Clinical efficacy of chemopreventive agents in oral cancer and oral potentially malignant disorders: A systematic review.

Oral squamous cell carcinoma (OSCC) is a significant global health concern, often developing from oral potentially malignant disorders (OPMDs). Given the poor prognosis associated with late-stage OSCC, there is growing interest in chemoprevention as a strategy to halt or reverse malignant transformation. This systematic review evaluated 37 randomised controlled trials examining the effectiveness of various chemopreventive agents, including retinoids, antioxidants, herbal compounds, immune checkpoint inhibitors, and anti-inflammatory drugs. Retinoids demonstrated potential in reducing second primary tumors and malignant progression but were hindered by toxicity and high recurrence rates. Antioxidants showed limited preventive benefit, though they may alleviate treatment-related side effects. Herbal agents and combination therapies, such as those containing β-carotene, isotretinoin, IFN-α 2a, and vitamin E, have shown encouraging results, although the long-term benefits remain uncertain. Novel approaches, including COX-2 inhibitors and immunotherapies, appear promising but need further validation. While chemopreventive strategies offer potential, their clinical application remains limited by inconsistent outcomes and adverse effects. Advancing this field requires the development of targeted therapies, personalised approaches based on molecular profiling, and innovative delivery systems like nanocarriers to improve therapeutic efficacy and safety.