Oral cancers are ideal candidates for screening, early detection, and secondary prevention given the amenability for visual inspection and specimen collection and the availability of recognized precursors. Yet, there are currently no guidelines for screening, treatment, or follow-up of patients with oral cancer precursors, in part, owing to the current gaps in knowledge regarding the natural history of precursor lesions. We propose to conduct a prospective cohort study of patients with oral cancer precursors to address these knowledge gaps and to investigate novel etiologic factors.