Epithelial cancers of the aerodigestive tract account for one third of all cancer deaths each year. The development of squamous cell carcinomas in this region is closely connected with tobacco smoking and alcohol consumption. These exogenous factors are believed to play a major role in the complex multistep process of carcinogenesis in the aerodigestive tract epithelium. The induction of biologic and clinical changes in the epithelium of the oropharnyx, larynx, esophagus, trachea, and the lungs by common carcinogens has been termed field cancerization. The incidence of second primary tumors is especially high in head and neck cancers, presumably because of the diffuse mucosal initiation and promotion by exogenous factors such as alcohol and tobacco. Although oral squamous cell carcinomas account for only a small portion of cancers, they provide an excellent model system for the study of genetic changes. All histopathologic stages and their morphologic appearance during carcinogenesis in the oral epithelium are well defined and can easily be monitored without the need for invasive procedures. The current knowledge about epidemiology, etiology, and histopathology of benign and malignant oral lesions will be summarized in chapter 2 of this volume.
While recent advances in therapeutic management have improved the prognosis in some human tumors, others, such as squamous cell carcinomas arising in the upper aerodigestive tract, seem to be less sensitive to current therapeutic regimens. Patients with tumors of the oropharynx must not only face a life-threatening disease, they also have to cope with the prospect of a potentially disfiguring treatment despite great advances in reconstructive surgery. The standard multimodal treatment of oral squamous cell carcinomas today involves surgery in combination with radiation therapy and/or chemotherapy. Despite encouraging response rates in new combination therapies, the mortality rate for head and neck squamous cell carcinomas has remained almost unchanged during the last 30 years.
Oral carcinogenesis appears to be a multistep process similar to that shown in other human tumors. Tumor formation is almost certainly a consequence of accumulated genetic changes in oral epithelial cells. The possibility of a genetic predisposition in some cases is suggested by the sporadic occurrence of head and neck squamous cell cardinomas in young, nonsmoking adults, though genetics is an unlikely explanation in the majority of cases. In recent years two groups of genes, oncogenes and tumor suppressor genes, have been discovered. These genes play an important role in the control of cell proliferation and the development of the malignant phenotype. Oncogenes are the cellular counterparts of viral oncogenes that in general promote cell growth, whereas tumor suppressor genes act as dominant suppressors of malignancies.
Loss of function of the p53 tumor suppressor gene is involved in nearly all human cancers. The vital role of the p53 gene has been defined as a "guardian of the genome". By interacting with proteins of the cell cycle machiner, p53 mediates cell-cycle arrest, allowing for repair of damaged DNA, or cell death. The retinoblastoma tumor suppressor gene (Rb) encodes a nuclear phosphoprotein that is found in a mutated form in a wide range of human tumors. Rb plays an important role in the control of cell division and differentiation and seems to be ubiquitously expressed in normal human tissue, including oral squamous epithelium.
Recent developments in molecular biology techniques have made it possible to study basic cellular mechanisms during malignant transformation and growth. For further progress in the diagnosis and treatment of oral preneoplastic and neoplastic lesions, it is important that the action of cancer-related genes in cell growth control and differentiation be understood. The current knowledge and the most recent results concerning the role of tumor suppressor genes in oral carcinogenesis are described in chapters 2,3, and 4. Chapter 5 discusses the importance of understanding the basic principles of oral carcinogenesis and the application of molecular biology techniques in the diagnosis of the disease and patient follow-up for the development of new and more successful therapeutic strategies in oral premalignancies and oral cancer.