Benefits of P16/Ki- 67 Cytology as a Co-Test for High-Risk HPV Positive Women in a “See and Treat Strategy”

Abstract

Background: While the high-risk human papilloma virus DNA (hr-HPV-DNA) test is the primary tool for cervical cancer screening, with visual inspection with acetic acid (VIA) serving as a triage test where Pap cytology is not available, the low inter-observer agreement associated with VIA means that its reliability is limited and a more efficient test is still required. The aim of this study was to compare the performance of p16/Ki-67 cytology with that of VIA in the detection of cervical precancer and its feasibility as an alternative triage method in the “see and treat strategy”. Methods: In this hospital-based cross-sectional study, we utilised stored, provider-collected specimens from a previous study involving women referred with cervical abnormalities to a tertiary hospital in Kisumu County, Kenya. The samples were analysed using both Xpert testing and p16/Ki-67 dual staining. All high-risk HPV–positive women with cervical lesions were triaged using VIA and p16/Ki-67 cytology. Cervical intraepithelial neoplasia grade 2 or worse (≥CIN2) was defined as the clinical endpoint. Results: Compared with VIA, p16/Ki-67 immunostaining had a significantly greater sensitivity (84.6% vs. 59.0%), specificity (44.0% vs. 62.0%), positive predictive value (28.2% vs. 28.8%) and negative predictive value (91.7% vs. 85.3%). Conclusion: p16/Ki-67 immunostaining for the detection of ≥CIN2 demonstrated high sensitivity and a high negative predictive value in our study, consistent with findings from several previous studies. These results suggest that the assay is superior to VIA for identifying ≥CIN2 and could serve as an alternative tool for triaging women who test positive for primary HPV within the current “see-and-treat” strategy.