Original Research

Treatment of Cervical Intraepithelial Neoplasia With Topical Imiquimod

A Randomized Controlled Trial

Grimm, Christoph MD; Polterauer, Stephan MD; Natter, Camilla MD; Rahhal, Jasmin MD; Hefler, Lukas MD; Tempfer, Clemens B. MD; Heinze, Georg PhD; Stary, Georg MD; Reinthaller, Alexander MD; Speiser, Paul MD

Author Information

From the Department of General Gynaecology and Gynaecological Oncology, Comprehensive Cancer Center, the Center for Medical Statistics, Informatics and Intelligent Systems, Section for Clinical Biometrics, and the Division of Immunology, Allergy and Infectious Diseases, Medical University of Vienna, and the Karl Landsteiner Institute for Gynecologic Surgery and Oncology, Vienna, Austria; and the Department of Obstetrics and Gynecology, Ruhr University Bochum, Bochum, Germany.

Supported by the Fellinger Cancer Research Fund, MEDA Pharmaceuticals. MEDA Pharmaceuticals provided the study medication and an unrestricted research grant to the Department of Obstetrics and Gynecology, Medical University of Vienna.

The authors thank R. Horvat and H. Wiener, both pathologists specialized in Gynecologic Pathology at the Clinical Institute for Pathology, Medical University of Vienna, Austria, for reviewing all histopathologic specimens.

Presented as a poster at the American Society for Clinical Oncology Annual Meeting, June 5–11, 2011, Chicago, Illinois, the 17th International Meeting of the European Society of Gynaecological Oncology, September 11–14, 2011, Milan, Italy, and as an oral presentation at the 27th International Papillomavirus Conference and Clinical Workshop, September 17–22, 2011, Berlin, Germany.

Corresponding author: Christoph Grimm, MD, Department of General Gynaecology and Gynaecological Oncology, Comprehensive Cancer Center, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria; e-mail: [email protected].

Financial Disclosure The authors did not report any potential conflicts of interest.

Obstetrics & Gynecology 120(1):p 152-159, July 2012. | DOI: 10.1097/AOG.0b013e31825bc6e8

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.

CLINCAL TRIAL REGISTRATION: 

ClinicalTrials.gov, www.clinicaltrials.gov, NCT00941252.

LEVEL OF EVIDENCE: 

I

© 2012 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.

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