Abstract
BackgroundA 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.ResultsIn 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%).ConclusionGynTect 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.
Highlights
A change of cervical cancer screening algorithms to an Human papillomavirus (HPV)-based screening setting is discussed in many countries, due to higher sensitivity of HPV testing compared to cytology
The real-time methylation specific PCR (qMSP) were run on a 7500 Real-Time Polymerase chain reaction (PCR) system (Life technologies; Thermo Scientific, USA) analysing the 6 methylation markers Astrotactin 1 (ASTN1), Distal-less homeobox 1 (DLX1), Integrin subunit alpha 4 (ITGA4), Relaxin/insulin like family peptide receptor 3 (RXFP3), SRY-box 17 (SOX17), and Zinc finger protein 671 (ZNF671), and two controls for each sample, a DNA quality control (ACHE) and a methylation control (IDS), each in a separate tube
In previous studies we have shown that hypermethylation of CpG islands in proximity to the genes DLX1, ITGA4, RXFP3, SOX17, and ZNF671 correlated with the presence of cervical precancerous lesions and cervical cancer [12]
Summary
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. On the other hand, limited specificity of the Pap smear leads to over-diagnosis and Testing for high-risk human papillomaviruses (hrHPV), the sexually transmitted infectious agents that evoke cervical cancer, could substantially improve the sensitivity of screening [2]. HPV screening has high sensitivity, but Schmitz et al BMC Cancer (2018) 18:1197 lacks, specificity, since most women infected with HPV will clear such an infection without developing lesions [4]. HPV-based cervical cancer screening only makes sense with the availability of triage methods that allow the detection of precancerous lesions and cancer cases among women tested HPV-positive [5]
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