A Novel Fibrosis-Integrated Nomogram for Predicting Survival in Oral Squamous Cell Carcinoma Patients with Oral Submucous Fibrosis: A Retrospective Cohort Study

Background: Oral squamous cell carcinoma (OSCC) with oral submucous fibrosis (OSF) represents a distinct clinicopathological entity with unique prognostic factors not captured by conventional TNM staging. We aimed to develop a fibrosis-integrated nomogram (FIN) for individualized survival prediction in this population. Methods: We conducted a retrospective cohort study of 314 consecutive OSCC patients with coexisting OSF treated between 2015 and 2022. Patients were randomly divided into training (n=220) and validation (n=94) sets. Independent prognostic factors were identified using Cox regression and integrated into a nomogram predicting 1-year, 3-year, and 5-year overall survival (OS). Model performance was assessed using C-index, time-dependent ROC curves, calibration plots, and decision curve analysis. Results: Six independent prognostic factors were identified: maximum mouth opening (HR 0.92, P< 0.001), areca nut chewing duration > 20 years (HR 1.78, P=0.002), N2-3 category (HR 1.89, P=0.001), poor differentiation (HR 1.56, P=0.018), perineural invasion (HR 1.67, P=0.007), and positive surgical margin (HR 2.03, P=0.001). The FIN demonstrated excellent discrimination, with C-indices of 0.79 (95% CI 0.75– 0.83) in the training set and 0.77 (95% CI 0.72– 0.82) in the validation set, significantly outperforming TNM staging (C-indices 0.68 and 0.66, respectively; both P< 0.01). Risk stratification identified three prognostic groups with 5-year OS rates of 78.6%, 48.3%, and 18.9% (log-rank P< 0.001). Conclusion: The fibrosis-integrated nomogram significantly improves survival prediction for OSCC patients with OSF by incorporating simple clinical measures of fibrosis severity and carcinogen exposure, enabling individualized risk assessment. Keywords: oral squamous cell carcinoma, oral submucous fibrosis, nomogram, survival prediction, areca nut chewing, maximum mouth opening, prognosis