Triple threats in cancer of oral cavity: Navigating pathological risk factors

Background: Despite multimodal treatment, oral cavity cancer (OCC) outcomes remain poor due to frequent presentation at advanced stages. Identifying reliable prognostic markers is crucial for improving outcomes. Lymphovascular invasion (LVI), perineural invasion (PNI), and depth of invasion (DOI) are key pathological features linked to aggressive tumor behavior. While each factor is associated with worse outcomes, their combined prognostic value remains underexplored. This study evaluates the combined prognostic value of LVI, PNI, and DOI on overall survival (OS) and recurrence-free survival (RFS) in OCC patients treated with curative intent. Methods: This retrospective study included 342 OCC cases treated from January 2017 to December 2021. Patients were stratified into six subgroups based on LVI (±), PNI (±), and DOI (> 1 cm or ≤ 1 cm). Survival outcomes were analyzed using Kaplan-Meier and log-rank tests. Independent prognostic factors were identified using Cox regression. A p-value < 0.05 was considered significant. Results: LVI, PNI, and DOI > 1 cm were present in 29.8%, 48.8%, and 43.3% of cases, respectively. Significant differences in OS and RFS were observed among the six subgroups. The worst outcomes were seen when all three risk factors were present, with a nearly fivefold higher risk of death. Shallower tumors (< 1 cm) were associated with improved survival, even in the presence of LVI or PNI. When both LVI and PNI were absent, OS and RFS differed significantly for deeper versus shallower tumours. Conclusion: Combined assessment of LVI, PNI, and DOI enables effective risk stratification in OCC and can guide forpersonalized patient treatment.