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. 2018 Dec 3;18(1):1197.
doi: 10.1186/s12885-018-5125-8.

Performance of a DNA methylation marker panel using liquid-based cervical scrapes to detect cervical cancer and its precancerous stages

Martina Schmitz  1 , Kristin Eichelkraut  2 , Dana Schmidt  2 , Ilona Zeiser  3 , Ziad Hilal  4 , Zena Tettenborn  4 , Alfred Hansel  2 , Hans Ikenberg  3
Affiliations

Performance of a DNA methylation marker panel using liquid-based cervical scrapes to detect cervical cancer and its precancerous stages

Martina Schmitz et al. BMC Cancer. .

Abstract

Background: A change of cervical cancer screening algorithms to an HPV-based screening setting is discussed in many countries, due to higher sensitivity of HPV testing compared to cytology. Reliable triage methods are, however, an essential prerequisite in such a setting to avoid overtreatment and higher screening costs.

Results: In this study, a series of cervical scrapes collected in PreservCyt liquid-based cytology (LBC) medium from women with cervical cancer (n = 5), cervical intraepithelial neoplasia grade 1-3 (n = 74), and normal cytology (n = 201; further n = 352 collected in SureThin®) were assessed for methylation of the marker regions ASTN1, DLX1, ITGA4, RXFP3, SOX17, and ZNF671 using the GynTect assay and compared to cobas® HPV and CINtec Plus® biomarker results. All samples from women with cervical cancer, 61.2% of CIN3, 44.4% of CIN2 and 20.0% of CIN1 cases were scored positive for the GynTect methylation assay. In contrast, all CIN, irrespective of severity grade, and carcinomas were positive by both, CINtec Plus and cobas HPV. The specificity of GynTect for CIN3+ was 94.6% compared to 69.9% for CINtec Plus and 82.6% for cobas HPV (all HPV types) and 90.6% for cobas HPV 16/18. DNA methylation analysis of this methylation marker panel (GynTect assay) in cervical scrapes consistently detects cervical cancer and the majority of CIN3 as well as a subset of CIN1/2 lesions. The detection rate among cytologically normal samples is extraordinarily low (1.5%).

Conclusion: GynTect shows excellent performance when using cervical scrape material collected in liquid-based cytology media, a prerequisite for employing such a test as a triage in screening programs. Compared to the other test systems used in this work, GynTect showed higher specificity while still detecting all cancer cases.

Keywords: Biomarkers; Cervical cancer; DNA methylation; Epigenetic markers; Human papillomavirus (HPV).

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Conflict of interest statement

Ethics approval and consent to participate

This study was designed as a quality development study, utilizing only residual material that otherwise would have been discarded. All patient samples were surplus samples and completely anonymized prior to use in the study. The study was performed following the guideline of the Declaration of Helsinki. According to German law an ethical approval is not required if using completely anonymized surplus samples in such a retrospective study setting.

Consent for publication

Not applicable.

Competing interests

MS, AH, KE and DS are shareholders and/or employees of oncgnostics GmbH, a company that aims to commercialize DNA methylation markers.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
GynTect score for a) all positively tested samples and b) for the total number of samples tested with GynTect
Fig. 2
Fig. 2
Performance of the different test systems
See this image and copyright information in PMC

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