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. 2025 Feb 1;156(3):659-667.
doi: 10.1002/ijc.35143. Epub 2024 Aug 22.

Recurrent cervical cancer detection using DNA methylation markers in self-collected samples from home

Mirte Schaafsma  1   2   3 , Rianne van den Helder  4   5 , Constantijne H Mom  6 , Renske D M Steenbergen  2   3 , Maaike C G Bleeker  2   3 , Nienke E van Trommel  1
Affiliations

Recurrent cervical cancer detection using DNA methylation markers in self-collected samples from home

Mirte Schaafsma et al. Int J Cancer. .

Abstract

Early detection of recurrent cervical cancer is important to improve survival rates. The aim of this study was to explore the clinical performance of DNA methylation markers and high-risk human papillomavirus (HPV) in cervicovaginal self-samples and urine for the detection of recurrent cervical cancer. Cervical cancer patients without recurrence (n = 47) collected cervicovaginal self-samples and urine pre- and posttreatment. Additionally, 20 patients with recurrent cervical cancer collected cervicovaginal self-samples and urine at time of recurrence. All samples were self-collected at home and tested for DNA methylation and high-risk HPV DNA by PCR. In patients without recurrent cervical cancer, DNA methylation levels decreased 2-years posttreatment compared to pretreatment in cervicovaginal self-samples (p < .0001) and urine (p < .0001). DNA methylation positivity in cervicovaginal self-samples was more frequently observed in patients with recurrence (77.8%) than in patients without recurrence 2-years posttreatment (25.5%; p = .0004). Also in urine, DNA methylation positivity was more frequently observed in patients with recurrence (65%) compared to those without recurrence (35.6%; p = .038). Similarly, high-risk HPV positivity in both cervicovaginal self-samples and urine was more frequent (52.6% and 55%, respectively) in patients with recurrence compared to patients without recurrence (14.9% and 8.5%, respectively) (p = .004 and p = .0001). In conclusion, this study shows the potential of posttreatment monitoring of cervical cancer patients for recurrence by DNA methylation and high-risk HPV testing in cervicovaginal and urine samples collected at home. The highest recurrence detection rate was achieved by DNA methylation testing in cervicovaginal self-samples, detecting 77.8% of all recurrences and, specifically, 100% of the local recurrences.

Keywords: DNA methylation levels; cervical cancer recurrence; remote monitoring; self‐sampling.

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Conflict of interest statement

The authors declare the following financial interests/personal relationships which may be considered as potential conflicts of interests: R.D.M. Steenbergen has a minority share in Self‐screen B.V., a spin‐off company of Amsterdam UMC, location VUmc. The remaining authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence this study.

Figures

FIGURE 1
FIGURE 1
DNA methylation levels in self‐samples of healthy controls (n = 115), cervical cancer patients without recurrence pre‐ and posttreatment (n = 47), and cervical cancer patients with recurrence collected at time of recurrence (n = 18). The panels represent the DNA methylation levels of the following markers: ASCL1 (A), LHX8 (B), GHSR (C), SST (D), and ZIC1 (E). N.S., not significant (p > .05).
FIGURE 2
FIGURE 2
DNA methylation levels in urine of healthy controls (n = 50), cervical cancer patients without recurrence pre‐ and posttreatment (n = 45), and cervical cancer patients with recurrence collected at time of recurrence (n = 20). Samples of cervical cancer patients pre‐ and posttreatment are paired. The panels represent the DNA methylation levels of the following markers: ASCL1 (A), LHX8 (B), GHSR (C), SST (D), and ZIC1 (E). N.S., not significant (p > .05).
FIGURE 3
FIGURE 3
DNA methylation and high‐risk human papillomavirus (HPV) positivity in self‐samples and urine of patients treated for cervical cancer without recurrence and with recurrence (local and distant). Each column represents one patient.
See this image and copyright information in PMC

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