Department of Pathology, VU University Medical Center, PO BOX 7057, 1000 MB Amsterdam, The Netherlands.
Department of Epidemiology and Biostatistics, VU University Medical Center, PO BOX 7057, 1000 MB Amsterdam, The Netherlands.
Br J Cancer. 2014 Mar 18;110(6):1579-86. doi: 10.1038/bjc.2014.34. Epub 2014 Feb 11.
Women with borderline/mildly dyskaryotic (BMD) cytology smears are currently followed up with repeat testing at 6 and 18 months. The objective of this study is to analyse the cross-sectional and longitudinal performance of p16/Ki-67 dual-stained cytology for the detection of cervical intraepithelial neoplasia (CIN) grade 3 or worse (CIN3+) and CIN2+ in women with BMD, and to compare the results with baseline human papillomavirus (HPV) testing.
Conventional Pap cytology specimens of 256 women with BMD were dual stained for p16/Ki-67 retrospectively, and compared with baseline HPV results and long-term follow-up results.
p16/Ki-67 dual-stained cytology showed a sensitivity of 100%, a specificity of 64.4% and a negative predictive value (NPV) of 100.% for CIN3+. Human papillomavirus testing demonstrated similar sensitivity (96.3%), and NPV (99.1%), but a significantly lower specificity (57.6%; P=0.024) for CIN3+. Sensitivity, specificity and NPV for CIN2+ of dual-stained cytology were 89.7%, 73.1% and 95.1%, respectively, which was similar when compared with HPV testing. Dual-stained cytology showed a significant lower referral rate than HPV testing (43.6% vs 49.1%; P=0.043). During long-term follow-up, no CIN3+ lesions developed in HPV-positive, dual-stained negative women.
Comparable sensitivity and NPV of dual-stained cytology for CIN3+, combined with a significantly higher specificity, makes p16/Ki-67 dual-stained cytology a viable alternative to HPV testing for triaging BMD.
目前，细胞学边界/轻度不典型（BMD）涂片的女性通过在 6 个月和 18 个月时重复检测进行随访。本研究的目的是分析 p16/Ki-67 双重染色细胞学在检测宫颈上皮内瘤变（CIN）3 级或更高级别（CIN3+）和 CIN2+的 BMD 女性中的横断面和纵向表现，并将结果与基线人乳头瘤病毒（HPV）检测进行比较。
回顾性地对 256 例 BMD 患者的常规巴氏涂片进行 p16/Ki-67 双重染色，并与基线 HPV 结果和长期随访结果进行比较。
p16/Ki-67 双重染色细胞学检测 CIN3+的敏感性为 100%，特异性为 64.4%，阴性预测值（NPV）为 100%。HPV 检测显示出相似的敏感性（96.3%）和 NPV（99.1%），但特异性显著降低（57.6%；P=0.024）。双重染色细胞学检测 CIN2+的敏感性、特异性和 NPV 分别为 89.7%、73.1%和 95.1%，与 HPV 检测相似。双重染色细胞学检测的转诊率明显低于 HPV 检测（43.6% vs 49.1%；P=0.043）。在长期随访中，HPV 阳性、双重染色阴性的女性均未发生 CIN3+病变。
p16/Ki-67 双重染色细胞学检测 CIN3+的敏感性和 NPV 与 HPV 检测相当，特异性显著提高，因此 p16/Ki-67 双重染色细胞学检测可能成为 BMD 患者 HPV 检测的替代方法。
