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.

Preliminary Study on the Expression of Testin, p16 and Ki-67 in the Cervical Intraepithelial Neoplasia

“…A similar correlation was observed according to the expression of Ki-67. It directly confirms the observation of other authors' research and indicates the validity of using commercial kits (CINtec PLUS Kit) to diagnose LSIL and HSIL [17][18][19][20]. Our study confirms the results of other research and indicates that p16 expression positively correlates with the degree of cervical lesions [21].…”

Architectural aspects of cell-blocks as small biopsies

“…In addition, ancillary tests like Ki-67 and p16 immunohistochemistry can aid in the diagnosis for equivocal cases. [ 22 , 23 ] Cell-blocks can also help avoid the overdiagnosis of tubal metaplasia as AGC by identifying endocervical glands with long terminal cilia [ Figure 2 ]. Many studies have addressed the utility of cell-blocks in the work-up of AGCs and their role in distinguishing glandular from squamous lesions, confirming that cell-block preparations improve the diagnostic rate and can avoid unnecessary biopsies.…”

How to prepare optimum cell blocks in lung cancer: Opinion

“…It also could handle multiple samples simultaneously. The overall loss of tissue particles during tissue processing was very minimal [5]. In lung cancer diagnosis, where biopsies were not possible, we used same technique on pulmonary cytology specimens and found it very effective.…”