Human papillomavirus vaccine-associated premature ovarian insufficiency and related adverse events: data mining of Vaccine Adverse Event Reporting System

Li Gong,Yun-Tao Jia,Ling-Yun Pan,Xue-Wen Tang,Xiao Chen,Huan-Huan Ji

doi:10.1038/s41598-020-67668-1

Abstract

We detected disproportionate reports of premature ovarian insufficiency (POI) and related events, including amenorrhea, menstruation irregular, FSH increased, and premature menopause, following human papillomavirus (HPV) vaccine from FDA Vaccine Adverse Event Reporting System (VAERS). The signal was detected by the methods of Bayesian Confidence Propagation Neural Network (BCPNN) and Multi-item Gamma Poisson Shrinker (MGPS). When both methods detected a positive result, a signal was generated. Besides, time-scan map is drawn based on the IC value and 95%CI of BCPNN, if the IC curve showed a steady upward trend and the 95%CI narrowed, the signal was stable and strong association.The results showed that there were not POI reports of HPV vaccine, but VAERS received a total of 2, 389, 27 POI related events for HPV2, HPV4, HPV9 respectively from the year of marketed to 2018. No signal was detected for HPV2. HPV4-POI ralated events were all detected as signals by two methods. There was only one signal of menstruation irregular for HPV9. Time scan of HPV4-POI ralated events showed those signals were stability and strong association, but not for HPV9. Our results only represent statistical association between HPV vaccine and POI related events, causal relationship needs further investigation.

Highlights

Human papillomavirus (HPV) is the most common viral infection of the reproductive tract and is the cause of a range of conditions in both men and women and cervical cancer is caused by certain types of human papillomavirus (HPV)
Between 2009 and 2018, Vaccine Adverse Event Reporting System (VAERS) received a total of 275,595 vaccinated alone reports, including 171 for HPV2; from 2006 to 2018, there were 322,932 single use reports, of which 27,386 were HPV4; 143,909 were extracted from 2015 to 2018 and 7,255 for HPV 9-valent recombinant vaccine (HPV9) (Fig. 1)
For the types of the reporter, it was mainly come from healthcare provider (HPV2 accounting for 100.00%, HPV4 for 54.76%, HPV9 for 29.63%), suggesting that the report was authentic and professional

Summary

Introduction

Human papillomavirus (HPV) is the most common viral infection of the reproductive tract and is the cause of a range of conditions in both men and women and cervical cancer is caused by certain types of HPV. Case reports and case series study reported a possible link about adolescent POI following HPV4 4, but a population-based retrospective cohort study found no elevated risk of POI after HPV4 administration 5. 9, to evaluate possible association between vaccine/drug and event combination, which including detection of novel signal, strengthening or weaking of existing signal and providing evidence for or against exicting safety concern not evaluated by data mining. We designed this study to evaluate the statistical association and detect the signal of POI and related events of three HPV vaccines, and to provide evidence for or against exicting HPV4-associated POI concern based on the data mining and signal detection method. The research data was obtained from the Vaccine Adverse Event Reporting System (VAERS)

Methods

Results

Discussion

Conclusion