Role of p16/INK4a and Ki-67 as specific biomarkers for cervical intraepithelial neoplasia: An institutional study

Abstract

BACKGROUND:P16/INK4a and Ki-67 have emerged as important biomarkers for the detection of high-risk human papilloma virus (HR-HPV) associated dysplastic changes in the cervical biopsy samples. The increasing inter- and intra-observer variability in the diagnosis of dysplastic lesions and immature squamous metaplasia on histopathology has led to the advent of these biomarkers. This study was taken up with an aim to study their role in increasing the diagnostic accuracy in equivocal cases on histopathology.MATERIALS AND METHODS:Fifty cervical biopsy specimens were stained with p16/INK4a and Ki-67 consisting of 10 cases each of cervical intraepithelial neoplasia (CIN I/II/III) along with five cases of squamous metaplasia. Histopathological diagnosis was considered as the gold standard. Statistical analysis was done by kappa statistics, and P value was calculated.RESULTS:The sensitivity and specificity of p16/INK4a and Ki-67 were 76.2%, 87.5%, 90.5%, and 87.5%, respectively. The overall agreement of both the immunostains with histopathological diagnosis was statistically significant (P < 0.05) and the diagnostic accuracy improved when both the stains were used in conjunction.CONCLUSION:Ki-67 and p16/INK4a can be used as complimentary tests in differentiating dysplastic and nondysplastic lesions and help in confirming the histopathological diagnosis. They aid in recognition of dysplasias caused by HR-HPV, which have higher tendency to progress to neoplasia. However, further research is advocated before the widespread use of these markers for screening of dysplasias.

Assessment of p16 and Ki67 Immunohistochemistry Expression in Squamous Intraepithelial Lesion with Cytohistomorphological Correlation

“…It was also observed that Ki67 expression was extending into the superficial third of the epithelial layer while LSIL demonstrated Ki67 expression which was limited to the basal third. These findings were similar to those by Srivastav S. et al and Hebbar A. et al (22,23).…”

“…Recently p16 has gained popularity not only in typing the lesion but also in predicting treatment response (21). Several authors have studied p16 expression using different positivity criteria in both preinvasive and invasive squamous carcinomas (22)(23)(24)(25). In this present study the grading used for p16 positivity, was proposed by Songkhun V. et al and later used by Alshenawy H. et al (12,20).…”

The Association of Molecular Biomarkers in the Diagnosis of Cervical Pre-Cancer and Cancer and Risk Factors in Senegalese

“…The low sensitivity of Pap smears and low specificity of HPV testing by HybridCapture2 are other factors which signifies the importance of the biomarkers. The role of HR-HPV in the causation of cervical dysplasias and neoplasia further helps to identify the utility of these markers, especially p16INK4a as its high expression is known to correlate with the prevalence of HR-HPV types (Hebbar and Murthy, 2017 ;Jiang et al, 2020).…”

Histopathological Findings in Symptomatizing Patients After Supracervical Hysterectomy: A Cross Sectional Study

“…Although the screening programs using pap smears are highly successful and being used routinely in some countries, a significant number of cases of cervical cancer have still been missed which can be attributed to false negative test results due to sampling errors, inter and intra observer variability [7].…”