P16/Ki-67双染检测技术在宫颈癌及癌前病变筛查中的价值

doi:10.3760/cma.j.cn371439-20191224-00099

摘要/Abstract

摘要：

目的探讨P16/Ki-67双染检测技术在宫颈癌及癌前病变筛查中的价值和临床意义。方法选取2018年9月至2019年5月山东省潍坊市人民医院妇科收治的110例宫颈上皮内瘤变(CIN)2级以下的患者、31例CIN2级患者、27例CIN3级患者和12例宫颈癌患者,分别评估人乳头瘤病毒(HPV)DNA、液基细胞学技术(TCT)和P16/Ki-67双染检测作为宫颈癌及癌前病变初筛方法的敏感性、特异性、阳性预测值和阴性预测值,并探讨P16/Ki-67双染检测技术用作高危型HPV阳性患者分流的可行性。结果 HPV DNA、TCT和P16/Ki-67双染检测诊断<CIN2级的敏感性分别为80.91%、75.45%、81.82%,特异性分别为91.43%、87.14%、97.14%,阳性预测值分别为93.68%、90.22%、97.83%,阴性预测值分别为75.29%、69.32%、77.27%,差异均具有统计学意义(χ²=1.593,P=0.042;χ²=4.736,P=0.034;χ²=4.667,P=0.037;χ²=1.564,P=0.048),P16/Ki-67双染检测的特异性高于HPV DNA及TCT,敏感性及阳性预测值均高于TCT(均P<0.012 5)。3种方法诊断CIN2级的敏感性分别为90.32%、83.87%、96.77%,差异具有统计学意义(χ²=2.952,P=0.029);特异性分别为80.91%、75.45%、81.82%,差异无统计学意义(χ²=2.505,P=0.066);阳性预测值分别为57.10%、49.10%、60.00%,差异无统计学意义(χ²=1.939,P=0.079);阴性预测值分别为96.70%、94.30%、98.90%,差异具有统计学意义(χ²=3.175,P=0.013);P16/Ki-67双染检测的敏感性、阴性预测值均高于TCT(均P<0.012 5)。3种方法诊断CIN3级的敏感性分别为92.59%、96.30%、96.30%,差异无统计学意义(χ²=0.497,P=0.780);特异性分别为80.91%、75.45%、81.82%,差异具有统计学意义(χ²=4.677,P=0.036);阳性预测值分别为54.30%、49.10%、56.50%,差异具有统计学意义(χ²=1.760,P=0.045);阴性预测值分别为97.80%、98.80%、98.90%,差异无统计学意义(χ²=0.441,P=0.802);P16/Ki-67双染检测的特异性、阳性预测值均高于TCT(均P<0.012 5)。3种方法诊断宫颈癌的敏感性分别为91.67%、75.00%、100.00%,差异具有统计学意义(χ²=3.293,P=0.034);特异性分别为80.91%、75.45%、81.82%,阳性预测值分别为34.40%、25.00%、37.50%,阴性预测值分别为98.90%、96.50%、100.00%,差异均无统计学意义(χ²=2.736,P=0.255;χ²=1.834,P=0.400;χ²=3.075,P=0.081);P16/Ki-67双染检测的敏感性高于TCT(P<0.012 5)。针对高危型HPV阳性患者的分流,P16/Ki-67双染检测及TCT诊断的敏感性分别为98.44%、89.06%,特异性分别为85.71%、61.90%,阴性预测值分别为94.70%、65.00%,差异均具有统计学意义(χ²=4.800,P=0.028;χ²=3.079,P=0.039;χ²=5.284,P=0.022);阳性预测值分别为95.50%、87.70%,差异无统计学意义(χ²=2.565,P=0.109)。结论细胞学P16/Ki-67双染检测诊断<CIN2级的特异性高于HPV DNA及TCT,敏感性及阳性预测值高于TCT;诊断CIN2级的敏感性、阴性预测值均高于TCT;诊断CIN3级的特异性、阳性预测值均高于TCT;诊断宫颈癌的敏感性高于TCT。在对高危型HPV阳性患者的分流当中,P16/Ki-67双染检测提供了一种更加灵敏和准确的分流路径。

关键词: 宫颈肿瘤, 人乳头状瘤病毒DNA检测, 基因, p16, Ki-67抗原

Abstract:

