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Squamous cell cancers of the head and neck (SCCHN), also known as head and neck cancers (HNC) encompass malignancies of the oral cavity, larynx, nasopharynx and pharynx, and are diagnosed in over 500,000 patients worldwide each year, accounting for 5% of all malignancies. In the past several years, there have been significant developments in understanding of HNC. It is now recognized that although alcohol and tobacco use has represented the likely predominant cause of SCCHN, the incidence of a second class of SCCHN related to oncogenic human papillomavirus (HPV) infection is increasing, with a four-fold increase in the past 2 decades, and now thought to represent up to 30% of cases. The first effective target for SCCHN, the EGFR-targeting antibody cetuximab, was approved as recently as in 2006; since then, a growing body of research has identified additional signaling pathways as important in disease pathogenesis, and in resistance to treatment. Proteins such as c-Met, Src, and HER2 are emerging as new therapeutic targets, with a considerable ferment in the clinical trial community. As a capstone of research progress, 2011 marked the first reports of high throughput sequencing of SCCHN tumors, with these efforts identifying unexpected players such as Notch as frequent subject of mutation, spawning new hypotheses for future research. This book will be of interest to researchers who are interested in better understanding the biology of head and neck cancers, with the goals of better designing therapies, identifying risk factors, or investigating the molecular basis of the disease.