Natural History of Oro-pharyngeal Cancer Precursors

Oro-pharyngeal cancers can develop from squamous dysplastic precursor lesions, which occur in
a subset of common white (leukoplakia), red (erythroplasia), or mixed oro-pharyngeal plaques.
Known risk factors for oro-pharyngeal cancer include tobacco smoke, alcohol consumption, diet
and, in a subset of tumors, human papillomavirus (HPV). Along the oro-pharyngeal disease
continuum, there may be variations in gene expression precursor lesions as a result of
exposure to smoking, alcohol and HPV. However, the components of gene expression that are
most likely associated with tumorigenesis in these tissues are poorly understood. This study
will focus upon early gene expression profiles in the oral cavity and oropharynx in subjects
who have precursor lesions and have been exposed to the common risk factors for carcinoma
development including smoking and HPV infection. This application is to conduct pilot testing
and establish appropriate procedures for an international prospective cohort study of the
natural history of oro-pharyngeal cancer precursors among men and women at high risk of
oro-pharyngeal cancer at Montefiore Medical Center, Bronx-NY. Brush biopsy specimens will be
used to collect a transepithelial sample of cells from oro-pharyngeal plaques, as well as
normal tissue from defined regions of the oral and pharyngeal mucosa. Measurement of gene
expression will employ novel high-throughput cDNA microarray analysis and PCR-based HPV DNA
testing. Oro-pharyngeal dysplasia will be diagnosed using cytopathology. Under this
application, we will assess our planned instruments and procedures on an initial sample of 40
subjects. This planning period will allow for precise identification of methodologies,
standardization of instruments and assays to be utilized by additional participating centers
in a subsequent application.