人乳头瘤病毒16/18E6蛋白检测在子宫颈癌筛查中的应用

Application of human papillomavirus 16/18 E6 protein detection for cervical cancer screening

目的评价检测人乳头瘤病毒（HPV）16/18 E6蛋白诊断子宫颈癌前病变及子宫颈癌的准确性和有效性.方法选取2014年5月至2015年1月在山西省肿瘤医院妇科就诊的有性生活史的女性439例,其中子宫颈上皮内瘤变（CIN）Ⅱ及以上（CINⅡ、CINⅢ及子宫颈癌）患者299例（病例组）,其余患者为对照组（140例）,所有研究对象均接受了液基薄层细胞检测（TCT）、HPV DNA、HPV 16/18 E6蛋白检测和阴道镜检查.结果病例组TCT、HPV DNA、HPV 16/18 E6蛋白检测的阳性率分别为97.0%（290/299）、94.3%（282/299）、66.9%（200/299）,对照组分别为44.3%（62/140）、21.4%（30/140）、2.9%（4/140）,两组差异均有统计学意义（均P〈0.05）;HPV DNA与HPV 16/18 E6蛋白检测对诊断的灵敏度分别为94.3%、66.9%,特异度分别为78.6%和97.1%;一致率为71.9%（κ=0.21）.病例组中,TCT与HPV DNA联合检测灵敏度为98.9%,特异度为82.8%,准确度为81.7%;TCT与HPV 16/18 E6蛋白联合检测灵敏度为97.9%,特异度为97.1%,准确度为95.0%.结论HPV 16/18 E6蛋白检测可提高子宫颈癌筛查的特异度,可作为HPV DNA检测无法开展或开展困难的欠发达地区的初筛方法,或作为HPV DNA阳性患者分流的方法,以更合理地分配有限的卫生资源.

Objective To evaluate the diagnostic accuracy and efficacy on cervical precancerous lesions and cervical cancer by HPV 16/18 E6 protein detection. Methods A total of 439 females with sexual activities were selected from Department of Gynaecology in Shanxi Cancer Hospital from May 2014 to January 2015, including 299 cases of cervical intraepithelial neoplasia （CIN）Ⅱ, CINⅢ or cervical cancer （the case group）, and the other 140 cases （the control group）. All the patients accepted the thinprep cytology test （TCT）, HPV DNA and HPV 16/18 E6 oncoprotein tests and colposcope examination. Results The positive rates of the TCT, HPV DNA, HPV 16/18 E6 oncoprotein in the case group were 97.0 % （290/299）, 94.3 % （282/299） and 66.9 % （200/299）, respectively, and those in the control group were 44.3 % （62/140）, 21.4 % （30/140） and 2.9%（4/140）, respectively, and there were significant differences between both groups （all P〈0.05）. The sensitivity and specificity of the HPV 16/18 E6 oncoprotein test in detecting CINⅡ and above were 66.9 %and 97.1 %, respectively, and both of HPV DNA test were 94.3 % and 78.6 %, respectively; The consistent rate between HPV 16/18 E6 and HPV DNA was 71.9 % （κ= 0.21）. In the case group, when TCT was associated with HPV DNA test, the sensitivity, specificity and accuracy were 98.9%, 82.8%and 81.7%, respectively, and when TCT was combined with HPV 16/18 E6 oncoprotein test, those were up to 97.9 %, 97.1 % and 95.0 %. Conclusion HPV 16/18 E6 oncoprotein test can improve the specificity of cervical cancer screening, so it may be used as a primary screening method in the less developed areas where HPV DNA test is difficult to be carried out, or as a shunt method for HPV DNA positive patients, which will allocate the limited health resources rationally.