Based on the existing knowledge about the molecular biology of head and neck cancers associated with high-risk HPV infection, one would expect HPV-driven tumors to show positive reactions in HPV-DNA-PCR, HPV-DNA-ISH, and p16-Ki67 dual stain, as well as high expression levels for p16 with low expression levels of Cyclin D1 and pRb. This evidence concerns the gene RB1 and head and neck cancer.