Postlicensure Safety Monitoring of Quadrivalent Human Papillomavirus Vaccine (HPV4)

Background:   HPV4 was licensed for use in females and males age 9-26 years in June 2006 and October 2009, respectively. 

Objectives:  The postlicensure safety of this vaccine is monitored using two large US surveillance systems: The Vaccine Safety Adverse Event Reporting System (VAERS) and the Vaccine Safety Datalink (VSD). 

Methods:  VAERS, a national passive surveillance system, serves as an early warning system for new or rare adverse events reported postlicensure as vaccines are widely used.  We performed detailed case reviews for VAERS reports of interest or concern.  Disproportional reporting analysis compared adverse event reports following HPV4 to reports following other vaccines administered  to females age 9 -26 years. VSD, through its near-real time surveillance system, monitored the following pre-specified outcomes weekly: Guillain Barré syndrome (GBS), stroke, venous thromboembolism (VTE), appendicitis, seizure, syncope, allergic reaction, and anaphylaxis.  Sequential analyses were done to detect associations between HPV4 and the pre-specified outcomes.

Results:  Through August 31, 2010, over 33 million doses of HPV4 were distributed nationwide.  VAERS received 16,422 reports (8% serious [e.g., hospitalized]) following HPV4 for females and 162 reports (3.2% serious) for males.   VAERS reports of VTE and syncopal episodes were disproportionally higher following HPV4 as compared to other vaccines among females.  VSD monitored 606,558 HPV4 doses. No significant associations were detected for the pre-specified outcomes in VSD, however a non-statistically significant relative risk of 1.98 was observed for VTE among females age 9-17 years. Chart review revealed exposed cases had other risk factors for VTE such as birth control use, obesity, and smoking. 

Conclusions: We continue to monitor HPV4 using both VAERS and VSD.  VSD confirmed no significant increased risk for any of the pre-specified adverse events after vaccination.  Although a significant increased risk of VTE was not demonstrated in VSD, further analyses are planned in both VAERS and VSD.