Institute of Pathology, Mannheim, Germany.
Cancer Cytopathol. 2011 Jun 25;119(3):158-66. doi: 10.1002/cncy.20140. Epub 2011 Mar 25.
The objective of this study was to analyze the diagnostic performance of a newly established immunocytochemical dual-stain protocol, which simultaneously detects p16(INK4a) and Ki-67 expression in cervical cytology samples, for identifying high-grade cervical intraepithelial neoplasia (CIN2+) in women with Papanicolaou (Pap) cytology results categorized as atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesions (LSIL).
Residual liquid-based cytology material from 776 retrospectively collected ASCUS/LSIL cases that were available from a recent study evaluating p16 cytology and HPV testing were subjected to p16/Ki-67 dual staining. The presence of 1 or more double-immunoreactive cell(s) was regarded as a positive test outcome, irrespective of morphology. Test results were correlated to histology follow-up.
Sensitivity of p16/Ki-67 dual-stain cytology for biopsy-confirmed CIN2+ was 92.2% (ASCUS) and 94.2% (LSIL), while specificity rates were 80.6% (ASCUS) and 68.0% (LSIL), respectively. Similar sensitivity/specificity profiles were found for both age groups of women aged <30 years versus women aged ≥30 years. Dual-stain cytology showed comparable sensitivity, but significantly higher specificity, when compared with human papillomavirus (HPV) testing.
The results of this study show that p16/Ki-67 dual-stain cytology provided a high sensitivity for the detection of underlying CIN2+ in women with ASCUS or LSIL Pap cytology results, comparable to the rates previously reported for HPV testing and p16 single-stain cytology. However, the specificity of this morphology-independent interpretation of p16/Ki-67 dual-stain cytology testing was further improved compared with the earlier p16 single-stain cytology approach, which required morphology interpretation, and it is significantly higher when compared with HPV testing.
本研究的目的是分析一种新建立的免疫细胞化学双重染色方案的诊断性能，该方案同时检测宫颈细胞学样本中 p16(INK4a)和 Ki-67 的表达，以识别巴氏涂片细胞学结果为非典型鳞状细胞意义不明确（ASCUS）或低级别鳞状上皮内病变（LSIL）的女性中的高级别宫颈上皮内瘤变（CIN2+）。
从最近一项评估 p16 细胞学和 HPV 检测的研究中回顾性收集了 776 例 ASCUS/LSIL 病例的剩余液基细胞学材料，这些材料可用于 p16/Ki-67 双重染色。无论形态如何，只要存在 1 个或多个双免疫反应细胞，就视为阳性试验结果。将试验结果与组织学随访进行相关性分析。
p16/Ki-67 双重染色细胞学对活检证实的 CIN2+的敏感性分别为 ASCUS 组的 92.2%和 LSIL 组的 94.2%，特异性率分别为 ASCUS 组的 80.6%和 LSIL 组的 68.0%。对于年龄<30 岁和年龄≥30 岁的女性，双重染色细胞学的敏感性/特异性谱相似。与 HPV 检测相比，双重染色细胞学具有相似的敏感性，但特异性显著提高。
本研究结果表明，p16/Ki-67 双重染色细胞学在 ASCUS 或 LSIL 巴氏涂片细胞学结果的女性中检测潜在的 CIN2+具有较高的敏感性，与之前报道的 HPV 检测和 p16 单染细胞学相当。然而，与之前需要形态学解释的 p16 单染细胞学方法相比，这种独立于形态学的 p16/Ki-67 双重染色细胞学检测的特异性进一步提高，并且与 HPV 检测相比显著提高。
