Abstract
Background: Host-cell DNA methylation analysis can be used to triage women with high-risk human papillomavirus (HPV)-positive self-collected cervicovaginal samples, but current data are restricted to under-/never-screened women and referral populations. This study evaluated triage performance in women who were offered primary HPV self-sampling for cervical cancer screening. Methods: Self-collected samples from 593 HPV-positive women who participated in a primary HPV self-sampling trial (IMPROVE study; NTR5078), were tested for the DNA methylation markers ASCL1 and LHX8 using quantitative multiplex methylation-specific PCR (qMSP). The diagnostic performance for CIN3 and cervical cancer (CIN3 +) was evaluated and compared with that of paired HPV-positive clinician-collected cervical samples. Results: Significantly higher methylation levels were found in HPV-positive self-collected samples of women with CIN3 + than control women with no evidence of disease (P values <0.0001). The marker panel ASCL1/LHX8 yielded a sensitivity for CIN3 + detection of 73.3% (63/86; 95% CI 63.9–82.6%), with a corresponding specificity of 61.1% (310/507; 95% CI 56.9–65.4%). The relative sensitivity for detecting CIN3+ was 0.95 (95% CI 0.82–1.10) for self-collection versus clinician-collection, and the relative specificity was 0.82 (95% CI 0.75–0.90). Conclusions: The ASCL1/LHX8 methylation marker panel constitutes a feasible direct triage method for the detection of CIN3 + in HPV-positive women participating in routine screening by self-sampling.
| Original language | English |
|---|---|
| Pages (from-to) | 104-111 |
| Number of pages | 8 |
| Journal | British Journal of Cancer |
| Volume | 129 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 27 Jul 2023 |
Bibliographical note
Funding Information:The authors gratefully acknowledge Peter Snijders who was one of the main investigators of the IMPROVE study. They thank all the women who participated in the IMPROVE study; the screening organisations Midden-West, Zuid-West and Oost; the National Institute for Public Health and the Environment; and the physicians, gynaecologists, and pathologists in the study regions. The authors would like to acknowledge Dutch Nationwide Pathology Databank (PALGA) for providing data and the Amsterdam UMC Biobank for their high-quality storage of the collected samples.
Funding Information:
This project was funded by the Dutch Cancer Society (grant number KWF 11337).
Funding Information:
DAMH, RDMS and CJLMM are minority shareholders of Self-screen B.V., a spin-off company of Amsterdam UMC, location VUmc; Self-screen B.V. develops, manufactures and licences high-risk HPV and methylation marker assays for cervical cancer screening and holds patents on these tests; JB had financial support from the European Commission (RISCC, grant number 847845); CJLMM is part-time CEO of Self-screen B.V., and has a very small number of shares of MDXHealth and previously QIAGEN, has received speakers fees from GSK, QIAGEN and SPMSD/Merck, and served occasionally on the scientific advisory boards of these companies; LV, MCGB, NP, RMFE, WJGM, RLMB, ACM, WGQ and FJvK declare no competing interests.
Publisher Copyright:
© 2023, The Author(s).
