Therefore, HPV-associated cancers are characterized with high p16 levels, low pRb and cyclin D1 protein levels, and wild-type p53 and pRb genes.44,45 On the contrary, typical for tobacco/ alcohol-associated head and neck cancers are downregulation of p16 protein, p53 gene mutation and overexpression of pRb and cyclin D1.44 Consequently, p16 overexpression proved to be a marker for oropharyngeal primary site and HPV-association.46 This evidence concerns the gene CCND1 and cancer.