Immunopathogenesis of HPV-Associated Cancers and Prospects for Immunotherapy.

Sigrun Smola

doi:10.3390/v9090254

Abstract

Human papillomavirus (HPV) infection is a causative factor for various cancers of the anogenital region and oropharynx, and is supposed to play an important cofactor role for skin carcinogenesis. Evasion from immunosurveillance favors viral persistence. However, there is evidence that the mere presence of oncogenic HPV is not sufficient for malignant progression and that additional tumor-promoting steps are required. Recent studies have demonstrated that HPV-transformed cells actively promote chronic stromal inflammation and conspire with cells in the local microenvironment to promote carcinogenesis. This review highlights the complex interplay between HPV-infected cells and the local immune microenvironment during oncogenic HPV infection, persistence, and malignant progression, and discusses new prospects for diagnosis and immunotherapy of HPV-associated cancers.

Highlights

15–20% of all cancers are caused by infectious agents [1] and around 5% by human papillomaviruses (HPVs) [2,3]
In addition to cervical cancer, a significant number of oropharyngeal, penile, anal, vaginal and vulvar cancers are induced by mucosal HPVs [5,6,7] and cutaneous HPVs have been implicated as cofactors in skin cancer development [8,9]
Over recent years it has become evident that the local microenvironment and the immune system plays a pivotal role in carcinogenesis [93,94]

Summary

Introduction

15–20% of all cancers are caused by infectious agents [1] and around 5% by human papillomaviruses (HPVs) [2,3]. That chronic inflammation and misled immune responses in the local immune microenvironment play a critical role during the progression of precancerous lesions to invasive cancer [11,12,13]. At later stages of the disease, HPV-transformed cells reprogram the local immune microenvironment and rather initiate chronic stromal inflammation, which serves to promote progression of precursor lesions to invasive cancer (Figure 1). At later stages of the disease, HPV-transformed cells reprogram the local and rather initiate chronic stromal inflammation, which serves to promote progression of precursor lesions to invasive cancer (Figure 1). HPV-infected cells suppress acute inflammation in the epithelium and immune recognition. This allows allows escape from immunosurveillance and viral persistence.

Immune Escape Paves the Way for HPV Persistence

Passive Mechanisms of Immune Escape

Suppression of the Recruitment of Professional APC

Chronic Stromal Inflammation during Progression to Cancer

Findings

Conclusions and Prospects for Diagnosis and Immunotherapy