title: Virological characteristics of cervical cancers carrying pure episomal form of HPV16 genome.
abstract: OBJECTIVE
  Many studies on integration have reported conflicting results regarding the role of HPV integration in cervical cancer. We hypothesized that high viral load and disruption of E2 gene associated with integration of HPV were not the only pathway leading to cancer development.
  
  
  METHODS
  This study analysed the viral load and integration status of HPV16, measured the HPV16 E6/E7 mRNA transcript levels, delineated the E2 and LCR sequence variation, and determined the methylation status of two E2 binding sites.
  
  
  RESULTS
  The results showed that viral load was not associated with the physical status of HPV genome. Levels of the three E6/E7 mRNA transcripts in invasive cervical cancers containing purely episomal viral genome were found to be similar to those containing integrated viral genome, suggesting that cancers containing episomal viral genome were also mediated by an up-regulated E6/E7 mRNA expression, and more importantly, did not depend on integration and disruption of the E2 gene.
  
  
  CONCLUSIONS
  The alternative mechanism that up-regulated the expression of E6 and E7 in invasive cancers harbouring episomal viral genome was likely to be a consequence of methylation of the two E2 binding sites located at the promoter region of HPV16. These observations are in line with the hypothesis that HPV integration was not the only mechanism leading to the development of cervical cancer.
authors.affiliation: Department of Microbiology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong Special Administrative Region.
authors.forename: Jo L K
authors.initials: JL
authors.lastname: Cheung
authors.forename: Tak-Hong
authors.initials: TH
authors.lastname: Cheung
authors.forename: Mei Y
authors.initials: MY
authors.lastname: Yu
authors.forename: Paul K S
authors.initials: PK
authors.lastname: Chan
mesh_terms: D000328:Adult; D000368:Aged; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D016679:Genome, Viral; D052162:Human papillomavirus 16 / Q000235:genetics*; D006801:Humans; D019901:Locus Control Region; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000235:genetics; D050725:Papillomavirus E7 Proteins / Q000235:genetics; D030361:Papillomavirus Infections / Q000821:virology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000821:virology*; D019562:Viral Load; D016662:Virus Integration
chemical_list: D004268:DNA-Binding Proteins; C054855:E2 protein, Human papillomavirus type 16; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16
keywords: Cervical cancer; E2 binding site; E2BS; Episomal genome; HPV; ICC; LCR; Methylation; Viral load; human papillomavirus; invasive cell carcinoma; long control region; mRNA transcript