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dc.contributor.authorGroves, Ianen
dc.contributor.authorColeman, Nicholasen
dc.date.accessioned2015-02-17T09:42:47Z
dc.date.available2015-02-17T09:42:47Z
dc.date.issued2014-12-08en
dc.identifier.citationIJ Groves, N Coleman, The Journal of Pathology 2015, 235, 527–538en
dc.identifier.issn0022-3417
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/246806
dc.description.abstractHuman papillomaviruses (HPVs) are a necessary cause of carcinoma of the cervix and other mucosal epithelia. Key events in high-risk HPV (HRHPV)-associated neoplastic progression include persistent infection, deregulated expression of virus early genes in basal epithelial cells and genomic instability causing secondary host genomic imbalances. There are multiple mechanisms by which deregulated virus early gene expression may be achieved. Integration of virus DNA into host chromosomes is observed in the majority of cervical squamous cell carcinomas (SCCs), although in ∼15% of cases the virus remains extrachromosomal (episomal). Interestingly, not all integration events provide a growth advantage to basal cervical epithelial cells or lead to increased levels of the virus oncogenes E6 and E7, when compared with episome-containing basal cells. The factors that provide a competitive advantage to some integrants, but not others, are complex and include virus and host contributions. Gene expression from integrated and episomal HRHPV is regulated through host epigenetic mechanisms affecting the virus long control region (LCR), which appear to be of functional importance. New approaches to treating HRHPV-associated mucosal neoplasia include knockout of integrated HRHPV DNA, depletion of virus transcripts and inhibition of virus early gene transcription through targeting or use of epigenetic modifiers.
dc.description.sponsorshipWe thank Cancer Research UK and the Medical Research Council for funding our research, some of which is described in this review.
dc.languageEnglishen
dc.language.isoenen
dc.publisherWiley
dc.subjecthuman papillomavirusen
dc.subjectmucosaen
dc.subjectoncogeneen
dc.subjectE6/E7en
dc.subjectepigeneticsen
dc.subjectintegrationen
dc.subjectsquamous cell carcinomaen
dc.titlePathogenesis of human papillomavirus-associated mucosal diseaseen
dc.typeArticle
dc.description.versionThis is the accepted version of the following article: IJ Groves, N Coleman, The Journal of Pathology 2015, 235, 527–538, which has been published in final form at http://dx.doi.org/10.1002/path.4496en
prism.endingPage538
prism.publicationDate2014en
prism.publicationNameThe Journal of Pathologyen
prism.startingPage527
prism.volume235en
dc.rioxxterms.funderCancer Research UK
dc.rioxxterms.funderMedical Research Council
dcterms.dateAccepted2014-12-03en
rioxxterms.versionofrecord10.1002/path.4496en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2014-12-08en
dc.contributor.orcidGroves, Ian [0000-0001-8882-6701]
dc.contributor.orcidColeman, Nicholas [0000-0002-5374-739X]
dc.identifier.eissn1096-9896
rioxxterms.typeJournal Article/Reviewen
rioxxterms.freetoread.startdate2016-01-20


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