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

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 <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.