Cross-protective efficacy of HPV-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by non-vaccine oncogenic HPV types: 4-year end-of-study analysis of the randomised, double-blind PATRICIA trial

Lancet Oncol. 2012 Jan;13(1):100-10. doi: 10.1016/S1470-2045(11)70287-X. Epub 2011 Nov 8.

Abstract

Background: We evaluated the efficacy of the human papillomavirus HPV-16/18 AS04-adjuvanted vaccine against non-vaccine oncogenic HPV types in the end-of-study analysis after 4 years of follow-up in PATRICIA (PApilloma TRIal against Cancer In young Adults).

Methods: Healthy women aged 15-25 years with no more than six lifetime sexual partners were included in PATRICIA irrespective of their baseline HPV DNA status, HPV-16 or HPV-18 serostatus, or cytology. Women were randomly assigned (1:1) to HPV-16/18 vaccine or a control hepatitis A vaccine, via an internet-based central randomisation system using a minimisation algorithm to account for age ranges and study sites. The study was double-blind. The primary endpoint of PATRICIA has been reported previously; the present analysis evaluates cross-protective vaccine efficacy against non-vaccine oncogenic HPV types in the end-of-study analysis. Analyses were done for three cohorts: the according-to-protocol cohort for efficacy (ATP-E; vaccine n=8067, control n=8047), total vaccinated HPV-naive cohort (TVC-naive; no evidence of infection with 14 oncogenic HPV types at baseline, approximating young adolescents before sexual debut; vaccine n=5824, control n=5820), and the total vaccinated cohort (TVC; all women who received at least one vaccine dose, approximating catch-up populations that include sexually active women; vaccine n=9319, control=9325). Vaccine efficacy was evaluated against 6-month persistent infection, cervical intraepithelial neoplasia grade 2 or greater (CIN2+) associated with 12 non-vaccine HPV types (individually or as composite endpoints), and CIN3+ associated with the composite of 12 non-vaccine HPV types. This study is registered with ClinicalTrials.gov, number NCT00122681.

Findings: Consistent vaccine efficacy against persistent infection and CIN2+ (with or without HPV-16/18 co-infection) was seen across cohorts for HPV-33, HPV-31, HPV-45, and HPV-51. In the most conservative analysis of vaccine efficacy against CIN2+, where all cases co-infected with HPV-16/18 were removed, vaccine efficacy was noted for HPV-33 in all cohorts, and for HPV-31 in the ATP-E and TVC-naive. Vaccine efficacy against CIN2+ associated with the composite of 12 non-vaccine HPV types (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68), with or without HPV-16/18 co-infection, was 46·8% (95% CI 30·7-59·4) in the ATP-E, 56·2% (37·2-69·9) in the TVC-naive, and 34·2% (20·4-45·8) in the TVC. Corresponding values for CIN3+ were 73·8% (48·3-87·9), 91·4% (65·0-99·0), and 47·5% (22·8-64·8).

Interpretation: Data from the end-of-study analysis of PATRICIA show cross-protective efficacy of the HPV-16/18 vaccine against four oncogenic non-vaccine HPV types-HPV-33, HPV-31, HPV-45, and HPV-51-in different trial cohorts representing diverse groups of women.

Funding: GlaxoSmithKline Biologicals.

Publication types

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

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Adolescent
  • Adult
  • Aluminum Hydroxide / administration & dosage*
  • Antigens, Viral / immunology
  • Asia
  • Australia
  • Cervical Intraepithelial Neoplasia / diagnosis
  • Cervical Intraepithelial Neoplasia / pathology
  • Cervical Intraepithelial Neoplasia / prevention & control*
  • Cervical Intraepithelial Neoplasia / virology
  • Cross Reactions
  • DNA, Viral / analysis
  • Double-Blind Method
  • Europe
  • Female
  • Human papillomavirus 16 / genetics
  • Human papillomavirus 16 / immunology*
  • Human papillomavirus 18 / genetics
  • Human papillomavirus 18 / immunology*
  • Humans
  • Lipid A / administration & dosage
  • Lipid A / analogs & derivatives*
  • Neoplasm Grading
  • North America
  • Papillomavirus Infections / diagnosis
  • Papillomavirus Infections / prevention & control*
  • Papillomavirus Infections / virology
  • Papillomavirus Vaccines / administration & dosage*
  • Precancerous Conditions / diagnosis
  • Precancerous Conditions / pathology
  • Precancerous Conditions / prevention & control*
  • Precancerous Conditions / virology
  • South America
  • Time Factors
  • Treatment Outcome
  • Uterine Cervical Neoplasms / diagnosis
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / prevention & control*
  • Uterine Cervical Neoplasms / virology
  • Young Adult

Substances

  • ASO4 mixture
  • Adjuvants, Immunologic
  • Antigens, Viral
  • DNA, Viral
  • Lipid A
  • Papillomavirus Vaccines
  • human papillomavirus vaccine, L1 type 16, 18
  • Aluminum Hydroxide

Associated data

  • ClinicalTrials.gov/NCT00122681