BACKGROUND: Head and
neck cancers are important to human life and health in both developed and underdeveloped countries. Management of established
cancers is difficult, and there is great interest in evaluating methods to prevent these
tumors from developing. METHODS: The biology of
carcinogenesis, including field
carcinogenesis, is reviewed, together with the biology and pharmacology of the
retinoids. Intervention studies of premalignant lesions have led to prospective clinical trials of the capability of various
retinoids to reduce the incidence of new
second cancers. RESULTS: High-dose
13-cis-retinoic acid (13cRA) has significant activity in reversing
oral leukoplakia but at a cost of substantial toxicity, and relapses occur early. An ongoing intergroup trial is underway to evaluate the capacity of low-dose (30 mg/d) 13cRA given for three years to reduce the incidence of second primary
tumors in patients with "cured" squamous head and
neck cancers. CONCLUSIONS: Molecular studies of loss of heterozygosity and p53 gene mutations are advancing our understanding of field
carcinogenesis and the biology, pharmacology, and effects of the
retinoids used in
cancer prevention. Translation of early clinical trials into large-scale intervention trials to prevent
second cancers are now underway.