Significance of location and extent of perineural invasion in early-stage oral cavity squamous cell carcinoma

Aims: Perineural invasion (PNI) is associated with survival in oral cavity squamous cell carcinoma (OCSCC). There is evidence to suggest that PNI location and extent may be of additional significance. The primary aim of this study was to evaluate the prognostic ability of PNI, including location and extent, in early-stage OCSCC.

Methods and results: This was a retrospective study, with the main cohort comprising of 129 patients with pT1/T2 pN0/Nx TNM8 OCSCC. Slides were re-reviewed in cases reported as having PNI to classify location as intratumoural (IT) and/or extratumoural (ET) and extent as unifocal (UF) or multifocal (MF). Univariate and multivariate analysis assessing impact of pathological features on survival outcomes was performed. On multivariate analysis, IT PNI was significantly associated with locoregional recurrence-free survival (LRS) [odds ratio = 5.69, 95% confidence interval (CI) = 1.50-21.63, P = 0.01]. Disease-specific survival (DSS) and overall survival (OS) were non-significant. In comparison, ET PNI was predictive of LRS (odds ratio = 20.57, 95% CI = 3.48-121.73, P = 0.001), DSS (odds ratio = 40.47, 95% CI = 5.17-316.96, P = 0.0004) and OS (odds ratio = 11.92, 95% CI = 2.18-65.22, P = 0.004). Multifocal PNI was significant on univariate analysis for all three outcome parameters evaluated, but these findings were not maintained on multivariate assessment.

Conclusions: Extratumoural PNI is strongly predictive of survival outcomes, including OS, in early-stage OCSCC. These findings support the reporting of PNI location as a mandatory data element. The impact of PNI extent requires further study.