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Immunology of HPV Infection

  • Management of HPV and Associated Cervical Lesions (L Denny, Section Editor)
  • Published:
Current Obstetrics and Gynecology Reports Aims and scope Submit manuscript

Abstract

Human papillomavirus (HPV) infection in the genital tract is common in young sexually active individuals, the majority of whom clear the infection without overt clinical disease. However, most of those who develop benign lesions eventually mount an effective cell-mediated immune response and the lesions regress. Regression of anogenital warts is accompanied histologically by a CD4+ T cell-dominated Th1 response, and animal models support this and provide evidence that the response is modulated by antigen-specific CD4+ T cell-dependent mechanisms. Failure to develop effective CMI to clear or control infection results in persistent infection and, in the case of the oncogenic HPVs, an increased probability of progression to high-grade intraepithelial neoplasia and invasive carcinoma. Effective evasion of innate immune recognition and activation of adaptive immune responses seem to be the hallmark of HPV infections. The viral infectious cycle is exclusively intraepithelial, there is no viraemia, no virus-induced cytolysis or cell death and viral replication, and release is not associated with inflammation. HPV globally downregulates the innate immune signalling pathways in the infected keratinocyte, pro-inflammatory cytokines particularly the type I interferons are not released, and the signals for Langerhans cell (LC) activation and migration together with recruitment of stromal dendritic cells and macrophages are either not present or inadequate. This immune ignorance results in chronic infections that persist over weeks and months. Progression to high-grade intraepithelial neoplasia with the concomitant upregulation of the E6 and E7 oncoproteins is associated with further deregulation of immunologically relevant molecules, particularly chemotactic chemokines and their receptors, on keratinocytes and endothelial cells of the underlying microvasculature limiting or preventing the ingress of cytotoxic effectors into the lesions.

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Conflict of Interest

Margaret Stanley declares that she received personal fees for being a consultant to MSD Merck, GSK Biologicals and SPMSD.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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  1. Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QP, UK

    Margaret Stanley

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  1. Margaret Stanley
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Correspondence to Margaret Stanley.

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This article is part of the Topical Collection on Management of HPV and Associated Cervical Lesions

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Stanley, M. Immunology of HPV Infection. Curr Obstet Gynecol Rep 4, 195–200 (2015). https://doi.org/10.1007/s13669-015-0134-y

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  • DOI: https://doi.org/10.1007/s13669-015-0134-y

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