Peritumoral Invasion and Survival in Patients with Oral Squamous Cell Carcinoma—The Role of Perineural and Lymphovascular Invasion

<b>Background/Objectives:</b> Perineural (PnI), lymphatic (LI), and vascular invasion (VI) in tumor specimens are supposed to worsen the clinical course of oral squamous cell carcinoma (OSCC) and negatively influence survival outcomes. Despite this, these histologic features have not been implemented in the international staging recommendation for OSCC and their prognostic role remains questionable due to inconsistent findings in the related literature. <b>Methods:</b> To investigate the impact of PnI, LI, and VI on oral cancer-specific (OCSS), recurrence-free (RFS), and overall survival (OS), we hypothesized that these histologic features are independent risk factors for poor survival and therefore considered within a prospectively maintained single-center cohort of patients with OSCC. LI and VI were assessed together and reported as lymphovascular invasion (LVI). <b>Results:</b> This study included 439 patients with primary OSCC. Sixty-nine Patients (21.9%) had at least one of the two risk factors. Within the 5-year follow-up period, 61 of these patients (64%) died, and 30 patients (31%) developed locoregional recurrences. Both perineural and lymphovascular invasion were strongly correlated with the presence of lymph node metastasis. PnI and LVI were investigated separately using an adjusted Cox's proportional hazards regression model. In addition to higher tumor size and the presence of nodal disease (higher stage) the presence of LVI was associated with poor OS, OCSS, and RFS on multivariate analysis, while PnI was associated with reduced OS. In stage III/IV postoperative radiotherapy improved survival in patients with PnI but not with LVI. <b>Conclusions:</b> We conclude that the evidence of LVI in tumor specimens should be considered a high-risk factor when planning adjuvant treatment and monitoring patients with OSCC.