Objective To explore the value and clinical significance of double staining detection of P16/Ki-67 in the screening of cervical cancer and precancerous lesions. Methods Patients admitted to Department of Gynecology of Weifang People's Hospital of Shandong Province from September 2018 to May 2019 were selected, including 110 patients with cervical intraepithelial neoplasia (CIN) below grade 2, 31 patients with CIN2, 27 patients with CIN3, and 12 patients with cervical cancer. The sensitivity, specificity, positive predictive value and negative predictive value of human papillomavirus (HPV) DNA, thinprep cytologic test (TCT) and P16/Ki-67 double staining detection as primary screening method for cervical cancer and precancerous lesions were evaluated, and the feasibility of P16/Ki-67 double staining detection as shunt for high-risk HPV positive patients was discussed. Results The sensitivities of HPV DNA, TCT and P16/Ki-67 double staining detection in the diagnosis of <CIN2 grade were 80.91%, 75.45%, 81.82%, the specificities were 91.43%, 87.14%, 97.14%, the positive predictive values were 93.68%, 90.22%, 97.83%, and the negative predictive values were 75.29%, 69.32%, 77.27% respectively, with statistically significant differences (χ ²=1.593, P=0.042; χ ²=4.736, P=0.034; χ ²=4.667, P=0.037; χ ²=1.564, P=0.048). The specificity of P16/Ki-67 double staining detection was higher than that of HPV DNA and TCT, and the sensitivity and positive predictive value were higher than those of TCT (all P<0.012 5). The sensitivities of HPV DNA, TCT and P16/Ki-67 double staining detection in the diagnosis of CIN2 grade were 90.32%, 83.87%, 96.77%, with a statistically significant difference (χ ²=2.952, P=0.029); the specificities were 80.91%, 75.45%, 81.82%, with no significant difference (χ ²=2.505, P=0.066); the positive predictive values were 57.10%, 49.10%, 60.00%, with no significant difference (χ ²=1.939, P=0.079); and the negative predictive values were 96.70%, 94.30%, 98.90%, with a statistically significant difference (χ ²=3.175, P=0.013). The sensitivity and negative predictive value of P16/Ki-67 double staining detection were higher than those of TCT (both P<0.012 5). The sensitivities of HPV DNA, TCT and P16/Ki-67 double staining detection in the diagnosis of CIN3 grade were 92.59%, 96.30%, 96.30%, with no significant difference (χ ²=0.497, P=0.780); the specificities were 80.91%, 75.45%, 81.82%, with a statistically significant difference (χ ²=4.677, P=0.036); the positive predictive values were 54.30%, 49.10%, 56.50%, with a statistically significant difference (χ ²=1.760, P=0.045); and the negative predictive values were 97.80%, 98.80%, 98.90%, with no significant difference (χ ²=0.441, P=0.802). The specificity and positive predictive value of P16/Ki-67 double staining detection were higher than those of TCT (both P<0.012 5). The sensitivities of HPV DNA, TCT and P16/Ki-67 double staining detection in the diagnosis of cervical cancer were 91.67%, 75.00%, 100.00%, with a statistically significant difference (χ ²=3.293, P=0.034); the specificities were 80.91%, 75.45%, 81.82%, the positive predictive values were 34.40%, 25.00%, 37.50%, and the negative predictive values were 98.90%, 96.50%, 100.00% respectively, with no significant differences (χ²=2.736, P=0.255; χ ²=1.834, P=0.400; χ ²=3.075, P=0.081). The sensitivity of P16/Ki-67 double staining detection was higher than that of TCT (P<0.012 5). For the shunt of high-risk HPV positive patients, the sensitivities of P16/Ki-67 double stain detection and TCT were 98.44% and 89.06%, the specificities were 85.71% and 61.90%, and the negative predictive values were 94.70% and 65.00% respectively, with statistically significant differences (χ ²=4.800, P=0.028; χ ²=3.079, P=0.039; χ ²=5.284, P=0.022); the positive predictive values were 95.50% and 87.70%, with no significant difference (χ ²=2.565, P=0.109). Conclusion Cytology P16/Ki-67 double staining detection is more specific than HPV DNA and TCT in the diagnosis of <CIN2 grade, and its sensitivity and positive predictive value are higher than those of TCT; the sensitivity and negative predictive value of diagnosis of CIN2 grade are higher than TCT; the specificity and positive predictive value of diagnosis of CIN3 grade are higher than those of TCT; the sensitivity of diagnosis of cervical cancer is higher than that of TCT. In the shunt of high-risk HPV positive patients, P16/Ki-67 double staining detection provides a more sensitive and accurate shunt path.

Key words: Uterine cervical neoplasms, Human papillomavirus DNA tests, Genes, p16, Ki-67 antigen

宋明泽, 程一鸣, 李刚, 王振明, 李世荣. P16/Ki-67双染检测技术在宫颈癌及癌前病变筛查中的价值[J]. 国际肿瘤学杂志, 2020, 47(11): 675-681.

Song Mingze, Cheng Yiming, Li Gang, Wang Zhenming, Li Shirong. Value of P16/Ki-67 double staining detection in screening cervical cancer and precancerous lesions[J]. Journal of International Oncology, 2020, 47(11): 675-681.

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诊断指标	≥CIN2级(n=70)		χ²值	P值	≥CIN3级(n=39)		χ²值	P值
诊断指标	TCT	P16/Ki-67	χ²值	P值	TCT	P16/Ki-67	χ²值	P值
敏感性	87.14	97.14	4.834	0.028	89.74	97.44	0.855	0.355
特异性	75.45	81.82	1.326	0.250	62.41	64.54	2.811	0.094
阳性预测值	69.32	77.27	1.422	0.233	39.77	43.18	1.906	0.167
阴性预测值	90.22	97.83	4.738	0.031	95.65	98.91	0.964	0.326
假阴性率	12.86	2.86	4.834	0.028	10.26	2.56	0.855	0.355
假阳性率	24.55	18.18	1.326	0.250	37.59	35.46	2.811	0.094