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%,p= 0.53). Of the 27 GynTect®-negative CIN3 lesions, 15 regressed (NPV = 56%, 90% CI 38–72%,p= 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岁的女性中。为减少过度治疗，可靠的预后生物标志物将具有重要价值。本研究的主要目的是分析甲基化标志物组合GynTect®对病变消退的阴性预测值。在这项前瞻性、多中心、纵向观察性概念验证研究中，对组织学确诊为CIN2（n=24）或CIN3（n=36）的≤29岁女性分别进行了长达24个月或12个月的无治疗密切监测。结局指标包括病变的消退、持续或进展。每位患者均采集单次基线样本（V0）用于细胞学、高危HPV检测和甲基化分析。在初步分析中，测定了V0时GynTect®检测结果为阴性对病变消退的阴性预测值。我们检验了原假设NPV≤70%与备择假设NPV≥90%。在18例GynTect®阴性的CIN2患者中，12例出现消退（NPV=67%，90% CI 44–85%，p=0.53）；27例GynTect®阴性的CIN3病变中，15例出现消退（NPV=56%，90% CI 38–72%，p=0.92）。尽管多数GynTect®阴性病变出现消退，但未观察到预设的≥90%的NPV。因此，将GynTect®检测应用于接受观察等待患者的临床相关性仍存疑。需开展更长期观察的进一步研究。
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