OC 12-16NOVEL DNA HYPERMETHYLATION MARKERS ARE FEASIBLE IN BOTH CERVICOVAGINAL LAVAGES AND CERVICAL SCRAPINGS

08. Screening methods
R.W. Van Leeuwen 1, A.G.J. Van Der Zee 1, J.J.H. Eijsink 2, E. Schuuring 3, G.B.A. Wisman 3.
1Department of Gynaecologic Oncology, Cancer Research Centre Groningen, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands (Netherlands), 2Department of Obstetrics & Gynaecology, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands (Netherlands), 3Department of Pathology, Cancer Research Centre Groningen, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands (Netherlands)

Background / Objectives

In 2017, the Dutch population-based screening program for the early detection of cervical cancer will be based on primary human papillomavirus (hrHPV) screening. However, the specificity of hrHPV testing, especially in a young screening population is relatively low, which may lead to unnecessary referrals to the gynaecologist, anxiety in the false-positive women, and higher costs for the health-care system. We have identified and validated a set of six new DNA methylation assays for early detection of cervical neoplasia in the hrHPV-positive subpopulation. In the new primary HPV screening program, it is expected that a significant number of women who did not participate in the current cervical cancer screening program will attend upon receiving a self-collection device. Here we assessed whether DNA hypermethylation analysis is feasible in self-collected specimens.


Methods

Using quantitative methylation-specific PCR (QMSP) six markers (ANKRD18CP, GFRA1, KCNIP4, SOX1, SOX14, ZSCAN1) were analysed on DNA extracted from 41 sample pairs (CIN0/1 n=7, CIN2 or worse (CIN2+) n=34) that were simultaneously collected by Delphi screener and routine collection. Concordance in test classification was determined with Cohen’s kappa and Spearman’s rho. Comparisons between receiver-operator characteristics (ROC) were analysed using DeLong’s test. Data on four additional methylation markers (C13orf18, EPB41L3, JAM3 and TERT), liquid-based cytology and Hybrid Capture II hrHPV testing was also available.


Results

Between sampling types, all methylation markers showed significant concordance (each κ ≥ .50, each p’ < .01) and a significant correlation (each ρ ≥ .74, each p’ < 10-6). No differences were observed between paired ROCs (each p’ > .1). Of all tests performed, ZSCAN1 and EPB41L3 showed the highest diagnostic potential to detect CIN2+ with an area under the ROC (AUC) of .97 and .91 in clinician-collected smears and .93 and .84 in lavages, respectively.


Conclusion

Analysis of these methylation markers is feasible in cervicovaginal lavages. This research further encourages the introduction of methylation analysis to detect cervical neoplasia in the new population-based screening program irrespective of sampling type.


References