Journal
HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK
Volume 42, Issue 9, Pages 2375-2389Publisher
WILEY
DOI: 10.1002/hed.26244
Keywords
E6; E6*; E7; head and neck cancer; human papillomavirus; influence score; survival
Categories
Funding
- National Cancer Institute, National Institutes of Health [R01CA158286, P30CA046592]
- University of Michigan Specialized Programs of Research Excellence (SPORE) Grant [P50CA097248]
- University of Michigan Medical School Advanced Genomics Core
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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.
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