Evaluation of p16/Ki67 dual staining compared with high-risk HPV testing to assess liquid-based cytology with atypical squamous cells of unknown significance

Objective: To compare the clinical performance of p16/Ki67 dual staining and high risk-human papilloma virus (HR-HPV) testing as an auxiliary monitoring index to triage atypical squamous cells of undetermined significance (ASCUS). Materials and Methods: Fifty-four patients diagnosed with ASCUS by liquid-based cytology were inspected by colposcopy-guided biopsy and cervical histopathological examination. The cytological samples were tested for HR-HPV with Cervista HPV assays, and the cell morphology was evaluated with dual staining using the CINtec PLUS kit. ROC curves were used to evaluate the diagnostic value of p16/Ki67 dual staining and HR-HPV assays to detect underlying CIN2+ in ASCUS patients. The kappa value assessed the reliability of p16/Ki67 dual staining and HR-HPV, and the diagnostic advantages of the two tests were analyzed using logistic regression analysis. Results: Twenty-two of the 54 ASCUS cases were diagnosed as CIN2+ by histopathology. The area under the ROC curve was 0.776 (95% CI 0.647-0.904) and 0.689 (95% CI 0.548-0.830) for CIN2+ detection using p16/Ki67 dual-staining cytology and HR-HPV, respectively. P16/Ki67 dual staining demonstrated a sensitivity and negative predictive value similar to that of HR-HPV for detecting underlying CIN2+ in ASCUS (86.36% vs. 90.91%, 88.00% vs. 88.24%). There was a certain degree of concordance between the p16/Ki67 dual staining cytological assay and the HR-HPV test (kappa = 0.315, p = 0.015). The accuracy of CIN2+ diagnosis using p16/Ki67 dual staining cytology was higher than that of HR-HPV (OR = 11.025 vs. OR = 6.026, p = 0.001). Conclusions: P16/Ki67 dual staining and HR-HPV can be used as an auxiliary monitoring index to triage ASCUS. The diagnostic value of p16/Ki67 dual staining was superior to that of HR-HPV for detecting underlying CIN2+ in ASCUS.