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

Shu Yuan Liao, William H. Rodgers, James Kauderer, Thomas A. Bonfiglio, Joan L. Walker, Kathleen M. Darcy, Randy Carter, Masayuji Hatae, Lyuba Levine, Nick M. Spirtos, Eric J. Stanbridge

    Research output: Contribution to journalArticle

    17 Citations (Scopus)

    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.

    Original languageEnglish (US)
    Pages (from-to)2434-2440
    Number of pages7
    JournalInternational Journal of Cancer
    Volume125
    Issue number10
    DOIs
    StatePublished - Nov 15 2009

    Fingerprint

    Uterine Cervical Dysplasia
    Biomarkers
    Neoplasms
    Cervix Uteri
    human CA9 protein
    Papanicolaou Test
    Papillomavirus Infections
    Cell Biology
    Carbonic Anhydrase IX
    Carcinoma
    Sensitivity and Specificity

    Keywords

    • AGC diagnosis
    • CA-IX
    • Cervix
    • HPV

    ASJC Scopus subject areas

    • Cancer Research
    • Oncology

    Cite this

    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. / Liao, Shu Yuan; Rodgers, William H.; Kauderer, James; Bonfiglio, Thomas A.; Walker, Joan L.; Darcy, Kathleen M.; Carter, Randy; Hatae, Masayuji; Levine, Lyuba; Spirtos, Nick M.; Stanbridge, Eric J.

    In: International Journal of Cancer, Vol. 125, No. 10, 15.11.2009, p. 2434-2440.

    Research output: Contribution to journalArticle

    Liao, Shu Yuan ; Rodgers, William H. ; Kauderer, James ; Bonfiglio, Thomas A. ; Walker, Joan L. ; Darcy, Kathleen M. ; Carter, Randy ; Hatae, Masayuji ; Levine, Lyuba ; Spirtos, Nick M. ; Stanbridge, Eric J. / 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. In: International Journal of Cancer. 2009 ; Vol. 125, No. 10. pp. 2434-2440.
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    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.",
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    AU - Rodgers, William H.

    AU - Kauderer, James

    AU - Bonfiglio, Thomas A.

    AU - Walker, Joan L.

    AU - Darcy, Kathleen M.

    AU - Carter, Randy

    AU - Hatae, Masayuji

    AU - Levine, Lyuba

    AU - Spirtos, Nick M.

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