Evaluation of the effectiveness and immunogenicity of quadrivalent HPV vaccination over 10 years

Objective This study aimed to evaluate the effectiveness and long-term immunogenicity of the quadrivalent HPV vaccine(4v HPV vaccine) in Chinese women aged 20-45 years after 10 years of vaccination. Methods A long-term follow-up study was conducted from October 2019 to April 2020 on participants of the phase III clinical trial of the 4v HPV vaccine (NCT00834106). Participants were categorized into vaccinated, catch-up vaccinated, and control groups based on their vaccination status during the clinical trial and catch-up vaccination after trial completion. Follow-up assessments included questionnaire surveys, venous blood sampling, gynecological examinations, and cervical cancer screening based on liquid-based cytology. Individuals with abnormal cytology results were referred for colposcopy, and cervical lesions identified during colposcopy were biopsied. Biopsy samples were used for histopathological diagnosis and HPV DNA testing. Serum samples from participants were assessed for HPV6, 11, 16, and 18 neutralizing antibody titers using a pseudovirus-based neutralization assay (PBNA) to evaluate vaccine immunogenicity. Results A total of 889 participants were included in the 10-year follow-up, with 240, 453, and 196 individuals in the control, vaccinated, and catch-up vaccinated groups, respectively. In terms of effectiveness, no cervical lesions of any grade associated with the vaccine type were found in the vaccination group, and the proportions of abnormal cytology and histopathology results were lower than those in the control group (3.7% vs. 9.6%, P=0.002; 0.4% vs. 2.1%, P=0.052). Regarding immunogenicity, neutralizing antibody positivity rates of vaccine types were significantly higher in the vaccination group compared with the control group(P<0.001). The positivity rates of neutralizing antibodies for HPV6, 11, 16, and 18 in the vaccinated group versus the control group were 84.3% vs. 18.3%, 62.0% vs. 4.2%, 95.1% vs. 12.1%, 35.5% vs. 4.2%, respectively, and geometric mean titer (GMT) ratio ranging from 2.62 to 25.33. In the catch-up vaccinated group, the positivity rates of neutralizing antibodies for HPV6, 11, 16, and 18 were 94.4%, 92.9%, 96.9%, and 76.0%, respectively, with GMT ratio versus the control group ranging from 9.05 to 83.08. Conclusion Protective HPV vaccine-induced antibody titres can be detected up to 10 years after vaccination, contributing to a reduced risk of cytological abnormalities and cervical lesions associated with the vaccine types for at least 10 years.