Interventions for Treating Actinic Cheilitis: A Systematic Review

Background: Actinic cheilitis (AC) is a sun-related oral potentially malignant disorder with no established optimal treatment. This systematic review aimed to evaluate the therapeutic efficacy of available treatments for AC. Methods: Randomized Clinical Trials (RCTs) comparing AC treatments with placebo or other interventions were included. In February 2025, a literature search was conducted in PubMed, Cochrane Central, SciELO, ClinicalTrials.gov, Scopus, and Web of Science. Risk of bias was assessed using the RoB2 tool. A qualitative synthesis was performed for each clinical outcome. Results: Eight RCTs, involving 230 participants, were included. Treatments assessed included daylight or conventional photodynamic therapy (PDT) with or without methyl aminolevulinate (MAL), imiquimod, and CO2 laser, among others. The highest 3-month clearance rates were observed with MAL plus indoor daylight PDT, CO2 laser, and electrodessication. At 6 months, the CO2 laser remained most effective. Limitations include five trials with a high risk of bias and the inability to perform meta-analysis due to outcome measures heterogeneity and lack of standardized RCTs. Conclusion: Due to limitations, the most effective AC treatment remains undetermined. Future research must improve methodology, assess standardized therapies, and include long-term follow-up to assess recurrences and malignant transformation. Trial Registration: PROSPERO: CRD42024561899.