Huachun Zou

Effect of HPV integration on prognosis of young women with CIN2 in China: protocol for a multicentre prospective cohort study

Introduction Cervical cancer, a major global health concern, is primarily caused by human papillomavirus (HPV) infection. Although cervical intraepithelial neoplasia grade 2 (CIN2), a precancerous lesion, exhibits high spontaneous regression rates (50%–60%), particularly in younger women, current clinical management lacks accurate risk stratification. This study examines HPV integration status as a prognostic biomarker in women aged 18–45 diagnosed with CIN2, with the objective of developing a predictive tool for personalised therapeutic strategies and minimising overtreatment in this high-regression population. Method and analysis This multicentre cohort study will be implemented across 20 tertiary Grade A hospitals in China, encompassing eastern, western, central and northern regions. It will recruit 240 CIN2 patients, collecting sociodemographic, lifestyle and medical history data via questionnaires. Clinical examinations will be performed at baseline and follow-up. Disease regression ((to cervical intraepithelial neoplasia grade 1 [CIN1] or lower)) and non-regression (persistent CIN2 or progression) will be evaluated. Prognostic factors will be analysed using Cox proportional hazards models, adjusting for confounders such as age, weight and socioeconomic status. Ethics and dissemination The cohort study protocol and informed consent procedures adhere to the Declaration of Helsinki and pertinent Chinese clinical research regulations. Ethical approval has been obtained from the Clinical Research Review Committee of the Fujian Maternal and Child Health Hospital (2022KYLLR01018) and from the participating hospitals. Written informed consent is secured from all participants prior to enrolment, with detailed information provided regarding study objectives, procedures, potential risks and benefits and participants’ rights. Results will be published in peer-reviewed scientific journals, presented at academic meetings and conferences and released to the public through press releases. Trial registration number ClinicalTrials.gov ( NCT05282095 ); Pre-results.

Characteristics of Human Papillomavirus Prevalence and Infection Patterns Among Women Aged 35–65 in Fujian Province, China: A Nine‐Year Retrospective Observational Study

ABSTRACTThe assessment of human papillomavirus (HPV) genotype distribution could inform targeted cervical cancer prevention strategies. The epidemiology of HPV genotypes in terms of age and cervical lesions in Fujian Province, China has not been well described. This 9‐year retrospective study aimed to delineate the prevalence pattern and trend of HPV genotypes among a large‐scale community‐based population. Deidentified data were retrieved from the national cervical cancer screening program in China. We included eligible women aged 35–65 years who underwent cervical cancer screening between 2014 and 2022 in Fujian Province. The HPV prevalence within distinct subpopulations was calculated, and trends in HPV prevalence over the years and across age groups were examined using the Cochran‐Armitage trend test. A total of 551 604 women (median age 49 years [42, 54]; 0.10% with cervical cancer) were included in this study. The overall HPV prevalence was 11.72% (95% CI: 11.63%–11.80%), with HR‐HPV (high‐risk HPV) and HPV 16/18 prevalence at 10.02% (9.94%–10.10%) and 1.74% (1.71%–1.78%), respectively. HPV‐52, 58, 16, 39, 51, and 68 were the most predominant genotypes in the general population. Nearly all genotypes, except for HPV‐39 and 66, showed a decreasing trend in prevalence over the years, while a relatively high prevalence of HR‐HPV was observed across all age groups. As lesion severity increased, HR‐HPV and 9v‐HPV prevalence also increased. Our study underscores the importance of ongoing surveillance of HPV prevalence in China. While the overall decline in HPV infections over the years is encouraging, the relatively high prevalence of HR‐HPV warrants continued attention. Strengthening public health strategies—including prioritizing and promoting the current 9‐valent vaccination, extending HPV testing and cervical cancer screening to older women where feasible, and developing future vaccines targeting more HR‐HPV genotypes—will be crucial in eliminating cervical cancer and HPV‐related disease in China and beyond.

Incidence, persistence and clearance of cervical human papillomavirus among women in Guangdong, China 2007–2018: A retrospective cohort study

Previous studies showed the incidence, persistence and clearance of cervical human papillomavirus (HPV) among women varies from regions. There is no study on dynamic changes of HPV infection among women in Guangdong. It is a retrospective cohort study that included gynecological outpatients aged ≥15 years and retested for HPV within 24 months in Guangdong Women and Children Hospital to estimate HPV incidence, persistence and clearance. Outcomes were estimated through the proportion of HPV incidence, persistence and clearance in HPV-negative or HPV-positive women. Moreover, we examined HPV incidence, persistence and clearance among women who retested in four calendar periods: 0-6, 6-12, 12-18, 18-24 months after the first test. 33,328 gynecological outpatients were included in our study. Incidence rates of any HPV, high-risk (HR) HPV and low-risk (LR) HPV were 10.58%, 8.68% and 4.83%. The most common incident HR HPV were HPV52 (2.69%), HPV16 (1.23%) and HPV58 (1.23%). Persistence rates of any HPV, HR HPV and LR HPV were 47.55%, 42.77% and 33.88%. HPV52 (42.33%), HPV58 (40.74%) and HPV68 (32.36%) were commonly found persistent types. And clearance rates of any HPV, HR HPV and LR HPV were 52.44%, 57.23% and 66.12%.The lowest clearance rates were observed for HPV52 (57.67%), HPV68 (67.64%) and HPV39 (68.56%). HPV incidence and persistence were higher among women aged 15-19 years and ≥55 years. HPV incidence and persistence were found higher among women who retested within 6 months than others in other periods. HPV52, 58, 68, and 39 were the more likely to cause incident and persistent infection, and less likely to be cleared among women in Guangdong. HPV incidence and persistent infection were higher among women aged both younger and older women compared to middle aged women. HPV retesting period may impact the detection of HPV incidence, persistence and clearance.

