Perineural invasion and its significance in oral mucosal cancer

Factors of unfavorable prognosis in oral squamous cell carcinoma are of great importance in terms of the development of treatment tactics and in the prognosis of the disease. Many authors have noted a high incidence of perineural invasion (PNI) in oral squamous cell carcinoma (up to 30%). Perineural invasion is most common in tongue and floor cancers, and this is due to the high density of neural tissue in these anatomical regions. In recent years, many investigators have studied the characteristics of PNI, such as single and multifocal invasion, the diameter of the affected nerves, and which nerve structures are involved in tumor invasion. The median time to local recurrence was significantly shorter in the presence of PNI than in the absence of PNI (p = 0.002). Multifocal PNI was associated with decreased survival compared to unifocal invasion, emphasizing the prognostic significance of such PNI features. The combination of TNM staging, especially T3-4 and PNI, was associated with worse disease-free survival in patients with oral squamous cell carcinoma at both early clinical stages (p = 0.011) and advanced stages (p = 0.001). The 5-year recurrence-free survival rates for early (stage I-II) and late (stage III-IV) clinical stage oral cancer with PNI were 60.0% and 41.7%, respectively. The prognostic value of PNI and its efficacy in tumor prognostic models are increasingly recognized. Postoperative irradiation is reasonable for patients with G2-G3 tumor differentiation, perineural invasion, and invasion depth greater than 5mm. Postoperative chemoradiotherapy in the presence of PNI improved 5-year overall survival compared to adjuvant radiation therapy (p=0.018). The potential of immunotherapy in the presence of PNI has recently been reported. The effect of calcitonin gene-related peptide (CGRP), which directly suppresses CD8 T-cell activity in vitro, blocks sensory nerve function and increases CD8 and CD4 T-cell activity in vivo, was observed, which may allow the future use of immunotherapy in the presence of PNI.