M H Uijterwaal1, M van Zummeren2, M Kocken3, R Luttmer4, J Berkhof5, B I Witte6, W M van Baal7, G C M Graziosi8, R H M Verheijen9, T J M Helmerhorst10, D K E van Dijken11, J W M Spruijt12, F J van Kemenade13, N Fransen-Daalmeijer14, M Bekker-Lettink15, D A M Heideman16, P J F Snijders17, R D M Steenbergen18, C J L M Meijer19. 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.
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.
Authors: Sandra Meršaková; Veronika Holubeková; Marián Grendár; Jozef Višňovský; Marcela Ňachajová; Michal Kalman; Erik Kúdela; Pavol Žúbor; Tibor Bielik; Zora Lasabová; Ján Danko Journal: Oncol Lett Date: 2018-09-26 Impact factor: 2.967
Authors: J Bosschieter; S Bach; I V Bijnsdorp; L I Segerink; W F Rurup; A P van Splunter; I Bahce; P W Novianti; G Kazemier; R J A van Moorselaar; R D M Steenbergen; J A Nieuwenhuijzen Journal: PLoS One Date: 2018-08-24 Impact factor: 3.240