Predictive value of p16-ki67 double staining of cell block in high-grade cervical intraepithelial neoplasia and grades above it

Objectives: we performed p16-ki67 immunohistochemical double staining on cervical cytological specimens to shunt patients with high risk human papillomavirus positive(HR-HPV) and cytological diagnosis of atypical squamous sells of undetermined significance(ASC-US), and to explore its expression in cervical intraepithelial neoplasia grade 2 and above (Cin2 +) patients. Methods: : Age 21-74 years old woman, who were screened for cervical cancer, tested for HPV and cervical cytology in Haidian District Maternal and Child Health care Hospital from January to December 2021 were selected as the research objects. A subset of paired cervical and vaginal specimens (n = 261) were selected to undergo p16-Ki-67 dual-stain cytology, liquid-based cytology and HR-HPV detection. Results: : (1) 1) 239 HR-HPV positive patients (239 / 261), of which 80 had histopathological results of Cin2 + and 159 had histopathological results of negative. The sensitivity, specificity, positive predictive value and negative predictive value of Cin2 + detected by HR-HPV were 98.8% (80 / 81), 11.7% (21 / 180), 33.5% (80 / 239) and 95.5% (21 / 22) respectively; Among 261 patients, 80 cases were positive for p16-Ki67 double staining and 181 cases were negative.The sensitivity, specificity, positive predictive value and negative predictive value of patients with Cin2 + were 86.4% (70 / 81), 94.4% (170 / 180), 87.5% (70 / 80) and 93.9% (170 / 181) respectively; Among the 261 patients, 233 were above ASC-US and 28 were negative. The sensitivity, specificity, positive predictive value and negative predictive value of Cin2 + patients were 91.4% (74 / 81), 11.7% (21 / 180), 31.8% (74 / 233) and 75% (21 / 28), respectively; 2)The kappa values of patients with HR-HPV infection, p16-ki67 double staining and TCT diagnosis above ASC-US and histopathological results were 0.068, 0.811 and 0.02 respectively. (2) The positive rates of p16-ki67 double staining in 239 HR-HPV positive patients and 22 negative patients were 33% (79 / 239) and 4.5% (1 / 22), respectively, with significant difference（ χ2=7.703，p=0.006）. (3) The results showed that TCT had statistical significance for patients with Cin2 + detected in histology (P = 0.041). The positive expression of p16-ki67 double staining was a risk factor for Cin2 + patients (P < 0.05). Conclusion: Our study shows that p16-Ki67 double staining has certain sensitivity and specificity, and has high application value for screening Cin2 + population. In particular, it can be used as an important reference index for negative TCT, ASC-US and low grade squamous intraepithelial lesion(LSIL) results.