title: Carbonic anhydrase IX (CA-IX) and high-risk human papillomavirus (H-HPV) as diagnostic biomarkers of cervical dysplasia/neoplasia in Japanese women with a cytologic diagnosis of atypical glandular cells (AGC): a Gynecologic Oncology Group (GOG) Study.
abstract: BACKGROUND
  High-risk human papillomavirus (H-HPV) infection is linked to cervical neoplasia but its role in detecting cervical glandular lesions (GLs) is unclear. Carbonic anhydrase IX (CA-IX) is a hypoxic biomarker that is highly expressed in neoplastic cervical GLs. The diagnostic utility of these biomarkers was evaluated by the Gynecologic Oncology Group in Japanese women with a cytological diagnosis of atypical glandular cells.
  
  
  METHODS
  Immunostaining was used to detect CA-IX in a conventional Pap smear. Immunoreactivity of CA-IX was interpreted by a panel of pathologists blinded to the histological diagnosis. Polymerase chain reaction was used to detect H-HPV in a liquid-based cytology specimen.
  
  
  RESULTS
  Significant cervical lesions (SCLs), defined as cervical intraepithelial neoplasia (CIN2, CIN3), adenocarcinoma in situ or invasive carcinoma, were observed in 37/88 (42%) of women. CA-IX testing alone (n=88) had a sensitivity of 89, 100 or 73% for SCLs, GLs or significant squamous lesions (SLs), respectively, with a false negative rate (FNR) of 14%. Testing for H-HPV (n=84) had a sensitivity of 65, 53 or 80% for SCLs, GLs or SLs, respectively, with a FNR of 22%. The combination of CA-IX and H-HPV testing had a sensitivity of 97, 100 or 93% for SCLs, GLs or SLs, respectively, with a FNR of 5%. Among eight H-HPV-negative GLs, six (75%) had a diagnosis of lobular endocervical glandular hyperplasia (LEGH).
  
  
  CONCLUSIONS
  The combination of CA-IX and HPV testing improved the diagnostic accuracy. The low rate of H-HPV positivity in the GLs was associated with coexisting LEGH independent of H-HPV.
authors.affiliation: Department of Epidemiology, School of Medicine, University of California at Irvine, Irvine, CA 92868, USA. syliao@uci.edu
authors.forename: S-Y
authors.initials: SY
authors.lastname: Liao
authors.forename: W H
authors.initials: WH
authors.lastname: Rodgers
authors.forename: J
authors.initials: J
authors.lastname: Kauderer
authors.forename: T A
authors.initials: TA
authors.lastname: Bonfiglio
authors.forename: K M
authors.initials: KM
authors.lastname: Darcy
authors.forename: R
authors.initials: R
authors.lastname: Carter
authors.forename: L
authors.initials: L
authors.lastname: Levine
authors.forename: N M
authors.initials: NM
authors.lastname: Spirtos
authors.forename: N
authors.initials: N
authors.lastname: Susumu
authors.forename: K
authors.initials: K
authors.lastname: Fujiwara
authors.forename: J L
authors.initials: JL
authors.lastname: Walker
authors.forename: M
authors.initials: M
authors.lastname: Hatae
authors.forename: E J
authors.initials: EJ
authors.lastname: Stanbridge
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D052685:Alphapapillomavirus / Q000235:genetics / Q000472:pathogenicity*; D002256:Carbonic Anhydrases / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006801:Humans; D007564:Japan; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000201:enzymology / Q000821:virology
chemical_list: D002256:Carbonic Anhydrases