高危型人乳头状瘤病毒DNA检测与细胞学联合检查对子宫颈癌前病变筛查的研究

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癌前病变筛查的效果。方法2003年1月至2004年6月,对广东省人民医院妇科门诊5210名妇女进行宫颈癌前病变筛查,采用第二代杂交捕获试验(HC-Ⅱ)检测高危型HPV DNA联合细胞学检查,同时进行阴道镜检查,并以宫颈活检的组织病理学结果为确诊标准。结果受检者平均年龄(34±9)岁,筛查并最后经病理诊断为HPV感染890例,宫颈上皮内瘤变(CIN)Ⅰ级83例,CINⅡ73例,CINⅢ80例,宫颈浸润癌54例,子宫内膜癌5例,阴道上皮内瘤样病变1例,宫颈结核1例。以组织病理学为确诊标准,高危型HPV DNA检测CINⅡ、Ⅲ的敏感度是92·22%,特异度是74·71%,阳性预测值5·19%,阴性预测值99·84%。宫颈细胞学筛查CINⅡ、Ⅲ,以未明确诊断意义的不典型鳞状上皮细胞(ASCUS)为分界点的敏感度、特异度、阳性预测值和阴性预测值分别是90·00%、80·34%、11·94%和99·63%;以低度鳞状上皮内病变(LSIL)为分界点的敏感度、特异度、阳性预测值和阴性预测值分别是70·13%、91·58%、11·11%和99·51%;以高度鳞状上皮内病变(HSIL)为分界点的敏感度、特异度、阳性预测值和阴性预测值分别是48·05%、98·46%、31·90%和99·21%。高危型HPV DNA检测联合细胞学检查筛查CINⅡ、Ⅲ的敏感度、特异度、阳性预测值和阴性预测值分别是98·70%、73·08%、5·21%和100·00%。高危型HPV DNA在不同宫颈病变中的阳性率分别是:宫颈癌85·2%(46/54),CINⅢ92·5%(74/80),CINⅡ86·3%(63/73)和CINⅠ45·8%(38/83)。结论高危型HPV DNA检测在宫颈癌前病变的筛查中有很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可使敏感度和阴性预测值有提高,但特异度未能提高。

Combining high-risk human papillomavirus DNA test and cytological test to detect early cervical dysplasia

OBJECTIVE: To assess the value of combining high-risk human papillomavirus (HPV) DNA test and cytological test in detection of early cervical dysplasia. METHODS: During January 2003 to June 2004, a total of 5210 women were screened by combining high-risk HPV DNA test (hybrid capture II, HC-II) and cytological test (liquid-based ThinPrep cytology test), and the abnormal cytological or HPV DNA findings were further biopsied under the colposcope. RESULTS: The age of the patients was between 17 to 80, the average was 34 +/- 9. Final pathological diagnosis was HPV infection in 890 cases, cervical intraepithelial neoplasia (CIN) I in 83 cases, CIN II in 73 cases, CIN III in 80 cases, invasive cervical cancer in 54 cases, endometrial cancer in 5 cases, vaginal intraepithelial neoplasia in 1 case and cervical tuberculosis in 1 case. Based on the criteria of histology and pathology, the sensitivity, specificity, positive-predictive value and negative-predictive value of high-risk HPV DNA test for detecting all cases of CIN II, III were 92.22%, 74.71%, 5.19% and 99.84% respectively. In detecting all cases of CIN II, III by cytological test, for atypical squamous cell of undetermined signification (ASCUS), the sensitivity, specificity, positive-predictive value and negative-predictive value were 90.00%, 80.34%, 11.94% and 99.63% respectively; for low-grade squamous intraepithelial lesion (LSIL), the sensitivity, specificity, positive-predictive value and negative-predictive value were 70.13%, 91.58%, 11.11% and 99.51% respectively; for high-grade squamous intraepithelial lesion (HSIL), the sensitivity, specificity, positive-predictive value and negative-predictive value were 48.05%, 98.46%, 31.90% and 99.21% respectively. By the combination of high-risk HPV DNA test and cytological test, the sensitivity, specificity, positive-predictive value and negative-predictive value for detecting all cases of CIN II, III were 98.70%, 73.08%, 5.21% and 100.00% respectively. The infection rate of HPV in cervical cancer was 85.2% (46/54), in CIN III 92.5% (74/80), in CIN II 86.3% (63/73) and in CIN I 45.8% (38/83). 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, but it does not increase the specificity. The performance of biopsy under the colposcope can help the diagnosis of cervical dysplasia.