Imiquimod for Cervical and Vaginal Intraepithelial Neoplasia: A Systematic Review and Meta-analysis.

To evaluate the treatment efficacy and the risk of adverse events of imiquimod for cervical intraepithelial neoplasia (CIN) and vaginal intraepithelial neoplasia (VAIN), compared with placebo or no intervention. We searched Cochrane, PubMed, ISRCTN registry, ClinicalTrials.gov , and the World Health Organization International Clinical Trials Registry Platform up to November 23, 2022. We included randomized controlled trials and prospective nonrandomized studies with control arms that investigated the efficacy of imiquimod for histologically confirmed CIN or VAIN. The primary outcomes were histologic regression of the disease (primary efficacy outcome) and treatment discontinuation due to side effects (primary safety outcome). We estimated pooled odds ratios (ORs) of imiquimod, compared with placebo or no intervention. We also conducted a meta-analysis of the proportions of patients with adverse events in the imiquimod arms. Four studies contributed to the pooled OR for the primary efficacy outcome. An additional four studies were available for meta-analyses of proportions in the imiquimod arm. Imiquimod was associated with increased probability of regression (pooled OR 4.05, 95% CI 2.08-7.89). Pooled OR for CIN in the three studies was 4.27 (95% CI 2.11-8.66); results of one study were available for VAIN (OR, 2.67, 95% CI 0.36-19.71). Pooled probability for primary safety outcome in the imiquimod arm was 0.07 (95% CI 0.03-0.14). The pooled probabilities (95% CI) of secondary outcomes were 0.51 (0.20-0.81) for fever, 0.53 (0.31-0.73) for arthralgia or myalgia, 0.31 (0.18-0.47) for abdominal pain, 0.28 (0.09-0.61) for abnormal vaginal discharge or genital bleeding, 0.48 (0.16-0.82) for vulvovaginal pain, and 0.02 (0.01-0.06) for vaginal ulceration. Imiquimod was found to be effective for CIN, whereas data on VAIN were limited. Although local and systemic complications are common, treatment discontinuation is infrequent. Thus, imiquimod is potentially an alternative therapy to surgery for CIN. PROSPERO, CRD42022377982.

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Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.

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Financial Disclosure Koji Kawakami receives research funds from Eisai Co., Ltd.; Kyowa Kirin Co., Ltd.; Sumitomo Pharma Co., Ltd.; Mitsubishi Corporation, and Real World Data Co., Ltd.; consulting fees from LEBER Inc.; JMDC Inc.; Shin Nippon Biomedical Laboratories Ltd.; and Advanced Medical Care Inc.; executive compensation from Cancer Intelligence Care Systems, Inc.; and honoraria from Mitsubishi Corporation, Pharma Business Academy, and Toppan Inc. Toshiaki A. Furukawa reports personal fees from Boehringer-Ingelheim, DT Axis, Kyoto University Original, Shionogi and SONY, and a grant from Shionogi, outside the submitted work; In addition, Toshiaki A. Furukawa has patents 2020–548587 and 2022–082495 pending, and intellectual properties for Kokoro-app licensed to Mitsubishi-Tanabe. The other authors did not report any potential conflicts of interest. The authors disclosed that this article discusses the off-label use of imiquimod for cervical and vaginal intraepithelial neoplasia.