A genetic progression model of oral cancer: current evidence and clinical implications.

Based on recent genetic studies, we propose a progression model for the development of oral squamous cell carcinoma. In the initial phase, a stem cell acquires a genetic alteration; subsequently a patch is formed, a clonal unit consisting of the stem cell with its daughter cells that all share the DNA alteration. The next critical step is the conversion of a patch into an expanding field as a result of additional genetic alterations. This mucosal field replaces the normal epithelium and in the oral cavity such fields have been detected with dimensions of over 7 cm in diameter. Sometimes these fields are visible as leukoplakia. Ultimately, clonal selection leads to the development of carcinoma within this contiguous field of pre-neoplastic cells. An important clinical implication of this model is that fields often remain after surgery of the primary tumor and may lead to new cancers, presently designated by clinicians as second primary tumors or local recurrences.