Two separate lines of research are now converging to unravel the complex series of events that lead to cancer. One area has clearly identified site-specific alterations of oncogenes such as EGFR and tumor suppressor genes such as p53. The other is based on epidemiological evidence that has linked exposure to exogenous agents to the development of specific forms of cancer. For example, epidemiological studies have strongly implicated chemical carcinogens, such as those in tobacco, with lung and laryngeal cancer. Exposure to ultraviolet light has been strongly associated with carcinoma of the lower lip. Additionally, evidence is emerging for the role of specific viruses in cancers such as those arising in hematopoietic and lymphoid tissues, those of the uterine cervix and carcinoma of the oropharynx.3
- Chemical carcinogens
Animal studies have shown that the application of certain chemical carcinogens, such as DMBA, to the oral mucosa will induce the formation of squamous cell carcinoma. However, the link between chemical carcinogens that theoretically might be encountered in daily life such as those ingested in drinking water and oral cancer is not known.
Cigarette smoking is well established as an important risk factor in oral cancer. Tobacco smoke contains a large number of chemical carcinogens including aromatic hydrocarbons such as benzopyrene and nitrosamines. These carcinogens have been shown to induce specific genetic changes of the p53 and H-ras genes.
All forms of alcohol have been implicated in the development of oral cancer. Importantly, the effects of tobacco and alcohol are additive with alcohol acting synergistically to promote the carcinogenic effects of tobacco products. The mechanism by which alcohol contributes to oral cancer is not well understood but it probably acts directly on the epithelial cells of the oral mucosa by increasing permeability and through its dehydrating effects. In addition, there may also be an indirect effect via altered liver metabolism.4 Interestingly, there is some experimental evidence that alcohol might act to alter the p53 gene directly.
Actinic radiation has long been associated with cancer of the lower lip. Ultraviolet light is a potent DNA damaging agent inducing DNA cross-linking, single strand and double strand DNA breaks and nucleotide substitution.
- Herpes Group
The Herpes group of viruses has been implicated in the development of several cancers in man. Epstein-Barr virus (EBV) has been strongly associated with African Burkitt’s lymphoma and nasopharyngeal carcinoma. In oral carcinoma, some authors have detected Herpes simplex viral proteins in malignant cells whilst others have shown a co-carcinogenic effect of this virus with other carcinogens in cell culture studies. The precise oncogenic effects of HSV on the pathogenesis of oral cancers however, have not been established.
- Human Papilloma Virus (HPV)
Over 100 types of human papilloma virus have been identified. The wart (verruca vulgaris) is caused by HPV 2 and 4, whilst condylomata accuminata (genital warts) are caused by HPV 6 and 11. Heck’s disease (Focal epithelial hyperplasia) is associated with HPV 13 and 32. Of interest is the finding that HPV, particularly types 16 and less frequently type 18, is associated with most squamous cell carcinomas of the oropharynx (tonsil) and base of the tongue.5 Acquisition of high risk HPV16 is linked to sexual activity with a higher risk of cancer in those with a greater number of sexual partners.