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Bhatia R, Kavanagh K, Stewart J, et al. Host chemokine signature as a biomarker for the detection of pre-cancerous cervical lesions. Oncotarget. 2018;9(26):18548-18558doi: 10.18632/oncotarget.24946.
Bhatia, R., Kavanagh, K., Stewart, J., Moncur, S., Serrano, I., Cong, D., Cubie, H. A., Haas, J. G., Busby-Earle, C., Williams, A. R. W., Howie, S. E. M., & Cuschieri, K. (2018). Host chemokine signature as a biomarker for the detection of pre-cancerous cervical lesions. Oncotarget, 9(26), 18548-18558. https://doi.org/10.18632/oncotarget.24946
Bhatia, Ramya, et al. "Host chemokine signature as a biomarker for the detection of pre-cancerous cervical lesions." Oncotarget vol. 9,26 (2018): 18548-18558. doi: https://doi.org/10.18632/oncotarget.24946
Bhatia R, Kavanagh K, Stewart J, Moncur S, Serrano I, Cong D, Cubie HA, Haas JG, Busby-Earle C, Williams ARW, Howie SEM, Cuschieri K. Host chemokine signature as a biomarker for the detection of pre-cancerous cervical lesions. Oncotarget. 2018 Apr 06;9(26):18548-18558. doi: 10.18632/oncotarget.24946. eCollection 2018 Apr 06. PMID: 29719625; PMCID: PMC5915092.
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Oncotarget. 2018 Apr 06;9(26):18548-18558. doi: 10.18632/oncotarget.24946. eCollection 2018 Apr 06.

Host chemokine signature as a biomarker for the detection of pre-cancerous cervical lesions.

Oncotarget

Ramya Bhatia, Kim Kavanagh, June Stewart, Sharon Moncur, Itziar Serrano, Duanduan Cong, Heather A Cubie, Juergen G Haas, Camille Busby-Earle, Alistair R W Williams, Sarah E M Howie, Kate Cuschieri

Affiliations

  1. Human Papillomavirus Research Group, Division of Pathology, University of Edinburgh, Edinburgh, United Kingdom.
  2. Department of Mathematics and Statistics, Strathclyde University, Glasgow, United Kingdom.
  3. Centre for Inflammation research, University of Edinburgh, Edinburgh, United Kingdom.
  4. Division of Infection and Pathway Medicine, University of Edinburgh, Edinburgh, United Kingdom.
  5. Global Health Academy, University of Edinburgh, Edinburgh, United Kingdom.
  6. Simpson Centre for Reproductive Health, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom.
  7. Scottish HPV Reference Laboratory, NHS Lothian, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom.

PMID: 29719625 PMCID: PMC5915092 DOI: 10.18632/oncotarget.24946

Abstract

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.

Keywords: HPV; biomarkers; cervical screening; chemokines; triage

Conflict of interest statement

CONFLICTS OF INTEREST None.

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