1887

Abstract

Persistent infection with high-risk human papillomaviruses (HR-HPVs) is the causal factor in over 99 % of cervical cancer cases, and a significant proportion of oropharyngeal and anogenital cancers. The key drivers of HPV-mediated transformation are the oncoproteins E5, E6 and E7. Together, they act to prolong cell-cycle progression, delay differentiation and inhibit apoptosis in the host keratinocyte cell in order to generate an environment permissive for viral replication. The oncoproteins also have key roles in mediating evasion of the host immune response, enabling infection to persist. Moreover, prolonged infection within the cellular environment established by the HR-HPV oncoproteins can lead to the acquisition of host genetic mutations, eventually culminating in transformation to malignancy. In this review, we outline the many ways in which the HR-HPV oncoproteins manipulate the host cellular environment, focusing on how these activities can contribute to carcinogenesis.

Keyword(s): cancer , HPV , keratinocyte , oncoprotein and signalling
Funding
This study was supported by the:
  • Biotechnology and Biological Sciences Research Council (Award BB/M011151/1)
    • Principle Award Recipient: MollyR. Patterson
  • Wellcome Trust (Award 204825/Z/16/Z)
    • Principle Award Recipient: EthanL. Morgan
  • Medical Research Council (Award MR/S001697/1)
    • Principle Award Recipient: AndrewMacdonald
  • Medical Research Council (Award MR/ K012665)
    • Principle Award Recipient: AndrewMacdonald
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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2021-01-11
2021-10-26
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