Desai Fanny, Singh Lisam Shanjukumar, Majachunglu Gracy, Kamei Helen
Consultant Pathologist and Research Scholar, Cancer Cell Biology Division, Department of Biotechnology, Manipur University, India. Email:
District AIDS Control Officer, Tamenglong, India.
Asian Pac J Cancer Prev. 2019 Mar 26;20(3):917-923. doi: 10.31557/APJCP.2019.20.3.917.
Background: Liquid based cytology with dual biomarkers has improved sensitivity and specificity in detecting high grade cervical intraepithelial neoplasia (CIN). In low resource settings, especially in organized camps, LBC is costly and immunohistochemistry on conventional pap smears is difficult to standardize with consumption of lots of reagents. In present study, to improve the accuracy of conventional pap smears and reduce the cost of biomarker testing, we evaluated conventional cell blocks (CCBs) preparations with biomarkers to detect high-grade CIN in resource-poor organized screening programs. We also studied feasibility of using CCB as primary screening test. Material and Methods: A total of 350 participants were included in the cross-sectional evaluation of the screening tests. A conventional Papanicolaou (Pap) smear was obtained, and another sample was then collected and placed in 10% neutral buffered formalin for CB preparation. All abnormal Pap tests and CBs were stained for the biomarkers p16INK4a and Ki67. Histopathology with p16INK4a expression was considered the gold standard. Diagnostic tests were compared using MacNemar’s test and receiver operating curves were plotted. Results: The sensitivity, specificity, and diagnostic accuracy of CCB cytology, CB + p16 cytology and CB + p16Ki67 cytology for detecting CIN2+ lesions were 85.71%, 100%, 97.44%; 100%, 93.75%, 94.87%; and 85.71%, 100%, 97.44%, respectively. The Ki67 index could further categorize low grade lesions into lesions with low proliferative index and with high proliferative index (Pearson chi-square p value <0.001). Conclusion: If CB preparation is standardized, CCB cytology with biomarkers can have better diagnostic accuracy than conventional cytology, can classify low grade lesions likely to progress and can be used in field settings as primary screening test.
采用双重生物标志物的液基细胞学检查提高了检测高级别宫颈上皮内瘤变(CIN)的敏感性和特异性。在资源匮乏地区,尤其是在有组织的筛查营地,液基细胞学检查成本高昂,而传统巴氏涂片的免疫组织化学检测因消耗大量试剂而难以标准化。在本研究中,为提高传统巴氏涂片的准确性并降低生物标志物检测成本,我们评估了使用生物标志物的传统细胞块(CCB)制备方法,以在资源匮乏的有组织筛查项目中检测高级别CIN。我们还研究了将CCB用作初筛试验的可行性。材料与方法:共有350名参与者纳入筛查试验的横断面评估。获取一份传统巴氏涂片,然后收集另一份样本并置于10%中性缓冲福尔马林中用于制备细胞块。所有异常巴氏涂片和细胞块均进行生物标志物p16INK4a和Ki67染色。以p16INK4a表达的组织病理学检查为金标准。使用麦克尼马尔检验比较诊断试验,并绘制受试者工作曲线。结果:CCB细胞学、细胞块 + p16细胞学和细胞块 + p16Ki67细胞学检测CIN2+病变的敏感性、特异性和诊断准确性分别为85.71%、100%、97.44%;100%、93.75%、94.87%;以及85.71%、100%、97.44%。Ki67指数可进一步将低级别病变分为增殖指数低的病变和增殖指数高的病变(Pearson卡方检验p值<0.001)。结论:如果细胞块制备标准化,使用生物标志物的CCB细胞学检查比传统细胞学检查具有更好的诊断准确性,能够对可能进展的低级别病变进行分类,并且可在现场环境中用作初筛试验。