基于 HPV 的初次筛查中，对自采样的 HPV 阳性样本进行 ASCL1 和 LHX8 DNA 甲基化标志物评估。
Evaluation of DNA methylation biomarkers ASCL1 and LHX8 on HPV-positive self-collected samples from primary HPV-based screening.
发表日期：2023 Apr 26
作者：
Lisanne Verhoef, Maaike C G Bleeker, Nicole Polman, Renske D M Steenbergen, Renée M F Ebisch, Willem J G Melchers, Ruud L M Bekkers, Anco C Molijn, Wim G Quint, Folkert van Kemenade, Chris J L M Meijer, Johannes Berkhof, Daniëlle A M Heideman
来源：
BRITISH JOURNAL OF CANCER
摘要：
宿主细胞DNA甲基化分析可用于筛查高危人乳头状瘤病毒（HPV）阳性的自取宫颈阴道样本女性，但当前数据仅局限于未/从未接受筛查的女性和被推荐人群。该研究评估了在接受原发性HPV自取采样进行宫颈癌筛查的女性中对筛查的性能。使用定量多重甲基化特异性PCR（qMSP）测试593个参加原发性HPV自取采样试验（IMPROVE研究; NTR5078）的HPV阳性女性的自取样本，检测DNA甲基化标记ASCL1和LHX8。评估了CIN3和宫颈癌（CIN3 + ）的诊断性能，并与配对的HPV阳性临床医生取的宫颈样本进行比较。在CIN3 + 患者的自取样本中发现甲基化水平显著高于无疾病证据的对照女性（P值<0.0001）。 ASCL1 / LHX8标记面板的CIN3 + 检测敏感性为73.3％（63/86; 95％ CI 63.9-82.6％），相应的特异性为61.1％（310/507; 95％ CI 56.9-65.4％）。自收集与临床医生收集相比，检测CIN3 +的相对灵敏度为0.95（95％ CI 0.82-1.10），相对特异性为0.82（95％ CI 0.75-0.90）。 ASCL1 / LHX8甲基化标记面板是用于自取采样例行筛查中检测CIN3 + 的可行的直接筛查方法。 ©2023. 作者（们）。
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.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.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).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.© 2023. The Author(s).