A controlled trial of a human papillomavirus type 16 vaccine

N Engl J Med. 2002 Nov 21;347(21):1645-51. doi: 10.1056/NEJMoa020586.

Abstract

Background: Approximately 20 percent of adults become infected with human papillomavirus type 16 (HPV-16). Although most infections are benign, some progress to anogenital cancer. A vaccine that reduces the incidence of HPV-16 infection may provide important public health benefits.

Methods: In this double-blind study, we randomly assigned 2392 young women (defined as females 16 to 23 years of age) to receive three doses of placebo or HPV-16 virus-like-particle vaccine (40 microg per dose), given at day 0, month 2, and month 6. Genital samples to test for HPV-16 DNA were obtained at enrollment, one month after the third vaccination, and every six months thereafter. Women were referred for colposcopy according to a protocol. Biopsy tissue was evaluated for cervical intraepithelial neoplasia and analyzed for HPV-16 DNA with use of the polymerase chain reaction. The primary end point was persistent HPV-16 infection, defined as the detection of HPV-16 DNA in samples obtained at two or more visits. The primary analysis was limited to women who were negative for HPV-16 DNA and HPV-16 antibodies at enrollment and HPV-16 DNA at month 7.

Results: The women were followed for a median of 17.4 months after completing the vaccination regimen. The incidence of persistent HPV-16 infection was 3.8 per 100 woman-years at risk in the placebo group and 0 per 100 woman-years at risk in the vaccine group (100 percent efficacy; 95 percent confidence interval, 90 to 100; P<0.001). All nine cases of HPV-16-related cervical intraepithelial neoplasia occurred among the placebo recipients.

Conclusions: Administration of this HPV-16 vaccine reduced the incidence of both HPV-16 infection and HPV-16-related cervical intraepithelial neoplasia. Immunizing HPV-16-negative women may eventually reduce the incidence of cervical cancer.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Viral / blood
  • DNA, Viral / analysis
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Papillomaviridae* / genetics
  • Papillomaviridae* / immunology
  • Papillomaviridae* / isolation & purification
  • Papillomavirus Infections / epidemiology
  • Papillomavirus Infections / prevention & control*
  • Papillomavirus Vaccines*
  • Tumor Virus Infections / epidemiology
  • Tumor Virus Infections / prevention & control*
  • Uterine Cervical Dysplasia / epidemiology
  • Uterine Cervical Dysplasia / prevention & control*
  • Uterine Cervical Dysplasia / virology
  • Uterine Cervical Neoplasms / epidemiology
  • Uterine Cervical Neoplasms / prevention & control*
  • Uterine Cervical Neoplasms / virology
  • Viral Vaccines* / adverse effects
  • Viral Vaccines* / immunology

Substances

  • Antibodies, Viral
  • DNA, Viral
  • Papillomavirus Vaccines
  • Viral Vaccines