Indeed, nearly half of oral cavity cancers in patients will recur [6-8] and 5-year survival in this scenario is a dismal 35%C45% [6,9]

Indeed, nearly half of oral cavity cancers in patients will recur [6-8] and 5-year survival in this scenario is a dismal 35%C45% [6,9]. with 350 000 of these predicted to be fatal [1]. Treatment of head and neck cancer has evolved significantly over the past half century with improvements in surgical technique as well as advancements in the fields of medical and radiation oncology. Recently, a more detailed understanding of the molecular pathogenesis of HNSCC was made possible with whole genome sequencing of these tumors [2], invigorating the field of targeted chemotherapeutics. Despite these substantial technological advances, significant impact on the survival of patients afflicted by these cancers has not been observed. For example, the 5-year survival rate of patients with larynx cancer was 66% from 1975 to 1977 and 63% from 2007 to 2013i. Much of the difficulty in studying and treating HNSCC lies in the fact that they are a heterogeneous group of cancers arising from distinct anatomic subsites, associated with varied risk factors and possessing diverse molecular Tetrodotoxin pathology. Classically, tobacco and alcohol consumption were the primary risk factors associated with HNSCC and these factors demonstrate independent, synergistic, and dose-response increases in relative risk [3]. Chronic exposure to tobacco and alcohol is thought to promote diffuse and progressive molecular alterations in grossly normal epithelium. Additionally, as in other solid tumors, HNSCC has been associated with dysregulation of various oncogenes and tumor suppressor genes; the molecular disruption in HNSCC was eloquently reviewed recently [4]. The current paradigm for diagnosis and treatment of HNSCC is complicated by the varied roles of surgery, radiation, and chemotherapy that are dependent on anatomic subsite, stage, and tumor pathology IL18 antibody (Box 1). Further complicating the picture was the rise in rates of oropharyngeal cancer over the past two decades, despite decreases in smoking and a decline in smoking-related HNSCC. Human papilloma virus (HPV; see Glossary) infection was eventually identified as the key risk factor for this aberration and HPV-related oropharyngeal cancer has since demarcated itself as a distinct clinical entity among HNSCC that has reached epidemic levels [5]. Box 1. Current Management of Head and Neck Cancer DiagnosisRadiographic imaging (to include primary tumor, nodal drainage pathways, and distant pulmonary sites) and tissue sampling for Tetrodotoxin pathologic diagnosis are the initial steps taken when encountering a new head and neck tumor. As treatment varies based on location, identifying the specific subsite of origin is of utmost importance (Figure I). Clinical assessment of the primary tumor (T stage), nodal disease (N stage), and distance metastasis (M stage) based on American Joint Committee on Cancer guidelines follows and guides treatment decision-making and prognosis [130]. Primary TreatmentFor tumors of the oral cavity, extirpative surgical resection with neck dissection when indicated is the treatment of choice, with the goal being complete surgical cure with negative margins. This is an anatomically complex region with obvious speech, swallowing, and airway morbidity; extensive reconstruction is often necessary. For cancer of the oropharynx, primary radiotherapy is the therapeutic modality of choice, with treatment of the neck as indicated. Alternatively, trans-oral surgical resection of the tumor also provides similar outcomes and this option is typically offered to patients. For larger tumors (T3 or T4), concurrent primary chemoradiation is employed if surgical resection is deferred. In primary laryngeal/hypopharyngeal cancer, the is preservation of function (voice and swallowing). Though the treatment algorithms for these anatomic regions and their subsites are complex, Tetrodotoxin in general, small early lesions can be treated with primary radiotherapy or minimally invasive surgical extirpation. For larger lesions, primary chemoradiation or more aggressive surgical resection are necessary, both of which sacrifice functional outcomes. Adjuvant TreatmentPostoperative radiation therapy is frequently employed for high-risk cohorts, including those with large tumors (T3 or T4), positive surgical margin, presence of lympho-vascular or perineural invasion, N2 or greater nodal disease, and gross extracapsular extension. Additionally, positive surgical margins or extracapsular extension are an indication for the addition of adjuvant.