Abstract
Background:Colposcopy was referred in cases with severe abnormalities in co-testing. However, approximately 60%-80% patients did not receive proper benefits. Although p16/Ki67 dual staining reduced the referral rate, its sensitivity and specificity need to be enhanced. Methods:The expression of p16, Ki-67, SMAD3, YAP1, RELA were evaluated inthe colposcopy referral population. Results:The sensitivity and specificity of p16+ combined with Ki-67+ for predicting CIN2+ were 62.1% and 89.5%, respectively. p16+ combined with YAP1+ and/or RELA+ provided a sensitivity and specificity of 70.9% and 89.5%, respectively, while 72.8% and 86.4% were achieved by p16+ combined with YAP1+ and/or SMAD3+ and/or RELA+. In HPV16/18+ and LSIL subgroups, the sensitivity and specificity of p16+ combined with Ki-67+ for predicting CIN2+ were 67.7% and 87.6%, respectively, for the former group and 58.6%, 88.8%, respectively, for the latter group, whereas those of RELA alone were 76.9% and 90.5%, respectively, and 82.8% and 92.1%, respectively. p16+, YAP1+/RELA+ showed a better performance for predicting CIN2+ with a better sensitivity (86.7% vs. 52.2%, p=0.028) and considerable specificity (86.7% vs. 90.0%, p=0.486) in the other HPV+ combined with ASCUS groupthan were achieved by p16+ combined with Ki-67+. RELA+ and the combination of p16 and RELA/YAP1 also provided the Max AUC area. Conclusions:Our study shows that RELA and the combination of p16 and RELA/YAP1 achieved better sensitivity and specificity for detecting morphologically CIN2+ lesions.