Systematic Review and Meta-analysis of Postlicensure Observational Studies on Human Papillomavirus Vaccination and Autoimmune and Other Rare Adverse Events

Abstract

Background: Because of the limited number of subjects in prelicensure studies, autoimmune diseases and other rare adverse effects of vaccines may go undetected. Since 2006, millions of human papillomavirus (HPV) vaccine doses have been distributed and a considerable amount of postlicensure safety data has been generated. The objective of this study was to review available HPV postlicensure safety studies and to summarize risk estimates of autoimmune and other rare diseases. Methods: For this systematic review and meta-analysis, we searched literature databases to identify any postlicensure safety studies related to HPV vaccination and autoimmune adverse events from inception to April 16, 2019. Pooled risk estimates were computed using fixed-or randomeffects models if at least 2 estimates per disease and per HPV vaccine were available. Results: Twenty-two studies met our inclusion criteria. The studies applied various methodologies and used different types of data sources and outcome definitions. Quadrivalent HPV vaccine (4vHPV) was most commonly assessed. Type 1 diabetes mellitus, immune thrombocytopenia purpura and thyroiditis diseases were most frequently reported. The meta-analysis was conducted on 35 diseases corresponding to 48 pooled risk estimates. Majority of the pooled estimates showed no significant effect (n = 43). Three negative (paralysis, immune thrombocytopenia purpura and chronic fatigue syndrome) and 2 positive (Hashimoto and Raynaud diseases) associations were detected. Conclusion: Our study demonstrated an absence of clear association between HPV vaccines and autoimmune and other rare diseases. The review also highlights the need for more systematic collaborations to monitor rare safety adverse events.

Association between human papillomavirus vaccination and serious adverse events in South Korean adolescent girls: nationwide cohort study

“…Several studies have found no association between HPV vaccination and autoimmune diseases, a major concern in vaccine safety studies. 13 14 19 37 Although a recent meta-analysis highlighted no clear association between HPV vaccines and autoimmune diseases, the study also suggested a significant increase in the risk 38 We speculated that this increased risk resulted from the unmasking phenomenon, which can occur when vaccinated groups are compared with unvaccinated groups. 22 Visiting a medical institution for vaccination offers an opportunity to assess symptoms that might not have been assessed…”

Do Vaccines Have a Role as a Cause of Autoimmune Neurological Syndromes?

“…The safety of HPV was further demonstrated in a recent review and meta-analysis of post-licensure observational studies. The OR for MS was 0.96 (95% CI, 0.77-1.21), and for all the other CNS demyelinating syndromes it was 1.02 (95% CI, 0.77-1.33) (25).…”

Vaccinations and Autoimmune Diseases

“…Another meta-analysis which comprised twenty-two studies revealed that DM-1, immune thrombocytopenia purpura and chronic thyroiditis were the most frequently reported after HPV vaccination. However, this study demonstrated the absence of a clear association between HPV vaccines and autoimmune diseases and other rare diseases [ 96 ].…”