On the basis of the increasing incidence of HPV-related tumors, the current information regarding the clinical differences between HPV-related and unrelated tumors, and the discovery of promising molecular prognosis factors like ANO1, we believe it is crucial to study in depth the molecular alterations involved in HNSCC and their relationship with HPV infection, in order to have a better understanding of the pathogenesis of the disease with the ultimate goal of establishing the path for the development of new and more effective treatment strategies. Here, ANO1 is linked to head and neck squamous cell carcinoma.