高危型人乳头状瘤病毒联合肿瘤标志物检测在宫颈癌诊断中的价值

The diagnostic value of combined detection of high - risk human papillomavirus with serum tumor markers in cervical cancer

目的探讨高危型人乳头状瘤病毒（HR．HPV）联合多项血清肿瘤标志物检测在宫颈癌诊断中的应用价值。方法选取249例宫颈癌患者、30例宫颈上皮内瘤变（CIN）患者、60例健康对照组作为研究对象。采用化学发光微粒子免疫分析（CMIA）法检测血清癌胚抗原（CEA）、糖类抗原125（CAl25）、糖类抗原19-9（CA19-9）、鳞状细胞癌抗原（SCCA）的水平，采用电化学发光免疫测定（ECLI）法检测血清糖类抗原72-4（CA72-4）、人附睾蛋白（HE4）的水平。采用导流杂交基因芯片技术检测上述研究对象的生殖道HPV感染状况。结果宫颈癌组血清CA72-4水平[3．13（2．25，7．63）rig／mL]明显高于CIN组的2．37（1．98，6．25）ng／mL和对照组的2．69（2．35，3．35）ng／mL，差异均有统计学意义（P=0．028；P=0．003）；宫颈癌组血清CEA水平[3．08（2．28，4．75）ng／mL]明显高于CIN组的1．45（1．00，1．83）ng／mL和对照组2．13（1．45，2．67）ng／mL，差异均有统计学意义（均P=0．000）；宫颈癌组血清CAl25水平[24．4（20．30，44．15）U／mL]明显高于CIN组的12．85（7．90，16．23）U／mL和对照组的12．33（11．26，17．11）U／mL，差异均有统计学意义（均P=0．000）；宫颈癌组血清CAl9-9水平[27．05（18．48，38．01）U／mL]明显高于CIN组的13．01（8．79，17．12）U／mL和对照组的12．83（10．89，17．93）U／mL，差异均有统计学意义（均P=0．000）；宫颈癌组血清SCCA水平[1．7（0．90，4．75）ng／mE]明显高于CIN组的0．80（0．60，1．10）ng／mL和对照组的0．60（0．50，0．70）ng／mL，差异均有统计学意义（均P=0．000）。三组间HE4水平差异无统计学意义（P〉0．05）。宫颈癌组HR-HPV感染率92．4％，CIN组90．0％，均明显高于对照组的15．0％，差异均有统计学意义（X2=46．875，P=0．000；X2=165．178，P=0．000）。宫颈癌患者中，血清肿瘤标志物表达水平与宫颈癌的临床分期显著相关（P〈0．05）。ROC曲线显示在筛选宫颈癌的应用上，HR—HPV敏感度最高。除外HE-4，HPV与其余5种肿瘤标志物联合检测在宫颈癌诊断的敏感性为97．99％，明显高于单项检测敏感性（CA72425．30％，CEA20．89％，CA12527．71％，CAl9924．90％，SCCA52．61％，HPV92．37％），差异均有统计学意义（x2=278．237，P=0．000；x2=307．036，P=0．000；x2=263．348，P=0．000；x2=280．769，P=0．000；x2=137．864，P=0．000；x2=8．580，P=0．003）。结论HR—HPV联合多项肿瘤标志物检测有利于提高宫颈癌的诊断率，具有重要的临床意义。

Objective To investigate the significance of the combined detection of several serum tumor markers with high - risk human papillomavirus （ HR - HPV） in the diagnosis of cervical cancer. Methods Chemiluminescent microparticle immunoassay（CMIA） was employed to measure the levels of serum CA125 ,CA19 -9,SCCA and CEA in peripheral blood samples collected from 249 patients with cervical cancer,30 patients with cervix intraepithelial neoplasia（CIN） ,and 60 healthy controls. The levels of serum CA72 - 4, HF~ were measured by eleetrochemilumineseence immunoassay（ ECLI）. Flow- through hybridization and gene chip technology （HybriMax） was employed to measure the HPV genotypes in all the 339 cases of women. Results Serum CA72 - 4 level in the cervical cancer group [ 3.13 （2.25,7.63） ng/mL ] was significantly higher than that in the CIN group [ 2.37 （1.98,6.25）ng/mL ] and the control group[2.69（2.35,3.35 ）ng/mL] （P = 0. 028;P = 0. 003 ）. Serum CEA level in the cervical cancer group 3.08 （ 2. 28,4.75 ） ng/mL was significantly higher than that in the CIN group [ 1.45 （ 1.00,1.83 ） ng/mL ] and the control group [ 2.13 （ 1.45,2.67 ） ng/mL ] （ P = 0. 000 ; P = 0. 000）. Serum CA125 level in the cervical cancer group [ 24.4 （20.30,44.15） U/mL] was significantly higher than that in the CIN group[ 12.85 （7.90, 16.23） U/mL] and the control group[ 12.35 （ 11.26,17.11 ） U/mL] （ P = 0. 000 ; P = 0. 000）. Serum CA19 - 9 level in the cervical cancer group [ 27.05 （ 18.48,38.01 ） U/mL ] was significantly higher than that in the CIN group [ 13.01 （ 8.79,17.12 ） U/mL ] and the control group[ 12.83 （ 10.89,17.93 ） U/mL 1 （ P = 0. 000 ; P = 0. 000 ）. Serum SCCA level in the cervical cancer group [ 1.7 （0.90,4.75） ng/mL ] was significantly higher than that in CIN group [ 0.8 （0.60,1.10） ng/mL ] and the control group [ 0.6 （0.50,0.70） ng/mL ] （ P = 0.000 ; P = 0. 000 ）. However, there was no significant difference of HE - 4 among three groups （ P 〉 0.05 ）. The HR - HPV infection rates in the cervical cancer （ 92.4% ） and CIN patients （90.0%） were significantly higher than that in controls （15.0%） （X2 = 46. 875 ,P = 0. 000;X2 = 165. 178, P = 0. 000）. In the cervical cancer patients, the levels of serum tumor marker was associated with Federation International of Gynecology and Obstetrics （FIGO） stage （P 〈 0.05 ）. ROC curves showed HR - HPV was the most sensitive in the diagnosis of cervical cancer. The sensitivity of the diagnosis of cervical cancer by serum tumor markers combined with HR - HPV （97.99%） was significantly higher than that of single marker, CA724 25.30%, CEA 20.89%, CA125 27.71%, CA199 24.90% ,SCCA 52.61%, HPV 92.37% （X2 = 278. 237, P = 0. 000;X2 = 307. 036, P = 0. 000 ; X2 = 263. 348, P = 0. 000 ; X2 = 280. 769, P = 0. 000 ; X2 = 137. 864, P = 0. 000 ; X2 = 8. 580, P = 0. 003 ）. Conclusion Serum tumor markers combined with HR - HPV check can improve the detection rate of cervical cancer and has important clinical value.