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  • Head and neck cancers are diverse. In this chapter, we focus on the management of squamous cell carcinomas of the head and neck (HNSCC).

  • Tobacco and alcohol use are major risk factors, and the human papillomavirus (HPV) is a risk factor for oropharyngeal cancer (OPC).

  • All patients should undergo a multidisciplinary evaluation that includes surgical, medical, and radiation oncology specialists.

  • For early-stage HNSCC, surgery or definitive radiation provides excellent local control.

  • Most patients present with locally advanced disease requiring a multimodality approach focusing on organ preservation, managing metastatic risk, and minimizing acute and chronic toxicities.

  • Immune checkpoint inhibitors are now standard in recurrent and/or metastatic HNSCC.


In the United States, head and neck cancer is estimated to represent approximately 3.6% (65,630) of new cancer cases and 2% (14,500) of cancer deaths as of 2020.1 However, the disease is more common in many developing countries, with a worldwide annual incidence of more than 800,000 cases.2 In more than 90% of these tumors, the histology is squamous cell carcinoma (SCC). Squamous cell carcinoma of the head and neck (HNSCC) primarily affects men, and the median age at diagnosis is 60 years old. Established risk factors include tobacco and alcohol use. Although public health efforts have led to a decrease in tobacco use and thus a reduction in smoking-related malignancies, the incidence of oropharyngeal cancer (OPC) has been steadily rising as a result of the impact of human papillomavirus (HPV) infection.3,4


The majority of head and neck cancers are multifactorial diseases influenced by the interaction between carcinogens and/or oncogenic viruses and genetic susceptibility. Certain genetic factors, such as metabolic polymorphisms, DNA repair gene polymorphisms, and variations in other pathways may contribute to carcinogenesis.5–7 Impaired apoptosis (programmed cell death) may increase the risk of malignancy.8,9 In HPV-related HNSCC, only a small proportion of HPV-infected individuals have cancer, likely because of genetic susceptibility.8,10–12 Rare germline mutations have been associated with familial atypical multiple-mole melanoma and Fanconi anemia and confer a risk for the development of HNSCC.13–15


The risk of developing HNSCC increases with age; most patients are older than age 50 years. Moreover, there is a clear association with HNSCC development and the use of tobacco and alcohol. Smokeless tobacco and betel quid (combination of betel leaf, lime, and areca nut), commonly used in India and areas of Asia, are associated with the development of oral cavity cancers. Molecular studies provide evidence that carcinogens found in these substances have a causal role. Mutations in the tumor suppressor gene p53 are prominent in cancers of patients with a history of tobacco and alcohol use.16 Cancers of the oral cavity, larynx, and hypopharynx are uncommon in individuals with no smoking history. Patients with HNSCC with heavy tobacco and alcohol ...

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