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 <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.