Comparative analysis of HPV-Human Protein Interaction Networks in Oropharyngeal and Oral Squamous cell carcinomas

Oral Squamous Cell Carcinoma (OSCC) accounts for more than 90% of reported head and neck cancers which is the sixth leading cancer worldwide. Oropharyngeal squamous cell carcinoma (OPSCC) cases, a closely located but a different sub-type of head and neck cancer, are also rising worldwide specifically among young individuals with risk factors including viral infection, smoking and alcohol. HPV infection specifically the subtype HPV16 is a significant risk factor in the initiation and progression of OPSCC, but has not been reported to play a role in OSCC. This study sets out to decipher mechanistic differences at the molecular level by comparing the viral-human protein-protein interaction (PPI) networks both in oropharyngeal squamous cell carcinoma (OPSCC) and oral squamous cell carcinoma (OSCC). We found that the unbiased HPV16-Human network consisted of 479 nodes, including 7 HPV16 proteins and 472 human proteins. Enrichment analysis revealed significant involvement of the identified human proteins in ubiquitination, protein degradation, and cancer-related pathways. A subset of 37 genes showed differential expression in HPV-positive OPSCC and OSCC, with TP53 over-expressed and ENDOD1 under-expressed in both cancers. Six genes (NUTM1, MYC, SCN9A, COL27A1, ITGB4, and GNB2) exhibited distinct changes in HPV-positive OPSCC compared to the other groups, where NUTM1 was the most over-expressed in OPSCC HPV+. The identified genes and pathways could serve as potential targets for precision medicine and therapeutic interventions in HPV-associated cancers. Further investigations are required to validate their clinical implication in in vitro and in vivo models.