Clinical trial and post-licensure safety profile of a prophylactic human papillomavirus (types 6, 11, 16, and 18) l1 virus-like particle vaccine

Pediatr Infect Dis J. 2010 Feb;29(2):95-101. doi: 10.1097/INF.0b013e3181b77906.


Background: We describe the safety of the human papillomavirus (HPV)-6/11/16/18 vaccine using updated clinical trial data (median follow-up time of 3.6 years) and summarize up to 3 years of post-licensure surveillance.

Methods: In 5 clinical trials, 21,480 girls/women aged 9 to 26 years and boys aged 9 to 16 years received >or=1 dose of HPV-6/11/16/18 vaccine or placebo. All serious and non-serious adverse experiences (AEs) and new medical conditions were recorded for the entire study period(s). As of June 2009, >25 million doses of HPV-6/11/16/18 vaccine had been distributed in the United States with >50 million doses globally. Post-licensure safety as summarized by the Centers for Disease Control and Prevention using the United States Vaccine Adverse Event Reporting System database is also reported.

Results: Eight subjects experienced a treatment-related serious AE (0.05% vaccine; 0.02% placebo). Of 18 deaths (0.1% vaccine; 0.1% placebo), all were considered unrelated to study treatment. New medical conditions which were potentially consistent with autoimmune phenomena were reported in 2.4% of both vaccine and placebo recipients. Pain, the most common injection-site AE, occurred more frequently with vaccine (81% vaccine; 75% placeboaluminum; 45% placebo-saline). No differences were seen in the incidence of the most common non-serious AEs-headache and pyrexia. The Vaccine Adverse Event Reporting System has received 14,072 reports for the HPV-6/11/16/18 vaccine since licensure, with only 7% being serious AEs, about half the average reported for licensed vaccines in general.

Conclusions: HPV-6/11/16/18 vaccination was associated with more injection-site pain than placebo but similar incidences of systemic and serious AEs and new medical conditions potentially consistent with autoimmune phenomena. Based on review of post-licensure safety information, the benefits of vaccination to prevent the majority of genital tract precancers and cancers continue to far outweigh its risks.

Publication types

  • Clinical Trial, Phase II
  • Clinical Trial, Phase III
  • Clinical Trial, Phase IV
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Drug-Related Side Effects and Adverse Reactions
  • Female
  • Fever
  • Headache
  • Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18
  • Humans
  • Incidence
  • Male
  • Pain
  • Papillomavirus Infections / prevention & control*
  • Papillomavirus Vaccines / adverse effects*
  • Papillomavirus Vaccines / immunology*
  • Placebos / administration & dosage
  • Product Surveillance, Postmarketing
  • United States
  • Vaccines, Virosome / adverse effects
  • Vaccines, Virosome / immunology
  • Young Adult


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