Is oral squamous cell carcinoma arising in the background of oral submucous fibrosis a distinct entity? A systematic review and meta-analysis of clinicopathological and prognostic outcomes.

This systematic review and meta-analysis was performed to assess and compare clinicopathological and survival outcomes in oral squamous cell carcinoma (OSCC) arising in the background of oral submucous fibrosis (OSCC-OSMF) and OSCC without any background of OSMF (non-OSMF-OSCC). A literature search in PubMed, Scopus, and Web of Science was performed up to August 2025. Studies comparing clinicopathological features between OSCC-OSMF and non-OSMF-OSCC were considered. Demographics, tumour site, stage, histopathology, nodal and other histological features, and survival data were extracted. Random-effects meta-analysis was performed to determine clinicopathological risk factors and survival in OSCC-OSMF compared to non-OSMF-OSCC. Risk of bias was assessed using the Newcastle-Ottawa Scale. Twelve observational studies were included. Patients with OSCC-OSMF were younger and predominantly male, and the buccal mucosa was the most common site. OSCC-OSMF presented more often at earlier stages (odds ratio (OR) 2.19, 95% confidence interval (CI) 1.29-3.73) and was histologically well-differentiated (OR 1.81, 95% CI 1.32-2.48). Nodal metastasis (OR 0.53, 95% CI 0.38-0.73) and extracapsular spread (OR 0.33, 95% CI 0.21-0.51) were significantly less common in OSCC-OSMF. The 5-year overall survival rate was better for OSCC-OSMF (OR 2.35, 95% CI 1.56-3.54). OSCC-OSMF has a unique set of clinicopathological characteristics and two-fold lower metastatic potential compared to non-OSMF-OSCC, and may be associated with improved long-term survival. The study data indicate that OSCC-OSMF is a unique subset within the OSCC category that requires consideration for surveillance and treatment.