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Head and neck cancers are a diverse group of diseases, each with distinct epidemiologic, anatomic, and pathologic features. The natural history and treatment considerations may vary widely. In this chapter, our focus is on the primary management of squamous cell carcinomas (SCCs) of the head and neck (HNSCC). In recent years, we have observed significant advances in diagnosis and treatment and recognition of the human papillomavirus (HPV) as a significant causative agent and prognostic factor for cancers of the oropharynx. Tumor imaging is increasingly precise. Primary therapy eradicates disease in a majority of patients with early-stage HNSCC, and the long-term management of these patients currently involves an emphasis on general medical care, avoiding known carcinogens such as alcohol and tobacco, and participation in chemoprevention strategies to reduce the risk of second primary tumors. Therapy for patients with locally advanced disease is multimodal, and success has been achieved in improving local tumor control, disease remission, organ preservation, and overall survival. The integration of chemotherapy and novel “targeting” systemic treatment approaches with surgery and/or radiotherapy is under study and discussed.


In the United States, HNSCC is estimated to represent approximately 3% (46,000) of new cancer cases and 2% (9,000) of cancer deaths in 2015 (1). However, the disease is more common in many developing countries, with a worldwide annual incidence of more than 500,000 (2).

The risk of developing head and neck cancer increases with age; most patients are older than age 50. There has been a clearly demonstrated association with tobacco and alcohol use. Molecular studies provide evidence that carcinogens found in these substances have a causal role. The prevalence and spectrum of p53 mutations are prominent in cancers of patients with a history of tobacco and alcohol use (3). Cancers of the oral cavity, larynx, and hypopharynx are uncommon in persons with no smoking history.

Human papillomavirus infection is now widely accepted as another etiologic factor for HNSCC. In the United States, more than 50% of cancers arising in the oropharynx, particularly in the palatine tonsils and tongue base, harbor oncogenic HPV (4). The incidence of oropharyngeal cancer in the United States is increasing, primarily due to HPV-associated cases in men (5). It appears that the HPV-positive oropharyngeal malignancy represents a distinct clinical and pathologic subgroup of HNSCC, with poorly differentiated basaloid histopathology (6) and marked tumor responsiveness to radiation and chemotherapy. Moreover, HNSCCs with transcriptionally active HPV-16 DNA are characterized by occasional chromosomal loss, whereas those lacking HPV DNA typically have gross deletions, involving chromosomal arms known to be abnormal in HNSCC (7). Thus, HPV-16 infection may be an early carcinogenic event. Patients with HPV DNA–positive tumors, particularly those associated with E6 and E7 proteins, have improved survival after chemoradiotherapy when compared to patients with HPV-negative tumors (8,9...

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