Ting Wu

Variations in the Natural History of High-Risk HPV Types Following HPV-16/18 Bivalent Vaccination in Females Aged 18-45 Years

Existing evidence regarding the impact of vaccination on the natural history of high-risk human papillomavirus (HPV) infections remains limited, understanding such effects is essential for optimizing cervical cancer screening in post-vaccination era. Using 10-year follow-up data from a phase 3 randomized trial of the Escherichia coli-produced HPV-16/18 bivalent vaccine (NCT01735006) and its extension study (NCT05045755, NCT04969445), we compared the spectra and natural history (persistence, clearance, and progression) of high-risk HPV infections between vaccinated and unvaccinated females aged 18-45 years. Data was analyzed using the Cox regression and the competing risk model. Our findings indicate that vaccination reduces the burden of HPV-16/18-associated lesions (HR = 0.12, p = 0.0041) primarily by preventing incident infections (HR = 0.45, p < 0.0001) and modifying the natural history of breakthrough infections (enhancing clearance: 98.5% vs. 93.8%, p < 0.0001; and attenuating progression: 1.5% vs. 6.2%, p = 0.0420). Conversely, the elevated burden of HPV-52-associated lesions (HR = 3.06, p = 0.0303) observed in the vaccine group stems mainly from altered natural history (reduced clearance: 90.3% vs. 97.9%, p = 0.0144; and increased progression: 9.7% vs. 2.1%, p = 0.0421), rather than an increase in incidence (HR = 1.09, p = 0.2669). In this work, the observed shifts in HPV infection profiles and natural history between vaccinated and unvaccinated populations suggest that cervical cancer screening recommendations may warrant adjustment for vaccinated individuals.

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

AbstractData 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.

Type‐ and age‐specific natural history of high‐risk human papillomavirus infections in healthy women: A prospective cohort study in China

Abstract As cervical cancer screening shifts from cytology to HPV testing, clarifying the type‐ and age‐specific natural history of HR‐HPV is crucial, especially in regions with bimodal prevalence patterns where longitudinal data remain limited. We analyzed baseline HR‐HPV‐positive participants from the control arm of a bivalent HPV‐16/18 vaccine trial in China, with follow‐up over 5.5 years. Cox regression and competing risk models were applied to evaluate the progression, clearance, and persistence of these HR‐HPV infections. Among 534 HR‐HPV‐positive women at baseline, 98 CIN2+ lesions were identified (52 at baseline, 46 during follow‐up). HPV‐16 and HPV‐31 exhibited the highest immediate CIN2+ risk (21.1%), followed by HPV‐33 (17.1%) and HPV‐58 (12.7%). When stratified by baseline cytology, the LSIL+ group showed the highest immediate risk of CIN2+ (29.5% among the HR‐HPV‐positive participants), followed by the ASC‐US (10.5%). In the longitudinal analysis, competing risk models revealed significant type‐specific differences in progression (Gray's test P  = 0.0158) and clearance (Gray's test P  &lt;0.0001). HPV‐16, ‐31, ‐18, and ‐58 showed relatively high progression (27.1%, 19.2%, 16.1%, and 11.2%) and low clearance (72.9%, 69.2%, 83.9%, and 88.8%). CIN2+ risk was strongly genotype‐dependent; beyond HPV‐16/18, types ‐31, ‐33, and ‐58 also warrant particular attention in screening and clinical management. Additionally, although a slightly higher CIN2+ progression risk was observed in younger women compared to older women, the difference was not statistically significant (Gray's test P =  0.4389), indicating the need for confirmation in larger studies. These findings enhance the understanding of the natural history of type‐specific HR‐HPV and age‐specific progression in initially screen‐positive populations.