title: Integration of human papillomavirus correlates with high levels of viral oncogene transcripts in cervical carcinogenesis.
abstract: A prospective, cross-sectional study was conducted to investigate the correlation between the integration of high-risk human papillomavirus and disease severity of cervical lesions. 720 liquid-based cytology specimens including 422 normal cytology, 78 low-grade squamous intraepithelial lesions, 172 high-grade squamous intraepithelial lesions, and 48 women with cervical cancers were examined using HPV blot and type-specific E6 PCR. Positive HPV DNA types 16, 18, 52 and 58 were examined for viral DNA using real-time PCR. Expression of E6 transcripts was 89.5% (pure integration), 71.7% (mixed type), and 47.1% (pure episomal) (p<0.0001). Geometric mean levels ranged from 110.6 (episomal form) to 508.4 (mixed form), and 5966.2 (integration form) by real-time PCR (p<0.0001). Geometric mean levels of E6 transcript in HPV 16, 18, 52, and 58 correlated with the severity of cervical lesions and the physical integration state of the viral genome (p<0.0001). We conclude that this is the first paper to point out that integration of high-risk HPVs not only 16 and 18 but also 52 and 58 is correlated with high levels of oncogene transcripts from normal cervix, CIN to cervical cancer.
authors.affiliation: Gynecologic Cancer Center, Department of Obstetrics and Gynecology, Cathay General Hospital, Taipei, Taiwan.
authors.forename: Chih-Ming
authors.initials: CM
authors.lastname: Ho
authors.forename: Bor-Heng
authors.initials: BH
authors.lastname: Lee
authors.forename: Shwu-Fen
authors.initials: SF
authors.lastname: Chang
authors.forename: Tsai-Yen
authors.initials: TY
authors.lastname: Chien
authors.forename: Shih-Hung
authors.initials: SH
authors.lastname: Huang
authors.forename: Chiu-Cho
authors.initials: CC
authors.lastname: Yan
authors.forename: Weng-Fang
authors.initials: WF
authors.lastname: Cheng
mesh_terms: D000328:Adult; D052685:Alphapapillomavirus / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology; D002584:Cervix Uteri / Q000473:pathology / Q000821:virology; D003430:Cross-Sectional Studies; D005260:Female; D015967:Gene Expression Regulation, Viral; D006801:Humans; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000235:genetics* / Q000378:metabolism; D030361:Papillomavirus Infections / Q000473:pathology / Q000821:virology*; D011446:Prospective Studies; D014158:Transcription, Genetic; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000821:virology*; D016662:Virus Integration
chemical_list: D009856:Oncogene Proteins, Viral