Diagnostic Accuracy of Conventional Cell Blocks Along with p16INK4 and Ki67 Biomarkers as Triage Tests in Resource-poor Organized Cervical Cancer Screening Programs

Abstract

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.