HPV and the Risk of HIV Acquisition in Women.

Romaniya Zayats,Lyle R Mckinnon,Thomas T Murooka

doi:10.3389/fcimb.2022.814948

Abstract

The risk of HIV acquisition is low on a per-contact basis but increased by transmission co-factors such as other sexually transmitted infections (STIs). Human papillomavirus (HPV) is a prevalent STI that most individuals will acquire HPV in their lifetime. Current HPV vaccines can prevent newly acquired infections, but are largely ineffective against established HPV, complicating worldwide eradication efforts. In addition to being the causative agent of cervical cancer, accumulating evidence suggests that HPV infection and/or accompanying cervical inflammation increase the risk of HIV infection in men and women. The fact that immunological features observed during HPV infection overlap with cellular and molecular pathways known to enhance HIV susceptibility underscore the potential interplay between these two viral infections that fuel their mutual spread. Here we review current insights into how HPV infection and the generation of anti-HPV immunity contribute to higher HIV transmission rates, and the impact of HPV on mucosal inflammation, immune cell trafficking, and epithelial barrier function.

Highlights

Human papillomavirus (HPV) is the most common viral infection of reproductive tracts and the vast majority of sexually active individuals will acquire this virus at some point in their lives (Chesson et al, 2014)
A majority of HPV infections are cleared without treatment within a few months of acquisition, and 90% of the infections are cleared within 2 years
TLR gene polymorphisms may contribute to cancer susceptibility: TLR2 del allele is significantly associated with cervical cancer susceptibility and TLR2 ins/del genotype is strongly associated with tobacco usage in women with cervical cancer, while TLR4 Thr/Ile genotype was significantly associated with the early stage of cervical cancer in North Indian women (Pandey et al, 2009)

Summary

INTRODUCTION

HPV is the most common viral infection of reproductive tracts and the vast majority of sexually active individuals will acquire this virus at some point in their lives (Chesson et al, 2014). Regional production of pro-inflammatory cytokines leads to the subsequent activation of Langerhans cells (LCs) and tissue resident macrophages and function to recruit CD4+, CD8+, and CD56+ cells to the site of lesion (Monnier-Benoit et al, 2006; Woo et al, 2008; Karim et al, 2013) As part of their immune evasion strategy, HPV-infected keratinocytes express low amounts of viral proteins to limit antigen presentation during the early phases of infection (Stoler et al, 1992). The mechanism of IDO1-driven immunosuppression includes generation of regulatory T cells and suppressing effector responses by depleting tryptophan, which is important for T cell function (Kobayashi et al, 2008; Mittal et al, 2013) These studies are consistent with clinical observations that HPV+ cervical lesions express high levels of IDO1 (Kobayashi et al, 2008), suggesting that IDO1+ DCs may drive cancer progression by generating Tregs and/or inducing T cell anergy. NK cells correlate with HPV clearance (Prata et al, 2015; Bjorkstrom et al, 2021), but NK cells were shown to be biomarkers of increased HIV risk (Naranbhai et al, 2012)

CONCLUDING REMARKS

Findings

16 Proteins E6 and E7