OC 11-03PERFORMANCE OF CADM1/MAL-METHYLATION ANALYSIS FOR MONITORING WOMEN TREATED FOR HIGH-GRADE CIN

13. Molecular markers
M. Van Zummeren 1, M.H. Uijterwaal 1, M. Kocken 1, R. Luttmer 1, J. Berkhof 2, B.I. Witte 2, M.W. Van Baal 3, P.G.C.M. Graziosi 4, R.H.M. Verheijen 5, T.J.M. Helmerhorst 6, D.K.E. Van Dijken 7, J.W. Spruijt 8, F.J. Van Kemenade 9, D.A.M. Heideman 1, P.J.F. Snijders 1, R.D.M. Steenbergen 1, C.J.L.M. Meijer 1.
1Department of Pathology, VU University Medical Center, Amsterdam (Netherlands), 2Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands (Netherlands), 3Department of Obstetrics and Gynecology, Flevo Hospital, Almere, The Netherlands (Netherlands), 4Department of Obstetrics and Gynecology, Sint Antonius Hospital, Nieuwegein, The Netherlands (Netherlands), 5Department of Women and Baby, University Medical Center Utrecht, The Netherlands (Netherlands), 6Department of Obstetrics and Gynecology, Erasmus University Medical Center, Rotterdam, The Netherlands (Netherlands), 7Department of Obstetrics and Gynecology, Onze Lieve Vrouwen Gasthuis West, Amsterdam, The Netherlands (Netherlands), 8Department of Obstetrics and Gynecology, VU University Medical Center, Amsterdam, The Netherlands (Netherlands), 9Department of Pathology, Erasmus University Medical Center, Rotterdam, The Netherlands (Netherlands)

Background / Objectives

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


Methods

A multicenter prospective clinical cohort study was conducted among 364 women treated for CIN2/3. Cervical scrapes were taken prior to treatment, and 6 and 12 months post-treatment and tested for cytology, hrHPV (plus genotype) and CADM1/MAL-methylation. If at 6 months either of these tests was positive, a colposcopy-directed biopsy was obtained. At 12 months, all women underwent an exit-colposcopy with mandatory biopsy. In case of rCIN2/3, a re-treatment (re-LLETZ) was done. Primary outcome measure was ≥rCIN2 at 6 or 12 months post-treatment. 


Results

We found 28 rCIN2 (7.7%) and 14 rCIN3 (3.8%), resulting in a total recurrence percentage 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. The 5 incident (hrHPV type-switch) rCIN2 were all CADM1/MAL-methylation negative, whereas the 3 carcinomas found after re-treatment were all CADM1/MAL-methylation positive. CADM1/MAL-methylation positivity at baseline and in follow-up significantly increased the risk of ≥rCIN3 from 0.7% to 18.4% respectively, and for ≥rCIN2 from 8.2% to 36.8%, compared to negative test results (p-value: <0.001).


Conclusion

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


References