Bhatia, Ramya

Busby-Earle, Camille

Cuschieri, Kate

Howie, Sarah

Kavanagh, Kimberley

Moncur, Sharon

Stewart, June

Williams, Alistair

English

Edinburgh Research Explorer

     Edinburgh Research Explorer                                      A novel biomarker panel for triage of HPV positive women withhigh specificity for detection of clinically relevant cervicaldisease.Citation for published version:Bhatia, R, Stewart, J, Moncur, S, Cuschieri, K, Busby-Earle, C, Williams, A, Kavanagh, K & Howie, S 2017,'A novel biomarker panel for triage of HPV positive women with high specificity for detection of clinicallyrelevant cervical disease.', International Papillomavirus Conference 2017, Cape Town, South Africa,28/02/17 - 4/03/17.Link:Link to publication record in Edinburgh Research ExplorerDocument Version:Peer reviewed versionGeneral rightsCopyright for the publications made accessible via the Edinburgh Research Explorer is retained by the author(s)and / or other copyright owners and it is a condition of accessing these publications that users recognise andabide by the legal requirements associated with these rights.Take down policyThe University of Edinburgh has made every reasonable effort to ensure that Edinburgh Research Explorercontent complies with UK legislation. If you believe that the public display of this file breaches copyright pleasecontact openaccess@ed.ac.uk providing details, and we will remove access to the work immediately andinvestigate your claim.Download date: 23. Jul. 2021A novel biomarker panel for triage of HPV positive women with high specificity for detection of clinically relevant cervical diseaseIntroductionHR-HPV based primary cervical screening is now being implemented in several countries. Robust objective triage strategies for management of HR-HPV positive women are needed. The objective of this study was to identify proteins involved in innate immunity at epithelial surfaces which could be used as biomarkers to risk stratify HR-HPV positive women.SHINeRamya Bhatia1, June Stewart2, Sharon Moncur2, Kate Cuschieri3, Camille Busby-Earle4, Alistair Williams4, Kim Kavanagh5, and Sarah Howie2.1. HPV Research Group, University of Edinburgh, UK, 2. Centre for Inflammation research, University of Edinburgh, UK, 3. Scottish HPV Reference Laboratory, Royal Infirmary of Edinburgh, UK, 4. Simpson Centre for Reproductive Health, Royal Infirmary of Edinburgh, UK, 5. Department of Mathematics and Statistics, Strathclyde University, UK. MethodsResultsSamples- Liquid based cytology (LBC) sampleswere obtained from both screening and colposcopypopulations from the Scottish HPV archive.HPV typing was done using the Abbott rtHPV test.Protein extraction was done using chloroformisopropanol method (Canham et al, 2014).Chemokine levels were measured usingProcartaPlex kit (Affymetrix eBioscience, UK)according to manufacturer’s guidelines.Figure 1. Differences in chemokine proteinsbetween CIN3 and all other groups. Pooledprotein extracts from LBC samples (10mg ofprotein from each of 9 women) from women withdifferent grades of disease and normal controlswere analysed using chemokine proteomic array(R&D Systems, UK). Left- Each chemokine isprinted in duplicate in the array. Patients withCIN3 showed a very different pattern ofchemokine expression from any other group.Right– Expression level of chemokines in HR-HPV positive CIN3 relative to +ve control dots.0510152025Cytology normal/CIN1 n=459CIN2+n=268***CCL20510152025Cytology normal/CIN1 n=459CIN2+n=268***CCL3Cytology normal/CIN1 n=459CIN2+n=268CCL4050100150200250 ***0250500750Cytology normal/CIN1 n=459CIN2+n=268***CXCL1050010001500200025003000350040004500Cytology normal/CIN1 n=459CIN2+n=268***CXCL8050100150200250300350Cytology normal/CIN1 N=459CIN2+n=268***CXCL12Protein (pg/200 ug)Protein (pg/200 ug)Figure 2. Six chemokines are upregulated in HR-HPV positive women with CIN2+. Results of a casecontrol study of LBC samples from HR-HPV positivewomen with CIN2+ (cases, n-=268) and cytologynormal or CIN1 (controls, n=459) using ProcartaPlexkit. Left- Barcharts indicating levels of protein, *** =p<0.001 (Kruskal-Wallis test with Dunn’s multiplecomparison post-test). Right– Multivariate analysisof different predictive models to assess sensitivity(Sens), Specificity (Spec), Positive Predictive Value(PPV) and Negative Predictive Value (NPV) fordetection of CIN2+.CXCL10CXCL5CCL2GP130CXCL9CHEMERINTRANSFERRIN RCXCL12CCL28CXCL11CXCL8CXCL7IL16CXCL4CXCL1CCL22MIDKINECCL19CCL26CCL17CCL21CCL18LYMPHOTACTINCCL1CCL3, CCL4CCL70 5000 10000 15000 20000HPV+ve CIN3CCL5Sens Spec PPV NPVCXCL1 55.5% 75.6% 68.8% 63.7%CCL2 and CXCL1 65.5% 72.4% 69.6% 68.5%CXCL1 and CXCL8 62.2% 76.4% 71.8% 67.6%CCL2, CXCL1 and CXCL8 71.4% 65.0% 66.4% 70.2%CCL2, CCL3, CCL4, CXCL1, CXCL8, CXCL12 67.2% 72.4% 70.2% 69.5%OutcomeA panel of chemokines has been identified which could serve as an objective biomarker for HPV infection associated with CIN2+. This has potential as a triage strategy for HPV primary screening. References: Canham M, Charsou C, Stewart J, Moncur S, Hoodless L, Bhatia R, Cong D, Cubie H, Busby-Earle C, Williams A, McLoughlin V, Campbell JD, Cuschieri K, Howie S. Increased cycling cell numbers and stem cell associated proteins as potential biomarkers for high grade human papillomavirus+ve pre-neoplastic cervical disease. PLoS One. 2014 Dec 22;9(12):e115379. doi: 10.1371/journal.pone.0115379. 

A novel biomarker panel for triage of HPV positive women with high specificity for detection of clinically relevant cervical disease.

https://www.research.ed.ac.uk/files/34169372/A_novel_biomarker_panel_for_triage_of_HPV_positive_women_with_high_specificity_for_detection_of_clinically_relevant_cervical_disease.pdf

A novel biomarker panel for triage of HPV positive women with high specificity for detection of clinically relevant cervical disease.

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