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Key events in high\u2010risk <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">HRHPV<\/jats:styled-content>)\u2010associated 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 <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> into host chromosomes is observed in the majority of cervical squamous cell carcinomas (<jats:styled-content style=\"fixed-case\">SCCs<\/jats:styled-content>), although in \u223c15% 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 <jats:styled-content style=\"fixed-case\">E6<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">E7<\/jats:styled-content>, when compared with episome\u2010containing 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 <jats:styled-content style=\"fixed-case\">HRHPV<\/jats:styled-content> is regulated through host epigenetic mechanisms affecting the virus long control region (<jats:styled-content style=\"fixed-case\">LCR<\/jats:styled-content>), which appear to be of functional importance. New approaches to treating <jats:styled-content style=\"fixed-case\">HRHPV<\/jats:styled-content>\u2010associated mucosal neoplasia include knockout of integrated <jats:styled-content style=\"fixed-case\">HRHPV DNA<\/jats:styled-content>, depletion of virus transcripts and inhibition of virus early gene transcription through targeting or use of epigenetic modifiers. Copyright \u00a9 2014 Pathological Society of Great Britain and Ireland. 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