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Cited by 999Cervical Cancer and HPV ResearchHead and Neck Cancer StudiesGenital Health and Disease

Carcinogenic human papillomavirus infection

Schiffman, Mark, Doorbar, John, Wentzensen, Nicolas, de Sanjosé, Silvia, Fakhry, Carole, Monk, Bradley J., Stanley, Margaret A., Franceschi, Silvia·2016·Nature Reviews Disease Primers
DOI 10.1038/nrdp.2016.86
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Abstract

Infections with human papillomavirus (HPV) are common and transmitted by direct contact. Although the great majority of infections resolve within 2 years, 13 phylogenetically related, sexually transmitted HPV genotypes, notably HPV16, cause - if not controlled immunologically or by screening - virtually all cervical cancers worldwide, a large fraction of other anogenital cancers and an increasing proportion of oropharyngeal cancers. The carcinogenicity of these HPV types results primarily from the activity of the oncoproteins E6 and E7, which impair growth regulatory pathways. Persistent high-risk HPVs can transition from a productive (virion-producing) to an abortive or transforming infection, after which cancer can result after typically slow accumulation of host genetic mutations. However, which precancerous lesions progress and which do not is unclear; the majority of screening-detected precancers are treated, leading to overtreatment. The discovery of HPV as a carcinogen led to the development of effective preventive vaccines and sensitive HPV DNA and RNA tests. Together, vaccination programmes (the ultimate long-term preventive strategy) and screening using HPV tests could dramatically alter the landscape of HPV-related cancers. HPV testing will probably replace cytology-based cervical screening owing to greater reassurance when the test is negative. However, the effective implementation of HPV vaccination and screening globally remains a challenge.

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Crossref · 10.1038/nrdp.2016.86

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  • Truncation at age 40 years was motivated by the reduced likelihood of infections acquired beyond this age progressing to cancer due to postmenopausal hormonal patterns and shorter time to develop cervical cancer in older age.

    “truncation at this age was motivated by the reduced likelihood of infections acquired beyond this age to progress to cancer due to the hormonal patterns after menopause, and the shorter time to develop cervical cancer in this older age group.34, 35”

    From Evidence-based impact projections of single-dose human papillomavirus vaccination in India: a modelling study (2022) · cites this paper as [34]

  • Individual factors unique to mucosal surface such as epithelial surface integrity, mucosal secretions, and immune regulation likely play a role in HPV persistence and progression to cancer.

    “Individual factors unique to the mucosal surface such as epithelial surface integrity, mucosal secretions, and immune regulation likely play a role in HPV persistence and progression to cancer (Pyeon et al., 2009; Schiffman et al., 2016).”

    From Viral Infections, the Microbiome, and Probiotics (2021) · cites this paper as Schiffman et al., 2016

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Authors
Schiffman, M., Doorbar, J., Wentzensen, N., de Sanjosé, S., Fakhry, C., Monk, B. J., Stanley, M. A., & Franceschi, S.
Affiliations
  • National Institutes of Health (US)
  • University of Cambridge (GB)
  • Johns Hopkins University (US)
  • University of Arizona (US)
  • Centre international de recherche sur le cancer (FR)
Corresponding author
Schiffman, Mark
ORCID
Venue
Nature Reviews Disease Primers
Publisher
Springer Science and Business Media LLC
Published
2016-12-01
Volume
2
Issue
1
Pages
16086-16086
ISSN
2056-676X (ISSN-L)
DOI
10.1038/nrdp.2016.86
OpenAlex
W2559124996
Cited by
999
References
210
Citations by year
2026: 98 · 2025: 96 · 2024: 131 · 2023: 135 · 2022: 120 · 2021: 132 · 2020: 106 · 2019: 78 · 2018: 66 · 2017: 33 · 2012: 1
FWCI
7.99
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Nature Reviews Disease Primers (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • World Health Organization
  • Medical Research Council (MC_PC_13050)
Topics
  • Health Sciences › Medicine › Epidemiology › Cervical Cancer and HPV Research
  • Health Sciences › Medicine › Otorhinolaryngology › Head and Neck Cancer Studies
  • Health Sciences › Medicine › Surgery › Genital Health and Disease
Keywords
human papillomavirus, HPV oncogenesis, HPV16, E6 oncoprotein, E7 oncoprotein, cervical cancer, anogenital cancer, oropharyngeal cancer, HPV vaccination, HPV testing, cervical cancer screening, precancerous lesions, abortive infection, HPV genotypes
MeSH terms
Carcinogens, Uterine Cervical Neoplasms, Female, Humans, Male, Mass Screening, Incidence, Papillomaviridae, Papillomavirus Infections, Papillomavirus Vaccines, Early Detection of Cancer

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