Significant association between host transcriptome-derived HPV oncogene E6* influence score and carcinogenic pathways, tumor size, and survival in head and neck cancer

Head Neck. 2020 Sep;42(9):2375-2389. doi: 10.1002/hed.26244. Epub 2020 May 14.


Background: Human papillomavirus (HPV) oncogenes E6, E7, and shorter isoforms of E6 (E6*) are known carcinogenic factors in head and neck squamous cell carcinoma (HNSCC). Little is known regarding E6* functions.

Methods: We analyzed RNA-seq data from 68 HNSCC HPV type 16-positive tumors to determine host genes and pathways associated with E6+E7 expression (E6E7) or the percent of full-length E6 (E6%FL). Influence scores of E6E7 and E6%FL were used to test for associations with clinical variables.

Results: For E6E7, we recapitulated all major known affected pathways and revealed additional pathways. E6%FL was found to affect mitochondrial processes, and E6%FL influence score was significantly associated with overall survival and tumor size.

Conclusions: HPV E6E7 and E6* result in extensive, dose-dependent compensatory effects and dysregulation of key cancer pathways. The switch from E6 to E6* promotes oxidative phosphorylation, larger tumor size, and worse prognosis, potentially serving as a prognostic factor for HPV-positive HNSCC.

Keywords: E6; E6*; E7; head and neck cancer; human papillomavirus; influence score; survival.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alphapapillomavirus*
  • Carcinogens
  • Female
  • Head and Neck Neoplasms* / genetics
  • Head and Neck Neoplasms* / virology
  • Humans
  • Male
  • Oncogene Proteins, Viral* / genetics
  • Oncogenes
  • Papillomaviridae / genetics
  • Papillomavirus E7 Proteins / genetics
  • Papillomavirus Infections* / genetics
  • Repressor Proteins / genetics
  • Transcriptome


  • Carcinogens
  • Oncogene Proteins, Viral
  • Papillomavirus E7 Proteins
  • Repressor Proteins