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 (p= 0.50). Single test specificity was significantly higher for GynTect®(90%, 95% CI 71–98% vs. 62%, 95% CI 40–80%) (p= 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%的患者在治疗后2年内复发，对CIN3女性进行治疗后随访是必要的。基于高危型HPV-DNA/细胞学联合检测的标准随访方案具有高敏感性但特异性有限。我们的概念验证性病例对照研究旨在评估甲基化检测GynTect®在随访期间检测CIN2/3复发的性能。我们利用近期一项前瞻性、多中心、观察性研究的剩余临床材料进行进一步分析。研究样本包括17例在24个月随访期内确诊的CIN2/3复发病例和31例未复发对照。对基线期（CIN3手术前即刻）及最多三次随访的宫颈刮片DNA进行高危型HPV和GynTect®甲基化状态分析，细胞学数据来自前期研究。总体而言，基线期有12例病例和21例对照呈GynTect阳性。在这些亚组中，首次随访时GynTect®的单次检测敏感性为67%（95% CI 39–87%），而高危型HPV检测为83%（95% CI 55–96%）（p=0.50）。GynTect®的单次检测特异性显著更高（90%，95% CI 71–98% vs. 62%，95% CI 40–80%）（p=0.03）。在联合检测模式下，高危型HPV/细胞学与GynTect®/细胞学组合均能检测出所有复发病例。GynTect®/细胞学组合的特异性高于高危型HPV/细胞学组合，但差异无统计学意义。总之，对于初始GynTect阳性的患者，高危型HPV和GynTect®检测对复发性病变的敏感性相近，但GynTect®检测具有更高的特异性。新发高危型HPV感染和/或持续存在的多灶性高危型HPV感染（无临床病变）很可能是导致高危型HPV检测特异性较低的主要原因。未来需要开展前瞻性验证研究，以确定GynTect®/细胞学联合检测在治疗后监测中是否能优于高危型HPV/细胞学联合检测。
肿瘤(癌症)患者之家