The loss of p16INK4A expression defines a subgroup of oropharyngeal cancer patients with worse clinical outcome [16] whereas p16 protein over-expression has been proposed as surrogate marker of HPV infection initially in cervical cancer by Amortegui et al., [25,26], followed by squamous cell carcinomas from other sites than uterine cervix [27], and especially in Head and Neck Cancers [28,29]. This evidence concerns the gene CDKN2A and head and neck cancer.