The 13-year long-term follow-up on the effectiveness and immunogenicity of the quadrivalent human papillomavirus vaccine in Chinese females vaccinated at 20-45 years of age

The quadrivalent human papillomavirus (qHPV) vaccine demonstrated high efficacy against vaccine-type-related precancers in Chinese females through a 6.6-year double-blind, randomized control trial (V501-041, NCT00834106). We present results for its long-term follow-up (LTFU) phase, evaluating vaccine effectiveness and immunogenicity throughout 13 years post Dose 1. Participants receiving qHPV vaccines at ages 20-45 in the V501-041 study constituted the early vaccination group (EVG). Those who received the placebo in V501-041 but were vaccinated during 2018-2020 formed the catch-up vaccination group (CVG), while the control group (CG) comprised those remaining unvaccinated throughout V501-041 and LTFU. The primary endpoint was histopathologically-confirmed cervical intraepithelial neoplasia (CIN) 2+ tested PCR-positive for HPV-16/18. Antibodies against HPV-6, 11, 16, and 18 were assessed using an immunoglobulin G (IgG) Luminex immunoassay at year 13. A total of 1100 participants from V501-041, of whom 978 were followed in LTFU, were included with a median follow-up of 152.2 months. No cases of the primary endpoint were observed in the EVG during 5513.6 person-years of follow-up, while one case was observed in the CG over 2951.4 person-years of follow-up, indicating a 100% risk reduction in the EVG compared to the CG. In the CVG, no cases were detected from vaccination to the latest follow-up (0.0 per 10 000 person-years), contrasting with an incidence of 22.3 per 10 000 person-years prior to vaccination. Seropositivity rates at year 13 remained >92% (for HPV-6/11/16) and 84% (HPV-18). These findings demonstrated continued vaccine protection against cervical precancers and sustained immunogenicity through 13 years post-vaccination. The LTFU study was registered at the Chinese Clinical Trial Registry, ChiCTR2100052313.