Head and neck squamous carcinoma (SCC) arises from the squamous mucosal lining of the oral cavity, oropharynx, and larynx and is the sixth most common cancer with an estimated 500,000 new cases diagnosed worldwide annually. Conventional SCC of the oral cavity accounts for ~15 % of all head and neck malignancies, leading to 7000 deaths per year in the USA [2, 3]. Risk factors for conventional oral SCC include smoking and chewing tobacco, heavy alcohol consumption, and chewing betel quid. Recently, a new subtype that typically originates from the oropharyngeal mucosa has been recognized [4]. The tongue is the most common site for oral cancer among European and US populations, accounting for 40–50 % of oral cancers [2, 5], and the buccal mucosa is the most common site of the Indian subcontinent due to betel quid/tobacco chewing habits [5]. Predicting the phenotypic progression of high risk premalignant lesions is fundamental to early intervention and ultimately to the prevention of SCC. This chapter will discuss the phenotypic and biological events associated with early SCC tumorgenensis and advances in early detection.
