Papillomaviruses and cancer - commonalities and differences in HPV carcinogenesis at different sites of the body

Sep 24, 2026

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Human papillomavirus (HPV) is linked to about 5% of cancers worldwide across multiple body sites, including cervix, anus, penis, vagina, vulva, and oropharynx, with more than 400,000 deaths annually. Persistent HPV infection and viral oncogenes are key drivers, yet only a subset of infected individuals or lesions progress to cancer. The cancer burden varies by gender and anatomical site, and site-specific epithelial cells and the local microenvironment likely shape malignant transformation by regulating viral gene expression and the HPV life cycle. Understanding these site-specific biology supports improved diagnosis, treatment, and management of HPV-associated cancers and precancerous lesions.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages9

Reading Time23 min

AccessFree to download

Introduction

HPV pathogenesis

Viral oncogenes (E6 and E7)

Site-specific factors and malignant transformation

International Journal of Clinical Oncology (2023) 28:956–964 [https://doi.org/10.1007/s10147-023-02340-y](https://doi.org/10.1007/s10147-023-02340-y) Papillomaviruses and cancer: commonalities and differences in HPV carcinogenesis at different sites of the body Nagayasu Egawa1 Received: 15 March 2023 / Accepted: 7 April 2023 / Published online: 18 May 2023 © Crown 2023, corrected publication 2025 Abstract Human papillomavirus (HPV) is associated with 5% of all cancers globally at a range of body sites, including cervix, anus, penis, vagina, vulva, and oropharynx. These cancers claim >400,000 lives annually. The persistent infection of HPV and the function of viral oncogenes are the primary causes of HPV-related cancers. However, only some HPV-infected persons or infected lesions will progress to cancer, and the burden of HPV-associated cancer varies widely according to gender and the part of the body infected. The dissimilarity in infection rates at different sites can explain only a small part of the differences observed. Much responsibility likely sits with contributions of specific epithelial cells and the cellular microenvironment at infected sites to the process of malignant transformation, both of which affect the regulation of viral gene expression and the viral life cycle. By understanding the biology of these epithelial sites, better diagnosis/treatment/management of HPVassociated cancer and/or pre-cancer lesions will be provided. Keywords HPV · Cancer · Carcinogenesis Introduction It was presumed from epidemiological facts that cervical cancer was caused by infectious factors related to sexual intercourse but for a long time the details were unknown [1]. Forty years ago, Harald zur Hausen and colleagues discovered the first link between human papillomavirus (HPV) and cervical cancer, by finding new types of HPV, HPV16 and HPV18, in cervical cancer tissues [2, 3] . Since then, studies confirmed the direct role of several mucosal HPV types, which are now categorised as high-risk HPVs, in the development of cervical cancer and other epithelial tumours, including cancers of the oropharyngeal, anus, penis, vulva, vagina, and skin [4] . The Nobel Prize in Physiology of Medicine, in 2008, was awarded to Dr zur Hausen for his discoveries that led to the expansion of the spectrum of HPV-related cancers and the understanding of the viral carcinogenesis mechanisms. The discovery that cervical cancer is a form of viral infection has had significant impact, leading to the development of vaccines to prevent HPV infection * Nagayasu Egawa [ne259@cam.ac.uk](ne259@cam.ac.uk) 1 Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK and a more accurate cervical cancer screening algorithm using HPV tests [5], which will lead us to the elimination of cervical cancer and HPV-related cancer (WHO: Cervical cancer elimination initiative. [https://www.who.int/initi](https://www.who.int/initi)[atives/cervicalcancereliminationinitiative](atives/cervicalcancereliminationinitiative)) . One of the most distinctive characteristics of HPV is the genotype-specific preference for distinct anatomical sites (tropism) of particular HPV types, where they cause lesions with distinctive clinical pathologies (reviewed in [6, 7]) . The origin of papillomaviruses is linked to changes in the epithelium of their ancestral host that occurred at least 350 million years ago [8] . Since then, they have co-evolved as their different host species have evolved but appear not to have followed an identical evolutionary path to that of their hosts. Rather, they have paralleled the evolution of host resources or attributes, such as the presence or absence of fur or the evolution of sweat glands [7] . HPV is required to evolve distinctive viral gene functions and regulation of viral gene expression during adaptation to the sites of infection, which must have different biology. As consequence, this has resulted in the diversity of p

FAQs

What causes HPV-associated cancers to develop?

Persistent HPV infection and viral oncogenes are identified as primary causes. Progression to cancer occurs only in some infected persons or lesions, indicating additional site- and biology-specific determinants.

Why does HPV-associated cancer burden vary across different body sites?

Differences in infection rates explain only a small portion of the observed variation. The process of malignant transformation likely depends on specific epithelial cells and the cellular microenvironment at each infected site, which affect viral gene expression and the viral life cycle.

What roles do the HPV oncogenes E6 and E7 play in carcinogenesis?

E6 and E7 are described as central to malignant transformation. High-risk E6 interacts with and degrades TP53 and BAK, suppressing growth arrest and apoptosis after DNA damage and promoting mutation accumulation.

Sep 24, 2026

Upload by Angel