(A-355) Post-marketing safety surveillance for bivalent human papillomavirus vaccine in a regional healthcare database in China

Background: Extensive research has been conducted to investigate the potential association between HPV vaccination and the development of potential immune-mediated disorders (pIMDs) as well as adverse pregnancy outcomes (APOs), which continues to be a key focus in vaccine safety studies.

Objectives: To assess the incidence of new-onset pIMDs and APOs among females aged 9–45 years receiving the Cecolin vaccine or not in Xiamen.

Methods: A retrospective-prospective cohort study was conducted using the Xiamen Health and Medical Big Data Center. A cohort of females who received Cecolin (2vHPV vaccine) between September 1, 2020 and December 31, 2023 was matched 1:4 to those who did not receive any HPV vaccine. A systematic case validation was conducted on the identified pIMDs and APOs cases. Through a deep medical chart review, the case identification methods were adjudicated to ensure PPV>70%. Confirmed cases with new-onset pIMDs (systemic lupus erythematosus, rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, idiopathic thrombocytopenic purpura, optic neuritis) and APOs (maternal and live births) were identified using the validated algorithms. The incidence of pIMDs and APOs was estimated for the Cecolin exposed and HPV-vaccine unexposed cohort, respectively, and the incidence rate ratio was calculated by Poisson regression, odds ratio was calculated by logistic regression for controlling confounders.

Results: 57,683 eligible females were enrolled in the pIMDs cohort, and 187 females got conception forming the APOs Cohort. The incidence rate of pIMDs in Cecolin exposed cohort was 41.20 per 100,000 person-year (95% CI: 28.18–58.17) with 32 confirmed pIMDs cases, while, in the HPV-vaccine unexposed cohort, was 52.55 per 100,000 person-year (95% CI: 44.79–61.27) with 163 confirmed pIMDs cases. The IRR was 0.23 (95%CI: 0.08–0.65, P = 0.0056). The incidence rate of APOs (maternal) in Cecolin exposed cohort was 3.21% (95% CI: 1.19–6.85) with 6 confirmed APOs (maternal) cases, while, in the HPV-vaccine unexposed cohort, was 7.89% (95%CI: 6.06–10.06) with 59 confirmed APOs (maternal) cases. The OR was 0.39 (95%CI: 0.18–0.83, P = 0.0153). The incidence rate of APOs (live births) in Cecolin exposed cohort was 1.15% (95% CI: 0.14–4.09) with 2 confirmed APOs (live births) cases, while, in the HPV-vaccine unexposed cohort, was 1.22% (95%CI: 0.56–2.31) with 9 confirmed APOs (live births) cases. The OR was 0.92 (95%CI: 0.62–1.38, P = 0.6944).

Conclusions: The Cecolin administered to females aged 9-45 years does not appear to increase the risk of developing any of the pIMDs and APOs investigated. This study provides evidence supporting the safety of the Cecolin in large-scale populations during post-marketing surveillance.