The upregulation of genes encoded for p16 requires the transcription of E7 oncogene, therefore the squamous carcinoma where p16 protein overexpression is noted is supposed to result in an action of HPV; as a consequence, p16 is considered a biomarker for HPV oncogenic action and a surrogate marker for HPV infection [137]. This evidence concerns the gene CDKN2A and squamous cell carcinoma.