Natural history of oro-pharyngeal cancer precursors

Abstract

Oro-pharyngeal cancers (including the oral cavity and oropharynx) are among the 10 most common malignancies of both men and women worldwide, with 5-year survival rates of only 50%. Known risk factors include tobacco smoke, alcohol consumption, diet and, in a subset of tumors, human papillomavirus (HPV). Almost all oro-pharyngeal cancers are thought to develop from squamous dysplastic precursor lesions, which occur in a subset of common white (leukoplakia) or red (erythoplasia) plaques in the oral and oropharyngeal mucosa. While as much as 30% of the population may develop such plaques in their lifetime (point prevalence in the North America from 5-15%) only 8% have dysplasia; the likelihood of such lesions transforming into invasive carcinoma and cancer can be as little as 4% and as high as 40%. Prediction of biologic behavior and identification of which lesion will develop into cancer is poorly understood. Our hypothesis is that use of gene profiling of dysplastic lesions will allow identification of the population at highest risk to develop cancer. Fortunately, active screening with cytopathology allows identification of high-grade precursor or severe dysplasia, which will serve as our ultimate ethical endpoint. As part of this pilot study, we will address the following specific aims: 1) to implement and evaluate research protocols and questionnaires for recruitment and follow-up, of individuals with visible or suspicious plaques in the oral cavity and oropharynx, based on established tools and methods employed in previous natural history studies; 2) to optimize standardized interview and specimen collection protocols for epidemiological and molecular analyses; 3) to conduct molecular analyses of specimens collected and compare distributions of biomarkers of exposure and genetic alterations by lesion severity. (AU)