The effects of HPV oncoproteins on host communication networks: Therapeutic connotations

J Med Virol. 2023 Dec;95(12):e29315. doi: 10.1002/jmv.29315.

Abstract

Human papillomavirus (HPV) infections are a leading cause of viral-induced malignancies worldwide, with a prominent association with cervical and head and neck cancers. The pivotal role of HPV oncoproteins, E5, E6, and E7, in manipulating cellular events, which contribute to viral pathogenesis in various ways, has been extensively documented. This article reviews the influence of HPV oncoproteins on cellular signaling pathways within the host cell, shedding light on the underlying molecular mechanisms. A comprehensive understanding of these molecular alterations is essential for the development of targeted therapies and strategies to combat HPV-induced premalignancies and prevent their progress to cancer. Furthermore, this review underscores the intricate interplay between HPV oncoproteins and some of the most important cellular signaling pathways: Notch, Wnt/β-catenin, MAPK, JAK/STAT, and PI3K AKT/mTOR. The treatment efficacies of the currently available inhibitors on these pathways in an HPV-positive context are also discussed. This review also highlights the importance of continued research to advance our knowledge and enhance therapeutic interventions for HPV-associated diseases.

Keywords: E5; E6; E7; HPV; JAK/STAT; MAPK; Notch; PI3K/AKT/mTOR; Wnt/β-catenin; cervical cancer; head and neck cancer.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Female
  • Humans
  • Oncogene Proteins, Viral*
  • Papillomavirus E7 Proteins
  • Papillomavirus Infections* / complications
  • Papillomavirus Infections* / drug therapy
  • Phosphatidylinositol 3-Kinases / metabolism
  • Signal Transduction
  • Uterine Cervical Neoplasms*

Substances

  • Oncogene Proteins, Viral
  • Phosphatidylinositol 3-Kinases
  • Papillomavirus E7 Proteins