Cervical cancer remains a significant health burden, and effective screening is essential, yet the age-specific performance of HPV primary screening is rarely studied. This multicenter study evaluates age-specific performance of primary human papillomavirus (HPV) testing as cross-sectional and longitudinal screening for cervical cancer among 28,501 Chinese women. At baseline, HPV screening with cytology triage demonstrates higher sensitivity (96.9% vs. 79.7%) but slightly lower specificity (88.8% vs. 92.7%) than cytology with HPV triage for cervical intraepithelial neoplasia grade 2 or worse (CIN2+). HPV sensitivities remain high across age groups (≤35: 100.0%; 36-45: 96.4%; >45: 96.8%), consistently exceeding the corresponding cytology sensitivities (66.7%, 75.7%, and 84.9%). Over a three-year follow-up, HPV screening maintains superior sensitivity (93.1% vs. 58.1%) and slightly lower specificity (89.6% vs. 92.4%) compared with cytology. Age-stratified analyses in the longitudinal setting reveal trends similar to those observed in the cross-sectional analyses. Women positive for HPV16/18 have a 43.0% three-year risk of CIN2+, compared with 0.2% for HPV-negative women. These findings support the durable protection of HPV-based screening and the feasibility of extending screening intervals.
© 2025. The Author(s).