Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2007-7-12
pubmed:abstractText
An important occurrence in cervical carcinogenesis is deregulated expression of the high-risk human papillomavirus (HR-HPV) oncogenes E6 and E7. Several risk factors for cervical neoplastic progression are likely to contribute to viral oncogene deregulation, particularly integration of HR-HPV into the host genome. Integration represents a by-product of viral infection that is detected in almost 90% of cervical carcinomas. The mechanism of integration is not fully understood, although there is a clear predilection for chromosomal common fragile sites, most likely due to their accessibility for insertion of foreign DNA. Recent work has suggested that an important intermediate stage in cervical carcinogenesis is characterized by transcriptionally silent HR-HPV integrants, which co-exist with viral episomes in infected cells. As episome-derived E2 protein inhibits integrant transcription, clearance of episomes (eg by host innate immunity) is associated with loss of integrant silencing and integrant selection. The process of integration and subsequent clonal selection of integrants can therefore be considered as two independent and biologically distinct events. Indeed, integrated HPV may be viewed as selectable because it represents a form of the virus that is resistant to host mechanisms of viral clearance, enabling infected cells to maintain viral oncogene expression and avoid cell death. Care should be taken in interpreting studies of HPV integration frequency in clinical samples, as the techniques used have assessed either the presence of integrated viral DNA or evidence of transcriptional activity from integrants, but not both.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0022-3417
pubmed:author
pubmed:copyrightInfo
Copyright (c) 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
pubmed:issnType
Print
pubmed:volume
212
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
356-67
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Integration of high-risk human papillomavirus: a key event in cervical carcinogenesis?
pubmed:affiliation
Medical Research Council Cancer Cell Unit, Hutchison/MRC Research Centre, Hills Road, Cambridge, CB2 0XZ, UK.
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't