Host chemokine signature as a biomarker for the detection of pre-cancerous cervical lesions
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Ramya Bhatia1, Kim Kavanagh2, June Stewart3, Sharon Moncur3, Itziar Serrano4, Duanduan Cong3, Heather A. Cubie5, Juergen G. Haas4, Camille Busby-Earle6, Alistair R.W. Williams6, Sarah E.M. Howie3,* and Kate Cuschieri7,*
1Human Papillomavirus Research Group, Division of Pathology, University of Edinburgh, Edinburgh, United Kingdom
2Department of Mathematics and Statistics, Strathclyde University, Glasgow, United Kingdom
3Centre for Inflammation research, University of Edinburgh, Edinburgh, United Kingdom
4Division of Infection and Pathway Medicine, University of Edinburgh, Edinburgh, United Kingdom
5Global Health Academy, University of Edinburgh, Edinburgh, United Kingdom
6Simpson Centre for Reproductive Health, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom
7Scottish HPV Reference Laboratory, NHS Lothian, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom
*These authors contributed equally to this work
Ramya Bhatia, email: [email protected]
Keywords: chemokines; HPV; cervical screening; triage; biomarkers
Received: February 15, 2018 Accepted: March 12, 2018 Published: April 06, 2018
Background: The ability to distinguish which hrHPV infections predispose to significant disease is ever more pressing as a result of the increasing move to hrHPV testing for primary cervical screening. A risk-stratifier or “triage” of infection should ideally be objective and suitable for automation given the scale of screening.
Results: CCL2, CCL3, CCL4, CXCL1, CXCL8 and CXCL12 emerged as the strongest, candidate biomarkers to detect underlying disease [cervical intraepithelial neoplasia grade 2 or worse (CIN2+)]. For CIN2+, CCL2 had the highest area under the curve (AUC) of 0.722 with a specificity of 82%. A combined biomarker panel of six chemokines CCL2, CCL3, CCL4, CXCL1, CXCL8, and CXCL12 provides a sensitivity of 71% and specificity of 67%.
Conclusion: The present work demonstrates that the levels of five chemokine-proteins are indicative of underlying disease. We demonstrate technical feasibility and promising clinical performance of a chemokine-based biomarker panel, equivalent to that of other triage options. Further assessment in longitudinal series is now warranted.
Methods: A panel of 31 chemokines were investigated for expression in routinely taken archived and prospective cervical liquid based cytology (LBC) samples using Human Chemokine Proteomic Array kit. Nine chemokines were further validated using Procartaplex assay on the Luminex platform.
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