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

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

Research output: Contribution to journalArticle

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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.
Original languageEnglish
Pages (from-to)18548–18558
Number of pages11
JournalOncotarget
Volume9
Issue number26
DOIs
Publication statusPublished - 6 Apr 2018

Keywords

  • chemokines
  • HPV
  • cervical screening
  • triage
  • biomarkers

Cite this

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