FC 12-05Diagnostic value of methylation markers in cervical cancer screening

16. Methylation
N. Li 1, A. Boers 1, G. De Bock 2, Y. Hu 3, A.G. Van Der Zee 1, E. Schuuring 4, G.B. Wisman 1.
1Gynecology Oncology, University of Groningen, University Medical Centre Groningen, Cancer Research Centre Groningen, Groningen, The Netherlands (Netherlands), 2Epdemiology, University of Groningen, University Medical Centre Groningen, Cancer Research Centre Groningen, Groningen, The Netherlands (Netherlands), 3Epdemiology, University of Groningen, University Medical Centre Groningen, Cancer Research Centre Groningen, Groningen, The Netherlands (China), 4Pathology, University of Groningen, University Medical Centre Groningen, Cancer Research Centre Groningen, Groningen, The Netherlands (Netherlands)

Background / Objectives

DNA methylation analysis has been assessed as a potential biomarker for early cervical cancer detection. In this review, we summarize the studies analyzing the diagnostic potential of methylation markers in cervical scrapings by Quantitative Methylation Specific PCR(QMSP).


Methods

All studies, until February 1 2017, were systematically searched from three electronic databases (Pubmed/Medline, Embase and Cochrane). Studies on cervical scrapings that used (Q)MSP for methylation analysis and histology as the golden standard were retrieved. Sensitivity and specificity of methylation markers were extracted to assess the diagnostic values of methylation markers. Data were stratified for studies using methylation markers analysis as primary test versus those as triage test after primary HPV screening.


Results

In total 699 studies were retrieved, of which 68 studies describing 89 genes fulfilled our criteria. Preliminary analysis revealed 21 methylation markers as primary test comparing normal/low-grade squamous intraepithelial lesions (LSIL) versus high-grade (H)SIL and cancer. Six genes (including EPB41L3 and JAM3) were identified with relatively high sensitivity (49%-100%) and specificity (67%-100%) to detect HSIL. Eight genes (including EPB41L3 and JAM3) showed high sensitivity (70%-100%) and specificity (78%-100%) for detecting cancer. Methylation analysis as triage test in HPV positive women resulted in 19 genes, of which 11 genes (including  EPB41L3 and JAM3) showed combined high sensitivity (53%-100%) and specificity (71%-100%) for HSIL or worse, which was comparable or higher than other triage strategies.


Conclusion

The preliminary results of this review reveal that multiple methylation markers have been analyzed in either primary or triage test. Especially, triaging hrHPV positive women by methylation analysis is interesting for implementation in population-based screening where sensitivity can be even improved by combining markers without losing specificity. However, to confirm the relevance of selected methylation markers, further validation needs to be performed in large population-based settings.


References