poses a serious health risk, with the American Cancer Society projecting that approximately 36,500 new cases of will be diagnosed in the United States and that 11,000 American deaths will result from head and neck malignancies in 2003. While accounts for only 3% of all new cancer cases and 2% of all cancer deaths in the United States annually, it is the fifth most common malignancy worldwide. Tobacco and alcohol are the primary etiologic agents in these cancers, suggesting prevention should be a primary public health goal in the field. Emerging evidence suggests that inherited factors and exposure to other agents play important roles, and these may help refine prevention strategies.

Nearly identical percentages are reported from Britain, but s have a much greater impact in certain other parts of the world, especially where tobacco and/or betel nut chewing is common, and are the leading causes of cancer mortality worldwide. Despite improvements in diagnosis and local management, long-term survival rates in have not increased significantly over the past 40 years and are among the lowest worldwide of the major cancers. The problem is even worse for select populations such as African Americans, for whom survival rates have actually decreased. Oropharyngeal cancer, the largest subgroup of s, has a 5-year relative survival rate of only 59% for United States whites and 35% for blacks.

Although early-stage s (especially laryngeal and oral cavity) have high cure rates, over 60% of patients present with advanced disease. Cure rates decrease, of course, in locally advanced cases, whose probability of cure is inversely related to tumor size and even more so to the extent of regional node involvement.

Survival advantages provided by new treatment modalities have been undermined by the significant percentage of patients cured of head and neck squamous cell carcinoma (HNSCC) who subsequently develop second primary tumors. Second primaries are the major threat to long-term survival after successful therapy of early-stage HNSCC. Their high incidence results from the same carcinogenic exposure responsible for the initial primary process, called field cancerization. In addition to the problem of long-term survival in the face of second primary risk, HNSCC patients also face tremendous impacts on quality of life after definitive therapy. Despite marked advances in reconstructive surgery and rehabilitation, intensity-modulated radiotherapy (IMRT) and conservation approaches to certain malignancies, patients continue to have significant functional deficits. These compelling problems are responsible for the emerging importance of primary chemotherapy and chemoprevention of HNSCC.

New strategies for the management of cancers of the mucous membranes of the upper aerodigestive tract (UADT) are badly needed. A team concept is required. Already the role of each treatment modality is becoming more clearly defined. New combined-modality approaches (eg, sequential and synchronous chemoradiotherapy) and advances in organ preservation and chemoprevention are beginning to offer realistic hopes for improvements in HNSCC patients? survival rates and quality of life. HNSCC research, both clinical and basic, is becoming a model for research into other epithelial cancers. This section reviews both the current status of and future investigative directions for the epidemiology, biology, chemoprevention, diagnosis, and therapy of .