Perineural invasion in oral cancer: challenges, controversies and clinical impact

Oral squamous cell carcinoma (OSCC) corresponds to 95% of head and neck cancers and it is the 6^th most frequent cancer worldwide (1). Although numerous advances in diagnosis and treatment have been reported, the overall 5-year survival rate for OSCC remains almost unchanged within the past three decades (2). OSCC is characterized by invasive growth patterns, frequently associated with perineural invasion (PNI), high risk of regional lymph node metastases, and a considerable rate of loco-regional recurrences and second primary cancers. Many patients have advanced-stage tumors at diagnosis that must be managed with aggressive multimodality treatment that frequently cause significant morbidity and mortality (3).