-45 years.

Performance of HPV Genotyping Combined with p16/Ki-67 in Detection of Cervical Precancer and Cancer Among HPV-Positive Chinese Women.

Women with positive high-risk human papillomavirus (hrHPV) need efficient triage testing to determine colposcopy referrals. Triage strategies of combining p16/Ki-67 with extended HPV genotyping were evaluated in this study. In total, 899 women attending cervical cancer screening program and 858 women referred to colposcopy from five hospitals were recruited. All the participants were tested by HPV assays and p16/Ki-67 dual staining. Colposcopy and biopsy were performed on women with any abnormal results. HPV genotypes were divided into four strata (HPV16/18, HPV31/33/58/52, HPV45/59/56/66, and HPV51/39/68/35) according to their risks for cervical intraepithelial neoplasia grade 3 or worse (CIN3+). The positive rates of four genotype strata among CIN3+ women were 3.47% (HPV51/39/68/35), 7.73% (HPV45/59/56/66), 14.7% (HPV31/33/58/52), and 78.1% (HPV16/18), respectively (P trend < 0.001). The positive rates of p16/Ki-67 increased with the elevation of HPV risk hierarchical from 65.0% in HPV51/39/68/35-positive women to 88.0% in HPV16/18-positive women (P trend < 0.001). p16/Ki-67 was an effective method for risk stratification of CIN2+ among HPV31/33/58/52- and HPV45/59/56/66-positive women [HPV31/33/58/52: OR for dual stain+ (ORDS+) of 26.7 (16.8-42.4) and OR for dual stain- (ORDS-) of 3.87(1.89-7.91); HPV45/59/56/66: ORDS+ of 10.3(5.05-21.0) and ORDS- of 1.27(0.38-4.26)]. The combination of HPV16/18 genotyping and p16/Ki-67 triage of HPV31/33/58/52/45/59/56/66-positive women resulted in a lower referral rate (40.1% vs. 41.3%; P < 0.001) as compared with triage of 12 other HPV-positive women with p16/Ki-67, although sensitivity and specificity levels for these two strategies were identical. Combining HPV extended genotyping and p16/Ki-67 can be considered as a promising strategy for cervical cancer screening and triage.