P16/Ki-67双染联合密封蛋白4检测对宫颈高级别上皮内瘤变的诊断效能分析

Diagnostic value of P16/Ki-67 double staining combined with CLDN4 detection in high grade cervical intraepithelial neoplasia

摘要:

目的 探讨P16/Ki-67双染联合密封蛋白4（CLDN4）检测对宫颈高级别上皮内瘤变的诊断价值。方法 回顾性分析2020年8月—2021年3月在华中科技大学同济医学院附属武汉儿童医院就诊并经宫颈切片病理诊断为低级别上皮内瘤变、高级别上皮内瘤变及慢性宫颈炎患者各32例，所有患者均行阴道镜直视下活检，且所有宫颈阻止标本均经P16/Ki-67双染和CLDN4检测。比较P16/Ki-67双染诊断结果与病理检查诊断结果；比较CLDN4诊断结果与病理检查诊断结果；比较P16/Ki-67双染、CLDN4联合诊断结果与病理检查诊断结果。绘制受试者工作特征（ROC）曲线评价P16/Ki-67双染联合CLDN4检测对宫颈高级别上皮内瘤变的诊断效能。结果 P16/Ki67双染用于诊断宫颈高级别上皮内瘤变，有27例阳性患者与病理检查诊断结果一致，52例阴性患者与病理活检诊断结果一致，经一致性检验，两种诊断方法的一致性一般（κ =0.622，P =0.000）；CLDN4用于诊断宫颈高级别上皮内瘤变，有25例阳性患者与病理检查诊断结果一致，51例阴性患者与病理检查诊断结果一致，经一致性检验，两种诊断方法的一致性一般（κ =0.552，P =0.000）；P16/Ki-67双染、CLDN4联合诊断宫颈高级别上皮内瘤变，有30例阳性患者与病理检查诊断结果一致，62例阴性患者与病理检查诊断结果一致，经一致性检验，两种诊断方法的一致性较好（κ =0.906，P =0.000）。ROC曲线分析结果显示，P16/Ki-67双染、CLDN4及两者联合对宫颈高级别上皮内瘤变诊断的敏感性分别为84.38%（95% CI：0.665，0.941）、78.13%（95% CI：0.596，0.901）、93.75%（95% CI：0.778，0.989），特异性分别为81.25%（95% CI：0.692，0.895）、79.69%（95% CI：0.674，0.883）、96.88%（95% CI：0.882，0.995），曲线下面积分别为0.828（95% CI：0.738，0.897）、0.789（95% CI：0.694，0.866）、0.953（95% CI：0.890，0.986）。结论 P16/Ki-67双染联合CLDN4检测对宫颈高级别上皮内瘤变的诊断效能较高。

Abstract:

Objective To investigate the diagnostic value of P16/Ki-67 double staining combined with claudin 4 (CLDN4) detection in high grade cervical intraepithelial neoplasia (HSIL).Methods Retrospective analysis was made on 32 cervical tissue samples from patients with low grade intraepithelial neoplasia (LSIL), HSIL, and chronic cervicitis who were treated in our hospital from April 2020 to March 2021 and were pathologically diagnosed as low grade intraepithelial neoplasia (LSIL), HSIL, and chronic cervicitis. All patients underwent colposcopy biopsy under direct vision, and all cervical cut samples were detected by P16/Ki-67 double staining and CLDN4. The results of P16/Ki-67 double staining diagnosis and pathological examination were compared. The results of CLDN4 diagnosis and pathological examination were compared. The results of P16/Ki-67 double staining, CLDN4 combined diagnosis and pathological examination were compared. To analyze the diagnostic value of P16/Ki-67 double staining combined with CLDN4 in cervical HSIL.Results P16/Ki-67 double staining was used for the diagnosis of cervical HSIL. There were 27 positive patients and 52 negative patients who were consistent with the results of pathological biopsy. Through the consistency test, the two diagnostic methods were generally consistent (κ = 0.622, P = 0.000). CLDN4 is used for the diagnosis of cervical HSIL. There are 25 positive patients and 51 negative patients who are consistent with the results of pathological biopsy. Through the consistency test, the two diagnostic methods are generally consistent (κ = 0.552, P = 0.000). P16/Ki-67 double staining and CLDN4 combined to diagnose cervical HSIL, 30 positive patients were consistent with pathological biopsy results, and 62 negative patients were consistent with pathological biopsy results. Through consistency test, the two diagnostic methods were consistent (κ = 0.906, P = 0.000). The analysis of the receiver operating characteristic curve (ROC) of the subjects showed that the sensitivity of P16/Ki-67 double staining, CLDN4 and their combination to the diagnosis of cervical HSIL was 84.38% (95% CI: 0.665, 0.941), 78.13% (95% CI: 0.596, 0.901), 93.75% (95% CI: 0.778, 0.989), specificity was 81.25% (95% CI: 0.692, 0.895), 79.69% (95% CI: 0.674,0.883), 96.88% (95% CI: 0.882, 0.995), and the area under the curve (AUC) was 0.828 (95% CI: 0.738, 0.897), 0.789 (95% CI: 0.694, 0.866), 0.953 (95% CI: 0.890, 0.986), respectively.Conclusion P16/Ki-67 double staining combined with CLDN4 detection has a high diagnostic efficiency for cervical HSIL.