Mao Constance, Balasubramanian Akhila, Yu Mujun, Kiviat Nancy, Ridder Ruediger, Reichert Anja, Herkert Matthias, von Knebel Doeberitz Magnus, Koutsky Laura A
Department of Obstetrics and Gynecology, University of Washington, Seattle, WA 98104-2499, USA.
Int J Cancer. 2007 Jun 1;120(11):2435-8. doi: 10.1002/ijc.22612.
p16(INK4a), a cell cycle regulation protein, accumulates in abnormal epithelial cells infected with high-risk human papilloma virus (HPV). In immunostaining studies, p16(INK4a) has shown potential as a marker of high grade cervical intraepithelial neoplasia (CIN) and invasive cervical cancer. To evaluate its potential use in cervical cancer screening, we conducted a feasibility study to compare the performance of a new enzyme linked immunosorbant assay (ELISA) for p16(INK4a) (mtm laboratories, Heidelberg, Germany) to that of the Hybrid Capture 2 (hc2) test for high-risk HPV DNA for the detection of CIN3. Three hundred and nineteen women were referred from Western Washington Planned Parenthood clinics for colposcopy examination and cervical biopsy because of abnormal Pap test results. Cervical samples were obtained from study participants for p16(INK4a) ELISA, liquid-based cytology and hc2. The order (first and second) for obtaining samples for cervical cytology and p16(INK4a) ELISA changed with every other subject. Concentrations of p16(INK4a) protein were higher when the sample was taken before the cytology. The sensitivity of p16(INK4a) ELISA (concentration > or = 8 units/ml) taken as first sample was 90.0% for CIN3, and the sensitivity of HC2 taken as a second sample was 85%. In the same group, the specificity of p16(INK4a) ELISA (46.9%) was slightly better than hc2 (35.4%) Results from this proof-of-concept study suggest that p16(INK4a) ELISA has a similar sensitivity and slightly better specificity for CIN3 compared to hc2. These findings support proceeding with a larger study with samples from a population of women presenting for routine cytology screening.
p16(INK4a)是一种细胞周期调节蛋白，在感染高危型人乳头瘤病毒（HPV）的异常上皮细胞中会积聚。在免疫染色研究中，p16(INK4a)已显示出作为高级别宫颈上皮内瘤变（CIN）和浸润性宫颈癌标志物的潜力。为评估其在宫颈癌筛查中的潜在用途，我们进行了一项可行性研究，比较一种用于检测p16(INK4a)的新型酶联免疫吸附测定（ELISA）（德国海德堡的mtm实验室）与杂交捕获2（hc2）高危型HPV DNA检测法在检测CIN3方面的性能。319名因巴氏试验结果异常而从华盛顿州西部计划生育诊所转诊来进行阴道镜检查和宫颈活检的女性参与了研究。从研究参与者处获取宫颈样本用于p16(INK4a) ELISA检测、液基细胞学检查和hc2检测。获取宫颈细胞学样本和p16(INK4a) ELISA样本的顺序（第一次和第二次）每隔一名受试者就会改变。在细胞学检查之前采集样本时，p16(INK4a)蛋白的浓度更高。作为第一个样本的p16(INK4a) ELISA（浓度≥8单位/毫升）对CIN3的敏感性为90.0%，作为第二个样本的HC2的敏感性为85%。在同一组中，p16(INK4a) ELISA的特异性（46.9%）略优于hc2（35.4%）。这项概念验证研究的结果表明，与hc2相比，p16(INK4a) ELISA对CIN3具有相似的敏感性和略好的特异性。这些发现支持对来自进行常规细胞学筛查的女性群体的样本开展更大规模的研究。
