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

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    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 (US)
    Pages (from-to)353-360
    Number of pages8
    JournalBritish Journal of Cancer
    Volume104
    Issue number2
    DOIs
    StatePublished - Jan 18 2011

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

    PY - 2011/1/18

    Y1 - 2011/1/18

    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

    KW - CA-IX

    KW - cervix

    KW - H-HPV

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