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


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.


CONCLUSIONS
Topical imiquimod is an efficacious and feasible treatment for patients with CIN 2-3.
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. christoph.grimm@meduniwien.ac.at
Christoph
C
Grimm
Stephan
S
Polterauer
Camilla
C
Natter
Jasmin
J
Rahhal
Lukas
L
Hefler
Clemens B
CB
Tempfer
Georg
G
Heinze
Georg
G
Stary
Alexander
A
Reinthaller
Paul
P
Speiser
D000328:Adult; D000634:Aminoquinolines / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D000077271:Imiquimod; D030361:Papillomavirus Infections / Q000188:drug therapy / Q000821:virology; D012074:Remission Induction; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000821:virology; D019562:Viral Load; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000188:drug therapy* / Q000821:virology
D000634:Aminoquinolines; D000970:Antineoplastic Agents; D000077271:Imiquimod