Abstract:

Objective To explore the value and clinical significance of double staining detection of P16/Ki-67 in the screening of cervical cancer and precancerous lesions. Methods Patients admitted to Department of Gynecology of Weifang People's Hospital of Shandong Province from September 2018 to May 2019 were selected, including 110 patients with cervical intraepithelial neoplasia (CIN) below grade 2, 31 patients with CIN2, 27 patients with CIN3, and 12 patients with cervical cancer. The sensitivity, specificity, positive predictive value and negative predictive value of human papillomavirus (HPV) DNA, thinprep cytologic test (TCT) and P16/Ki-67 double staining detection as primary screening method for cervical cancer and precancerous lesions were evaluated, and the feasibility of P16/Ki-67 double staining detection as shunt for high-risk HPV positive patients was discussed. Results The sensitivities of HPV DNA, TCT and P16/Ki-67 double staining detection in the diagnosis of <CIN2 grade were 80.91%, 75.45%, 81.82%, the specificities were 91.43%, 87.14%, 97.14%, the positive predictive values were 93.68%, 90.22%, 97.83%, and the negative predictive values were 75.29%, 69.32%, 77.27% respectively, with statistically significant differences (χ ²=1.593, P=0.042; χ ²=4.736, P=0.034; χ ²=4.667, P=0.037; χ ²=1.564, P=0.048). The specificity of P16/Ki-67 double staining detection was higher than that of HPV DNA and TCT, and the sensitivity and positive predictive value were higher than those of TCT (all P<0.012 5). The sensitivities of HPV DNA, TCT and P16/Ki-67 double staining detection in the diagnosis of CIN2 grade were 90.32%, 83.87%, 96.77%, with a statistically significant difference (χ ²=2.952, P=0.029); the specificities were 80.91%, 75.45%, 81.82%, with no significant difference (χ ²=2.505, P=0.066); the positive predictive values were 57.10%, 49.10%, 60.00%, with no significant difference (χ ²=1.939, P=0.079); and the negative predictive values were 96.70%, 94.30%, 98.90%, with a statistically significant difference (χ ²=3.175, P=0.013). The sensitivity and negative predictive value of P16/Ki-67 double staining detection were higher than those of TCT (both P<0.012 5). The sensitivities of HPV DNA, TCT and P16/Ki-67 double staining detection in the diagnosis of CIN3 grade were 92.59%, 96.30%, 96.30%, with no significant difference (χ ²=0.497, P=0.780); the specificities were 80.91%, 75.45%, 81.82%, with a statistically significant difference (χ ²=4.677, P=0.036); the positive predictive values were 54.30%, 49.10%, 56.50%, with a statistically significant difference (χ ²=1.760, P=0.045); and the negative predictive values were 97.80%, 98.80%, 98.90%, with no significant difference (χ ²=0.441, P=0.802). The specificity and positive predictive value of P16/Ki-67 double staining detection were higher than those of TCT (both P<0.012 5). The sensitivities of HPV DNA, TCT and P16/Ki-67 double staining detection in the diagnosis of cervical cancer were 91.67%, 75.00%, 100.00%, with a statistically significant difference (χ ²=3.293, P=0.034); the specificities were 80.91%, 75.45%, 81.82%, the positive predictive values were 34.40%, 25.00%, 37.50%, and the negative predictive values were 98.90%, 96.50%, 100.00% respectively, with no significant differences (χ²=2.736, P=0.255; χ ²=1.834, P=0.400; χ ²=3.075, P=0.081). The sensitivity of P16/Ki-67 double staining detection was higher than that of TCT (P<0.012 5). For the shunt of high-risk HPV positive patients, the sensitivities of P16/Ki-67 double stain detection and TCT were 98.44% and 89.06%, the specificities were 85.71% and 61.90%, and the negative predictive values were 94.70% and 65.00% respectively, with statistically significant differences (χ ²=4.800, P=0.028; χ ²=3.079, P=0.039; χ ²=5.284, P=0.022); the positive predictive values were 95.50% and 87.70%, with no significant difference (χ ²=2.565, P=0.109). Conclusion Cytology P16/Ki-67 double staining detection is more specific than HPV DNA and TCT in the diagnosis of <CIN2 grade, and its sensitivity and positive predictive value are higher than those of TCT; the sensitivity and negative predictive value of diagnosis of CIN2 grade are higher than TCT; the specificity and positive predictive value of diagnosis of CIN3 grade are higher than those of TCT; the sensitivity of diagnosis of cervical cancer is higher than that of TCT. In the shunt of high-risk HPV positive patients, P16/Ki-67 double staining detection provides a more sensitive and accurate shunt path.

Key words: Uterine cervical neoplasms, Human papillomavirus DNA tests, Genes, p16, Ki-67 antigen