Dieleman, M. (2021) The predictive value of methylation markers to develop a recurrence in women with high-grade cervical intraepithelial lesions. thesis, Medicine.
Full text available on request.Abstract
Background To prevent the burden of cervical cancer, population based cervical cancer screening has been implemented in the Netherlands. The screening consists of hrHPV testing and cytology. To refer more women with (pre)malignant disease than based on hrHPV and triage cytology screening alone, DNA methylation markers with high sensitivity and specificity to detect high-grade cervical intraepithelial neoplasia (CIN) have been identified. CIN2+ lesions found at colposcopic examination are most often treated with a large loop excision of the transformation zone (LLETZ). This treatment is effective, but recurrence rates are high. The same DNA methylation markers could be of great value in predicting recurrent CIN2+ (rCIN2+) lesions. Aim To evaluate the predictive value of DNA methylation markers for ANKRD18CP, C13orf18, JAM3, SOX1, ZSCAN1 and EPB41L3 for the development of rCIN2+ lesions. Material and methods Data on treatment and follow-up of women treated for CIN2/3 lesions in the UMCG between 2004-2017 was collected through the Electronic Patient Record of the UMCG. Cervical scrapings of 18 women with a rCIN2+ and 32 matched women without rCIN2+ were selected. Methylation levels for six genes were determined by quantitative methylation-specific PCR (QMSP). Results In total, 685 women were treated by LLETZ for a CIN2/3 lesion. 423 provided an informed consent. 25 women developed an rCIN2+ lesion within two years post-treatment. Dichotomous defined methylation positivity of JAM3, SOX1, ZSCAN1 and EPB41L3 was significantly related with recurrence status. In terms of methylation levels, out of the six methylation markers, only methylation levels of EPB41L3 (p = 0.022) were related with the recurrence status. Conclusion Our study showed that positivity of methylation markers and/or level as determined in cervical scraping prior to LLETZ, are predictive for developing an rCIN2+. This might indicate that women with methylation positive markers at baseline are more at risk to develop an rCIN2+ lesion, than women that are methylation negative. Surveillance strategies could be tailored according to these findings.
| Item Type: | Thesis (UNSPECIFIED) |
|---|---|
| Supervisor name: | Wisman, G.B.A. and Bock, G.H. de and Schuuring, E. |
| Faculty: | Medical Sciences |
| Date Deposited: | 24 Dec 2021 10:35 |
| Last Modified: | 24 Dec 2021 10:35 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/2910 |
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