P12-09AN MRNA PANEL FOR TRIAGE OF HPV POSITIVE WOMEN WITH HIGH SPECIFICITY FOR DETECTION OF CLINICALLY RELEVANT CERVICAL DISEASE

12. Molecular markers
R. Bhatia 1, S. Moncur 2, J. Stewart 2, K. Cuschieri 3, J. Haas 4, C. Busby-Earle 5, A. Williams 5, S. Howie 2.
1Human Papillomavirus Research Group, Division of Pathology, University of Edinburgh, Edinburgh (United Kingdom), 2Centre for Inflammation research, University of Edinburgh, Edinburgh, (United Kingdom), 3Scottish HPV Reference Laboratory, NHS Lothian, Royal Infirmary of Edinburgh, Edinburgh (United Kingdom), 4Division of Infection and Pathway Medicine, University of Edinburgh, Edinburgh (United Kingdom), 5Simpson Centre for Reproductive Health, Royal Infirmary of Edinburgh, Edinburgh (United Kingdom)

Background / Objectives

HR-HPV based primary cervical screening modalities are 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 mRNA levels of chemokines in liquid based cytology samples for use as biomarkers for the risk stratification of HR-HPV positive women.


Methods

A panel of cervical liquid based cytology samples derived from both screening and colposcopy populations were tested for HR-HPV using the rT-HPV Test (Abbott, USA) and mRNA expression levels of eight chemokines CCL2, CCL3, CCL4, CCL11, CXCL1, CXCL8, CXCL10 and CXCL12  through singleplex TaqMan RT-PCR. A case-control analysis comparing samples from HR-HPV positive women with CIN2+ (n=48) to women with no disease (defined as normal colposcopy or histology <= CIN1, n=80) was performed with ROC curve analysis in order to determine initial clinical performance of the chemokine markers. 


Results

Significant differences (p≤0.05) were seen in expression of CCL2 and CCL5 between women with and without significant disease. AUC of CCL2 is 0.61 (95% CI- 0.51- 0.71) and CCL5 is 0.60 (95% CI– 0.49- 0.71). 


Conclusion

Our initial data show that assessment of chemokine mRNA levels for the detection of HPV associated significant disease has promise. Future work will be aimed at further development and optimisation including the generation of a multiplex real-time PCR which will incorporate the most informative targets.


References