Smoking Status and Recurrence in Oral Tongue Squamous Cell Carcinoma: Evidence for Convergent Clinical Behavior

Objectives: Oral tongue squamous cell carcinomas (SCCOT) arising in never-smokers and smokers have similar genomic profiles, suggesting tobacco exposure may not be the dominant driver of tumor biology at this site. We investigated whether smoking is related to recurrence risk in SCCOT. Methods: We analyzed disease-free survival (DFS) in two SCCOT cohorts: a discovery cohort of 86 patients and a validation cohort of 410 patients, both treated and followed at MD Anderson Cancer Center with available smoking histories and demographic, clinical, and pathologic information. The initial validation cohort included 424 patients; however, 14 patients overlapping with the discovery cohort were excluded to preserve cohort independence. The risk of recurrence was assessed using univariate and multivariable Cox regression models adjusted for prognostic factors. Smoking was evaluated as ever-smoker versus never-smoker and as high versus low cumulative exposure (> 15 vs. ≤ 15 pack-years). Results: In the discovery cohort, no statistically significant differences in DFS were observed by smoking status (log-rank p = 0.227) or cumulative exposure (log-rank p = 0.460). Additionally, neither smoking status (aHR: 0.96; 95% CI: 0.46–1.20) nor exposure (aHR: 0.99; 95% CI: 0.48–2.03) was associated with recurrence. These findings were consistent in the validation cohort. Conclusion: These findings suggest smoking history was not independently associated with recurrence risk in SCCOT. Larger prospective studies are required to validate these findings. Further studies integrating genomic and transcriptomic profiling are needed to define high-risk SCCOT biology and identify biomarkers for personalized treatment. Impact: By demonstrating smoking status does not influence recurrence risk, our findings provide clinical support for prior genomic evidence of similarity between SCCOT in smokers and never-smokers, arguing against the use of smoking history to define prognostic subgroups. Level of Evidence: 2.