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Nat Rev Dis Primers. 2016 Dec 1;2:16086. doi: 10.1038/nrdp.2016.86.

Carcinogenic human papillomavirus infection.

Author information

National Cancer Institute, Division of Cancer Epidemiology and Genetics, Room 6E544, 9609 Medical Center Drive, Rockville, Maryland 20850, USA.
Department of Pathology, University of Cambridge, Cambridge, UK.
Catalan Institute of Oncology, IDIBELL, Cancer Epidemiology Research Programme and CIBER Epidemiologia Y Salud Publica, Barcelona, Spain.
Department of Otolaryngology, Johns Hopkins Medicine, Baltimore, Maryland, USA.
Division of Gynecologic Oncology, US Oncology Network, University of Arizona-Phoenix, Phoenix, Arizona, USA.
International Agency for Research on Cancer, Infections and Cancer Epidemiology Group, Lyon, France.


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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