Diagnostic performance of p16 Ki-67 dual immunostaining at different number of positive cells in cervical smears in women referred for colposcopy

Abstract

Objective: Evaluating the diagnostic accuracy of p16/Ki-67 dual immunostaining (p16/Ki-67 DS) in cervical cytology and the number of positive p16/Ki-67 cells to diagnose high grade cervical intraepithelial neoplasia (CIN2+) in colposcopy population.

Materials and methods: We performed an analysis on a subset cohort of 174 women enrolled within a large-scale randomised controlled HPV self-sampling project organised as part of the population-based Cervical Cancer Screening Programme ZORA in Slovenia. This subset cohort of patients was invited to the colposcopy clinic, underwent p16/Ki-67 DS cervical cytology and had the number of p16/Ki-67 positive cells determined.

Results: 42/174 women (24.1%) had histologically confirmed CIN2+. The risk for CIN2+ was increasing with the number of positive cells (p˂0.001). The sensitivity of p16/Ki-67 DS for detection of CIN2+ was 88.1%, specificity was 65.2%, positive predictive value was 44.6% and negative predictive value was 94.5%.

Conclusions: Dual p16/Ki-67 immunostaining for the detection of CIN2+ has shown high sensitivity and high negative predictive value in our study, which is comparable to available published data. The number of p16/Ki-67 positive cells was significantly associated with the probability of CIN2+ detection. We observed a statistically significant and clinically relevant increase in specificity if the cut-off for a positive test was shifted from one cell to three cells.