Koos Boeve

11 General introduction and scope of this thesis GENERAL INTRODUCTION Cancer of the head and neck Head and neck cancer is the seventh most common cancer worldwide with an incidence of 600.000 cases per year [1]. These head and neck tumours mainly arise from the epithelial layers of the upper aerodigestive tract resulting inmore than 90% squamous cell carcinomas (HNSCC) [1]. Other malignant tumours like adenocarcinomas, melanomas and lymphomas are less common in the head and neck area [2]. The upper aerodigestive tract includes the anatomical locations of the oral cavity, pharynx, larynx and the mucosa of the lip (Figure 1A). HNSCC is provoked by random (epi)genetic aberrations that, in the majority of the cases, are caused by smoking or heavy alcohol consumption. Tobacco and alcohol use have a synergetic effect, i.e. the combination of smoking and alcohol consumption resulted in a higher risk of developing a HNSCC than the sumof the individual effects [3]. Other etiological factors for HNSCC are human papilloma virus infection, which is almost completely restricted to base of tongue and tonsil tumours [4], Epstein-Barr virus infection in nasopharynx tumours [5] and ultraviolet light exposure (sunlight) for the lower lip tumours [6]. Betel nut can induce carcinogenesis and is especially an important etiological factor for oral cancer in Asian cultures, where chewing betel quid is popular [7]. A higher incidence of HNSCC is also seen in the elderly [8]. The role of chronic inflammation, such as oral lichen planus, in HNSCC is not completely understood, but data suggest that patients with these chronic diseases might have a higher risk of malignant transformation of involved epithelium [9]. Treatment protocols differ between anatomical locations of HNSCC, e.g. oral cavity tumours are primarily treated by surgical resection of the tumour, while pharyngeal tumours have radiotherapy as primary treatment. The different anatomical locations, etiological factors and treatment protocols demonstrate the heterogeneity of HNSCC. Squamous cell carcinoma of the oral cavity Oral squamous cell carcinoma (OSCC) is the most frequently diagnosed subtype of HNSCC [2,10]. In 2018, the incidence in the Netherlands was 967 new cases for OSCC [11]. Most affected oral cavity side is the lateral tongue, followed by the floor of the mouth. In general, OSCCs metastasize first to lymph nodes in the cervical neck levels I-III (Figure 1B), thereby following the lymphatic drainage patterns, before metastasizing to lymph nodes in other neck levels or further down in the body [12] or haematologically to other organs as lung, skin and liver [13]. Metastasis to cervical neck levels is known as regional metastasis, while spread of tumour cells to other parts of the body is known as distant metastasis. Primary treatment with curative intent of OSCCs consists of surgical resection of the tumour. In case of a clinically positive lymph node or high chance of lymph node involvement (defined as >4 mm tumour infiltration depth), tumour resection is combined with a neck dissection.