Based on these observations and on the results of gene expression profiles of HNC, we postulate that the pronounced EMT observed in HPV-negative cancers may be the result of mutations or permanent epigenetic changes, while in HPV-driven cancers EMT may be a dynamic response to TGFβ and/or to the overexpression of the homeobox transcription factor SIX1 [39],[73]-[76]. The gene discussed is SIX1; the disease is cancer.