Postlicensure Safety Surveillance for Quadrivalent Human Papillomavirus Recombinant Vaccine

Abstract

The quadrivalent human papillomavirus (qHPV) (types 6, 11, 16, and 18) recombinant vaccine was licensed by the US Food and Drug Administration (FDA) in 2006 for use in females aged 9 to 26 years. Within 1 month after licensure, the Advisory Committee on Immunization Practices recommended the vaccine for routine vaccination of girls aged 11 to 12 years. Clinical trials conducted before licensure in more than 21,000 women reported no significant differences in the incidence of solicited systemic clinical adverse events after immunization (AEFIs) between the vaccine group (59%) and the placebo group (60%). Similar rates of serious AEFIs were also found in the 2 groups. This study summarized data for AEFIs reported to the Vaccine Adverse Event Reporting System (VAERS) for females who had received qHPV within 2.5 years after licensure. VAERS reports were classified as serious according to the FDA regulatory definition of a serious AEFI. Separate analyses for individual adverse events were based on prelicensure safety data, public attention to reported AEFIs, and identification of AEFIs of unusual severity. To detect disproportionality in reporting (occurrence more frequent than expected), the empirical Bayesian geometric mean method and the proportional reporting ratio were used. The primary outcome measures were frequency of AEFIs, reported rates per 100,000 doses of distributed vaccine or per person-years at risk and comparison with expected background rates. During the study period, 12,424 reports of AEFIs following qHPV distribution were received by VAERS; this represents a rate of 53.9 reports per 100,000 doses distributed. Of the 12,424 reports, 772 (6.2%) were serious, including 32 reports of death. Reporting rates per 100,000 vaccine doses distributed were as follows: 8.2 for syncope, 7.5 for local site reactions, 6.8 for dizziness, 5.0 for nausea, 4.1 for headache, 3.1 for hypersensitivity reactions, 2.6 for urticaria, 0.2 for venous thromboembolic events, autoimmune disorders, and Guillain- Barré syndrome, 0.1 for anaphylaxis and death, 0.04 for transverse myelitis and pancreatitis, and 0.009 for motor neuron disease. There was disproportional reporting of syncope and venous thromboembolic events among the AEFIs. These findings show that AEFI rates were no greater than the background rates for most patients receiving qHPV in the 2.5 years after licensing, However, disproportional reporting was found for 2 AEFIs, syncope and venous thromboembolic events.