Efficacy of Human Papillomavirus (HPV)-16/18 AS04-adjuvanted Vaccine Against Cervical Infection and Precancer Caused by Oncogenic HPV Types (PATRICIA): Final Analysis of a Double-Blind, Randomised Study in Young Women

Lancet. 2009 Jul 25;374(9686):301-14. doi: 10.1016/S0140-6736(09)61248-4. Epub 2009 Jul 6.

Abstract

Background: The human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine was immunogenic, generally well tolerated, and effective against HPV-16 or HPV-18 infections, and associated precancerous lesions in an event-triggered interim analysis of the phase III randomised, double-blind, controlled PApilloma TRIal against Cancer In young Adults (PATRICIA). We now assess the vaccine efficacy in the final event-driven analysis.

Methods: Women (15-25 years) were vaccinated at months 0, 1, and 6. Analyses were done in the according-to-protocol cohort for efficacy (ATP-E; vaccine, n=8093; control, n=8069), total vaccinated cohort (TVC, included all women receiving at least one vaccine dose, regardless of their baseline HPV status; represents the general population, including those who are sexually active; vaccine, n=9319; control, n=9325), and TVC-naive (no evidence of oncogenic HPV infection at baseline; represents women before sexual debut; vaccine, n=5822; control, n=5819). The primary endpoint was to assess vaccine efficacy against cervical intraepithelial neoplasia 2+ (CIN2+) that was associated with HPV-16 or HPV-18 in women who were seronegative at baseline, and DNA negative at baseline and month 6 for the corresponding type (ATP-E). This trial is registered with ClinicalTrials.gov, number NCT00122681.

Findings: Mean follow-up was 34.9 months (SD 6.4) after the third dose. Vaccine efficacy against CIN2+ associated with HPV-16/18 was 92.9% (96.1% CI 79.9-98.3) in the primary analysis and 98.1% (88.4-100) in an analysis in which probable causality to HPV type was assigned in lesions infected with multiple oncogenic types (ATP-E cohort). Vaccine efficacy against CIN2+ irrespective of HPV DNA in lesions was 30.4% (16.4-42.1) in the TVC and 70.2% (54.7-80.9) in the TVC-naive. Corresponding values against CIN3+ were 33.4% (9.1-51.5) in the TVC and 87.0% (54.9-97.7) in the TVC-naive. Vaccine efficacy against CIN2+ associated with 12 non-vaccine oncogenic types was 54.0% (34.0-68.4; ATP-E). Individual cross-protection against CIN2+ associated with HPV-31, HPV-33, and HPV-45 was seen in the TVC.

Interpretation: The HPV-16/18 AS04-adjuvanted vaccine showed high efficacy against CIN2+ associated with HPV-16/18 and non-vaccine oncogenic HPV types and substantial overall effect in cohorts that are relevant to universal mass vaccination and catch-up programmes.

Funding: GlaxoSmithKline Biologicals.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Cervical Intraepithelial Neoplasia* / prevention & control
  • Cervical Intraepithelial Neoplasia* / virology
  • Double-Blind Method
  • Female
  • Human papillomavirus 16*
  • Human papillomavirus 18*
  • Humans
  • Mass Vaccination
  • Neoplasm Staging
  • Papillomavirus Infections* / complications
  • Papillomavirus Infections* / virology
  • Papillomavirus Vaccines / immunology*
  • Precancerous Conditions / prevention & control
  • Precancerous Conditions / virology
  • Safety
  • Sexual Behavior
  • Treatment Outcome
  • Uterine Cervical Neoplasms* / prevention & control
  • Uterine Cervical Neoplasms* / virology
  • Vaginal Smears
  • Young Adult

Substances

  • Papillomavirus Vaccines
  • human papillomavirus vaccine, L1 type 16, 18

Associated data

  • ClinicalTrials.gov/NCT00122681