Scientists now understand that oral cancers, which are included in the category of head and neck cancers, result from a multistep process of accumulated genetic mutations caused by many factors. Tobacco and alcohol use, diet, viruses, and a possible genetic susceptibility may all work together in various combinations to cause these cancers.
Using tobacco -- including cigarettes, pipes, cigars, and spit tobacco-is a well-established risk factor for oral cancer, as it is for some other cancers. Tobacco in any form contains carcinogens and nicotine, an addictive chemical that can keep the user hooked. A popular betel quid-spit tobacco mixture, used throughout India, has been implicated in the high rate of oral cancer in that part of the world.
Excessive alcohol consumption can also increase a person's chance of developing oral cancer. One theory suggests that alcohol generates metabolites, or byproducts of metabolism, that are carcinogenic to humans; the major metabolite of ethanol is acetaldehyde, a recognized animal carcinogen. Alcohol also might "grease the wheels" for tobacco by acting as a solvent and making it easier for carcinogenic agents to penetrate the oral tissues.
Using both tobacco and alcohol produces a much greater risk for oral cancer than using either substance alone. It is estimated that approximately 75 percent of all oral and pharyngeal cancers in the United States are caused by smoking and drinking, with most of these cases caused by tobacco and alcohol working synergistically.Viruses, too, are thought to be involved in the development of these cancers. The human papillomavirus (HPV), particularly the HPV-16 and HPV-18 strains, and the herpes viruses are now considered possible contributors to some cases of oral cancer. DNA from HPV and certain herpes viruses, including Epstein-Barr, cytomegalovirus, and herpes simplex, has been detected in oral cancer biopsies. Genes encoded within these viruses are implicated in the initiation of the multiple steps required for a normal cell to become malignant. Interestingly, scientists have recently linked a new virus with AIDS-related Kaposi's sarcoma (KS), a cancer that has a preference for the head and neck. Oral lesions are present in about half of KS cases and the hard palate and gingiva are the most commonly affected areas. The newly identified virus, called human herpesvirus 8, has been found in all forms of KS, suggesting it might be involved in the sarcoma's development. A direct causal role, however, has not yet been established.
Research also suggests that a diet lacking fruits and vegetables could contribute to oral cancer, an idea postulated about other cancers as well. These foods contain antioxidants that trap harmful molecules, a process that can help prevent cancer-causing genetic mutations. The consumption of Cantonese salted fish from early childhood on has been associated with oral cancer in some Asian countries.
Virtually all oral cancers are squamous cell carcinomas, cancers of the epithelial cells that line many parts of the body, including the mouth. These cancers can develop in any part of the oral cavity or oropharynx. The most common sites are the tongue, the lips, and the floor of the mouth. Cancers of the hard palate are uncommon in the United States. Research has shown that changes in oral epithelial cells often are manifested as lesions called leukoplakia, a white patch, or erthyroplakia, a red patch, which can be early signs of oral cancer.Research is revealing what goes on beneath the cell surface -- at the genetic level -- to set the cancer process in motion. Scientists now realize that multiple mutations in specific classes of genes contribute to head and neck cancer. The two classes most fully characterized to date are proto-oncogenes and tumor suppressor genes. Proto-oncogenes code for proteins that stimulate cell division; altered forms, called oncogenes, can cause stimulatory proteins to be overactive, with the result that the cell divides more rapidly than usual. Scientists have so far identified the oncogenes (EGFR)/c-erb 1, ras family, c-myc, int-2, hst-1, PRAD-1 (CCND1 or cyclin D1), and bcl-1 as possible participants in head and neck cancers.
Tumor suppressor genes code for proteins that inhibit cell division. When these genes mutate, the corresponding protein may no longer be produced correctly and cell division may occur when it should not. Inactivated tumor suppressor genes that are suspected in head and neck cancer include Rb, p16 (MTS1 or CDKN2), and p53, whose failure is already implicated in approximately 60 percent of all human cancers. p53 has been of great interest to cancer researchers since it was discovered that the molecule could stop tumors from forming when it is functioning properly. Located on the short arm of chromosome 17, p53 works by recognizing damage to a cell's DNA and stopping the process of cell growth and division until the damage is repaired. If that fails, p53 can launch the cell's 'suicide' software, causing the cell to undergo apoptosis.
As more and more genetic events are implicated in head and neck cancers,
scientists are now converging on the next question: in what order do those
events occur to cause tumor development? One team has already proposed part
of the answer by developing a preliminary genetic progression model for
head and neck cancers.