The papillomavirus E5 gene does not affect EGFR transcription and overall survival in cervical cancer

J Med Virol. 2020 Aug;92(8):1283-1289. doi: 10.1002/jmv.25624. Epub 2019 Nov 18.

Abstract

Introduction: The human papillomavirus (HPV) E5 gene encodes a small and highly hydrophobic oncoprotein that affects immune evasion, cell proliferation, loss of apoptotic capacity and angiogenesis in tumors. E5 shows an affinity for biological membranes and was associated with an increase of epidermal growth factor/epidermal growth factor receptor (EGF/EGFR) signaling through the accumulation of EGFR in cellular membranes. Due to the frequent integration of the HPV genome into the host cell genome, E5 is frequently not transcribed in cervical tumors.

Aim: In this study we looked forward to verifying whether the potential expression of E5 protein in human papillomavirus 16 positive (HPV16+ ) and human papillomavirus 18 positive (HPV18+ ) cervical tumors was associated with levels of EGFR and vascular endothelial growth factor A (VEGFA) transcription and with patients overall survival.

Results: Association between the presence of E5 transcripts and viral genome disruption was observed for HPV16+ and HPV18+ tumors. Association was not observed between tumors potentially capable of translating E5 and EGFR or VEGFA transcriptional levels. Similarly, the capability of translating E5 and overall survival in patients with HPV16+ squamous cell carcinoma tumors stage ≥ IB2 were not associated.

Conclusion: The likely presence of E5 transcripts was neither associated to a higher activity of the EGFR-VEGFA pathway nor to the overall survival of patients with HPV16+ squamous cell carcinoma in stages ≥ IB2.

Keywords: E5 oncogene; HPV16; HPV18; cervical cancer; epidermal growth factor receptor; human papillomavirus; vascular endothelial growth factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Carcinoma, Squamous Cell / classification
  • Carcinoma, Squamous Cell / virology*
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism
  • Female
  • Genome, Viral
  • Humans
  • Middle Aged
  • Oncogene Proteins, Viral / genetics*
  • Signal Transduction
  • Survival Analysis
  • Transcription, Genetic*
  • Uterine Cervical Neoplasms / virology*
  • Vascular Endothelial Growth Factor A / genetics

Substances

  • Oncogene Proteins, Viral
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • oncogene protein E5, Human papillomavirus type 16
  • EGFR protein, human
  • ErbB Receptors