9 General introduction Head and neck squamous cell carcinoma Head and neck cancers (HNCs) are a diverse group of malignant tumors that arise in the oral cavity, oropharynx, hypopharynx, or larynx (Figure 1A). In 2020, HNC accounted globally for an incidence of approximately 750,000 cases (+/- 40,000 in Western Europe), and over 350,000 deaths (+/- 15,000 in Western Europe). These numbers made HNC the seventh most common cancer worldwide, accounting for around 3.6% of all cancer related deaths that year. Approximately 90% of HNCs are squamous cell carcinomas (HNSCCs) that originate in the epithelial cells forming the mucosal linings of the upper aerodigestive tract. Despite the fact that HNSCCs originate from one cell type residing in one tissue, these cancers behave surprisingly heterogeneous. This can be explained by differences in anatomical localisations, aetiologies, and the variety of molecular changes underlying this disease (1-3). Figure 1: Anatomy of head and neck cancer (HNC). A. Anatomical sites in which HNCs arise. B. Anatomical subsites of the oral cavity in which oral cancers arise. Oral squamous cell carcinoma Over 40% of HNSCC arise in the oral cavity (OSCC), classically presenting with a chronic sore or ulcer (2, 4). The oral cavity encompasses complex functional anatomy that facilitates speech, swallowing, and facial projection. The oral cavity contains the following anatomical subsites: mucosal lip, oral tongue, floor of mouth, mandibular and maxillary gingiva, retromolar trigone, buccal mucosa, and hard-palate subsites (Figure 1B) (5). 1
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