(A-345) Assessment of the Safety of Human Papillomavirus Vaccination in Japan: VENUS Study

Background: The human papillomavirus (HPV) vaccine prevents infection from HPV, which can cause cervical and other cancers. As Japan has one of the lowest HPV vaccination rates in the world, there is few safety evidence in the Japanese population.

Objectives: We evaluated the risk of adverse events of special interests (AESIs) after vaccination with 2-valent and 4-valent HPV vaccines in people eligible for routine (12-15y, females: since fiscal year [FY] 2015) and catch-up vaccination (16-26y, females: since FY2022).

Methods: We conducted a population-based cohort study and self-controlled case series (SCCS) in five cities in Japan, using medical claim data and the vaccine registry, from April 2015 to March 2023. The study included women born between April 2, 1997, and April 1, 2011, and followed them from the cohort entry date (CED), defined as the later of either April 2 of the year they turned 12 (FY2015- FY2022) or turned 16 years old (FY2022), one year after their first medical claim. Based on vaccination status, the observation period for each patient was categorized into four periods: unvaccinated period and first, second, third risk period (each risk period lasting up to 180 days after vaccination, ending earlier if subsequent vaccination occurred). We evaluated 66 AESIs of HPV vaccine, defined as outcomes using ICD-10 codes and/or drug prescriptions. In the cohort study, follow-up ended at the earliest of three dates: April 1 of the year the individual turned 27, the last medical claim data date, or the first outcome date. Adjusted rate ratios (aRR) and 95% confidence intervals (CIs) for each risk periods compared with unvaccinated period were estimated using Poisson regression with time-dependent exposure, including baseline covariates (city, type of insurance, Pediatric comorbidity index, and number of medical care in the year prior to CED) and time-dependent covariates (age and calendar year). In the SCCS study, only cases were included and analyzed. A 2-week pre-exposure period was applied before each vaccination. The aRR and 95% CIs for each risk period were estimated.

Results: We identified 25,131 women (56,298 person-years). The average age at the CED was 15 years. Among them, 1,763 individuals received the first dose, 1,492 the second, and 975 the third. Quantitative analysis was feasible for five: migraine, hypotension, asthma, polycystic ovary syndrome, and postural orthostatic tachycardia syndrome. Increased risk was not observed for any outcomes.

Conclusions: This study did not find a clear increased risk with HPV vaccination; however, the sample size was limited. Further large-scale studies are needed.