Distribution and diagnostic value of single and multiple high-risk HPV infections in detection of cervical intraepithelial neoplasia: A retrospective multicenter study in China.

The risk associated with single and multiple human papillomavirus (HPV) infections in cervical intraepithelial neoplasia (CIN) remains uncertain. This study aims to explore the distribution and diagnostic significance of the number of high-risk HPV (hr-HPV) infections in detecting CIN, addressing a crucial gap in our understanding. This comprehensive multicenter, retrospective study meticulously analyzed the distribution of single and multiple hr-HPV, the risk of CIN2+, the relationship with CIN, and the impact on the diagnostic performance of colposcopy using demographic information, clinical histories, and tissue samples. The composition of a single infection was predominantly HPV16, 52, 58, 18, and 51, while HPV16 and 33 were identified as the primary causes of CIN2+. The primary instances of dual infection were mainly observed in combinations such as HPV16/18, HPV16/52, and HPV16/58, while HPV16/33 was identified as the primary cause of CIN2+. The incidence of hr-HPV infections shows a dose-response relationship with the risk of CIN (p for trend <0.001). Compared to single hr-HPV, multiple hr-HPV infections were associated with increased risks of CIN1 (1.44, 95% confidence interval [CI]: 1.20-1.72), CIN2 (1.70, 95% CI: 1.38-2.09), and CIN3 (1.08, 95% CI: 0.86-1.37). The colposcopy-based specificity of single hr-HPV (93.4, 95% CI: 92.4-94.4) and multiple hr-HPV (92.9, 95% CI: 90.8-94.6) was significantly lower than negative (97.9, 95% CI: 97.0-98.5) in detecting high-grade squamous intraepithelial lesion or worse (HSIL+). However, the sensitivity of single hr-HPV (73.5, 95% CI: 70.8-76.0) and multiple hr-HPV (71.8, 95% CI: 67.0-76.2) was higher than negative (62.0, 95% CI: 51.0-71.9) in detecting HSIL+. We found that multiple hr-HPV infections increase the risk of developing CIN lesions compared to a single infection. Colposcopy for HSIL+ detection showed high sensitivity and low specificity for hr-HPV infection. Apart from HPV16, this study also found that HPV33 is a major pathogenic genotype.

Ye Z ，Zhao Y ，Chen M ，Lu Q ，Wang J ，Cui X ，Wang H ，Xue P ，Jiang Y ... -  《-》

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

Yu YQ ，Jiang MY ，Zhang X ，Pan QJ ，Dang L ，Feng RM ，Ali NM ，Chen W ，Qiao YL ... -  《-》

Liquid-based cytology and human papillomavirus testing: a pooled analysis using the data from 13 population-based cervical cancer screening studies from China.

The objective of this study was to evaluate the impact of introducing HR-HPV testing in cytology regarding cervical cancer screening practice. A pooled analysis of liquid-based cytology (LBC) and HR-HPV testing using data from 13 population-based cervical cancer screening studies conducted in China was performed. Participants (n=25,404) received LBC and HR-HPV testing. Women found to be positive on screening were referred for colposcopy and biopsy. The effectiveness of screening strategies that use: LBC with HR-HPV triage for atypical squamous cells of undetermined significance (ASC-US), HR-HPV testing with cytology triage for HPV positive tests, or LBC and HPV cotesting was compared with that of LBC screening alone. LBC with HR-HPV triage for ASC-US had similar sensitivity compared with LBC alone, but significantly increased specificity for both cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and CIN3 or worse (CIN3+) endpoints, and had the best balance between sensitivity and specificity among the strategies. LBC and HR-HPV cotesting had the highest sensitivity and negative predictive value (NPV) and could permit a safe extension of screening intervals. Through the use of an immediate colposcopy threshold of ASC-US or worse for HR-HPV positive women and the use of a raised threshold of low-grade squamous intraepithelial lesion (LSIL) or worse for HR-HPV negative women, LBC and HR-HPV cotesting could provide the same effectiveness as LBC testing with HR-HPV triage for ASC-US at baseline tests. The results of the current study support the use of the cervical cancer screening guidelines in China.

Pan QJ ，Hu SY ，Guo HQ ，Zhang WH ，Zhang X ，Chen W ，Cao J ，Jiang Y ，Zhao FH ，Qiao YL ... -  《-》

The variations in the natural history of high-risk human papillomavirus infections in Chinese healthy women aged 27-45 years compared with 18-26 years: A prospective cohort study.

