The effect of p16/Ki-67 and p16/mcm2 on the detection of cervical intraepithelial neoplasia: a prospective study from China.

2,067 women who underwent cervical cancer screening were included in this study. p16/Ki-67 and p16/mcm2 were performed on the remaining liquid-based cytology (LBC) samples of 125 HPV-positive women and 114 randomly selected HPV-negative women. Women with HR-HPV infection or cytological abnormalities (≥ASC-US) were referred for colposcopy and biopsy. A third-year follow up visit was performed on all women except for CIN2+. The expression of p16/Ki-67 and p16/mcm2 in the HPV16/18 group and in the other 12 HR-HPV group was significantly higher than that in HPV negative group (P<0.05), with odds ratios (ORs) of 16.27 (95% CI: 4.38-60.47) and 4.52 (95% CI: 2.16-9.45) for p16/Ki-67, and 31.28 (95% CI: 6.33-154.56) and 9.10 (95% CI: 4.52-18.33) for p16/mcm2, respectively. The sensitivities to detect CIN2+ and CIN3 + were 94.1% (95% CI: 73.0-99.0) and 92.9% (95% CI: 68.5-98.7) for p16/Ki-67, and 88.2% (95% CI: 65.7-96.7) and 85.7% (95% CI: 60.1-96.0) for p16/mcm2, respectively. Both the sensitivities of the two biomarkers were significantly higher than that of LBC and HPV16/18 genotyping (P<0.05). The three-year cumulative risks of CIN2+ were 69.0%, 48.4%, 34.8% and 50.0% for p16/Ki-67, p16/mcm, LBC and HPV16/18 genotyping. Women who tested positive on both p16/Ki-67 and p16/mcm2 at baseline had the highest RR value (39.64 [95% CI: 9.78-160.72]) of progressing to CIN2+ when compared to those who were negative for both. To conclude, p16/Ki-67 and p16/mcm2 dual staining can enhance the sensitivity of cytology in a single round of screening, and they can be predictors of high grade cervical lesions in the following years.