Prevotella as the hub of the cervicovaginal microbiota affects the occurrence of persistent human papillomavirus infection and cervical lesions in women of childbearing age via host NF‐κB/C‐myc

AbstractThere is evidence that coinfection of cervicovaginal high‐risk human papillomavirus (HR‐HPV) and bacteria is common in women of childbearing age. However, the relationship between bacterial vaginosis (BV) and persistent HR‐HPV infection in women of childbearing age and the underlying mechanisms remain unclear. In this study, we determined whether BV affects persistent HR‐HPV infection in women aged 20–45 years and explored the possible mechanisms of their interactions. From January 1 to April 30, 2020, we recruited women aged 20–45 years with and without BV at a ratio of 1:2 from Fujian Maternity and Child Health Hospital. All women were followed up at 0, 12, and 24 months. A BV assay, HR‐HPV genotyping and cervical cytology were performed at each follow‐up. At 0 months, additional vaginal secretions and cervical exfoliated cells were collected for 16S ribosomal RNA sequencing, bacterial metabolite determination, and POU5F1B, C‐myc, TLR4, NF‐κB, and hTERT quantification. A total of 920 women were included. The abundance of Prevotella (p = 0.016) and Gardnerella (p = 0.027) were higher, whereas the abundance of Lactobacillus was lower (p = 0.001) in women with persistent HR‐HPV infection and high‐grade squamous intraepithelial lesions (HSIL). The abundance of Prevotella (p = 0.025) and Gardnerella (p = 0.018) increased in the vaginas of women with persistent HPV16 infection, whereas only the abundance of Prevotella (p = 0.026) was increased in women with persistent HPV18 infection. The abundance of Prevotella in the vagina was significantly positively correlated with the expression levels of TLR4, NF‐κB, C‐myc, and hTERT in host cervical cells (p < 0.05). Our findings suggest that overgrowth of Prevotella in the vagina may influence the occurrence of persistent HR‐HPV infection‐related cervical lesions through host NF‐κB and C‐myc signaling.

Identifying Data-Driven Clinical Subgroups for Cervical Cancer Prevention With Machine Learning: Population-Based, External, and Diagnostic Validation Study

Abstract Background Cervical cancer remains a major global health issue. Personalized, data-driven cervical cancer prevention (CCP) strategies tailored to phenotypic profiles may improve prevention and reduce disease burden. Objective This study aimed to identify subgroups with differential cervical precancer or cancer risks using machine learning, validate subgroup predictions across datasets, and propose a computational phenomapping strategy to enhance global CCP efforts. Methods We explored the data-driven CCP subgroups by applying unsupervised machine learning to a deeply phenotyped, population-based discovery cohort. We extracted CCP-specific risks of cervical intraepithelial neoplasia (CIN) and cervical cancer through weighted logistic regression analyses providing odds ratio (OR) estimates and 95% CIs. We trained a supervised machine learning model and developed pathways to classify individuals before evaluating its diagnostic validity and usability on an external cohort. Results This study included 551,934 women (median age, 49 years) in the discovery cohort and 47,130 women (median age, 37 years) in the external cohort. Phenotyping identified 5 CCP subgroups, with CCP4 showing the highest carcinoma prevalence. CCP2–4 had significantly higher risks of CIN2+ (CCP2: OR 2.07 [95% CI: 2.03‐2.12], CCP3: 3.88 [3.78‐3.97], and CCP4: 4.47 [4.33‐4.63]) and CIN3+ (CCP2: 2.10 [2.05‐2.14], CCP3: 3.92 [3.82‐4.02], and CCP4: 4.45 [4.31‐4.61]) compared to CCP1 (P<.001), consistent with the direction of results observed in the external cohort. The proposed triple strategy was validated as clinically relevant, prioritizing high-risk subgroups (CCP3-4) for colposcopies and scaling human papillomavirus screening for CCP1-2. Conclusions This study underscores the potential of leveraging machine learning algorithms and large-scale routine electronic health records to enhance CCP strategies. By identifying key determinants of CIN2+/CIN3+ risk and classifying 5 distinct subgroups, our study provides a robust, data-driven foundation for the proposed triple strategy. This approach prioritizes tailored prevention efforts for subgroups with varying risks, offering a novel and scalable tool to complement existing cervical cancer screening guidelines. Future work should focus on independent external and prospective validation to maximize the global impact of this strategy.