Hoyer Heike, Scheungraber Cornelia, Mehlhorn Grit, Hagemann Ingke, Scherbring Sarah, Wölber Linn, Petzold Annett, Wunsch Kristina, Schmitz Martina, Hampl Monika, Böhmer Gerd, Hillemanns Peter, Runnebaum Ingo B, Dürst Matthias
Institut für Medizinische Statistik, Informatik, Datenwissenschaften (IMSID), Universitätsklinikum Jena, 07743 Jena, Germany.
Frauenarztpraxis, Westbahnhofstraße 2, 07745 Jena, Germany.
Cancers (Basel). 2024 Aug 30;16(17):3022. doi: 10.3390/cancers16173022.
Post-treatment follow-up in women with CIN3 is mandatory due to relapse in up to 15% of patients within 2 years. Standard follow-up care based on hrHPV-DNA/cytology co-testing has high sensitivity but limited specificity. The aim of our proof-of-concept case-control study was to evaluate the performance of the methylation test GynTect for the detection of recurrent CIN2/3 during follow-up. Residual clinical material from a recent, prospective, multicenter, observational study was available for further analysis. We studied a sample of 17 cases with recurrent CIN2/3 diagnosed within 24 months of follow-up and 31 controls without recurrence. DNA from cervical scrapes at baseline (immediately before CIN3 surgery) and up to three follow-up visits were analyzed for hrHPV and GynTect methylation status. Cytology data were available from the previous study. Overall, 12 cases and 21 controls were GynTect-positive at baseline. In these subgroups, single test sensitivity at first follow-up was 67% (95% CI 39-87%) for GynTect compared to 83% (95% CI 55-96%) for hrHPV ( = 0.50). Single test specificity was significantly higher for GynTect (90%, 95% CI 71-98% vs. 62%, 95% CI 40-80%) ( = 0.03). In a co-testing setting, both hrHPV/cytology and GynTect/cytology detected all recurrences. Specificity for GynTect/cytology was higher than for hrHPV/cytology, but this difference was not statistically significant. In conclusion, for initially GynTect-positive patients, both hrHPV and GynTect tests detected recurrent disease with similar sensitivity, but the GynTect assay has a higher specificity. Incident hrHPV infection and/or persisting multifocal hrHPV infections without clinical disease are most likely responsible for the poorer specificity of the hrHPV test. A future prospective validation study will have to show whether GynTect/cytology co-testing can outperform hrHPV/cytology co-testing in post-treatment surveillance.
由于高达15%的CIN3患者会在2年内复发，因此对CIN3女性患者进行治疗后随访是必要的。基于高危型人乳头瘤病毒（hrHPV）DNA/细胞学联合检测的标准随访护理具有高敏感性，但特异性有限。我们的概念验证病例对照研究旨在评估GynTect甲基化检测在随访期间检测复发性CIN2/3的性能。最近一项前瞻性、多中心、观察性研究的剩余临床材料可用于进一步分析。我们研究了17例在随访24个月内诊断为复发性CIN2/3的病例样本和31例无复发的对照样本。分析了基线时（CIN3手术前即刻）以及多达三次随访时宫颈刮片的DNA的hrHPV和GynTect甲基化状态。细胞学数据可从前一项研究中获得。总体而言，12例病例和21例对照在基线时GynTect检测呈阳性。在这些亚组中，首次随访时GynTect的单项检测敏感性为67%（95%CI 39 - 87%），而hrHPV为83%（95%CI 55 - 96%）（P = 0.50）。GynTect的单项检测特异性显著更高（90%，95%CI 71 - 98%对62%，95%CI 40 - 80%）（P = 0.03）。在联合检测设置中，hrHPV/细胞学和GynTect/细胞学均检测到了所有复发情况。GynTect/细胞学的特异性高于hrHPV/细胞学，但这种差异无统计学意义。总之，对于最初GynTect检测呈阳性的患者，hrHPV和GynTect检测在检测复发性疾病方面具有相似的敏感性，但GynTect检测具有更高的特异性。新发hrHPV感染和/或持续存在的无临床疾病的多灶性hrHPV感染很可能是hrHPV检测特异性较差的原因。未来的前瞻性验证研究将必须表明GynTect/细胞学联合检测在治疗后监测中是否能优于hrHPV/细胞学联合检测。
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