HR-HPV检测与细胞学联合检查在宫颈病变筛查中的应用

Application of high-risk human papillomavirus detection and liquid-based cytology in cervical lesion screening

目的评价高危型人乳头状瘤病毒(HPV)DNA检测联合宫颈细胞学检查对宫颈病变筛查的效果。方法 2008年8月～2010年4月,对该院宫颈疾病诊治中心就诊的4 144名妇女进行宫颈癌前病变筛查,采用第2代杂交捕获试验(HC-2)检测(HR-HPV检测)联合细胞学检查,同时对其880例细胞学阳性患者进行阴道镜检查,并以宫颈活检的组织病理学结果为确诊标准。比较2种方法在宫颈病变筛查中的意义。结果 4144例研究病例中,细胞学异常(≥ASCUS)占21.24%(880/4 144),高危型HPV检测阳性率为32.41%(1 343/4 144)。880例细胞学异常者HR-HPV阳性率为47.84%,其中ASC 34.47%(202/586),LSIL 69.32%(113/163),HSIL89.08%(106/119),SCC 100%。880例经病理学诊断为慢性炎症237例、CINI382例、CINII96例、CINIII111例和宫颈浸润癌54例,其HR-HPV阳性率分别为15.19%(36/237)、41.88%(160/382)、80.21%(77/96)、97.30%(108/111)和98.15%;880例细胞学异常中病理学≥CINI者占73.07%(643/880),421例HR-HPV阳性中,病理学≥CINI占91.69%(386/421)。对宫颈低度以上病变,细胞学(≥LSIL)、HR-HPV、HR-HPV+细胞学(≥LSIL)3种方法的敏感度分别为45.26%、61.90%、77.14%;特异度分别为98.73%、85.23%、77.14%;不同检查方法差异有显著性(P<0.05);阴性预测值分别为39.93%、44.01%及%44.37%;经统计差异无显著性(P>0.05)。对宫颈高度病变,细胞学(≥LSIL)、HR-HPV、HR-HPV+细胞学(≥LSIL)的敏感性分别为81.23%、93.10%及97.70%;不同方法间差异有显著性(P<0.05);特异性分别为76.27%、68.50%及64.80%;阴性预测值分别为91.13%、92.35%和99.15%;不同方法间差异无显著性(P>0.05)。结论高危型HPV-DNA检测在宫颈病变的筛查中具有较高的敏感度和阴性预测值,高危型HPV-DNA检测联合细胞学检查进一步提高其敏感度和阴性预测值,是防治宫颈癌的关键。但特异度未能提高,阴道镜下多点活检术可提高宫颈病变诊断的准确性。

【Objective】 To assess the value of combining high-risk human papillomavirus（HPV） test and cytological test in cervical lesion screening.【Methods】 During August 2008 to April 2010,a total of 4144 women were screened by combining high-risk HPV DNA test（hybrid capture Ⅱ,HC-Ⅱ） and cytological test（liquid-based Thin Prep cytology test）,and the 880 abnormal cervical smear cases were further biopsied under the colposcope.【Results】 In the 4144 cases,the positive rate of cytology and HR-HPV test were 21.24%,32.41%.Among the 880 abnormal cervical smear cases,the positive rate of HR-HPV of ASC 34.47%（202/586）,LSIL69.32%（113/163）,HSIL89.08%（106/119）,SCC100%.In 880 cases under gonecolposcopy,the pathology diagnosis as cervicitis,CINI,CINII,CINIII,SCC were 237,382,96,111,54,and the positive rates of HR-HPV of the above five groups were 15.19%（36/237）,41.88%（160/382）,80.21%（77/96）,97.30%（108/111） and 98.15%;The rate of pathology diagnosis more than CINI was 73.07% in 880 abnormal cervical smear cases and 91.69% in 421 positive HR-HPV cases.For the detection of cervical intraepithelial neoplasia（≥CINI）,the sensitivity of cytology,HR-HPV,cytology combined with HR-HPV were 45.26%,61.90%,77.14%,respectively and the specificity of cytology,HR-HPV,cytology combined with HR-HPV were 98.73%,85.23%,77.14%,respectively.Significant differences among the three methods were observed（P 0.05）.The negative-predictive value of cytology,HR-HPV,cytology combined with HR-HPV were 39.93%,44.01%,44.37%,there was no significant differences observed（P 0.05）.For the detection of high-grade cervical intraepithelial neoplasia（≥CINI）,the sensitivity of cytology,HR-HPV,cytology combined with HR-HPV were 81.23%,93.10%,97.70%,respectively.Significant differences among the three methods were observed（P 0.05）.The specificity of cytology,HR-HPV,cytology combined with HR-HPV were 76.27%,68.50%,64.80%,respectively and the negative-predictive value of cytology,HR-HPV,cytology combined with HR-HPV were 91.13%,92.35%,99.15% respectively,there was no significant differences observed（P 0.05）.【Conclusions】 High-risk HPV DNA test has high sensitivity and negative-predictive value.The combination of high-risk HPV DNA test and cytological test increases the sensitivity and negative-predictive value,it was the key of cervical cancer screening.The performance of biopsy under the colposcope can help the diagnosis of cervical dysplasial.