Discrete Perineural Invasion Focus Number in Quantification for T1-T2 Oral Squamous Cell Carcinoma

Objective: Perineural invasion (PNI) has been an established poor prognostic feature for T1-T2 oral squamous cell carcinoma (OSCC). Different presentations and amounts of PNI are commonly observed, but PNI is currently recorded as being present or absent. This study asked whether the quantification of PNI provides additional information for early OSCC. Study Design: Retrospective cohort study. Setting: Tertiary referral medical center. Subjects and Methods: Pathologic reevaluations were performed for 314 patients with T1-T2 OSCC who underwent curative surgery from June 2001 to August 2009. A novel parameter, PNI focus number, was defined for PNI quantification. With 5 PNI foci as the cutoff, patients were categorized into 3 groups: no PNI (0 PNI foci), low PNI (PNI foci, 1-5), and high PNI (PNI foci >5). Rate of cervical lymph node metastasis (LN+), 5-year disease-specific survival (DSS), and 5-year overall survival (OS) were analyzed among these groups. Results: PNI focus number independently predicted for LN+, poor DSS, and poor OS in multivariate analysis after controlling for T classification, lymphovascular invasion, differentiation, margin, and tumor thickness. The 5-year DSS demonstrated a dose-dependent decrease among the 3 groups (no PNI, 88.6%; low PNI, 75.2%; high PNI, 33.8%; P <.001). Moreover, the 5-year DSS of the high PNI group was significantly worse than that of the low PNI group. Conclusion: PNI focus number can be a novel parameter for PNI quantification in early OSCC. Although optimal quantification methods still require further investigation, this study offers clear clinical support for the nerve-tumor interaction hypothesis and advocates further mechanistic research for the exploration of PNI-related treatment concepts for OSCC.