Sun Meng, Shen Yang, Ren Mu-Lan, Dong Yi-Min
Department of Obstetrics and Gynecology, School of Medicine, Zhongda Hospital, Southeast University, Nanjing 210009, China.
Department of Pathology, University of Arizona College of Medicine, Tucson, AZ 85724, USA.
J Cancer Res Ther. 2018 Sep;14(Supplement):S587-S593. doi: 10.4103/0973-1482.183216.
Although routine screening contributes to substantial reductions in cervical cancer morbidity and mortality, the low specificity of HPV detection and limited sensitivity of cervical cytology necessitates the application of more optimized markers, such as the newly-introduced p16/Ki-67 dual-staining method. Here we reviewed several studies to evaluate the performance of this method in cervical cancer screening.
An electronic database search was performed on PubMed, Web of Science, CNKI and Wanfang Database for studies assessing p16/Ki-67 dual immunostaining in the diagnosis of high-grade cervical intraepithelial neoplasm (HGCIN) with abnormal cytological morphologies. Two reviewers screened literatures, extracted data and assessed the quality of the included studies independently. Meta-analysis was performed using ReV. Man 5.2 and Meta-DiSc 1.2 software packages.
The absolute sensitivity of p16/Ki-67 dual staining for diagnosing HGCIN ranged from 80% to 94%, while the sensitivity of triage method with hrHPV testing ranged from 78% to 96%. The specificity of p16/Ki-67 testing and hrHPV detection for predicting absence of CIN2+ ranged from 39% to 79% and 15% to 44%, respectively. Quantitative meta-analysis showed that the pooled sensitivity of p16/ki-67 dual staining is 0.88 [95'CI (0.86-0.90)], the pooled specificity is 0.58 [95'CI (0.56-0.60)]. For hrHPV testing, the pooled sensitivity and pooled specificity is 0.94 [95'CI (0.93-0.96)] and 0.32 [95'CI (0.29-0.34)], respectively.
p16/Ki-67 dual immunostaining had comparable sensitivity and improved specificity in screening HGCIN or CC when compared with hrHPV detection. Further studies may be beneficial to assess the efficacy of this novel biomarker, which can be potentially used as one of the initial screening assays.
尽管常规筛查有助于大幅降低宫颈癌的发病率和死亡率，但人乳头瘤病毒（HPV）检测的低特异性和宫颈细胞学检查有限的敏感性使得有必要应用更优化的标志物，如新引入的p16/Ki-67双重染色法。在此，我们回顾了多项研究以评估该方法在宫颈癌筛查中的性能。
在PubMed、科学网、中国知网和万方数据库中进行电子数据库检索，查找评估p16/Ki-67双重免疫染色诊断具有异常细胞学形态的高级别宫颈上皮内瘤变（HGCIN）的研究。两名审阅者独立筛选文献、提取数据并评估纳入研究的质量。使用Rev. Man 5.2和Meta-DiSc 1.2软件包进行荟萃分析。
p16/Ki-67双重染色诊断HGCIN的绝对敏感性范围为80%至94%，而高危型HPV（hrHPV）检测分流方法的敏感性范围为78%至96%。p16/Ki-67检测和hrHPV检测预测无CIN2+的特异性分别为39%至79%和15%至44%。定量荟萃分析显示，p16/ki-67双重染色的合并敏感性为0.88 [95%置信区间（0.86 - 0.90）]，合并特异性为0.58 [95%置信区间（0.56 - 0.60）]。对于hrHPV检测，合并敏感性和合并特异性分别为0.94 [95%置信区间（0.93 - 0.96）]和0.32 [95%置信区间（0.29 - 0.34）]。
与hrHPV检测相比，p16/Ki-67双重免疫染色在筛查HGCIN或宫颈癌时具有相当的敏感性和更高的特异性。进一步的研究可能有助于评估这种新型生物标志物的疗效，其有可能用作初始筛查检测方法之一。
