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Gynecol Oncol. 2016 Oct;143(1):135-142. doi: 10.1016/j.ygyno.2016.07.089. Epub 2016 Jul 16.

Performance of CADM1/MAL-methylation analysis for monitoring of women treated for high-grade CIN.

Author information

1
Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands; Department of Obstetrics and Gynecology, Flevo Hospital, Almere, The Netherlands. Electronic address: m.uijterwaal@vumc.nl.
2
Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: ma.vanzummeren@vumc.nl.
3
Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: m.kocken@vumc.nl.
4
Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: r.luttmer1@vumc.nl.
5
Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: h.berkhof@vumc.nl.
6
Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: b.witte@vumc.nl.
7
Department of Obstetrics and Gynecology, Flevo Hospital, Almere, The Netherlands. Electronic address: mbaal@flevoziekenhuis.nl.
8
Department of Obstetrics and Gynecology, Sint Antonius Hospital, Nieuwegein, The Netherlands. Electronic address: p.graziosi@antoniusziekenhuis.nl.
9
Department of Gynecological Oncology, UMCU Utrecht Cancer Center, The Netherlands. Electronic address: r.verheijen@umcutrecht.nl.
10
Department of Obstetrics and Gynecology, Erasmus MC University Medical Center, Rotterdam, The Netherlands. Electronic address: t.helmerhorst@erasmusmc.nl.
11
Department of Obstetrics and Gynecology, Onze Lieve Vrouwen Gasthuis West, Amsterdam, The Netherlands. Electronic address: d.dijken@olvg.nl.
12
Department of Obstetrics and Gynecology, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: jwm.spruijt@vumc.nl.
13
Department of Pathology, Erasmus University Medical Center, Rotterdam, The Netherlands. Electronic address: f.vankemenade@erasmusmc.nl.
14
Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: d.vd.vegt@quicknet.nl.
15
Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: M.Lettink@vumc.nl.
16
Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: dam.heideman@vumc.nl.
17
Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: pjf.snijders@vumc.nl.
18
Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: r.steenbergen@vumc.nl.
19
Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: cjlm.meijer@vumc.nl.

Abstract

INTRODUCTION:

Recent studies have shown that CADM1/MAL-methylation testing detects high-grade CIN lesions with a high short-term progression risk for cervical cancer. Women treated for CIN2/3 are at risk of post-treatment disease, representing either persistent (incompletely treated) or incident (early onset) lesions. Here, we evaluated CADM1/MAL-methylation analysis as potential tool for detecting recurrent high-grade CIN lesions (rCIN2/3).

METHODS AND MATERIALS:

A multicenter prospective clinical cohort study was conducted among 364 women treated for CIN2/3. Cervical scrapes were taken prior to treatment, and six and 12months post-treatment and tested for cytology, hrHPV (plus genotype) and CADM1/MAL-methylation. When at six months either of these tests was positive, a colposcopy-directed biopsy was obtained. At 12months, all women underwent an exit-colposcopy with biopsy. In case of rCIN2/3, re-treatment was done.

RESULTS:

We found 28 rCIN2 (7.7%) and 14 rCIN3 (3.8%), resulting in a total recurrence rate of 11.5%. All 14 women with rCIN3 and 15/28 (54%) with rCIN2 showed hrHPV type-persistence. Of these, 9/14 (64%) rCIN3 and 8/15 (53%) rCIN2 were CADM1/MAL-methylation positive. All incident rCIN2, characterized by hrHPV genotype-switch, were CADM1/MAL-methylation negative. All three carcinomas found after re-treatment were CADM1/MAL-methylation positive. CADM1/MAL-methylation positivity at both baseline and follow-up significantly increased the risk of ≥rCIN3 (from 0.7% to 18.4%), and ≥rCIN2 (from 8.2% to 36.8%), compared to a consistently CADM1/MAL-methylation negative result (p-value: <0.001).

CONCLUSION:

Post-treatment monitoring by CADM1/MAL-methylation analysis identifies women with an increased risk of rCIN2/3. Our results confirm previous data indicating that CADM1/MAL-methylation analysis provides a high reassurance against cancer.

KEYWORDS:

Cytology; DNA methylation; Human papillomavirus DNA test; Post-treatment; Re-LLETZ; Recurrent high-grade cervical intraepithelial neoplasia

PMID:
27430395
DOI:
10.1016/j.ygyno.2016.07.089
[Indexed for MEDLINE]

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