title: Association of elevated E6 oncoprotein with grade of cervical neoplasia using PDZ interaction-mediated precipitation of E6.
abstract: OBJECTIVE
  To determine the expression of human papillomavirus (HPV) type 16 E6 oncoprotein in cervical specimens of women with and without cervical intraepithelial neoplasia (CIN).
  
  
  METHODS
  Cervical specimens from 2,530 unscreened women aged 30 to 54 years from Shanxi, China, were obtained. All women were assessed by liquid-based cytology, high-risk HPV DNA tests, and colposcopy with directed biopsy and endocervical curettage as necessary. Women with abnormal cytologic results or positive HPV DNA results were recalled for colposcopy, 4-quadrant cervical biopsies, and endocervical curettage. Women with biopsy-proven CIN and cancer and a convenience sample of HC2-positive, disease-negative women were tested for the presence of HPV-16 infection via HPV-16 E6 DNA-specific polymerase chain reaction. A PDZ interaction-mediated E6 oncoprotein precipitation method followed by E6-specific Western blot was performed on specimens from women with HPV-16 infections. Associations between elevated expression of E6 oncoprotein and CIN 2 and 3 were determined using logistic regression and a reference category of CIN 1 and disease-negative.
  
  
  RESULTS
  A significant trend for the detection of HPV-16 E6 oncoprotein in specimen of women with proven HPV-16 infection was determined: 0% (0/12), 12.5% (1/8), 36.4% (4/11), and 42.9% (3/7) of those with negative findings, CIN 1, 2, and 3, respectively (p = .01). Compared with the category combining negative findings and CIN 1, detection of E6 oncoprotein was associated with CIN 2 (odds ratio = 10.9, p = .05) and CIN 3 (odds ratio = 14.3, p = .04).
  
  
  CONCLUSIONS
  There is a significant association between elevated expression of E6 oncoprotein and grade of CIN. This finding seems consistent with the role played by E6 oncoprotein in carcinogenesis.
authors.affiliation: PATH, Seattle, WA 9810, USA.
authors.forename: John W
authors.initials: JW
authors.lastname: Sellors
authors.forename: Johannes G
authors.initials: JG
authors.lastname: Schweizer
authors.forename: Peter S
authors.initials: PS
authors.lastname: Lu
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.forename: Bernhard H
authors.initials: BH
authors.lastname: Weigl
authors.forename: Jian Feng
authors.initials: JF
authors.lastname: Cui
authors.forename: Roger B
authors.initials: RB
authors.lastname: Peck
authors.forename: Kristen
authors.initials: K
authors.lastname: Lewis
authors.forename: Jeanette
authors.initials: J
authors.lastname: Lim
authors.forename: Michelle
authors.initials: M
authors.lastname: Howard
authors.forename: Charles W
authors.initials: CW
authors.lastname: Mahoney
authors.forename: Linda
authors.initials: L
authors.lastname: McAllister
authors.forename: Marthe
authors.initials: M
authors.lastname: Berard-Bergery
authors.forename: Claire
authors.initials: C
authors.lastname: Bry
authors.forename: Yassine A
authors.initials: YA
authors.lastname: Labiad
authors.forename: Haimin
authors.initials: H
authors.lastname: Li
authors.forename: Lilyn
authors.initials: L
authors.lastname: Liu
authors.forename: Jon
authors.initials: J
authors.lastname: Silver
authors.forename: Wen
authors.initials: W
authors.lastname: Chen
authors.forename: You Lin
authors.initials: YL
authors.lastname: Qiao
mesh_terms: D000328:Adult; D015153:Blotting, Western / Q000379:methods; D002584:Cervix Uteri / Q000473:pathology; D002681:China; D005260:Female; D052162:Human papillomavirus 16 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D030361:Papillomavirus Infections / Q000821:virology; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000821:virology*; D002578:Uterine Cervical Dysplasia / Q000378:metabolism / Q000473:pathology* / Q000821:virology*
chemical_list: C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins