Role of p16/Ki-67 dual-stained cytology in triaging women with high-risk human papilloma virus

Objective To assess the performance of p16/Ki-67 dual-stained cytology in triaging high-risk human papilloma virus (HR-HPV) positive women.

Methods A total of 776 HR-HPV positive women in Shanghai Minhang Central Hospital from September 2019 to May 2020 were included. The cervical exfoliated cells from eligible women were collected for p16/Ki-67 dual-stained cytology and thinprep cytologic test (TCT), and cervical biopsy using colposcopy was conducted. Histology diagnosis was used as the gold standard, the predictive value of p16/Ki-67 dual-stained cytology and TCT for cervical lesion in HR-HPV positive women was compared. Furthermore, the number of colposcopies required per high-grade squamons intraepithelial lesion (HSIL⁺) detected was calculated.

Results The positive rates of p16/Ki-67 dual-stained cytology (χ²=141.324, P < 0.001) and TCT (χ²=81.328, P < 0.001) were significantly increased with the increased histologic severity of the cervical lesion. For detection of HSIL⁺, p16/Ki-67 dual-stained cytology and TCT had similar specificity (80.3% vs 84.0%, P=0.070) and positive predictive value (28.9% vs 24.8%, P=0.405), but p16/Ki-67 dual-stained cytology had higher sensitivity (75.7% vs 50.0%, P=0.001) and negative predictive value (96.9% vs 94.1%, P=0.019). In other 12 types of HR-HPV, p16/Ki-67 dual-stained cytology required fewer colposcopies per HSIL⁺ detected compared with TCT (P=0.036).

Conclusions Among HR-HPV positive women, compared with TCT, p16/Ki-67 dual-stained cytology has higher sensitivity, negative predictive value, and requires fewer colposcopies, with simple operation and easy interpretation of results. This method will be beneficial for the regions where there is in shortage of cytologists and colposcopy physicians.