Figure 6.

Integration map, signaling pathways, and molecular processes enriched in HPV+ HNSCC patients. (A) Diagrammatic summary suggesting p16 activation as a “master” regulator in HPV−positive patients. As shown, p16 negatively regulates key mediators such as cyclin D1 or HIF1A to modify the transcription of gene characteristics of the HPV+ phenotype. Supportive data refers to expression data consistent with the signaling pathway regulated by the key hub p16. The conflicting data are differentially expressed transcripts whose expression is not explained by p16; thus, they may be regulated by different pathways such as the YAP/TAZ signaling route. (B) Main significantly enriched signaling pathways with inhibited status, as well as altered molecular processes in HPV+ samples (joint p values ≤ 0.001). Data produced from transcripts with differential expression greater and lesser than 1.5. Molecules in a red background proportionally indicate inhibition in HPV− samples. (C) Identification of potential drug targets and ongoing clinical trials.