| BackgroundCervical cancer is the most common gynecologic malignant tumor, in recent years, Domestic and abroad journals both have reported the incidence of cervical cancer is getting younger and younger. The cases of cervical cancer which under 35 years old increased. Therefore, cervical cancer screening and prevention is important. And cervical intraepithelial neoplasia (CIN) is a general term for a group of precancerous lesions which related with cervical cancer, including cervical dysplasia and cervical carcinoma in situ (carcinoma in situ, CIS). It reflects the continuous process of development of cervical cancer, this phase lasts for a long time, up to 10 to 20 years, from cervical dysplasia to carcinoma in situ and invasive carcinoma is a long process of development. To prevent the occurrence of cervical cancer, the key is to do the screening of cervical intraepithelial neoplasia[1]. At present, the diagnosis of cervical intraepithelial neoplasia methods mainly include:cervical cytology, human papillomavirus (HPV) testing, colposcopy, diagnostic conization and biopsy, genetic diagnosis. Chinese Medical Association recommended cervical lesions diagnosed three step procedure for cytology, colposcopy and cervical biopsy [2], In addition to agree that the traditional diagnosis method is effective, we also have to recognize their limitations in certain areas. Cervical cytology is the most common method of cervical cancer screening, but mainly through observation under the microscope, with the pathologist’s own experience to judge, there are some false negative and false positive rate; Colposcopy and cervical biopsy, as an invasive examination, diagnosis can be performed on patients, but not for all patients. Therefore, looking for simple and effective new method is imperative.In eukaryotic cells, the progression of cell division is controlled by a variety of cell cycle regulatory proteins. P16INK4a is part of the G1/S phase transformation control, and can trigger cell cycle arrest in the cell differentiation process. The P16INK4a which is expressed in normal cell cycle progression exhibit an antiproliferative effect. In terminally differentiated epithelial cells, the expression of P16INK4a is down to a level which immunocytochemistry can not be detected[3]. And Ki67 is a protein involved in cell proliferation, can only be detected in proliferating cell nucleus, G0 phase of resting cells do not express this antigen [4]. Cells with overexpressing P16INK4a only will actively proliferating when cell cycle regulation mechanism is damaged, so under normal physiological conditions, within the same cell proliferation markers Ki67 and p16 should be mutually exclusive. If both intracellular expression of Ki67 and P16INK4a, can be used as an indicator of cell cycle regulation disorders.This experiment is based on the above principle, on the basis of traditional diagnosis methods, further using immunocytochemistry method, detect p16 and Ki67 protein in cervical exfoliated cells. With cervical biopsy results as the gold standard, use statistical methods to calculate sensitivity and specific degree, etc., evaluation of the reliability and feasibility of detection of cervical intraepithelial neoplasia.ObjectiveStudy of P16/Ki67 protein detection (cintec plus double dyeing technology) value to the diagnosis of cervical intraepithelial neoplasia and cervical cancer screening.MethodsUsing BD Surepath cytology samples tools to collect outpatients’ cervical cell specimens, and using Roche’s CINTec@ Plus Cytology Kit for detection. With cervical biopsy results as the gold standard to calculate sensitivity, specificity and overall compliance rate, evaluating the application value of P16/Ki67 protein detection in the diagnosis of cervical cancer screening and cervical intraepithelial neoplasia. Using the matching chi-square test to verify cintec plus double staining with cervical liquid based cytology diagnosis differences are statistically significant.ResultsCollected specimens of all kinds of 104 cases, the sensitivity (positive coincidence rate) was 80.00%(95%CI:62.70%～90.50%),20.00% misdiagnosis rate, specificity (negative coincidence rate) was 75.68%(95% CI:64.79%～84.02%),24.32% misdiagnosis rate, Total coincidence rate was 76.92%(76.92% CI:67.95%～83.97%), Kappa value was 0.5, positive likelihood ratio (+LR) is 3.3, the negative likelihood ratio (-LR) is 0.26, Youden index (YI) is 0.56.Cervical liquid based cytology, the sensitivity of 60.00%,40% missed diagnosis, specific degree of 83.78%, the misdiagnosis rate was 16.22%, the total coincidence rate 76.92%, Kappa value 0.44, positive likelihood ratio of 3.7, negative likelihood ratio of 0.48, Youden index (YI) 0.44.The two parallel combined test, sensitivity was 83.3%, Specific degree was 68.9%, Kappa value 0,45, Youden index (YI) 0.522.ConclusionsP16/Ki67 protein detection (cintec plus double dyeing technology) for diagnosis of cervical intraepithelial neoplasia and cervical cancer screening have clinical application value. |
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