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DNA methylation analysis in self-sampled brush material as a triage test in hrHPV-positive women.

Abstract：

BACKGROUND:Primary high-risk human papillomavirus (hrHPV) testing in cervical cancer screening shows relatively low specificity, which makes triage testing necessary. In this study, DNA methylation analysis was compared with cytology for triage testing in hrHPV-positive women. Moreover, feasibility of DNA methylation analysis directly on brush-based self-sampled specimens was assessed. METHODS:Non-responding women from population-based screening were invited to self-collect a cervico-vaginal specimen for hrHPV testing; hrHPV-positive women were referred to a physician for triage liquid-based cytology. DNA methylation analysis was performed on 128 hrHPV-positive physician-collected triage samples and 50 matched brush self-samples with QMSP for C13ORF18, EPB41L3, JAM3 and TERT. RESULTS:In physician-taken triage material, DNA methylation analysis of JAM3 showed the highest combined specificity (88%) and sensitivity (82%) for detection of CIN3+, whereas cytology showed a specificity of 48% and a sensitivity of 91%. Out of 39 women with abnormal cytology and normal histology (false-positive by cytology), 87% were negative for JAM3 and 90% for C13ORF18 methylation. Agreement between DNA methylation analysis performed directly on the matched self-sampled material and physician-taken samples was 88% for JAM3 (κ=0.75, P<0.001) and 90% for C13ORF18 (κ=0.77; P<0.001). CONCLUSIONS:DNA methylation analysis as a triage test in hrHPV-positive women is an attractive alternative to cytology. Furthermore, DNA methylation is feasible directly on brush-based self-samplers and showed good correlation with matched physician-taken samples. Direct molecular triage on self-collected specimens could optimise the screening program, especially for non-responders, as this would eliminate the need for an additional physician-taken scraping for triage testing.

journal_name

Br J Cancer

journal_title

British journal of cancer

authors

Boers A,Bosgraaf RP,van Leeuwen RW,Schuuring E,Heideman DA,Massuger LF,Verhoef VM,Bulten J,Melchers WJ,van der Zee AG,Bekkers RL,Wisman GB

doi

10.1038/bjc.2014.392

subject

Has Abstract

pub_date

2014-09-09 00:00:00

pages

1095-101

issue

eissn

0007-0920

issn

1532-1827

pii

bjc2014392

journal_volume

111

pub_type

杂志文章

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DNA methylation analysis in self-sampled brush material as a triage test in hrHPV-positive women.