Theranostics 2017; 7(16):3814-3823. doi:10.7150/thno.21098

Research Paper

Serum Immune Profiling for Early Detection of Cervical Disease

Radwa Ewaisha1, Gitika Panicker2, Paul Maranian1, Elizabeth R. Unger2, Karen S. Anderson1✉

1. Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ.
2. Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, GA.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license ( See for full terms and conditions.
Ewaisha R, Panicker G, Maranian P, Unger ER, Anderson KS. Serum Immune Profiling for Early Detection of Cervical Disease. Theranostics 2017; 7(16):3814-3823. doi:10.7150/thno.21098. Available from

File import instruction


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, HPV, cervical cancer, cervical intraepithelial neoplasia, NAPPA, protein microarrays, serology, early detection