Role of Perineural Invasion as a Prognostic Marker in Oral Squamous Cell Carcinoma: A Cross-sectional Study

Abstract

Introduction: Oral Squamous Cell Carcinoma (OSCC) accounts for nearly 90% of oral malignancies and is often diagnosed at advanced stages. Perineural Invasion (PNI) is recognised as an important prognostic factor; however, its assessment lacks standardisation. Aim: To evaluate the prevalence, microanatomical location, and spatial density of PNI using the PNI classification system and evaluate its association with clinicopathological features in OSCC specimens at a tertiary care hospital in South India. Materials and Methods: A cross-sectional observational study was conducted on 50 histopathologically confirmed primary OSCC cases, including retrospective and prospective specimens collected between January and December 2025 at the Department of Pathology, Sri Devaraj Urs Medical College, Kolar, Karnataka, India. PNI was assessed according to the PNI classification system on routine Haematoxylin and Eosin (H&E) stained sections. Statistical analyses were performed using Statistical Package for Social Sciences (SPSS) version 29.0 (IBM Corp., Armonk, NY, USA). The associations between PNI and tumour grade or TNM stage tiers were evaluated using Fisher’s-exact test, with statistical significance set at p<0.05. Results: The PNI was identified in 17/50 (34.0%) of cases. All PNI-positive foci were confined to the intratumoural region 17/17 (100.0%), with no extratumoural involvement observed 0/17 (0.0%). Based on spatial density, 10/17 (58.8%) of cases demonstrated low-density PNI (1–3 involved nerves/section), while 7/17 (41.2%) showed high-density PNI (>3 involved nerves/ section). PNI was not significantly associated with gender (p=0.533) or histopathological grade (p=0.136). PNI showed no significant association with pathological T-stage (p=0.351), but demonstrated a statistically significant association with regional nodal metastasis (p<0.001). Conclusion: The PNI serves as a significant indicator of aggressive tumour behaviour in primary OSCC, showing a strong association with regional cervical lymph node metastasis and Lymphovascular Invasion (LVI). Standardised qualitative and quantitative reporting using the composite PNI classification system on routine H&E sections improves pathological risk stratification to support individualised postsurgical treatment planning.