Post-approval Safety Monitoring of Quadrivalent and Bivalent Human Papillomavirus Vaccines Based on Real-world Data from the Korea Adverse Events Reporting System (KAERS)

Background and Objectives: The vaccine adjuvant, AS04, present in bivalent human papilloma virus (bHPV) vaccines, induces greater local immune responses than the aluminum adjuvant in quadrivalent HPV (qHPV) vaccines. These distinctions might also result in disparities in immunogenicity and responsiveness, possibly contributing to differences in adverse events (AEs) between these vaccines. Here we comparatively analyzed AEs between qHPV and bHPV vaccines based on 10-year real-world AE data. Methods: We evaluated the Korea Adverse Events Reporting System (KAERS), a nationwide drug database including vaccines from January 2007 to December 2016, analyzing AEs reported for qHPV and bHPV vaccines. Vaccine-AE pairs were generated, and the characteristics of all reported AEs were analyzed. Signals were derived using the disproportionality method of signal detection algorithms (reporting odds ratios and information component). Results: Of the total 2566 HPV vaccine-associated AE reports, 2686 and 1994 were vaccine-AE pairs for qHPV and bHPV, respectively. Application site disorders were the most frequent AEs for both vaccines but were more frequently reported with the bHPV vaccine. The characteristics of non-application site AEs between the two vaccines were generally similar, but systemic AEs such as fever and fatigue were more common with the bHPV vaccine. Tremor, rash, eye pain, myopathy and circulatory failure were identified as signals in both qHPV and bHPV vaccines. Conclusions: Both application site disorders and systemic AEs were somewhat more frequent with the bHPV vaccine than with the qHPV vaccine. This might be caused by an immune response induced by adjuvants contained within the vaccines.