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However, it is not clear whether all <jats:styled-content style=\"fixed-case\">HRHPV<\/jats:styled-content> integration events provide cells with a selective growth advantage compared with the episome\u2010containing cells from which they originate. It is also unclear whether selection of cells containing a particular integrant from a mixed population simply reflects the highest levels of virus oncogene expression or has additional determinants. These early events in cervical carcinogenesis cannot readily be addressed by cross\u2010sectional studies of clinical samples. We used the <jats:styled-content style=\"fixed-case\">W12<\/jats:styled-content> model system to generate a panel of cervical squamous cell clones that were derived from an identical background under non\u2010competitive conditions and differed only by the genomic site of <jats:styled-content style=\"fixed-case\">HPV16<\/jats:styled-content> integration. Compared with the \u2018baseline\u2019 episome\u2010containing cells from which they were isolated, only 9\/17 clones (53%) showed significantly greater growth rates and only 7\/17 (41%) showed significantly greater expression of the major virus oncogenes <jats:styled-content style=\"fixed-case\">E7<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">E6<\/jats:styled-content>. There were significant variations in levels of <jats:styled-content style=\"fixed-case\">HPV16<\/jats:styled-content> transcription per <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> template, changes that were associated with histone modifications in the integrated virus chromatin. Cell growth rates showed only weak and non\u2010significant associations with protein and <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> levels for <jats:styled-content style=\"fixed-case\">E7<\/jats:styled-content>, <jats:styled-content style=\"fixed-case\">E6<\/jats:styled-content>, and the mean <jats:styled-content style=\"fixed-case\">E7<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">E6<\/jats:styled-content> values. We conclude that <jats:styled-content style=\"fixed-case\">HPV16<\/jats:styled-content> integration in basal cervical cells does not necessarily lead to increased levels of virus oncogenes, or to a competitive growth advantage, when compared with the initiating episome\u2010containing cells. \u00a9 2014 The Authors. <jats:italic>The Journal of Pathology<\/jats:italic> published by John Wiley &amp; Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.<\/jats:p>","DOI":"10.1002\/path.4358","type":"journal-article","created":{"date-parts":[[2014,4,17]],"date-time":"2014-04-17T06:22:32Z","timestamp":1397715752000},"page":"281-293","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Virus transcript levels and cell growth rates after naturally occurring <scp>HPV16<\/scp> integration events in basal cervical keratinocytes"],"prefix":"10.1002","volume":"233","author":[{"given":"Cinzia 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