The Association Between P16/Ki67, P16/mcm2 Expression And HPV E6/E7mRNA And Evaluate Their Detection Ability Of Cervical Lesions

Objective:To explore the relationship between p16/Ki67,p16/mcm2 with cervical cancer and precancerous lesions and high-risk HPV E6/E7mRNA infection and their detection ability of cervical cancer and precancerous lesions,evaluate the feasibility of p16/Ki67,p16/mcm2 replace cytology as early cervical cancer screening method and triage ability in HPV positive people.Methods:between September 2016 and June 2017497 women（age at 21-70）from three hospital of Changzhi,Shanxi province take part in this study,all the women in this study should have HPV E6/E7mRNA detection,LBC detection,p16/Ki67 dual stain and p16/mcm2dual stain.Results:1)the relationship between p16/Ki67 with cervical cancer and precancerous lesions and high-risk HPV E6/E7mRNA infection:the positive rate of p16/Ki67 dual stain increased with the increase of cytology diagnosis(χ²=139.0,P_trend<0.001);The positive rate of LBC and p16/Ki67increased with the increase of cervical lesions(χ²=46.6,P_trend<0.001,χ²=16.8,P_trend<0.001);The expression rate of p16/Ki67 in HPV positive population was 14.9 times higher than HPV negative population.In CIN2+women,the sensitivity of p16/Ki67 are equal to LBC and HPV E6/E7 mRNA,but the specificity of p16/Ki67 dual stain were higher than LBC and HPV E6/E7 mRNA（P<0.05）.In addition,the area under the ROC curve of p16/Ki67 is larger than LBC.In CIN3+women,the sensitivity of HPV E6/E7mRNA detection was higher than p16/Ki67,but the specify of p16/Ki67 was higher than HPV E6/E7mRNA detection.And LBC.The area under the ROC curve of HPV E6/E7mRNA and p16/Ki67 were larger than LBC detection（P=0.002,P=0.016）.In HPV E6/E7mRNA positive women,the sensitivity of p16/Ki67 was equal to LBC in CIN2+and CIN 3+women,but the specify of p16/Ki67 was higher than LBC（P<0.001）.2)the relationship between p16/mcm2 with cervical cancer and precancerous lesions and high-risk HPV E6/E7mRNA infection:the positive rate of p16/mcm2dual stain increased with the increase of cytology diagnosis(χ²=54.687,P_trend<0.001);The positive rate of p16/mcm2 and LBC increased with the increase of cervical lesions(χ²_p16/mcm2=23.617 P<0.001,χ²_LBC=16.818 P<0.001).The positive rate of p16/mcm2 in HPV E6/E7 mRNA positive women was higher than it in HPV E6/E7 mRNA negative women,the odds ratios was 6.451.In CIN2+women,the sensitivity of p16/mcm2,LBC and HPV E6/E7 mRNA detection were no statistical difference,but the specificity of p16/mcm2 was higher than LBC（P=0.013）;.In CIN3+women the sensitivity of HPV E6/E7 mRNA was higher than p16/mcm2（P=0.016）,In HPV E6/E7mRNA positive women,the sensitivity of p16/mcm2was equal to LBC in CIN2+and CIN3+women,but the specificity of p16/mcm2 was higher than LBC（P=0.041,P=0.041）.3)The expression of p16/Ki67 and p16/mcm2 in different cytological diagnosis level:The positive rate of p16/mcm2 in cytodiagnosis NILM,ASCUS,ASCUS-H,LSIL,SCC were higher than p16/Ki67（P<0.001）.In CIN2+and CIN3+cases,the sensitivity of p16/Ki67 dual stain was equal to p16/mcm2,but the specificity of p16/Ki67 was higher than p16/mcm2（P<0.001）.The area under the ROC curve of p16/Ki67 was also larger than p16/mcm2.In HPV E6/E7 mRNA positive women,the sensitivity of p16/Ki67 dual stain was equal to p16/mcm2 and the specificity of p16/Ki67 was higher than p16/mcm2（P<0.001）.Conclusion:1)the p16/Ki67 and p16/mcm2 were consistent with LBC,the high expression of p16/Ki67 and p16/mcm2 in HPV positive women shows that p16/Ki67 and p16/mcm2dual stain can be used as a potential biomarker for the detection of cervical cancer and precancerous lesion.2)The diagnostic value of p16/Ki67 p16/mcm2dual stain were higher than LBC,therefore in economic less-developed and less pathology doctors region,we can consider p16/Ki67and p16/mcm2 for the detection of cervical cancer and precancerous.Compared with LBC,p16/Ki67 and p16/mcm2dual stain can edification more disease-free women.3)For the triage of HPV positive women,p16/Ki67and p16/mcm2can effectively reduce the colposcopy referral rate and avoid the harm caused by excessive referral to women with the equal sensitivity to LBC.And for the triage effect of HPV positive women,the p16/Ki67was better than p16/mcm2 and LBC.