Journal
GYNECOLOGIC ONCOLOGY
Volume 143, Issue 1, Pages 135-142Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ygyno.2016.07.089
Keywords
Post-treatment; Human papillomavirus DNA test; Cytology; DNA methylation; Recurrent high-grade cervical intraepithelial neoplasia; Re-LLETZ
Categories
Funding
- Netherlands Cancer Society [KWF VU 2009-4413]
- European Research Council (ERC) [322986]
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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 12 months 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 12 months, 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 82% 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. (C) 2016 Elsevier Inc. All rights reserved.
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