Hoyer Heike, Stolte Claudia, Böhmer Gerd, Hampl Monika, Hagemann Ingke, Maier Elisabeth, Denecke Agnieszka, Hirchenhain Christine, Patzke Jan, Jentschke Matthias, Gerick Axel, Heller Tabitha, Hippe Juliane, Wunsch Kristina, Schmitz Martina, Dürst Matthias
Institut für Medizinische Statistik, Informatik und Datenwissenschaften, Universitätsklinikum Jena, 07743 Jena, Germany.
Institut für Zytologie und Dysplasie (IZD), 30159 Hannover, Germany.
Cancers (Basel). 2023 Aug 3;15(15):3951. doi: 10.3390/cancers15153951.
Cervical intraepithelial neoplasia (CIN) grade 2/3 has a high spontaneous regression rate, especially among women ≤29 years of age. To reduce overtreatment, reliable prognostic biomarkers would be helpful. The main aim of this study was to analyze the negative predictive value of the methylation marker panel GynTect for lesion regression. In this prospective, multicenter, longitudinal observational proof-of-concept study, women aged ≤29 years with histologically confirmed CIN2 (n = 24) or CIN3 (n = 36) were closely monitored without treatment for up to 24 or 12 months, respectively. The outcome was either regression, persistence, or progression of the lesion. For each patient, a single baseline sample (V0) for cytology, hrHPV detection and methylation analysis was taken. In a primary analysis, the negative predictive value (NPV) of a GynTect-negative test result at V0 for regression was determined. We tested the null hypothesis NPV ≤ 70% against the alternative hypothesis NPV ≥ 90%. Twelve of the eighteen GynTect-negative CIN2 patients showed regression (NPV = 67%, 90% CI 44-85%, = 0.53). Of the 27 GynTect-negative CIN3 lesions, 15 regressed (NPV = 56%, 90% CI 38-72%, = 0.92). Although the majority of GynTect-negative lesions regressed, the postulated NPV of ≥90% was not observed. Thus, the clinical relevance for an implementation of the GynTect assay for patients undergoing watchful waiting remains questionable. Further studies with longer observation periods should be undertaken.
宫颈上皮内瘤变（CIN）2/3级具有较高的自发消退率，尤其是在29岁及以下的女性中。为了减少过度治疗，可靠的预后生物标志物会有所帮助。本研究的主要目的是分析甲基化标志物检测组合GynTect对病变消退的阴性预测价值。在这项前瞻性、多中心、纵向观察性概念验证研究中，对年龄≤29岁、经组织学确诊为CIN2（n = 24）或CIN3（n = 36）的女性分别进行长达24个月或12个月的密切监测而不进行治疗。结局为病变的消退、持续或进展。为每位患者采集一份用于细胞学、高危型人乳头瘤病毒（hrHPV）检测和甲基化分析的单一基线样本（V0）。在初步分析中，确定V0时GynTect检测结果为阴性对病变消退的阴性预测值（NPV）。我们针对原假设NPV≤70%与备择假设NPV≥90%进行了检验。18例GynTect检测为阴性的CIN2患者中有12例病变消退（NPV = 67%，90%可信区间44 - 85%，P = 0.53）。27例GynTect检测为阴性的CIN3病变中，15例消退（NPV = 56%，90%可信区间38 - 72%，P = 0.92）。尽管大多数GynTect检测为阴性的病变消退了，但未观察到假定的NPV≥90%。因此，对于进行观察等待的患者实施GynTect检测的临床相关性仍存在疑问。应开展观察期更长的进一步研究。
