Abstract:
Oral epithelial dysplasia represents a clinically important precursor to oral squamous cell carcinoma, yet conventional
histopathological grading alone cannot reliably identify lesions that will progress. This comprehensive review examines
the value of integrating transcriptomic and immunohistochemical profiling of inflammatory biomarkers for earlier and
more accurate risk prediction. Evidence was synthesized across studies addressing molecular progression, cytokine and
chemokine signaling, immune-cell infiltration, immune-checkpoint activity, epithelial stress responses, stemness, stromal
remodeling, metabolic adaptation, and epithelial–mesenchymal transition. Transcriptomic approaches reveal dysregulated
gene-expression programs linked to inflammation, proliferation, immune suppression, and malignant transformation,
while immunohistochemistry confirms protein expression and preserves spatial relationships within epithelial and stromal
compartments. Biomarkers involving p53, Ki-67, p16, hypoxia-inducible factor 1 alpha, heat-shock proteins, programmed
death ligand 1, E-cadherin, vimentin, survivin, podoplanin, and cancer stem-cell markers show potential for distinguishing
biologically active dysplasia from more stable lesions. No single marker currently provides sufficient predictive accuracy
for routine clinical use. Multimarker models combining molecular signatures with histological grade, lesion phenotype,
anatomical site, and patient-related factors appear more clinically relevant. Standardized protocols, prospective
multicentre cohorts, longitudinal validation, spatial transcriptomics, multiplex immunohistochemistry, and digital
pathology are needed to translate integrated biomarker profiling into personalized surveillance, targeted biopsy, and earlier
intervention. Such integration may reduce delayed diagnosis, unnecessary treatment, and uncertainty in clinical decision
making.
