OBJECTIVETo confirm the relations between the expression of cyclin E, p16ink4, ki67 and HPV16/18 infection using cervical exfoliated cells, and evaluate the usefulness of cyclin E, p16ink4 and ki67 as biomarkers for screening of cervical carcinomas.

METHODSThe expression of cyclin E, p16ink4 oncoproteins and ki67 proliferative activity was evaluated immunohistochemically in 78 cervical exfoliated epithelial specimens. Human papillomavirus type16 and 18 (HPV16/18) infection was assessed by polymerase chain reaction (PCR) using type specific primers.

RESULTSCyclin E, p16ink4 and ki67 were all overexpressed in cervical preneoplasia and neoplasia cells, compared with little expressed in ASCUS (P less than 0.005). Overexpression of cyclin E was observed in CIN, (P less than 0.01), p16ink4 and ki67 overexpressed in invasive carcinoma(100 percent and 90.9 percent respectively). The degree of p16ink4 and ki67 expression correlated well with the degree of cervical neoplasia (P less than 0.005). HPV16 infection was assessed at all stages of cervical neoplasia samples, and a significant relationship with the degree of cervical epithelial lession was observed at the same time. The expression level of p16ink4 and ki67 seemed to be more closely associated with HPV16 infection than cyclin E did (rs=1.0 vs rs=0.4). HPV18 was found positive in only 1 case in CIN1 and in 4 cases in CIN2-3. Therefore no significance was found on statistical analysis (P less than 0.005).

CONCLUSIONCyclin E, p16ink4 and ki67 should be regarded as useful biomarkers of HPV-related cervical neoplasias, and be used for screening patients at high risk for developing cervical carcinomas. Moreover, cyclin E might be a significant cytologic marker for the primary screening of cervical carcinomas.