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.
@article{793d2167f92a4e79a48271550a63d767,
title = "Serum immune profiling for early detection of cervical disease",
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.",
keywords = "Antibodies, Cervical cancer, Cervical intraepithelial neoplasia, Early detection, HPV, NAPPA, protein microarrays, Serology",
author = "Radwa Ewaisha and Gitika Panicker and Paul Maranian and Unger, {Elizabeth R.} and Karen Anderson",
year = "2017",
doi = "10.7150/thno.21098",
language = "English (US)",
volume = "7",
pages = "3814--3823",
journal = "Theranostics",
issn = "1838-7640",
publisher = "Ivyspring International Publisher",
number = "16",

}

TY - JOUR

T1 - Serum immune profiling for early detection of cervical disease

AU - Ewaisha, Radwa

AU - Panicker, Gitika

AU - Maranian, Paul

AU - Unger, Elizabeth R.

AU - Anderson, Karen

PY - 2017

Y1 - 2017

N2 - 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.

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.

KW - Antibodies

KW - Cervical cancer

KW - Cervical intraepithelial neoplasia

KW - Early detection

KW - HPV

KW - NAPPA

KW - protein microarrays

KW - Serology

UR - http://www.scopus.com/inward/record.url?scp=85030632746&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85030632746&partnerID=8YFLogxK

U2 - 10.7150/thno.21098

DO - 10.7150/thno.21098

M3 - Article

VL - 7

SP - 3814

EP - 3823

JO - Theranostics

JF - Theranostics

SN - 1838-7640

IS - 16

ER -