Carcinogenesis of head and neck cancer and the role of chemoprevention in its reversal.

Head and neck cancer is an important public health problem worldwide, accounting for approximately 40,400 new cancer cases and 12,300 cancer deaths annually in the US. Although early-stage disease is often curable with surgery or radiotherapy, the majority of patients present with advanced disease in which despite advances in combined modality therapy the outcomes have not dramatically improved. Furthermore, patients cured of their initial early-stage head and neck squamous cell carcinoma are at high risk for development of second primary tumors, which pose the main threat to survival. An alternative approach in reducing the incidence and thus mortality associated with these cancers is chemoprevention, the use of agents to reverse, halt, or delay carcinogenesis. The carcinogenesis process in head and neck cancer results from a dysregulation of cellular proliferation, differentiation, and cell death resulting from field-wide exposure of the upper aerodigestive tract to tobacco smoking. Newly acquired knowledge in the field of tumor biology and of the genetic changes underlying carcinogenesis through the use of new molecular technology represents the basis on which chemoprevention efforts should be based.