Efficacy of topical treatments for high-risk human papillomavirus in preventing CIN II+ lesions: a systematic review

ObjectiveThis study aimed to systematically review the literature regarding topical therapies for reducing the risk of cervical intra-epithelial neoplasia (CIN) grade 2 or higher (CIN II+) lesions among women with high-risk human papillomavirus (HPV) infection and histologically confirmed CIN I or either no cervical lesions.MethodsWe conducted a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered the protocol in PROSPERO (CRD42024629608). We searched Ovid MEDLINE, Ovid EMBASE, Cochrane Central, and ClinicalTrials.gov from inception through December 16, 2024 for randomized controlled trials evaluating any cervical topical treatment in women with high-risk HPV and, at most, CIN I. The primary outcome was progression to histologically confirmed CIN II+. Secondary outcomes were treatment-related adverse events.ResultsOf 305 records, 19 full-text articles were reviewed. Finally, 16 trials were assessed. None met all our eligibility criteria, with some trials being excluded for multiple reasons. Twelve were excluded due to an inadequate study population (included women with CIN II+, lacked histologic confirmation of lesion grade, or lacked confirmatory high-risk HPV testing), 4 used inappropriate interventions, and 2 did not include a placebo or watchful waiting comparator. Although many studies reported HPV clearance or cytologic regression, none were powered or designed to assess progression to CIN II+.ConclusionsThe current evidence from randomized trials is insufficient to determine whether topical cervical therapies reduce the risk of progression to CIN II+ in women with high-risk HPV infection. Future trials should prioritize histologic outcomes and adhere to current management protocols to establish the clinical utility of such therapies.