Oropharyngeal cancer is a generic term that includes tumors arising within the anatomic confines of the posterior pharyngeal wall, soft palate, tonsillar region and posterior one-third (base) of the tongue. The vast majority of these tumors (>95%) includes squamous cell carcinomas of mucosal origin. Oropharyngeal squamous cell carcinomas (OPSCCs) are traditionally categorized as head and neck squamous cell carcinoma (HNSCC). High-risk human papillomavirus (HR-HPV) is now recognised as a causative agent in a subset of OPSCCs. HPV-driven OPSCC and tobacco- and alcohol-related OPSCC are biologically distinct entities. In the former, p53 and pRb are both inactivated at the protein level by, respectively, E6 and E7 viral oncoproteins. The majority of HPV-negative tumors, instead, harbor mutations in the TP53 gene, an increased epidermal growth factor receptor (EGFR) gene copy number and higher EGFR expression by immunohistochemistry (IHC).
