Eighty percent of FA patients survive beyond age 20, carry a high risk for squamous cell carcinoma (SCC) of the oropharyngeal and anogenital regions connected with high morbidity and mortality. In addition to intrinsic genetic instability, HSCT and a number of other factors contribute to the pathogenesis of SCC. It is unclear whether external risk factors for FA SCC are similar to or distinct from risk factors for the general population. The aggressive nature of these tumors mandates early surgical intervention and radiotherapy. In a pilot study of 466 patients, we evaluated the feasibility of replacing traditional invasive biopsy by non-invasive brush biopsy, followed by conventional cytology and/or DNA cytometry. Based on the experience and results of our pilot study, we propose a longitudinal screen of an international FA cohort for the early detection and follow up of head and neck cancer employing soft brush biopsy combined with cytology, DNA cytometry and LOH analysis. Included in these studies will be a questionnaire which correlates disease progression with exposure to environmental risk factors such as oral hygiene, alcohol and tobacco exposure. Cancer tissue from those diagnosed in the screen will be provided for basic and translational research in FA. Ultimate goal of the proposed study is improvement of early detection, timely diagnosis, individualized treatment, and understanding of pathogenesis and prognosis of SCC arising in the context of FA.