液基细胞学样本中P16（INK4a）免疫细胞化学检测在意义不明确的巴氏涂片检查中的应用：对意义不明确巴氏涂片检查女性管理的附加价值

P16(INK4a) immunocytochemistry in liquid-based cytology samples in equivocal Pap smears: added value in management of women with equivocal Pap smear.

作者信息

Monsonego Joseph, Pollini Giuseppe, Evrard Maria José, Sednaoui Patrice, Monfort Laura, Quinzat Dominique, Dachez Roger, Syrjänen Kari

机构信息

Alfred Fournier Institute, Paris, France.

出版信息

Acta Cytol. 2007 Sep-Oct;51(5):755-66. doi: 10.1159/000325839.

DOI:10.1159/000325839

PMID:17910346

Abstract

OBJECTIVE

To test whether p1l6(INK4a) immunocytochemistry (ICC) in liquid-based cytology (LBC) is useful with colposcopy in abnormal Pap smears.

STUDY DESIGN

A series of 248 women with abnormal Pap smear were analyzed for oncogenic (HR) human papillomavirus (HPV) types using the Hybrid Capture II assay and for p16(INK4a) expression using ICC on cervical samples in PreservCyt liquid media. Colposcopic and loop electrosurgical excision procedure (LEEP) cone biopsy were the gold standard.

RESULTS

p16(INK4a) ICC did best as predictor of high-grade squamous intraepithelial lesion, with OR 12.18 (2.72-54.57) (p = 0.0001), showing 88.2% sensitivity (SE), 61.9% specificity (SP), 14.6% positive predictive value (PPV) and 98.6% negative predictive value (NPV). In sorting discrepant cases, p16(INK4a) ICC results in 100% SE and 100% NPV in detecting cervical intraepithelial neoplasia (CIN) 2 lesions among Pap+/biopsy- women. In atypical squamous cells undetermined significance (ASCUS) cytology, adding p16(INK4a) ICC improves specificity of colposcopy from 27.3% to 81.8% and PPV from 42.8% to 71.4%. Best performance is obtained with p16(INK4a) ICC and colposcopy: 83.3% SE, 81.8% SP, 71.4% PPV and 90.0% NPV. CONCLUSION p16(INK4a) is useful in sorting clinically relevant discrepant cases, and p16(INK4a) ICC significantly improves SP and PPV of colposcopy in management of ASCUS cytology.

摘要

目的

检测液基细胞学（LBC）中p16（INK4a）免疫细胞化学（ICC）在异常巴氏涂片检查中与阴道镜检查联合使用是否有用。

研究设计

对248例巴氏涂片异常的女性进行分析，使用杂交捕获II检测法检测致癌性（HR）人乳头瘤病毒（HPV）类型，并在PreservCyt液体培养基中对宫颈样本使用ICC检测p16（INK4a）表达。阴道镜检查和环形电外科切除术（LEEP）锥形活检为金标准。

结果

p16（INK4a）ICC作为高级别鳞状上皮内病变的预测指标表现最佳，比值比（OR）为12.18（2.72 - 54.57）（p = 0.0001），敏感性（SE）为88.2%，特异性（SP）为61.9%，阳性预测值（PPV）为14.6%，阴性预测值（NPV）为98.6%。在分类不一致的病例中，p16（INK4a）ICC在检测巴氏涂片阳性/活检阴性女性中的宫颈上皮内瘤变（CIN）2级病变时，敏感性和阴性预测值均为100%。在意义不明确的非典型鳞状细胞（ASCUS）细胞学检查中，增加p16（INK4a）ICC可将阴道镜检查的特异性从27.3%提高到81.8%，阳性预测值从42.8%提高到71.4%。p16（INK4a）ICC与阴道镜检查联合使用时表现最佳：敏感性为83.3%，特异性为81.8%，阳性预测值为71.4%，阴性预测值为90.0%。结论：p16（INK4a）有助于分类临床相关的不一致病例，且p16（INK4a）ICC在ASCUS细胞学管理中显著提高了阴道镜检查的特异性和阳性预测值。