Post-marketing surveillance for the safety of the 9-valent human papillomavirus vaccine: a retrospective real-world study in China

ABSTRACT

Background

The 9-valent human papillomavirus (9vHPV) vaccine was introduced in China in 2018. This study was conducted to monitor the occurrence of new-onset autoimmune diseases (AIs) in Chinese women vaccinated with the 9vHPV vaccine and adverse pregnancy outcomes in infants born to mothers with inadvertent pregnancy exposure.

Research design and methods

Women who received the first dose of the 9vHPV vaccine at age 16–26 years in Ningbo between January 2019 and March 2021 were monitored in the Ningbo Regional Health Information Platform. New-onset cases of seven pre-specified AIs diagnosed within six months after vaccination were collected. Cases of stillbirth and 23 major congenital anomalies diagnosed within three months of birth in target infants were collected.

Results

A total of 102,670 doses of the 9vHPV vaccine were administered to 41,609 women who had received no other HPV vaccine. New-onset AIs were diagnosed in 36 women, comprising 21 Hashimoto’s, 11 Graves’, and 4 uveitis disease cases. Among 50 women with maternal vaccination exposure, no stillbirths were observed. One case of microtia was observed.

Conclusions

In this first post-marketing surveillance of the 9vHPV vaccine in China, no safety signals were identified when putting the results in context to published data.

KEYWORDS:

• 9-valent human papillomavirus vaccine
• safety
• product surveillance
• post-marketing
• autoimmune diseases
• pregnancy

Acknowledgments

We thank Susanne Hartwig Pharm D, Peng Jiang PhD, Xuedan You PhD, and Carol Koro PhD for their scientific contribution to the study protocol, statistical analysis plan, and manuscript. We also acknowledge the contribution of Yaqun Fu MM MS and Xin Ma MS in providing study management support. MSD did not have access to any patient-level data in the Ningbo Regional Health Information Platform. A relevant abstract entitled “Post-marketing surveillance for the safety of the 9-valent human papillomavirus vaccine in China: a retrospective real-world study” was submitted to the International Conference on Pharmacoepidemiology & Therapeutic Risk Management (ICPE) 2023.

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A reviewer of this manuscript has disclosed that they were an investigator on the Gardasil9 efficacy trial in young adults. A second reviewer has disclosed that they received support from GSK for an observational, retrospective study unrelated to HPV or HPV vaccines. Peer reviewers on this manuscript have no other relevant financial or other relationships to disclose.

Author contributions

Ruogu Meng and Siyan Zhan conceived and designed the study. Rui Ma and Jianmei Wang coordinated the data acquisition and standardization. Ruogu Meng, Peipei Liu, Zuoxiang Liu, Bingjie He, and Zhike Liu analyzed the data. Ruogu Meng drafted the manuscript. Ruogu Meng, Yu Yang, and Siyan Zhan contributed to the interpretation of the results and critical revision of the manuscript for important intellectual content. All authors reviewed and approved the final manuscript.

Ethical approval and patient consent

The study protocol was approved by the ethical review committee of the Peking University Health Science Center (IRB. No: IRB00001052-20101). The requirement for informed consent was waived. The study was conducted in accordance with the Declaration of Helsinki; Good Pharmacoepidemiology Practice Guidelines; and local laws, rules, and regulations.

Data availability statement

The data that supports the findings of this study is available from the Ningbo Center for Disease Control and Prevention, but restrictions apply to the availability of these data, which was used under license for the current study, and so is not publicly available. Data is however available from the authors upon reasonable request and with permission of the Ningbo Center for Disease Control and Prevention.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14760584.2023.2239911.

Additional information

Funding

This manuscript was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (EU PAS register number: EUPAS36132, CDE CTR register number: CTR20210666).