Pattern and localization of perineural invasion predict poor survival in oral tongue carcinoma

Background: Survival rate for oral tongue squamous cell carcinoma (OTSCC) is still poor and, despite Tumor–Node–Metastasis staging system has been recently updated, patients included under the same stage still show difference in prognosis. Perineural invasion (PNI) emerged to be an indicator of tumor aggressive behavior and unfortunate events. In this study, we investigate the clinic and prognostic value of PNI in a cohort of OTSCC patients. Methods: About 200 patients with OTSCC were retrospectively evaluated the presence of PNI. PNI was furtherly descripted as uni-/multifocal and as intra-/peritumoral. Disease-Specific and Relapse-Free Survival (DSS; RFS) were estimated; moreover, we included PNI in the current AJCC 8th Staging System, improving the prognostication model. Results: Perineural invasion was found in 40.5% of patients. Intratumoral PNI predicted patients at high risk of being diagnosed with lymph–node metastasis. Tumors with positive PNI reported a worse DSS (Hazard Ratio=1.878, p-value = 0.008). Moreover, patients exhibiting both multifocal intra- and peritumoral PNI reported poorest DSS (Hazard Ratio = 2.409, p-value = 0.010). Patients were reclassified in a new staging system in case of multifocal PNI, providing better stratification capacity. Conclusions: Perineural invasion might serve as an additional prognostic factor in OTSCC, and by integrating PNI in the staging system, further improvements in prognostication might be reached.