Abstract
Human papillomaviruses (HPVs) are small, DNA viruses that cause around 5% of all cancers in humans, including almost all cervical cancer cases and a significant proportion of anogenital and oral cancers. The HPV oncoproteins E5, E6 and E7 manipulate cellular signalling pathways to evade the immune response and promote virus persistence. The Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) pathway has emerged as a key mediator in a wide range of important biological signalling pathways, including cell proliferation, cell survival and the immune response. While STAT1 and STAT2 primarily drive immune signalling initiated by interferons, STAT3 and STAT5 have widely been linked to the survival and proliferative potential of a number of cancers. As such, the inhibition of STAT3 and STAT5 may offer a therapeutic benefit in HPV-associated cancers. In this review, we will discuss how HPV manipulates JAK/STAT signalling to evade the immune system and promote cell proliferation, enabling viral persistence and driving cancer development. We also discuss approaches to inhibit the JAK/STAT pathway and how these could potentially be used in the treatment of HPV-associated disease.
Highlights
Infection with high-risk human papillomaviruses (HR-Human papillomaviruses (HPVs)) accounts for around 5% of human cancer cases worldwide, causing the majority of cervical cancers (>99%) and around 70%of oropharyngeal cancers [1]
We demonstrated that inhibition or depletion of STAT3 significantly impaired genome maintenance in undifferentiated keratinocytes in addition to differentiation-dependent viral genome amplification
STAT5 is required for activation of the Ataxia-telangiectasia mutated (ATM) pathway in HPV-containing keratinocytes, and this is essential for viral genome amplification
Summary
Infection with high-risk human papillomaviruses (HR-HPVs) accounts for around 5% of human cancer cases worldwide, causing the majority of cervical cancers (>99%) and around 70%. HPVs have evolved efficient mechanisms to evade the immune system in order to establish persistence [7,8]. HPV infection is a critical driver of cellular transformation, infection alone is not sufficient for malignant progression and other mechanisms are required [9]. As a critical pathway involved in the response to pathogens, many viruses have evolved mechanisms to manipulate JAK/STAT signalling in order to evade the immune response and promote proliferation. This review will discuss how HPV modulates the JAK/STAT pathway, focusing on how this enables viral genome replication and persistence, and contributes towards cancer development. We will summarise the current methods of inhibiting the JAK/STAT pathway and how these could potentially be used to treat HPV infection or HPV-associated disease
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
