Natural History of Genital Warts: Analysis of the Placebo Arm of 2 Randomized Phase III Trials of a Quadrivalent Human Papillomavirus (Types 6, 11, 16, and 18) Vaccine

J Infect Dis. 2009 Mar 15;199(6):805-14. doi: 10.1086/597071.

Abstract

Background: The placebo arm of human papillomavirus (HPV) vaccine trials helps define the natural history of genital warts (GW).

Methods: Women enrolled in the placebo arm (n = 8800) of 2 randomized trials of a quadrivalent vaccine were examined for the presence of GW for up to 9 visits over approximately 4 years. A comprehensive examination of the perianal area, vulva, and vagina prompted biopsy. Biopsy samples were analyzed by a blinded panel of up to 4 histopathologists and tested for 14 HPV genotypes (6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59) by use of a polymerase chain reaction-based assay. Risk factors for the development of GW were assessed.

Results: Women were followed up for an average of 3.6 years (range, 0-4.9 years). Overall, 298 (3.4%) of 8800 participants developed GW related to HPV-6 or HPV-11 (incidence rate, 0.87 cases per 100 person-years-at-risk). In total, 520 distinct lesions were diagnosed as GW. HPV DNA was detected in 472 (90.8%) lesions, with HPV-6 and HPV-11 detected in 447 (86.0%) of these lesions (94.7% of 472 HPV DNA-positive lesions). We found high-risk HPV types in 161 (31.0%) of 520 lesions. Risk factors for HPV-6- and HPV-11-related GW included infection at baseline, acquisition of new sex partners, a higher number of sex partners, and DNA positivity at baseline for a high-risk HPV type.

Conclusions: We confirm the major role played by HPV-6 and HPV-11 in GW, as well as associated risk factors. A vaccine that includes these types of HPV could substantially reduce the overall burden of HPV disease.

Trial registration: ClinicalTrials.gov NCT00092521 NCT00092534.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Clinical Trials, Phase III as Topic
  • Condylomata Acuminata / epidemiology
  • Condylomata Acuminata / immunology*
  • Female
  • Follow-Up Studies
  • Genotype
  • Human papillomavirus 16 / genetics
  • Human papillomavirus 16 / immunology*
  • Human papillomavirus 18 / genetics
  • Human papillomavirus 18 / immunology*
  • Human papillomavirus 6 / genetics
  • Human papillomavirus 6 / immunology*
  • Humans
  • Papillomavirus Infections / epidemiology
  • Papillomavirus Infections / immunology*
  • Papillomavirus Infections / prevention & control
  • Randomized Controlled Trials as Topic
  • Risk Factors
  • Time Factors
  • Viral Vaccines / administration & dosage*
  • Young Adult

Substances

  • Viral Vaccines

Associated data

  • ClinicalTrials.gov/NCT00092521
  • ClinicalTrials.gov/NCT00092534