ABSTRACTBackground:Oral submucous fibrosis (OSMF) has a high prevalence in Southeast Asia with increased malignant transformation rates. Numerous biomarkers are currently being investigated to predict the disease prognosis and for early detection of malignant changes.Materials and Methods:A prospective study was conducted comprising 40 subjects with clinically and biopsy-proven OSMF being included in the study as experimental group (n = 28) and patients with no tobacco/betel nut habit, who underwent surgical removal of third molar, being included as control group (n = 12). About 5-μm sections from formalin-fixed paraffin-embedded tissue blocks were obtained for immunohistochemical (IHC) study. The expression of cyclooxygenase 2 (COX 2) was evaluated in the experimental group and compared in morphologically normal oral epithelium. The intensity of stain was assessed at different levels of epithelium (basal, stratum spinosum, superficial level) and connective tissue.Results:Based on IHC expression of COX 2, all the patients of the control group were negative for COX 2, and among the OSMF group, 19 patients (67.9%) were positive and 9 patients (32.1%) were found to be negative for COX 2. The association of COX2 expression on comparison of controls with OSMF was found to be statistically significant (χ2 =21.955; P = 0.000). On comparison of immune expression of COX 2 in different clinical stages based on functional staging, we found significant association of COX 2 expression with the stage of OSMF (χ2 = 7.368; P = 0.025).Conclusion:The significant expression of COX 2 in different clinical stages of OSMF when compared with normal shows the role of COX 2 in the pathogenesis of OSMF and could serve as a potent biomarker for assessing the disease progression.