Masri, Manar Al

Abstract Background: Perineural invasion (PNI) is a key prognostic factor in oral squamous cell carcinoma (OSCC). Recent studies have proposed the importance of subcategorizing PNI based on location in relation to the tumor. However, current gaps in definition of PNI subcategories limit its integration into staging system and treatment planning. This study evaluates the prognostic value of the presence of PNI and its location, in correlation with other tumor characteristics, and examines their relationship with survival and recurrence. Design: A total of 159 patients with histologically confirmed OSCC from February 2022–May 2025 were included in the study. PNI was subclassified into intratumoral, peripheral and extratumoral. Association of PNI metrics with other prognostic factors (margin status, lymph node metastasis [LN mets], and lymphovascular invasion [LVI]) were assessed using a Fisher’s exact test (categorical variables). Comparisons of disease-free survival (DFS) and overall survival (OS) between the PNI subgroups were made with a logrank test. Cox proportional hazards regression models were used to find univariate predictors of death and the composite outcome of recurrence or death. A p value <0.05 was considered statistically significant. Statistical analyses were performed using R Statistical Software (version 4.4.1; R Foundation for Statistical Computing, Vienna, Austria). Results: 49/159 cases were PNI positive. Median age: 69 years and male predominance (58.5%). Floor of mouth was the most common site. Presence of PNI correlated significantly with positive margins and positive LVI (p = 0.013 and 0.048 respectively). However, only peripheral PNI showed significant correlation with LN mets (p = 0.004). On univariate analysis, the strongest predictors of recurrence or death were larger tumor size (p <0.001); presence of PNI (p = 0.014), especially intratumoral (p = 0.003); positive LN mets (p = 0.024); and non-white race (p = 0.023). Both DFS and OS were significantly worse in patients with PNI compared with those without (DFS: p = 0.012, OS: p = 0.018). Subclassification of PNI showed a significantly poorer DFS and OS in cases with intratumoral PNI (DFS: p = 0.002, OS: p = 0.012), but not with extratumoral or peripheral PNI.