Head and neck squamous cell carcinoma (HNSCC) is one of the world’s top ten most common cancers. Current survival rates are poor with only 50% of patients expected to survive five years after diagnosis. The poor survival rate of HNSCC is partly attributable to the tendency for diagnosis at the late stage of the disease. One of the reasons for treatment failure is thought to be related to the presence of a subpopulation of cells within the tumour called cancer stem cells (CSCs). CSCs display stem cell-like characteristics that impart resistance to conventional treatment modalities and promote tumour initiation, progression, and metastasis. Specific markers for this population have been investigated in the hope of developing a deeper understanding of their role in the pathogenesis of HNSCC and elucidating novel therapeutic strategies. 1. Introduction HNSCC is the eighth and 13th most common malignancy in the world for males and females, respectively, with the majority of malignancies of the upper aerodigestive tract being oral squamous cell carcinomas [1–5]. Despite advances in the understanding and treatment of HNSCC, survival rates have not significantly improved for over 30 years, with the five-year survival rate after diagnosis remaining at 15–50% [1, 6–8]. Current treatments for HNSCC can be traumatic, painful, and disfiguring, drastically affecting quality of life [9–11]. At present, management of HNSCC includes surgical resection and/or combination chemotherapy and radiation therapy [2, 4, 6]. Despite these treatments, the prognosis of HNSCC remains poor due to late stage diagnosis, high rates of primary-site recurrence, and common metastases to locoregional lymph nodes [1, 3, 4, 6, 12]. A desire to improve diagnostic capabilities and treatment efficacy has led to a need for a better understanding of the pathogenesis and characteristics of HNSCC. Observations of the initiation, progression, and recurrence of cancer have led to two main hypotheses. The stochastic model suggests that there is an accumulation of numerous and varied individual mutations and microenvironmental signals that provide a selective advantage to certain tumour cells however all tumour cells have the ability to propagate the tumour [13, 14]. The probability of the necessary mutations in any given individual cell is very low [13, 15]. Conversely, the cancer stem cell hypothesis proposes a hierarchical model of tumour initiation and progression which suggests that only a specific subpopulation of self-sustaining cancer cells have the exclusive ability to maintain the tumour [7,
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