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

Bhatia, Ramya and Kavanagh, Kim and Stewart, June and Moncur, Sharon and Serrano, Itziar and Cong, Duanduan and Cubie, Heather A. and Haas, Juergen G. and Busby-Earle, Camille and Williams, Alistair R.W. and Howie, Sarah E.M. and Cuschieri, Kate (2018) Host chemokine signature as a biomarker for the detection of pre-cancerous cervical lesions. Oncotarget, 9 (26). 18548–18558. ISSN 1949-2553 (

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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.