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Background To investigate the overall and type-specific prevalence of high-risk human papillomavirus (HR-HPV) infection in China across different age groups and regions and to evaluate the triage of HPV-positive cases.Methods A prospective cross-sectional study recruited a total of 20 103 women aged 30–59 years from 13 provinces in China. Self-collected vaginal samples were tested for 14 HR-HPV types using next-generation sequencing or multiplex real-time PCR assays.Results The five most common types were HPV52, 58, 16, 39 and 51. The prevalence of single-type HR-HPV was 10.70%. The overall proportion of HPV16/18 was 20.67%, with a significant difference observed among provinces (p<0.05). The age-specific prevalence curve of HR-HPV followed a U-shaped pattern from 30 to 59 years, with a lower prevalence observed in women aged 40–44 years (12.35%), which subsequently changed with age. The proportion of women aged 30–34 years with HPV16 (21.59%) was significantly higher than that in other age groups, showing two peaks in young and older women. There was a significantly higher prevalence of HPV16 single-type infection in the youngest group, whereas HPV16 multi-type infection was higher in older women. Among cervical intraepithelial neoplasia grade 2 or higher (CIN)2+ cases, HPV16 infection accounted for 43.98%, HPV18 infection for 7.84%, and other 12 infections for 48.20%. HPV16 had the highest sensitivity for detecting CIN2+, reaching 42.7% among single HPV types, followed by HPV52 and HPV58. When HPV16/18/33 were combined for detection, the sensitivity for detecting CIN2+ increased to 66.67%.Conclusions The prevalence and genotype distribution of HR-HPV based on vaginal self-sampling varied across different regions and ages in China. HPV16 was more prevalent in both younger and older age groups. Different HPV subtypes have different detection rates for CIN2+, and combining HPV16/18/33 significantly improved the sensitivity for detecting CIN2+.