Human papillomavirus infection: protocol for a randomised controlled trial of imiquimod cream (5%) versus podophyllotoxin cream (0.15%), in combination with quadrivalent human papillomavirus or control vaccination in the treatment and prevention of recurrence of anogenital warts (HIPvac trial)

BMC Med Res Methodol. 2018 Nov 6;18(1):125. doi: 10.1186/s12874-018-0581-z.

Abstract

Background: Anogenital warts are the second most common sexually transmitted infection diagnosed in sexual health services in England. About 90% of genital warts are caused by human papillomavirus (HPV) types 6 or 11, and half of episodes diagnosed are recurrences. The best and most cost-effective treatment for patients with anogenital warts is unknown. The commonly used treatments are self-administered topical agents, podophyllotoxin (0.15% cream) or imiquimod (5% cream), or cryotherapy with liquid nitrogen. Quadrivalent HPV (qHPV) vaccination is effective in preventing infection, and disease, but whether it has any therapeutic effect is not known.

Methods and design: To investigate the efficacy of clearance and prevention of recurrence of external anogenital warts by topical treatments, podophyllotoxin 0.15% cream or imiquimod 5% cream, in combination with a three-dose regimen of qHPV or control vaccination. 500 adult patients presenting with external anogenital warts with either a first or subsequent episode of anogenital warts will be entered into this randomised, controlled partially blinded 2 × 2 factorial trial.

Discussion: The trial is expected to provide the first high-quality evidence of the comparative efficacy and cost-effectiveness of the two topical treatments in current use, as well as investigate the potential benefit of HPV vaccination, in the management of anogenital warts.

Trial registration: The trial was registered prior to starting recruitment under the following reference numbers: International Standard Randomized Controlled Trial Number (ISRCTN) Registry - ISRCTN32729817 (registered 25 July 2014); European Union Clinical Trials Register (EudraCT) - 2013-002951-14 (registered 26 June 2013).

Keywords: Anogenital warts; Human papillomavirus; Imiquimod; Podophyllotoxin; Quadrivalent HPV vaccine.

Publication types

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

MeSH terms

  • Adult
  • Drug Therapy, Combination
  • Female
  • Host-Pathogen Interactions / drug effects
  • Host-Pathogen Interactions / immunology
  • Humans
  • Imiquimod / therapeutic use*
  • Male
  • Papillomaviridae / drug effects*
  • Papillomaviridae / immunology
  • Papillomaviridae / physiology
  • Papillomavirus Infections / drug therapy*
  • Papillomavirus Infections / prevention & control
  • Papillomavirus Infections / virology
  • Papillomavirus Vaccines / immunology
  • Papillomavirus Vaccines / therapeutic use*
  • Podophyllotoxin / therapeutic use*
  • Recurrence
  • Treatment Outcome
  • Vaccination

Substances

  • Papillomavirus Vaccines
  • Podophyllotoxin
  • Imiquimod

Associated data

  • ISRCTN/ISRCTN32729817
  • EudraCT/2013-002951-14