(280) Post-marketing surveillance for the safety of the 4-valent human papillomavirus (HPV) vaccine in China: a retrospective real-world study

Background: The 4-valent human papillomavirus (4vHPV; Gardasil [Merck & Co., Inc., Rahway, NJ, USA]) vaccine was introduced in China in 2017 and is used widely. However, the safety of the 4vHPV vaccine administered to Chinese women as part of routine health care has previously not been studied.

Objectives: To monitor the occurrence of new-onset autoimmune diseases (AIs) and adverse pregnancy outcomes in Chinese women who received the 4vHPV vaccine.

Methods: A post-marketing surveillance of females who received at least one dose of the 4vHPV vaccine at age 20-45 years in Ningbo city between January 9th, 2018 to March 31st, 2021 was performed within the Ningbo Regional Health Information Platform (NRHIP). New-onset cases of Graves’ disease, Hashimoto’s thyroiditis, systemic lupus erythematosus, type 1 diabetes, multiple sclerosis, optic neuritis, and uveitis diagnosed within 6 months after each dose or between two doses (time interval ≤6 months) of the 4vHPV vaccine were to be reported. For adverse pregnancy outcomes, cases of stillbirth in women who received the 4vHPV vaccine within 30 days before conception or during pregnancy were to be reported as well as cases of 23 major congenital anomalies diagnosed within 3 months from birth in infants whose mothers had maternal exposure to 4vHPV vaccine were also reported. Disease occurrence from literature was summarized to provide background data.

Results: A total of 195,593 doses of the 4vHPV vaccine were administered to 76,212 women aged 20-45 years old who had received no other HPV vaccine. New-onset AIs were diagnosed in 113 women, comprising 71 cases of Hashimoto’s disease (incidence density, 130.84 per 100,000 person-years), 24 cases of Graves’ disease (44.21 per 100,000 person-years), 1 case of optic neuritis (1.84 per 100,000 person-years), and 17 cases of uveitis (31.31 per 100,000 person-years). Among the 168 women with 4vHPV maternal exposure, no stillbirths were observed. Five cases of congenital heart diseases were reported in infants whose mother had maternal exposure.

Conclusions: In this first post-marketing surveillance for the safety of the 4vHPV vaccine in China, no new safety concerns of new-onset AIs or adverse pregnancy outcomes were observed.