Serum immune profiling for early detection of cervical disease

Radwa Ewaisha, Gitika Panicker, Paul Maranian, Elizabeth R. Unger, Karen Anderson

    Research output: Contribution to journalArticle

    5 Citations (Scopus)

    Abstract

    Background: The most recent (2012) worldwide estimates from International Agency for Research on Cancer indicate that approximately 528,000 new cases and 270,000 deaths per year are attributed to cervical cancer worldwide. The disease is preventable with HPV vaccination and with early detection and treatment of pre-invasive cervical intraepithelial neoplasia, CIN. Antibodies (Abs) to HPV proteins are under investigation as potential biomarkers for early detection. Methods: To detect circulating HPV-specific IgG Abs, we developed programmable protein arrays (NAPPA) that display the proteomes of two low-risk HPV types (HPV6 and 11) and ten oncogenic high-risk HPV types (HPV16, 18, 31, 33, 35, 39, 45, 51, 52 and 58). Arrays were probed with sera from women with CIN 0/I (n=78), CIN II/III (n=84), or invasive cervical cancer (ICC, n=83). Results: Abs to any early (E) HPV protein were detected less frequently in women with CIN 0/I (23.7%) than women with CIN II/III (39.0%) and ICC (46.1%, p<0.04). Of the E Abs, anti-E7 Abs were the most frequently detected (6.6%, 19.5%, and 30.3%, respectively). The least frequently detected Abs were E1 and E2-Abs in CIN 0/I (1.3%) and E1-Abs in CIN II/III (1.2%) and ICC (7.9%). HPV16-specific Abs correlated with HPV16 DNA detected in the cervix in 0% of CIN 0/I, 21.2% of CIN II/III, and 45.5% of ICC. A significant number (29 - 73%) of E4, E7, L1, and L2 Abs had cross-reactivity between HPV types. Conclusion: HPV protein arrays provide a valuable high-throughput tool for measuring the breadth, specificity, and heterogeneity of the serologic response to HPV in cervical disease.

    Original languageEnglish (US)
    Pages (from-to)3814-3823
    Number of pages10
    JournalTheranostics
    Volume7
    Issue number16
    DOIs
    StatePublished - 2017

    Fingerprint

    Immune Sera
    Early Diagnosis
    Antibodies
    Protein Array Analysis
    Uterine Cervical Neoplasms
    Human papillomavirus 11
    International Agencies
    Human papillomavirus 18
    Cervical Intraepithelial Neoplasia
    Proteome
    Cervix Uteri
    Anti-Idiotypic Antibodies
    Vaccination
    Proteins
    Immunoglobulin G
    Biomarkers
    DNA
    Serum
    Research
    Neoplasms

    Keywords

    • Antibodies
    • Cervical cancer
    • Cervical intraepithelial neoplasia
    • Early detection
    • HPV
    • NAPPA
    • protein microarrays
    • Serology

    ASJC Scopus subject areas

    • Medicine (miscellaneous)
    • Pharmacology, Toxicology and Pharmaceutics (miscellaneous)

    Cite this

    Ewaisha, R., Panicker, G., Maranian, P., Unger, E. R., & Anderson, K. (2017). Serum immune profiling for early detection of cervical disease. Theranostics, 7(16), 3814-3823. https://doi.org/10.7150/thno.21098

    Serum immune profiling for early detection of cervical disease. / Ewaisha, Radwa; Panicker, Gitika; Maranian, Paul; Unger, Elizabeth R.; Anderson, Karen.

    In: Theranostics, Vol. 7, No. 16, 2017, p. 3814-3823.

    Research output: Contribution to journalArticle

    Ewaisha, R, Panicker, G, Maranian, P, Unger, ER & Anderson, K 2017, 'Serum immune profiling for early detection of cervical disease' Theranostics, vol. 7, no. 16, pp. 3814-3823. https://doi.org/10.7150/thno.21098
    Ewaisha, Radwa ; Panicker, Gitika ; Maranian, Paul ; Unger, Elizabeth R. ; Anderson, Karen. / Serum immune profiling for early detection of cervical disease. In: Theranostics. 2017 ; Vol. 7, No. 16. pp. 3814-3823.
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    AB - Background: The most recent (2012) worldwide estimates from International Agency for Research on Cancer indicate that approximately 528,000 new cases and 270,000 deaths per year are attributed to cervical cancer worldwide. The disease is preventable with HPV vaccination and with early detection and treatment of pre-invasive cervical intraepithelial neoplasia, CIN. Antibodies (Abs) to HPV proteins are under investigation as potential biomarkers for early detection. Methods: To detect circulating HPV-specific IgG Abs, we developed programmable protein arrays (NAPPA) that display the proteomes of two low-risk HPV types (HPV6 and 11) and ten oncogenic high-risk HPV types (HPV16, 18, 31, 33, 35, 39, 45, 51, 52 and 58). Arrays were probed with sera from women with CIN 0/I (n=78), CIN II/III (n=84), or invasive cervical cancer (ICC, n=83). Results: Abs to any early (E) HPV protein were detected less frequently in women with CIN 0/I (23.7%) than women with CIN II/III (39.0%) and ICC (46.1%, p<0.04). Of the E Abs, anti-E7 Abs were the most frequently detected (6.6%, 19.5%, and 30.3%, respectively). The least frequently detected Abs were E1 and E2-Abs in CIN 0/I (1.3%) and E1-Abs in CIN II/III (1.2%) and ICC (7.9%). HPV16-specific Abs correlated with HPV16 DNA detected in the cervix in 0% of CIN 0/I, 21.2% of CIN II/III, and 45.5% of ICC. A significant number (29 - 73%) of E4, E7, L1, and L2 Abs had cross-reactivity between HPV types. Conclusion: HPV protein arrays provide a valuable high-throughput tool for measuring the breadth, specificity, and heterogeneity of the serologic response to HPV in cervical disease.

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