液基薄层细胞学联合高危型人乳头状瘤病毒检测在宫颈癌前病变筛查中的应用

Application of thinprep cytologic test combined with high risk human papillomavirus test in diagnosis of cervical precancerous lesion

目的探讨液基薄层细胞学(TCT)联合高危型人乳头状瘤病毒(HPV)检测在宫颈病变筛查中的应用价值。方法收集同时行TCT、高危型HPV检测及阴道镜活检的患者1 049例,以组织学为金标准,对其检测结果进行分析。结果 1 049例患者中高危型HPV阳性者725例,总阳性率为69.11%。细胞学结果显示,未见上皮内病变或恶性细胞(NILM)414例(39.47%),未明确意义的非典型鳞状上皮细胞(ASCUS)275例(26.22%),不排除高度鳞状上皮内病变的非典型鳞状上皮细胞(ASC-H)73例(6.96%),低度鳞状上皮内病变(LSIL)168例(16.02%),高度鳞状上皮内病变(HSIL)109例(10.39%),鳞癌(SCC)10例(0.95%),NILM、ASCUS、LSIL、ASC-H、HSIL及SCC的患者高危型HPV阳性率依次为37.68%、86.55%、89.88%、90.41%、95.41%和100.00%。细胞学异常组的HPV阳性率均显著高于正常组(P=0.000 0),且随宫颈细胞学病变级别升高,高危型HPV阳性率明显上升。组织学结果显示,慢性宫颈炎703例(67.02%),湿疣样改变10例(0.95%),宫颈上皮内瘤变(CIN)Ⅰ131例(12.49%),CINⅡ40例(3.81%),CINⅢ133例(12.68%),SCC 32例(3.05%),高危型HPV阳性率依次为57.18%、70.00%、90.84%、95.00%、95.49%和100.00%。组织学异常组高危型HPV阳性率均显著高于慢性宫颈炎组及湿疣样改变组(P<0.05),且随组织学病变级别升高,高危型HPV阳性率明显上升。高危型HPV阳性时,HSIL中CINⅡ及以上病变的发生率为84.62%(88/104),较LSIL 20.53%(31/151)显著升高,差异有统计学意义(χ2=101.621 4,P=0.000 0)。细胞学为ASCUS且高危型HPV阳性者发生CIN的概率为29.83%(71/238),明显高于高危型HPV阴性患者发生CIN的13.51%(5/37),差异有统计学意义(χ2=4.263 8,P=0.038 9)。TCT联合高危型HPV检测可使宫颈病变漏诊率由8.96%(31/346)降至2.02%(7/346),差异有统计学意义(χ2=16.038 6,P=0.000 1)。TCT单独应用其敏感性、特异性、阳性预测值及阴性预测值分别为91.04%、54.48%、49.61%和92.51%,联合高危型HPV检测后分别为97.98%、35.70%、42.86%和97.29%,其敏感性及阴性预测值显著提高,差异有统计学意义(P<0.05)。结论 TCT联合高危型HPV检测可显著提高TCT检测的敏感性及阴性预测值,可作为宫颈病变筛查可靠的早期诊断方法。

Objective To investigate the clinical significance of thinprep cytologic test（ TCT） combined with high risk human papillomavirus（ HPV） test in the diagnosis of cervical precancerous lesion. Methods The clinical material of 1 049 patients who accepted the examinations of TCT,high risk HPV test and colposcope biopsy at the same time were collected. The histology was selected as gold standard to analyze the tested results. Results Seven hundred and twenty-five patients of 1 049 patients were infected by high risk HPV,the over all positive rate was 69. 11%. The results of cytology showed that 414（ 39. 47%） patients were negative for intraepithelial lesion or malignancy（ NILM）,275（ 26. 22%） patients were atypical squamous cells of undetermined signification（ ASCUS）,73（ 6. 96%） patients were atypical squamous cells-can＇ t exclude HSIL（ ASC-H）,168（ 16. 02%） patients were low-grade squamous intraepithelial lesion（ LSIL）,109（ 10. 39%） patients were highgrade squamous intraepithelial lesion（ HSIL） and 10（ 0. 95%） cases were squamous cells cancer（ SCC）. The positive rate of high risk HPV was 37. 68%,86. 55%,89. 88%,90. 41%,95. 41% and 100. 00% respectively. The positive rate of HPV in abnormal histology group was significantly higher than that in NILM group（ P = 0. 000 0）. The positive rate increased with severity of cervical cytologic lesions. According to the pathological diagnosis,703（ 67. 02%） patients were chronic cervicitis,10（ 0. 95%） patients were condylomata,131（ 12. 49%） patients were cervical intraepithelial neoplasia（ CIN） Ⅰ,40（ 3. 81%） patients were CINⅡ,133（ 12. 68%） patients were CINⅢ and 32（ 3. 05%） patients were SCC. The positive rate of high risk HPV was 57. 18%,70. 00%,90. 84%,95. 00%,95. 49% and 100. 00% respective. The positive rate of high risk HPV in abnormal histology group was significantly higher than that in chronic cervicitis group and condylomata group（ P〈0. 05）. The positive rate increased with severity of cervical histologic lesions. In HSIL group,the incidence rates of CINⅡor worse with high risk HPV infection were 84. 62%（ 88 /104）,which was significantly higher than 20. 53%（ 31 /151） of LSIL group,the difference was statistically significant（ χ2= 101. 621 4,P = 0. 000 0）. In ASCUS group,the incidence rate of CIN with high risk HPV infection was 29. 83%（ 71 /238）,which was significantly higher than 13. 51%（ 5 /37） of patients with high risk HPV negative,the difference was statistically significant（ χ2= 4. 263 8,P = 0. 038 9）. TCT combined with HPV test in the diagnosis of cervical lesions could decrease omission diagnose rate from 8. 96%（ 31 /346） to 2. 02%（ 7 /346）,the difference was statistically significant（ χ^2= 16. 038 6,P = 0. 000 1）. The sensibility,specificity,positive predictive value and negative predictive value of TCT were 91. 04%,54. 48%,49. 61% and 92. 51%. After combining with high risk HPV test,above index were 97. 98%,35. 70%,42. 86% and 97. 29% respectively. The sensibility and negative predictive value improved notably（ P〈0. 05）. Conclusion TCT combined with high risk HPV test can greatly improve sensibility and negative predictive value.