Safety monitoring of bivalent, quadrivalent, and 9-valent human papillomavirus vaccination in Japan: The vaccine effectiveness, networking, and universal safety (VENUS) study

Abstract

ABSTRACT Safety data on human papillomavirus (HPV) vaccination in the Japanese population remain limited owing to the lack of healthcare databases available for vaccine safety assessment. In this study, we assessed the risk of adverse events of special interest (AESIs) following HPV vaccination among females aged 12–26 y using medical claims data linked to routine or catch-up vaccination records provided by municipalities. We conducted a population-based cohort study and self-controlled case series (SCCS) from April 2015 to March 2023 for bivalent/quadrivalent vaccines and from April 2023 to March 2024 for the 9-valent vaccine. All females eligible for the vaccination program were included in the cohort study, whereas only those who experienced AESIs were included in the SCCS. The observation period was classified according to vaccination status as unvaccinated and post-vaccination risk periods following the first, second, and third doses. Adjusted rate ratios with 95% confidence intervals were estimated for the cohort and SCCS. In the bivalent/quadrivalent vaccines analysis cohort (25131 females), 1763, 1492, and 975 received the first, second, and third doses, respectively. In the 9-valent vaccine analysis cohort (38970 females), 3931, 2389, and 934 received the first, second, and third doses, respectively. Rates of 54 AESIs were calculated during unvaccinated periods. AESIs with feasible quantitative analyses for either the bivalent/quadrivalent or 9-valent vaccines included migraine, hypotension, asthma, polycystic ovary syndrome, postural orthostatic tachycardia syndrome, hypothyroidism, hyperthyroidism, and epilepsy. No statistically significant increased risk following HPV vaccination was observed for these AESIs. Larger datasets are needed to assess rarer AESIs.