Evaluation of p16/Ki-67 Dual-Stained Cytology in Triaging HPV-Positive Women during Cervical Cancer Screening

Background: We aimed to evaluate the utility of p16/Ki-67 dual-stained cytology for triaging human papillomavirus (HPV)-positive women. Methods: HPV-positive women ages >= 21 years were recruited in a multicenter prospective observational study between May 2016 and May 2017. The clinical performance of dual-stained cytology, with or without HPV16/18 genotyping, was evaluated for all HPV-positive women to detect cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Results: 846 HPV-positive women ages >= 21 years with valid cervical biopsies were enrolled for this study. For CIN2+ detection, dual-stained cytology showed statistically higher specificity (85.28%) than Pap cytology (80.00%, P < 0.001) and HPV16/18 genotyping (72.36%, P < 0.001), while the sensitivity of dualstained cytology (63.49%) remained comparable with that of Pap cytology (61.90%, P = 0.832) and HPV16/18 genotyping ( 61.90%, P = 0.897). HPV16/18 genotyping in combination with dual-stained cytology was more specific (62.50% vs. 58.06%, P < 0.001), while it showed similar sensitivity (86.51% vs. 85.71%, P = 1.000), as compared with HPV16/18 genotyping in combination with Pap cytology. Similar patterns were also observed for CIN3+. Conclusions: p16/Ki-67 dual-stained cytology, either alone or in combination with HPV16/18 genotyping, showed a good stratification with high specificity and comparable sensitivity for HPV-positive women. Impact: This is one of the few studies that has evaluated the performance of dual-stained cytology for triaging HPV-positive women in China. The higher specificity and comparable sensitivity of dual-stained cytology in comparison with Pap cytology in the detection of CIN2+ or CIN3+ is of vital importance to developing countries, where Pap cytology faces many challenges.