Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomised controlled trial

Lancet. 2004 Nov 13-19;364(9447):1757-65. doi: 10.1016/S0140-6736(04)17398-4.

Abstract

Background: Vaccination against the most common oncogenic human papillomavirus (HPV) types, HPV-16 and HPV-18, could prevent development of up to 70% of cervical cancers worldwide. We did a randomised, double-blind, controlled trial to assess the efficacy, safety, and immunogenicity of a bivalent HPV-16/18 L1 virus-like particle vaccine for the prevention of incident and persistent infection with these two virus types, associated cervical cytological abnormalities, and precancerous lesions.

Methods: We randomised 1113 women between 15-25 years of age to receive three doses of either the vaccine formulated with AS04 adjuvant or placebo on a 0 month, 1 month, and 6 month schedule in North America and Brazil. Women were assessed for HPV infection by cervical cytology and self-obtained cervicovaginal samples for up to 27 months, and for vaccine safety and immunogenicity.

Findings: In the according-to-protocol analyses, vaccine efficacy was 91.6% (95% CI 64.5-98.0) against incident infection and 100% against persistent infection (47.0-100) with HPV-16/18. In the intention-to-treat analyses, vaccine efficacy was 95.1% (63.5-99.3) against persistent cervical infection with HPV-16/18 and 92.9% (70.0-98.3) against cytological abnormalities associated with HPV-16/18 infection. The vaccine was generally safe, well tolerated, and highly immunogenic.

Interpretation: The bivalent HPV vaccine was efficacious in prevention of incident and persistent cervical infections with HPV-16 and HPV-18, and associated cytological abnormalities and lesions. Vaccination against such infections could substantially reduce incidence of cervical cancer.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Viral / blood
  • Capsid / immunology
  • Capsid Proteins
  • Cervical Intraepithelial Neoplasia / virology
  • Cervix Uteri / virology
  • Dose-Response Relationship, Immunologic
  • Double-Blind Method
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Immunization Schedule
  • Neutralization Tests
  • Oncogene Proteins, Viral / immunology*
  • Papillomaviridae / immunology*
  • Papillomavirus Infections / prevention & control*
  • Papillomavirus Vaccines*
  • Uterine Cervical Diseases / immunology
  • Uterine Cervical Diseases / prevention & control
  • Uterine Cervical Diseases / virology
  • Uterine Cervical Neoplasms / prevention & control*
  • Uterine Cervical Neoplasms / virology
  • Viral Vaccines / administration & dosage
  • Viral Vaccines / adverse effects
  • Viral Vaccines / immunology*

Substances

  • Antibodies, Viral
  • Capsid Proteins
  • HPV L1 protein, Human papillomavirus
  • Oncogene Proteins, Viral
  • Papillomavirus Vaccines
  • Viral Vaccines