Biological mechanisms underlying autofluorescence loss in oral potentially malignant disorders: implications for clinical interpretation.

OBJECTIVE: To review the biological mechanisms underlying autofluorescence loss in oral potentially malignant disorders and their implications for clinical interpretation of oral mucosal autofluorescence findings. METHODS: This narrative review summarizes published evidence on the biological and optical basis of tissue autofluorescence, with emphasis on epithelial, stromal, metabolic, and vascular alterations associated with oral carcinogenesis. Representative in vivo autofluorescence imaging studies were also considered to relate tissue-level changes to clinically observed fluorescence patterns. RESULTS: Autofluorescence loss in oral potentially malignant disorders is likely a multifactorial phenomenon rather than the result of a single biological event. Stromal collagen degradation, metabolic alterations affecting endogenous fluorophores, and increased vascularity leading to hemoglobin-mediated absorption may collectively contribute to fluorescence loss and heterogeneous fluorescence patterns among lesions. Published in vivo studies suggest that autofluorescence imaging may help highlight spatially abnormal mucosal regions for closer clinical assessment and support lesion documentation. However, similar autofluorescence patterns may also occur in inflammatory or hyperkeratotic lesions and across anatomically variable mucosal sites, thereby limiting disease specificity. Quantitative autofluorescence approaches have been investigated to document relative signal intensity and spatial heterogeneity, but their routine clinical use remains limited by methodological heterogeneity, lack of standardized protocols, and insufficient clinical validation. CONCLUSIONS: Autofluorescence loss should be interpreted as a biologically complex optical finding rather than a disease-specific diagnostic signature. Mechanism-based understanding of these alterations may improve the clinical interpretation of autofluorescence findings and support the cautious use of autofluorescence imaging as an adjunct to conventional oral mucosal assessment.