Genes and environmental interactions in oral and oropharyngeal cancer

Abstract

The dental profession has responsibility for the prevention and early diagnosis of cancer of the mouth and of the oropharynx, and is a major contributor to management of these devastating diseases. In Australia, cancer of the oral cavity itself is largely due to tobacco use and alcohol abuse, predisposed to by poor diets, and affects predominantly those in the lower socio-economic classes: the incidence is declining. On the other hand, cancer of the oropharynx is a completely different disease: the major risk factor is sustained infection by "high-risk" types of human papillomavirus; it tends to affect younger adults, and is associated with sexual activity. The approach to primary prevention is obvious in both situations. Secondary prevention by population screening is only viable in high risk populations. Cancer is a genetic disease. To a minor degree, the genes we inherit affect susceptibility. However it is the many types of genetic damage produced by our environment which is driving the growing epidemic of cancer worldwide. In all cancers, acquired defects in the structure and/or the expression of many genes drive uncontrolled cell proliferation, so that a malignant neoplasm spreads locally and throughout the body. The genes involved are those controlling cell division, cell death, cell nutrition, DNA repair, the supply of blood vessels to the neoplasm, and the immune response. Very many biochemical pathways are involved: it is rather like a map of the London Underground, but many times more complex. Defects in one or other of these pathways increase in number and complexity as the neoplasm "progresses". Some of these aberrations are common to many/most patients with a cancer of the mouth or oropharynx: others specific to a subset of patients, or unique to an individual. The mainstay in managing head and neck cancer remains surgery, with adjunctive radiotherapy and chemotherapy. These are highly toxic and disfiguring. We are thus moving towards biotherapies which seek to correct or block the key abnormal pathways of the individual patient. There is no such thing as a single magic bullet which will cure all patients, but drugs, monoclonal antibodies, and interfering ribonucleic acids targeted on the genetic damage for a particular patient are increasingly coming to clinical trial. Successes with some cancers of the breast and colon, for example, encourage the drive to better individualised treatment of head and neck squamous cell carcinoma. Many will continue to suffer, and our role in prevention, early diagnosis and rehabilitation remains essential - and challenging.