Postlicensure safety surveillance for quadrivalent human papillomavirus recombinant vaccine

JAMA. 2009 Aug 19;302(7):750-7. doi: 10.1001/jama.2009.1201.

Abstract

Context: In June 2006, the Food and Drug Administration licensed the quadrivalent human papillomavirus (types 6, 11, 16, and 18) recombinant vaccine (qHPV) in the United States for use in females aged 9 to 26 years; the Advisory Committee on Immunization Practices then recommended qHPV for routine vaccination of girls aged 11 to 12 years.

Objective: To summarize reports to the Vaccine Adverse Event Reporting System (VAERS) following receipt of qHPV.

Design, setting, and participants: Review and describe adverse events following immunization (AEFIs) reported to VAERS, a national, voluntary, passive surveillance system, from June 1, 2006, through December 31, 2008. Additional analyses were performed for some AEFIs in prelicensure trials, those of unusual severity, or those that had received public attention. Statistical data mining, including proportional reporting ratios (PRRs) and empirical Bayesian geometric mean methods, were used to detect disproportionality in reporting.

Main outcome measures: Numbers of reported AEFIs, reporting rates (reports per 100,000 doses of distributed vaccine or per person-years at risk), and comparisons with expected background rates.

Results: VAERS received 12 424 reports of AEFIs following qHPV distribution, a rate of 53.9 reports per 100,000 doses distributed. A total of 772 reports (6.2% of all reports) described serious AEFIs, including 32 reports of death. The reporting rates per 100,000 qHPV doses distributed were 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. Disproportional reporting of syncope and venous thromboembolic events was noted with data mining methods.

Conclusions: Most of the AEFI rates were not greater than the background rates compared with other vaccines, but there was disproportional reporting of syncope and venous thromboembolic events. The significance of these findings must be tempered with the limitations (possible underreporting) of a passive reporting system.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Adverse Drug Reaction Reporting Systems*
  • Child
  • Female
  • Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18
  • Humans
  • Papillomavirus Infections / prevention & control
  • Papillomavirus Vaccines / adverse effects*
  • United States
  • Uterine Cervical Neoplasms / prevention & control
  • Uterine Cervical Neoplasms / virology
  • Vaccination / standards
  • Young Adult

Substances

  • Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18
  • Papillomavirus Vaccines