The molecular differences between human papillomavirus-positive and -negative oropharyngeal squamous cell carcinoma: A bioinformatics study

Am J Otolaryngol. Jul-Aug 2019;40(4):547-554. doi: 10.1016/j.amjoto.2019.04.015. Epub 2019 Apr 23.


Objective: To investigate the genetic and epigenetic differences between human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) and HPV-negative OPSCC.

Methods: Microarray data of HPV-positive and -negative OPSCC were retrieved from NCBI GEO datasets. Differentially expressed genes (DEGs) and differentially expressed miRNAs (DE-miRNAs) were identified by performing differential expression analysis. A functional enrichment analysis was performed to explore the biological processes and signaling pathways that DEGs and DE-miRNAs were involved in, respectively. A protein-protein interaction (PPI) network of DEGs was constructed to identify hub genes. miRNA-target network and miRNA-miRNA functional synergistic network were each constructed in order to identify risk-marker miRNAs. An miRNA-target-pathway network was constructed in order to explore the function of identified risk-marker miRNAs.

Results: Microarray data from 3 datasets (GSE39366, GSE40774, and GSE55550) was included and analyzed. The PPI network identified 3 hub genes (VCAM1, UBD, and RPA2). MiR-107 and miR-142-3p were found to play the most significant role in both the DE-miRNA-target network as well as in the miRNA-miRNA functional synergistic network. MiR-107 was involved in HPV-induced tumorigenesis by targeting many genes (CAV1, CDK6, MYB, and SERPINB5) and regulating the p53 signaling pathway, the PI3K-Akt signaling pathway, and the autophagy pathway. In addition, miR-142-3p was implicated in HPV-induced tumorigenesis by targeting the PPFIA1 gene and regulating transcriptional dysregulation and other cancerous pathways.

Conclusion: Three genes (VCAM1, UBD, and RPA2), two miRNAs (miR-107 and miR-142-3p), and four pathways (p53, PI3K-Akt, autophagy, and transcription dysregulation in cancer) were identified to play critical roles in distinguishing HPV-positive OPSCC from HPV-negative OPSCC.

Keywords: Genes; Human papillomavirus; Oropharyngeal squamous cell carcinoma; Pathways; miRNAs.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Carcinogenesis / genetics*
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / virology*
  • Computational Biology*
  • Datasets as Topic
  • Epigenesis, Genetic / genetics*
  • Gene Expression*
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Microarray Analysis
  • Oropharyngeal Neoplasms / genetics*
  • Oropharyngeal Neoplasms / virology*
  • Papillomaviridae*
  • Protein Interaction Maps
  • Replication Protein A / genetics
  • Replication Protein A / metabolism
  • Ubiquitins / genetics
  • Ubiquitins / metabolism
  • Vascular Cell Adhesion Molecule-1 / genetics
  • Vascular Cell Adhesion Molecule-1 / metabolism


  • Adaptor Proteins, Signal Transducing
  • MIRN107 microRNA, human
  • MIRN142 microRNA, human
  • MicroRNAs
  • PPFIA1 protein, human
  • Replication Protein A
  • UBD protein, human
  • Ubiquitins
  • Vascular Cell Adhesion Molecule-1
  • RPA2 protein, human