Real-world effectiveness of HPV vaccination against high-risk type HPV DNA positivity among adult women aged 18 - 45years in China: A matched test-negative design study.

Extensive evidence confirms the high effectiveness of human papillomavirus (HPV) vaccines in young girls; however, real-world data on vaccine effectiveness (VE) among women vaccinated at ages 18-45 remain limited, particularly in China, where HPV status at vaccination is often unknown. We conducted a population-based matched test-negative design study using linked cervical cancer screening and immunization records in Shenzhen, China. Cases positive for vaccine-type high-risk HPV (hrHPV) DNA were matched 1:1 with negative controls by age, screening date, household registration, and screening type. VE for at least one dose was estimated using conditional logistic regression and stratified by time since vaccination, vaccine valency, and age at vaccination. Among 7,060 matched pairs, overall VE increased significantly with time since vaccination: 6.4% (95% CI: -3.9% to 15.7%) at <1y, 17.9% (5.5% to 28.7%) at 1-<2y, and 40.2% (29.6% to 49.2%) at ≥2y. Among women vaccinated ≥2y earlier, VE against HPV16/18 was 48.4% (33.7% to 59.8%) for 2-/4-valent vaccines and 54.4% (26.5% to 71.7%) for the 9-valent vaccine. Significant protection at≥2y was observed across all age-at-vaccination groups: 45.7% (25.0% to 60.7%) for ages 18-26, 39.6% (23.5% to 52.4%) for ages 27-35, and 35.5% (12.6% to 52.4%) for ages 36-45. In conclusion, HPV vaccination confers moderate protection against vaccine-type hrHPV DNA positivity among Chinese women vaccinated at ages 18-45. However, as this outcome reflects a single-time-point surrogate virologic endpoint rather than persistent infection or clinical disease, adult women should continue regular cervical cancer screening.