Carbonic anhydrase IX and human papillomavirus as diagnostic biomarkers of cervical dysplasia/neoplasia in women with a cytologic diagnosis of atypical glandular cells: a Gynecologic Oncology Group study in United States

Int J Cancer. 2009 Nov 15;125(10):2434-40. doi: 10.1002/ijc.24615.

Abstract

High-risk human papillomavirus (H-HPV) infection is strongly linked to cervical neoplasia, but its role in detecting glandular lesions (GLs) is unclear. In the cervix, carbonic anhydrase IX (CA-IX) is expressed in cervical neoplasia, but rarely in the benign cervix. The diagnostic utility of these biomarkers was evaluated in women with a cytologic diagnosis of atypical glandular cells (AGC). H-HPV was detected using hybrid capture 2 (HC2) in liquid-based cytology, and CA-IX immunoreactivity was studied on conventional Pap smears. Of 403 patients, 111 (28%) were positive for significant cervical lesions (SCLs) including CIN2, CIN3, adenocarcinoma in situ or invasive carcinoma. CA-IX testing alone (n = 403) had a sensitivity of 75, 95 or 65% for SCLs, significant GLs or squamous lesions (SLs), respectively, with a specificity of 88% and a false negative rate (FNR defined as 1 minus negative predictive value) of 10%. Testing for H-HPV (n = 122) had a sensitivity of 97, 100 or 96% for SCLs, GLs or SLs, respectively, with a specificity of 87% and a FNR of 1%. The combination of CA-IX and H-HPV testing (n = 122), collectively, had the same sensitivity, specificity and FNR for SCLs, GLs or SLs as H-HPV testing alone. The conclusions of our study are that both H-HPV and CA-IX testing are useful diagnostic markers for GLs. However, H-HPV testing is a better diagnostic marker for SLs. The combination of CA-IX with H-HPV testing does not improve the diagnostic accuracy for cervical neoplasia in women with AGC diagnosis over that of H-HPV testing alone.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / diagnosis
  • Adenocarcinoma / enzymology
  • Adenocarcinoma / virology
  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / metabolism*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases / metabolism*
  • Carcinoma, Squamous Cell / diagnosis
  • Carcinoma, Squamous Cell / enzymology
  • Carcinoma, Squamous Cell / virology
  • Cervical Intraepithelial Neoplasia / diagnosis*
  • Cervical Intraepithelial Neoplasia / enzymology
  • Cervical Intraepithelial Neoplasia / virology
  • Cytodiagnosis
  • DNA, Viral / genetics
  • Female
  • Genotype
  • Humans
  • Immunoenzyme Techniques
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Neoplasms, Glandular and Epithelial / diagnosis*
  • Neoplasms, Glandular and Epithelial / enzymology
  • Neoplasms, Glandular and Epithelial / virology
  • Papanicolaou Test
  • Papillomaviridae / genetics
  • Papillomaviridae / isolation & purification*
  • Papillomavirus Infections / diagnosis*
  • Papillomavirus Infections / enzymology
  • Papillomavirus Infections / virology
  • Polymerase Chain Reaction
  • Retrospective Studies
  • Risk Factors
  • Sensitivity and Specificity
  • Uterine Cervical Neoplasms / diagnosis*
  • Uterine Cervical Neoplasms / enzymology
  • Uterine Cervical Neoplasms / virology
  • Vaginal Smears
  • Young Adult

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • DNA, Viral
  • CA9 protein, human
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases