Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions

N Engl J Med. 2007 May 10;356(19):1915-27. doi: 10.1056/NEJMoa061741.

Abstract

Background: Human papillomavirus types 16 (HPV-16) and 18 (HPV-18) cause approximately 70% of cervical cancers worldwide. A phase 3 trial was conducted to evaluate a quadrivalent vaccine against HPV types 6, 11, 16, and 18 (HPV-6/11/16/18) for the prevention of high-grade cervical lesions associated with HPV-16 and HPV-18.

Methods: In this randomized, double-blind trial, we assigned 12,167 women between the ages of 15 and 26 years to receive three doses of either HPV-6/11/16/18 vaccine or placebo, administered at day 1, month 2, and month 6. The primary analysis was performed for a per-protocol susceptible population that included 5305 women in the vaccine group and 5260 in the placebo group who had no virologic evidence of infection with HPV-16 or HPV-18 through 1 month after the third dose (month 7). The primary composite end point was cervical intraepithelial neoplasia grade 2 or 3, adenocarcinoma in situ, or cervical cancer related to HPV-16 or HPV-18.

Results: Subjects were followed for an average of 3 years after receiving the first dose of vaccine or placebo. Vaccine efficacy for the prevention of the primary composite end point was 98% (95.89% confidence interval [CI], 86 to 100) in the per-protocol susceptible population and 44% (95% CI, 26 to 58) in an intention-to-treat population of all women who had undergone randomization (those with or without previous infection). The estimated vaccine efficacy against all high-grade cervical lesions, regardless of causal HPV type, in this intention-to-treat population was 17% (95% CI, 1 to 31).

Conclusions: In young women who had not been previously infected with HPV-16 or HPV-18, those in the vaccine group had a significantly lower occurrence of high-grade cervical intraepithelial neoplasia related to HPV-16 or HPV-18 than did those in the placebo group. (ClinicalTrials.gov number, NCT00092534 [ClinicalTrials.gov].).

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / epidemiology
  • Adenocarcinoma / prevention & control
  • Adolescent
  • Adult
  • Alphapapillomavirus*
  • Cervical Intraepithelial Neoplasia / epidemiology
  • Cervical Intraepithelial Neoplasia / prevention & control*
  • DNA, Viral / blood
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18
  • Human papillomavirus 16 / genetics
  • Human papillomavirus 16 / isolation & purification
  • Human papillomavirus 18 / genetics
  • Human papillomavirus 18 / isolation & purification
  • Humans
  • Papillomavirus Infections / prevention & control*
  • Papillomavirus Vaccines* / adverse effects
  • Time Factors
  • Treatment Outcome
  • Uterine Cervical Neoplasms / epidemiology
  • Uterine Cervical Neoplasms / prevention & control*

Substances

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

Associated data

  • ClinicalTrials.gov/NCT00092534