The comparative safety of human papillomavirus vaccines: A Bayesian network meta‐analysis

Background and Aims The safety of human papillomavirus (HPV) vaccines, one of the major challenges to public vaccination, has been controversial. This study assessed the adverse reactions of various HPV vaccines, including bivalent HPV (2vHPV), quadrivalent HPV (4vHPV), and 9‐valent HPV (9vHPV) vaccines. Methods PubMed, Embase, and Central databases were searched for randomized controlled trials (RCTs) on the comparative safety of HPV vaccines. A network meta‐analysis was performed based on the Bayesian framework random‐effects model. Results This study included 23 RCTs. Analysis across these reports indicated that the 2vHPV vaccine was associated with significantly more systemic adverse events than the 4vHPV vaccine (risk ratio [RR]: 1.28, 95% credible interval [CrI]: 1.14–1.44), 9vHPV vaccine (RR: 1.25, 95% CrI: 1.06–1.49), and placebo (RR: 1.31, 95% CrI: 1.18–1.46). However, there were no statistically significant differences in serious adverse events between the vaccinated and placebo groups. For injection‐site adverse events, there were substantial inconsistencies between the direct and indirect effects; therefore, the analysis results of the safety were presented only for systemic and serious adverse events. Conclusions The 2vHPV vaccine resulted in more systemic adverse events than other vaccines and placebo. No significant differences in serious adverse events were observed. Further studies are needed to obtain more information regarding the safety of HPV vaccines.