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Biological Pathways of HPV-Induced Carcinogenesis

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Sexually Transmitted Infections

Abstract

Human papillomavirus (HPV) infection is the most common sexually transmitted viral infection. The majority of genital HPV infections are transient and do not induce any clinical manifestations, because they are rapidly and efficiently cleared by the host immune system. Rarely, a persistent infection is established by high-risk (HR) mucosal HPV genotypes (e.g., HPV16), so that pre-neoplastic and neoplastic lesions may develop. HR-HPVs are involved in the development of about 5% of all human cancers, especially at anogenital sites but also in the head and neck region. Two viral oncoproteins, E6 and E7, are the main drivers of HPV-mediated carcinogenesis, because of their ability to bind to a surprisingly high number of cellular targets, including p53 and pRb tumor suppressors, and to subvert pathways involved in cell cycle regulation, immune response, and genome integrity. In addition, E6 and E7 profoundly alter the host epigenome, further deregulating the expression of cellular tumor suppressors, oncogenes, and immune-related genes. Over time, the interplay between these oncoproteins and the consequent disruption of key cellular pathways lead to the irreversible acquisition of a malignant phenotype. The monoclonal expansion of the HPV-infected cell(s) with the greatest growth advantage will ultimately lead to cancer. The complex and intimately linked series of events of mucosal HPV-induced tumorigenesis, which is mostly clarified for HPV-associated cervical cancer, is still largely unknown for other HPV-driven cancers. Certain cutaneous HPVs, particularly beta HPVs, appear to play a role in the etiology of skin cancer, although major gaps of knowledge remain about their carcinogenic mechanisms.

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Authors and Affiliations

  1. STI/HIV Unit, San Gallicano Dermatological Institute IRCCS, Rome, Italy

    Maria Gabriella Donà

  2. Infections and Cancer Biology Group, International Agency for Research on Cancer, Lyon, France

    Massimo Tommasino

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  1. Maria Gabriella Donà
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  2. Massimo Tommasino
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Correspondence to Massimo Tommasino .

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  1. STI/HIV Unit, San Gallicano Dermatological Institute, IRCCS, Rome, Italy

    Antonio Cristaudo

  2. STI/HIV Unit, San Gallicano Dermatological Institute, IRCCS, Rome, Italy

    Massimo Giuliani

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Donà, M.G., Tommasino, M. (2020). Biological Pathways of HPV-Induced Carcinogenesis. In: Cristaudo, A., Giuliani, M. (eds) Sexually Transmitted Infections . Springer, Cham. https://doi.org/10.1007/978-3-030-02200-6_18

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