Relations Between The Expression Of Cyclin E,p16ink4,ki67 And HPV16/18 Infection In Cervical Exfoliated Cells

Objective:To confirm the relations between the expression of cyclin E,p16ink4,ki67 and HPV16/18 infection using cervical exfoliated cells,andevaluate the usefulness of cyclin E,p16ink4 and ki67 as valuable biomarkers forscreening of cervical carcinomas. Methods:the expression of cyclin E,p16ink4 oncoproteins and ki67proliferative activity was evaluated immuohistochemically in 12 atypicalsquamous cells of undetermined significance ASCUS ,17 cervical intraepithelialneoplasia 1(CIN1),38 CIN2-3 and 11 invasive cervical carcinomas .humanpapillomavirus type16 and 18 (HPV16/18) infection was assessed bypolymerase chain reaction(PCR) using type specific primers.χ~2 test with FisherProbabilities and Spearman relation statistical analysis was used . Results:cyclin E,p16ink4 and ki67 were all overexpressed in cervicalpreneoplasia and neoplasia cells ,compared with little expressed in ASCUS( P<0.005) Overexpression of cyclin E was observed in CIN1(94.1% P<0.01),p16ink4 and ki67 overexpressed in invasive carcinoma(100% and 90.9%respectively). The degree of p16ink4 and ki67 expression correlated well withthe degree of cervical neoplasia ( P<0.005). HPV16 infection was assessed at allstage cervical neoplasia samples, and a significant relationship with the degreeof cervical epithelial lession was observed at the same time. The expressionlevel of p16ink4 and ki67 seems more close associated with HPV16 infectionthan cyclin E do(r_s=1.0 vs r_s=0.4). HPV18 positive samples were detected only1 case in CIN1 and 4 cases in CIN2-3. Therefore no significance was found bystatistical analysis (χ~2=3.682 P<0.005). Conclusion:cyclin E,p16ink4 and ki67 should be regarded as usefulbiomarkers of HPV-related cervical neoplasias,and be used for screening patients athigh risk of developing cervical carcinomas .Moreover, cyclin E might be asignificant cytologic marker for the primary screening of cervical carcinomas.