Post-Marketing Safety Surveillance of Autoimmune Diseases Following Bivalent Human Papillomavirus Vaccination in China

Abstract

Background/Objectives: The potential of vaccines to trigger autoimmune diseases (ADs) has been extensively investigated and remains a routine focus of vaccine-safety research. This post-marketing, real-world study compared the risk of ADs between females who received bivalent human papillomavirus (HPV) vaccine (Cecolin) and unvaccinated females. Methods: Eligible females aged 9–45 years registered in the Xiamen Health and Medical Big Data Center from September 2020 to December 2023 (post-Cecolin period) were enrolled. Cecolin recipients constituted the exposed cohort, and a matched unexposed cohort was generated in a 1:4 ratio based on age and calendar year. Case validation was conducted to determine optimal identification algorithms. Incidence rates (IRs) were calculated and incidence rate ratios (IRRs) with 95% confidence intervals (CIs) were derived from zero-inflated Poisson regression. Results: Overall incidence of ADs was 70.63 per 100,000 person-years (95% CI: 67.59–73.77) in the post-Cecolin period. Compared with matched unexposed cohorts, vaccinated females showed a significantly lower AD risk in both contemporaneously matched (IRR = 0.23, 95% CI: 0.08–0.65; p = 0.006) and historically matched (IRR = 0.21, 95% CI: 0.07–0.66; p = 0.008) analyses. Conclusions: Consistent with prior evidence, this study provides real-world evidence further confirming that Cecolin vaccination does not increase the risk of ADs. It adds the first large-scale post-marketing safety evidence for this Chinese domestic bivalent HPV vaccine, filling a critical evidence gap. These results may inform vaccination policy and guide post-licensure safety monitoring in China and other countries that have introduced this vaccine.