Redox biomarkers in oral leukoplakia: a narrative review and translational framework

Oral leukoplakia (OL) is a common oral potentially malignant disorder for which individualized malignant-transformation risk remains difficult to estimate. Redox biomarkers capture lipid oxidation, oxidative DNA damage, and antioxidant defense across saliva, blood, and lesional tissue. Oxidative and nitrative injury may contribute to genomic instability, while impaired antioxidant defense may permit persistent damage, providing a mechanistic rationale for studying progression. This focused narrative Review synthesizes recent systematic reviews and a targeted update of human primary studies through 9 September 2026 to define a translational framework for moving redox measurements from disease association to longitudinal risk stratification. Current evidence identifies a reproducible but compartment-dependent redox signal: malondialdehyde (MDA) is commonly increased, systemic antioxidant measures are often reduced, and 8-hydroxy-2-deoxyguanosine (8-OHdG) shows greater matrix-dependent heterogeneity. The key opportunity is prospective validation of whether standardized, platform-specific redox measurements add prognostic information beyond lesion phenotype, site, dysplasia, exposure history, and molecular comparators. We organize this opportunity into a staged pathway spanning analytical validity, clinical association, longitudinal validation, incremental information, and external clinical utility. A multicentre inception cohort with prespecified assays, standardized pre-analytics, pathology-confirmed follow-up, event-appropriate modelling, and independent validation offers one way to test this framework. Repeated within-patient trajectories are a potential monitoring use case once analytical and within-person biological variation are characterized. This Review positions redox biomarkers as a candidate layer for future OL risk stratification and specifies the evidence needed to determine their incremental clinical value.