Treatment of cervical intraepithelial neoplasia with topical imiquimod: a randomized controlled trial

Obstet Gynecol. 2012 Jul;120(1):152-9. doi: 10.1097/AOG.0b013e31825bc6e8.

Abstract

Objective: Alternatives to surgical therapy are needed for the treatment of high-grade cervical intraepithelial neoplasia (CIN 2-3). We aimed to estimate the efficacy of a treatment with imiquimod, a topical immune-response modulator, in patients with CIN 2-3.

Materials and methods: Fifty-nine patients with untreated CIN 2-3 were randomly allocated to a 16-week treatment with self-applied vaginal suppositories containing either imiquimod or placebo. The main outcome was efficacy, defined as histologic regression to CIN 1 or less after treatment. Secondary outcomes were complete histologic remission, human papillomavirus (HPV) clearance, and tolerability. Assuming a two-sided 5% significance level and a power of 80%, a sample size of 24 patients per group was calculated to detect a 35% absolute increase in CIN 2-3 regression.

Results: Histologic regression was observed in 73% of patients in the imiquimod group compared with 39% in the placebo group (P=.009). Complete histologic remission was higher in the imiquimod group (47%) compared with the placebo group (14%) (P=.008). At baseline, all patients tested positive for high-risk HPV. Human papillomavirus clearance rates were increased in the imiquimod group (60%) compared with the placebo group (14%) (P<.001). In patients with HPV-16 infection, complete remission rates were 47% in the imiquimod group compared with 0% in the placebo group (P=.003). Microinvasive cancer was observed in three of 59 (5% [1-14%]) patients, all within the placebo group. Topical imiquimod treatment was well tolerated, and no high-grade side effects were observed.

Conclusion: Topical imiquimod is an efficacious and feasible treatment for patients with CIN 2-3.

Trial registration: ClinicalTrials.gov NCT00941252.

Publication types

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

MeSH terms

  • Adult
  • Aminoquinolines / therapeutic use*
  • Antineoplastic Agents / therapeutic use*
  • Female
  • Humans
  • Imiquimod
  • Papillomavirus Infections / drug therapy
  • Papillomavirus Infections / virology
  • Remission Induction
  • Treatment Outcome
  • Uterine Cervical Dysplasia / drug therapy*
  • Uterine Cervical Dysplasia / virology
  • Uterine Cervical Neoplasms / drug therapy*
  • Uterine Cervical Neoplasms / virology
  • Viral Load
  • Young Adult

Substances

  • Aminoquinolines
  • Antineoplastic Agents
  • Imiquimod

Associated data

  • ClinicalTrials.gov/NCT00941252