Head and neck cancer prevention: the new challenge.

M ULTIPLE approaches of treatment, including neoadjuvant chemotherapy, for patients with squamous cell carcinoma (SCC) of the head and neck have produced a significant number of encouraging response rates, but they have not improved overall survival. The standard treatment for patients with SCC of the head and neck has been local therapy with surgery and/or irradiation. Chemotherapy with 5-flourouracil and cisplatin has been reserved for patients with large recurrent or second primary disease. The response rates with this regimen have been between 40% and 89%, with complete response rates between 4% and 20% in prospective randomized trials. 1 Head and neck cancer accounts for approximately 5% to 6% of all cancers in the United States. Head and neck cancer is directly associated with tobacco, and in the United States, 50 million people smoke cigarettes and 12 million chew tobacco, Worldwide, the corresponding figures are 1 billion and 600 million, z Despite the large number of smokers in the United States, the 1993 estimated incidence of head and neck cancer is 32,000 and the estimated mortality is 8000. 3 Hsu et al 4 investigated the response of cells of line 3640P by adding 2% and 4% alcohol to two of their three separate mediums and found that the 4% alcohol practically shut off DNA synthesis. The apparent conclusion is that alcohol actually exerts a toxic effect on DNA synthesis, thus creating a vulnerable cellular environment towards invasion of carcinogens. They also reported that concomitant smoking and alcohol appears to increase the risk of developing head and neck cancer. It was found in a study that the interaction between alcohol and tobacco smoke were such that they enhanced the genotoxicity of each other and a dose-response relationship between these two cocarcinogens increases the risk of development of head and neck cancer by 44.5%. 5 Sun exposure also contributes to the risk of squamous cell head and neck cancer. Choy et al 6 studied squamous cell cancer of the head and neck in Chinese patients from Hong Kong and they determined that they had a 10% to 14% risk of multiple primary cancer (MPC). Second primaries were reported in 1% to 35% of these patients. According to a study by Robinson eta/ , 7 the mean age of patients developing a first primary tumor was 61 years and the mean age of those developing a second primary tumor was 64 years. The study showed that out of 638 patients, males had a greater incidence than females, and whites developed the disease more than nonwhites. Kotwall et al,s reported that 150 of 832 patients with head and neck cancer showed evidence of MPC's at the time of autopsy, with an overall incidence of 18%. Patients with cancers of the oropharynx and the hypopharynx had the highest incidence of MPCs. A review of oral cancers by Garewal and Meyskens 9 indicated that even after successful primary therapy of early-stage or locally advanced tumors, 30% to 50% of patients experienced local or regional recurrence, 20% to 30% had distant metastasis, and 10% to 40% had a second primary tumor. Second primary tumors affect the overall outcome of the patient with head and neck cancers and are the chief cause of treatment failure and death in those who present with early-stage disease. The reason for this increased incidence is probably related to the concept of "field cancerization" (diffuse mucosal membrane initiation and promotion), whereby exogenous factors such as tobacco and alcohol may serve as tumor promoters in the development of second primary epithelial tumors in the upper aerodigestive tract. The exogenous factors begin to change and destroy the epithelial portion of the soft tissues early, creating a lifetime environment of carcinogenic exposure. This exposure destroys the mechanisms of DNA and RNA replication, preventing regeneration of healthy tissues. Scientists believe that genetic and/or environ-