Oral field cancerization: carcinogen-induced independent events or micrometastatic deposits?

Patients with a head and neck squamous cell carcinoma (HNSCC) often develop multiple (pre)malignant lesions. This finding led to the field cancerization theory, which hypothesizes that the entire epithelial surface of the upper aerodigestive tract has an increased risk for the development of (pre)malignant lesions because of multiple genetic abnormalities in the whole tissue region. Demonstration of alterations in histologically normal tumor-adjacent mucosa from HNSCC patients supported this hypothesis. Currently, the question has been raised whether multiple lesions develop independently from each other or from migrated malignant or progenitor cells. The majority of the mucosal alterations appear to be related to the exposure to alcohol and/or tobacco. Moreover, almost all primary remote tumors from HNSCC patients appear to be clonally unrelated. Therefore, there is more evidence that field cancerization is due to multiple independent events than to migration of genetically altered cells.