Evaluation of DNA methylation biomarkers ASCL1 and LHX8 on HPV-positive self-collected samples from primary HPV-based screening.

Verhoef, Lisanne; Bleeker, Maaike C. G.; Polman, Nicole; Steenbergen, Renske D. M.; Ebisch, Renée M. F.; Melchers, Willem J. G.; Bekkers, Ruud L. M.; Molijn, Anco C.; Quint, Wim G.; van Kemenade, Folkert; Meijer, Chris J. L. M.; Berkhof, Johannes; Heideman, Daniëlle A. M.

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.

British Journal of Cancer, 2023, Vol 129, Issue 1, p104

0007-0920

Academic Journal

10.1038/s41416-023-02277-z