Wentzensen Nicolas, Hampl Monika, Herkert Matthias, Reichert Anja, Trunk Marcus J, Poremba Christopher, Ridder Ruediger, von Knebel Doeberitz Magnus
Department of Applied Tumor Biology, Institute of Pathology, University of Heidelberg, Heidelberg, Germany.
Cancer. 2006 Nov 1;107(9):2307-13. doi: 10.1002/cncr.22247.
Current cervical cancer screening approaches are based on cytology supplemented by human papillomavirus (HPV) testing in some settings. Whereas cytology is laborious and depends on the cytologists' experience, HPV testing has limited specificity when it is used to detect high-grade lesions. A dichotomous test to identify high-grade lesions with greater specificity may be a useful tool for cervical cancer screening. p16(INK4a) is a cell-cycle regulator that has demonstrated strong overexpression in cervical precancer cells and cervical cancer induced by the deregulated expression of HPV oncogenes.
The authors used a sandwich enzyme-linked immunosorbent assay (ELISA) to quantify the amount of solubilized p16(INK4a) protein in lysates that were prepared from cervical samples to detect high-grade cervical lesions. In total, 187 specimens that were obtained after sampling for conventional cytology in women who attended a cervical colposcopy clinic were analyzed. Seventy-six women underwent a biopsy, and 45 of those women showed histologically confirmed, high-grade cervical intraepithelial neoplasia.
For 76 women with biopsy-proven diagnoses, receiver operating characteristic (ROC) analysis of different cutoff values showed an area under the ROC curve of 0.89 for the detection of high-grade cervical dysplasia. At a cutoff value of 8 U/mL, the sensitivity of the p16(INK4a) ELISA for detecting high-grade dysplastic cervical lesions was 96%.
The data obtained in this study suggested that ELISA-based quantification of solubilized p16(INK4a) protein may have high sensitivity for detecting cervical precancer. Further population-based studies will be necessary to analyze the specificity and predictive values of p16(INK4a) protein quantification in cervical samples.
当前宫颈癌筛查方法以细胞学检查为基础，在某些情况下辅以人乳头瘤病毒（HPV）检测。细胞学检查费力且依赖细胞学家的经验，而HPV检测用于检测高级别病变时特异性有限。一种能以更高特异性识别高级别病变的二分法检测可能是宫颈癌筛查的有用工具。p16（INK4a）是一种细胞周期调节因子，在HPV癌基因表达失调诱导的宫颈癌细胞和宫颈癌前细胞中表现出强烈的过表达。
作者使用夹心酶联免疫吸附测定（ELISA）对宫颈样本制备的裂解物中可溶性p16（INK4a）蛋白的量进行定量，以检测高级别宫颈病变。总共分析了187份在宫颈阴道镜诊所就诊的女性进行常规细胞学采样后获得的标本。76名女性接受了活检，其中45名女性经组织学证实患有高级别宫颈上皮内瘤变。
对于76名经活检确诊的女性，不同临界值的受试者操作特征（ROC）分析显示，检测高级别宫颈发育异常的ROC曲线下面积为0.89。在临界值为8 U/mL时，p16（INK4a）ELISA检测高级别发育异常宫颈病变的灵敏度为96%。
本研究获得的数据表明，基于ELISA对可溶性p16（INK4a）蛋白进行定量检测对检测宫颈癌前病变可能具有高灵敏度。有必要进行进一步的基于人群的研究，以分析宫颈样本中p16（INK4a）蛋白定量检测的特异性和预测价值。
