Importantly, we showed that p53-target genes, among others MDM2 was a central biomarker, potentially deriving the differential signature of significant molecular pathways between HPV+ and HPV- HNSCC patients which is consistent with previous findings showing that MDM2 genetic aberrations and related pathways play a central role in the carcinogenesis of head and neck cancers in addition to a particular correlation with HPV status (37). This evidence concerns the gene TP53 and head and neck squamous cell carcinoma.