Comorbidity Burden and Survival After Primary Surgery for Oral Cavity Squamous Cell Carcinoma: Tumor Stage as an Effect Modifier

Background/Objectives: To evaluate the association between comorbidity burden, quantified using the Charlson Comorbidity Index (CCI), and overall survival (OS) and disease-free survival (DFS) in patients treated surgically for oral cavity squamous cell carcinoma (OCSCC), and to determine whether this association is modified by tumor stage. Methods: We retrospectively analyzed 325 patients treated with primary surgery for OCSCC at a single institution (2009–2021). CCI was scored excluding the index malignancy component and evaluated as a continuous variable. Univariate and multivariable Cox proportional hazards models assessed the association between CCI and OS/DFS, including a formal CCI × stage interaction term. Kaplan–Meier curves stratified by CCI (>4 vs. ≤4) were generated separately in early- and advanced-stage subgroups and compared by log-rank test. Results: CCI was significantly associated with OS (HR 1.14 per point, 95% CI 1.04–1.25, p = 0.005) but not DFS (HR 1.02, 95% CI 0.92–1.12, p = 0.768). A significant CCI × stage interaction was observed (HR 0.82, 95% CI 0.68–0.99, p = 0.036): within early-stage patients, an elevated CCI (>4) was associated with a significantly worse 5-year OS (52.9% vs. 72.3%, p = 0.009), whereas no such difference was observed in advanced-stage patients (40.9% vs. 42.6%, p = 0.56). Conclusions: The comorbidity burden was associated with overall but not disease-free survival after surgery for OCSCC. The association differed by tumor stage and was most apparent in early-stage disease. A recurrence-based classification of deaths showed that non-cancer death accounted for a substantially larger share of mortality among early-stage than advanced-stage patients, supporting a competing-mortality mechanism; independently adjudicated cause-of-death data were not available to confirm this directly. CCI may provide additional prognostic information in early-stage OCSCC.