Improving Early Diagnosis of Cervical Cancer Lesions Using P16INK4a Biomarkers on Cellblocks from Cervical Smears

Abstract

Universally, cancer of cervical is the second utmost regular malignant growth in females after cancer of breast. Timely recognition of pre-malignant lesions is an essential segment for the decrease of related morbidity and mortality. Though Pap test has been a helpful screening device, however hampered by high Intra and inter-observer changeability, false negatives at 20-30% and false positives at 5-70%. Objective:The study determined the role of P16 INK4a biomarker in the identification of low grade squamous intra-epithelial abrasions in cell blocks prepared from Pap smears and subsequently compared previous Pap results with colposcopy and cellblock results Methods: This was a laboratory-based, prospective study with a parallel comparative arm at the Kenyatta National Hospital Reproductive health clinic (66). All patients who had abnormal Pap smear reports and referred for colposcopy, and consented for the study were enrolled. A smear was taken just before taking a colposcopy biopsy. The cytobrush was immediately put in Acid alcohol fixative centrifuged and deposits wrapped in a filter paper and processed histologically to form a cellblock. Colposcopy biopsies were then retrieved from the KNH histology lab and both samples subjected to Routine histological stain and eventually with biomarker P16. Total of 85 samples was collected. Results: There was a significant level of agreement between Pap smears and cellblock findings on the routine Histological stain. Of 58 cases analyzed Colposcopy had (39%) 27 negatives and (45%) 31 positives while cellblock had (48%) 33 negative and (36%) 25 positive for pre and malignancy with a confidence interval of 0.016 as the margin of error. Biomarker Colposcopy had (43%) 30 negativity and (41%) 28 positivity while cellblock had negativity of (46%) 32 and positivity of (38 %) 26. The specificity and sensitivity were based on the true values of colposcopy as the golden standard test for cervical cancer. Biomarker cellblock had the "sensitivity and specificity" of 93.3% and 93.8% respectively, while Haematoxyline and eosin-stained cellblock had sensitivity and specificity of 83.8% and 81.8% respectively. Conclusion:Poor inter-rater agreement resulting to mortality and morbidity associated with false positives and false negatives, cellblock prepared from residues of cytobrush stained with haematoxyline and eosin and biomarker is likely to circumvent all the above, together with minimizing loss to follow up as patients only visit health facility once and they acquire all the results without re-sampling hence drastically reducing the cost of colposcopy, which requires highly specialized equipment and experienced personnel who are very few and difficult to find.