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HPV and Cervical Cancer pp 45–61Cite as

The Immunobiology of Human Papillomavirus Associated Oncogenesis

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Abstract

The lifecycle of oncogenic HPV begins with entry into the basal cells of a target anogenital epithelium. Thereafter, virus production is entirely within and dependent on the differentiation of the epithelium which provides for the necessary coordinated cellular and viral gene expression leading to accumulation of infectious virions in the terminally differentiated cells. Natural immune control of such HPV infection derives initially from activation of innate immune mechanisms and these stimulate adaptive immunity such as specific cytotoxic T cells recognizing viral proteins E2, E6 and E7 that can clear the virally infected cells. About 50% of women who clear their infections also make neutralising antibodies but the levels are not necessarily protective against a subsequent infection by the same HPV type and are never therapeutic. Oncogenic HPVs have several immune evasion strategies which together with a lifecycle involving little or no damage in the epithelial located infection can allow for persistent infection, which is the major risk factor for development of intraepithelial neoplasia. Oncogenic HPV infection is necessary but insufficient for development of a cervical cancer and additional genetic changes are acquired over time through selection including those that allow for escape from immune surveillance. This review describes the current understanding natural immune control and identifies the unique hurdles in prophylactic and therapeutic vaccine design for HPV compared to other common viral pathogens.

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Authors and Affiliations

  1. CRUK Immunology Group, Paterson Institute for Cancer Research, University of Manchester, Manchester, M20 4BX, UK

    Peter L. Stern

  2. Division of Gynecologic Oncology, Albert Einstein College of Medicine & Montefiore Medical Center, 1695 Eastchester Rd, Suite 601, Bronx, NY, 10461, USA

    Mark H. Einstein M.D., M.S.

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    Franco Borruto

  2. Université Libre de Bruxelles, Brussels, Belgium

    Marc De Ridder

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Stern, P.L., Einstein, M.H. (2012). The Immunobiology of Human Papillomavirus Associated Oncogenesis. In: Borruto, F., De Ridder, M. (eds) HPV and Cervical Cancer. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-1988-4_3

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