Defining the Natural History of Squamous Cell Carcinoma in Fanconi Anemia

Study Description:

This is a natural history study involving questionnaires, clinical and research evaluations, clinical and research laboratory tests, review of medical records, and cancer surveillance. A prospective cohort of individuals with Fanconi anemia (FA) at very high risk of squamous cell carcinoma (SCC) will be screened and provide new information on oral potentially malignant lesion (OPML) development and robustly quantify the risk of progression of OPML to cancer in FA.

Objectives:

Primary Objectives:

• To establish a central program and a team of expert clinicians and scientists at the NIH Clinical Center to conduct a comprehensive longitudinal study of cancer screening in adolescent and young adults (AYA) with FA at high risk of SCC through detailed clinical evaluation and biospecimen collection.
• To characterize the clinical and pathological natural history of OPMLs in AYAs with FA using brush biopsies for cytopathologic diagnosis and DNA aneuploidy and correlate those findings with tissue biopsies and genomic analyses of oral epithelial dysplasia (OED) and SCC.
• To prospectively screen individuals with FA for early indicators for the development of esophageal and anogenital SCC and hematological malignancy.

Secondary Objectives:

• To identify genetic, epigenetic, and immunologic mechanisms underlying tumorigenesis and immune escape in individuals with FA.
• To facilitate the enrollment of individuals with FA with high-grade dysplasia or SCC in intra- and extra-mural precision intervention trials.

Endpoints:

Primary Endpoints:

• Characterize the natural history of OPMLs in FA, rates of progression, regression, and development of new lesions
• Determine the utility of brush biopsy to identify oral dysplasia and SCC in FA
• Identify potential precursor states for esophageal and anogenital cancers in FA
• Develop screening guidelines for esophageal and anogenital cancer in FA

Secondary Endpoints:

• Identify predictive biomarkers of oral SCC development
• Characterize genetic and epigenetic changes that lead to SCC development
• Facilitate patient enrollment in intervention trials

• INCLUSION CRITERIA:

• On referral, persons >= 12 years with FA primarily from North America will be included. An individual with FA who is 8 - 11 years can also be included if they have a history of persistent OPMLs, dysphagia, or other concerning symptoms.
• Individuals with prior cancer diagnosis are eligible.
• Individuals from other countries are eligible provided they can travel to the USA on their own.
• Ability to understand and/or the willingness of the individual, parent, LAR, or minor s legal guardian to provide informed consent.

Exclusion criteria

• Referred individuals for whom reported diagnosis of FA cannot be verified.
• Inability of the individual, parent, LAR, or legal guardian to understand and be willing to sign a written informed consent document.