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Oral squamous cell carcinoma (OSCC) is the most frequent type of tumor arising from the oral cavity. Surgery is the cornerstone of the treatment of these cancers. Tumor biology has long been overlooked as an important contributor to the outcome of surgical procedures, but recent studies are challenging this concept. Molecular analyses of tumor DNA or RNA provide a rich source of information about the biology of OSCC. We searched for relevant articles using PubMed. We examined in particular the prospect of applying molecular methods for minimally invasive ex