Chapter 084. Head and Neck Cancer (Part 1) pps

Head and Neck Cancer Head and Neck Cancer: Introduction Epithelial carcinomas of the head and neck arise from the mucosal surfaces in the head and neck area and typically are squamous

Chapter 084 Head and Neck Cancer

(Part 1)

Harrison's Internal Medicine > Chapter 84 Head and Neck Cancer

Head and Neck Cancer: Introduction

Epithelial carcinomas of the head and neck arise from the mucosal surfaces

in the head and neck area and typically are squamous cell in origin This category includes tumors of the paranasal sinuses, the oral cavity, and the nasopharynx, oropharynx, hypopharynx, and larynx Tumors of the salivary glands differ from the more common carcinomas of the head and neck in etiology, histopathology, clinical presentation, and therapy Thyroid malignancies are described in Chap

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Incidence and Epidemiology

The number of new cases of head and neck cancers in the United States was 40,500 in 2006, accounting for about 3% of adult malignancies The worldwide

incidence exceeds half a million cases annually In North America and Europe, the tumors usually arise from the oral cavity, oropharynx, or larynx, whereas nasopharyngeal cancer is more common in the Mediterranean countries and in the Far East

Etiology and Genetics

Alcohol and tobacco use are the most common risk factors for head and neck cancer in the United States Smokeless tobacco is an etiologic agent for oral cancers Other potential carcinogens include marijuana and occupational exposures such as nickel refining, exposure to textile fibers, and woodworking

Dietary factors may contribute The incidence of head and neck cancer is highest in people with the lowest consumption of fruits and vegetables Certain vitamins, including carotenoids, may be protective if included in a balanced diet

Supplements of retinoids such as cis-retinoic acid have not been shown to prevent

head and neck cancers (or lung cancer) and may increase the risk in active smokers

Some head and neck cancers may have a viral etiology The DNA of human papillomavirus (HPV) has been detected in the tissue of oral and tonsil cancers, and may predispose to oral and tonsillar cancer in the absence of tobacco and alcohol use These patients can present at a somewhat younger age The incidence

of HPV-related head and neck cancer may be increasing Epstein-Barr virus

(EBV) infection is associated with nasopharyngeal cancer Nasopharyngeal cancer occurs endemically in some countries of the Mediterranean and Far East, where EBV antibody titers can be measured to screen high-risk populations Nasopharyngeal cancer has also been associated with consumption of salted fish

No specific risk factors or environmental carcinogens have been identified for salivary gland tumors

Histopathology, Carcinogenesis, and Molecular Biology

Squamous cell head and neck cancers can be divided into well-differentiated, moderately well-well-differentiated, and poorly differentiated categories Poorly differentiated tumors have a worse prognosis than well-differentiated tumors For nasopharyngeal cancers, the less common differentiated squamous cell carcinoma is distinguished from nonkeratinizing and undifferentiated carcinoma (lymphoepithelioma) that contains infiltrating lymphocytes

Salivary gland tumors can arise from the major (parotid, submandibular, sublingual) or minor salivary glands (located in the submucosa of the upper aerodigestive tract) Most parotid tumors are benign, but half of submandibular and sublingual gland tumors and most minor salivary gland tumors are malignant Malignant tumors include mucoepidermoid and adenoidcystic carcinomas and adenocarcinomas

The mucosal surface of the entire pharynx is exposed to alcohol- and tobacco-related carcinogens and is at risk for the development of a premalignant or malignant lesion, such as erythroplakia or leukoplakia (hyperplasia, dysplasia), that can progress to invasive carcinoma Alternatively, multiple synchronous or metachronous cancers can develop In fact, over time patients with early-stage head and neck cancer are at greater risk of dying from a second malignancy than from a recurrence of the primary disease

Second head and neck malignancies are usually not therapy-induced; they reflect the exposure of the upper aerodigestive mucosa to the same carcinogens that caused the first cancer These second primaries develop in the head and neck area, the lung, or the esophagus Rarely, patients can develop a radiation therapy–induced sarcoma after having undergone prior radiotherapy for a head and neck cancer

Chromosomal deletions and other alterations, most frequently involving chromosomes 3p, 9p, 17p, and 13q, have been identified in both premalignant and malignant head and neck lesions, as have mutations in tumor suppressor genes, such as the p53 gene Amplification of oncogenes is less common, but overexpression of PRAD-1/bcl-1 (cyclin D1), bcl-2, transforming growth factor β, and the epidermal growth factor receptor (EGFR) have been described EGFR overexpression has been shown to be very common, and its extent seems to be of prognostic importance

Resected tumor specimens with histopathologically negative margins ("complete resection") can have residual tumor cells with persistent p53 mutations

at the margins Thus, a tumor-specific p53 mutation can be detected in some phenotypically "normal" surgical margins, indicating residual disease Patients with such submicroscopic marginal involvement may have a worse prognosis than patients with truly negative margins