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

S. Y. Liao, W. H. Rodgers, J. Kauderer, T. A. Bonfiglio, K. M. Darcy, R. Carter, L. Levine, N. M. Spirtos, N. Susumu, K. Fujiwara, J. L. Walker, M. Hatae, E. J. Stanbridge

Research output: Contribution to journalArticle

10 Citations (Scopus)

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). Conclusion: 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.

Original languageEnglish
Pages (from-to)353-360
Number of pages8
JournalBritish Journal of Cancer
Volume104
Issue number2
DOIs
Publication statusPublished - 2011 Jan 18

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Uterine Cervical Dysplasia
Biomarkers
Neoplasms
Hyperplasia
Papanicolaou Test
Cervical Intraepithelial Neoplasia
Papillomavirus Infections
Carbonic Anhydrase IX
Cell Biology
Carcinoma
Polymerase Chain Reaction

Keywords

  • AGC diagnosis
  • CA-IX
  • cervix
  • H-HPV

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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. / Liao, S. Y.; Rodgers, W. H.; Kauderer, J.; Bonfiglio, T. A.; Darcy, K. M.; Carter, R.; Levine, L.; Spirtos, N. M.; Susumu, N.; Fujiwara, K.; Walker, J. L.; Hatae, M.; Stanbridge, E. J.

In: British Journal of Cancer, Vol. 104, No. 2, 18.01.2011, p. 353-360.

Research output: Contribution to journalArticle

Liao, S. Y. ; Rodgers, W. H. ; Kauderer, J. ; Bonfiglio, T. A. ; Darcy, K. M. ; Carter, R. ; Levine, L. ; Spirtos, N. M. ; Susumu, N. ; Fujiwara, K. ; Walker, J. L. ; Hatae, M. ; Stanbridge, E. J. / 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. In: British Journal of Cancer. 2011 ; Vol. 104, No. 2. pp. 353-360.
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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). Conclusion: 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.",
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T1 - 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)

T2 - A Gynecologic Oncology Group (GOG) Study

AU - Liao, S. Y.

AU - Rodgers, W. H.

AU - Kauderer, J.

AU - Bonfiglio, T. A.

AU - Darcy, K. M.

AU - Carter, R.

AU - Levine, L.

AU - Spirtos, N. M.

AU - Susumu, N.

AU - Fujiwara, K.

AU - Walker, J. L.

AU - Hatae, M.

AU - Stanbridge, E. J.

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N2 - 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). Conclusion: 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.

AB - 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). Conclusion: 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.

KW - AGC diagnosis

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