Off-Label Use of Imiquimod for Lower Female Genital Tract Diseases: A Systematic Review

Objectives Imiquimod (IMQ) is an immunomodulatory topical drug with antiviral and antitumoral activity. Given its effectiveness and safety, IMQ is broadly off-label used for many vulvovaginal conditions as monotherapy and in association with other therapeutic approaches. However, standardized dose regimens and the total duration of therapy are still debated. This review aimed to summarize the current evidence on off-label uses of IMQ in different vulvovaginal conditions and compare its effectiveness to other gold standard treatments. Methods The literature review used PubMed/MEDLINE and ClinicalTrial.gov as primary sources, including articles from January 2000 to June 2024. Results Overall, 105 articles were included, of which 26 articles on vulvar Paget disease, 36 articles on vulvar intraepithelial neoplasia, 20 articles on vaginal intraepithelial neoplasia, 6 articles on vulvovaginal melanoma, and 17 articles on other conditions (molluscum contagiosum, herpes simplex type II infection, plasma cell vulvitis, and candidiasis). Most treatments included IMQ as monotherapy, or in combination and/or in alternative to other approaches, such as surgery, laser, human papillomavirus vaccination, systemic therapies (antiviral drugs, steroids), local therapies (1% cidofovir, 5% 5-fluorouracil, photodynamic therapy), and observation. The most frequent dose regimen was 3 times/week for 12-16 weeks. Outcomes widely varied among different conditions. Conclusion Off-label topical IMQ represents a noninvasive and effective option for treating lower genital tract conditions as monotherapy or in association with other treatments. The IMQ therapy must be personalized based on physician and patient preference.