Data investigating the natural history of high-risk human papillomavirus (HR-HPV) infection in mid-adult women compared with young adult women from regions exhibiting a bimodal distribution pattern are scarce. From November 2012 to September 2019, 3681 healthy women aged 18-45 years from the control group of a bivalent HPV vaccine Phase 3 trial in China were followed over 5.5 years. At scheduled visits (Day 0, months 7, 12, 18, 24, 30, 42, 54, and 66), cervical samples were collected for ThinPrep Pap tests and HPV DNA testing, women with abnormal cytology were referred for colposcopy. Data was analyzed using Cox regression model and a competing risk model. Sensitivity analyses were performed among participants attending all scheduled visits. The incidences of HR-HPV persistent infections (over 6 months [6mPIs]) were 35.5 and 29.0 per 1000 person-years (PYs) (hazard ratio [HR] = 1.21, 95% confidence interval [CI]: 1.00, 1.46), and HR-HPV associated CIN grade 2 or greater (CIN2+) were 4.3 and 1.9 per 1000 PYs (HR = 2.31, 95% CI: 1.25, 4.26) in women aged 18-26 and 27-45 years. Competing risk models showed that the cumulative incidence of HR-HPV infections that progressed to CIN2+ was significantly higher in women aged 18-26 than in women aged 27-45 (5.3% vs. 2.9%, Gray's test p = .0291). The cumulative clearance rates of HR-HPV infections in women aged 18-26 and 27-45 were similar (94.7% vs. 95.8%, Gray's test p = .3309) during the study period. In conclusion, although mid-adult women exhibit lower incidences of HR-HPV infection and associated cervical lesions compared to young women, this population continues to face a substantial risk of acquiring causal HPV infections, which may progress to cervical lesion.

Chen Q ，Yao X ，Quan J ，Jia X ，Li Y ，Zhu K ，Hu X ，Huang X ，Zhong G ，Qiu L ，Bi Z ，Liao M ，Chen L ，Kuang X ，Wang Z ，Hu S ，Zhuang C ，Huang S ，Wei L ，Chen W ，Su Y ，Zhao F ，Wu T ，Qiao Y ，Zhang J ，Xia N ... -  《-》

Retrospective analysis of HPV infection: Cotesting and HPV genotyping in cervical cancer screening within a large academic health care system.

In 2019, the American Society for Colposcopy and Cervical Pathology introduced fundamental shifts toward "risk-based" guidelines, with human papillomavirus (HPV) genotyping as a principal test for investigating squamous intraepithelial lesions. This study aims to provide practice-based evidence and supplement the updated guidelines by investigating HPV demographic distribution and uncovering the pathological features of high-grade squamous intraepithelial lesions (HSILs) caused by high-risk HPV (hrHPV) subtypes. Patients who underwent Papanicolaou screening and HPV testing in two hospital systems over the course of 4 years were recruited. The cytology results were categorized on the basis of the 2014 Bethesda classification. DNA sequences of 14 types of hrHPV were detected by Aptima test. The histological features of HSILs caused by different subtypes were compared between biopsies and excisions. A total of 63,709 cases were included. The HPV prevalence was 14.70%, predominantly in the 30 to 39-year-old age group, with slightly higher rates observed in African Americans. There was no significant racial distribution difference between HPV 16/18/45 and other types. HPV 16/18/45 infection was directly correlated with the severity of abnormal cytology, although the other subtypes were the major causes of cytological abnormalities. The trend for HPV prevalence was consistent across calendar years, and was associated with 8.77% negative for intraepithelial lesion or malignancy, 30.46% atypical squamous cell of undetermined significance, 64.62% low-grade squamous intraepithelial lesion, 66.75% atypical squamous cell-cannot exclude a high-grade squamous intraepithelial lesion, and 91.80% HSIL. Furthermore, 29.09% of HSILs associated with other subtypes were not detectable on subsequent resections. Given the HPV demographic distribution and the histological features of HSILs caused by different subtypes, cotesting with reflex HPV genotyping in specific populations, or expanding the subtypes in the primary HPV screening test, should be considered.

Feng FX ，Birdsong GG ，Wei J ，Dababneh MN ，Reid MD ，Hoskins M ，Wang Q ... -  《-》