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

• Published in: Gynecologic oncology 2016-10, Vol.143 (1), p.135-142
• Main Authors: Uijterwaal, M.H, van Zummeren, M, Kocken, M, Luttmer, R, Berkhof, J, Witte, B.I, van Baal, W.M, Graziosi, G.C.M, Verheijen, R.H.M, Helmerhorst, T.J.M, van Dijken, D.K.E, Spruijt, J.W.M, van Kemenade, F.J, Fransen-Daalmeijer, N, Bekker-Lettink, M, Heideman, D.A.M, Snijders, P.J.F, Steenbergen, R.D.M, Meijer, C.J.L.M
• Format: Article
• Language: English
• Subjects: Adult; Cell Adhesion Molecule-1; Cell Adhesion Molecules - genetics; Cervical Intraepithelial Neoplasia - genetics; Cytology; DNA Methylation; Female; Hematology, Oncology and Palliative Medicine; Human papillomavirus DNA test; Humans; Immunoglobulins - genetics; Middle Aged; Myelin and Lymphocyte-Associated Proteolipid Proteins - genetics; Obstetrics and Gynecology; Post-treatment; Prospective Studies; Re-LLETZ; Recurrent high-grade cervical intraepithelial neoplasia; Uterine Cervical Neoplasms - genetics
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1016/j.ygyno.2016.07.089

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 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 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.