Upper aerodigestive tract squamous cell carcinoma (UADT SCC) is associated with exposure to tobacco and ethanol and there is a high incidence of multifocal dysplasia, synchronous/metachronous lesions and local recurrence. These observations led to a 'field cancerization' hypothesis which proposes that the entire expanse of carcinogen-exposed mucosa is predisposed to neoplasia. This hypothesis implies that UADT SCC arises from multiple sites and is therefore polyclonal. To test this hypothesis, eight paired tumor and blood samples and 4 specimens of adjacent normal mucosa were tested for clonality by molecular X chromosome inactivation analysis. While tumor specimens were clonal, normal mucosa and blood were polyclonal. These findings demonstrate that UADT SCC is a clonal neoplasm that arises from polyclonal mucosa and supports an alternative interpretation of the 'field cancerization' theory which states that multiple sites are at risk and each neoplasm arising from these different sites is monoclonal.

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