不同检测策略在成都双流地区宫颈癌筛查中的价值研究

目的 评估高危HPV(high-risk HPV, hr-HPV)检测和宫颈细胞学(thinprep cytology test, TCT)的不同组合策略在成都双流地区宫颈癌筛查，特别是在高级别宫颈上皮内病变筛查中的临床价值。方法 本项目为基于人群的随机临床试验。纳入符合要求的35～65岁的女性。第一年基线筛查中受试者按1∶2随机分配进行细胞学或hr-HPV检测，其中hrHPV检测呈阳性者被随机分流行细胞学或阴道镜检查。24个月后召回所有受试者，对其均进行细胞学和hr-HPV联合筛查。以上述基线筛查结果阴性且进入第三年随访并完成随访的女性为研究对象。基于上述检查结果，提取相关数据，模拟4种不同的筛查方案：(1)TCT和hr-HPV联合筛查，任一阳性则转诊阴道镜检查；(2)TCT和hr-HPV联合筛查，同时阳性则转诊阴道镜检查；(3)TCT初筛阳性者进行hr-HPV分流，hr-HPV阳性者转诊阴道镜；(4)hr-HPV初筛阳性者进行TCT分流，TCT阳性者转诊阴道镜。以组织学病检出宫颈高级别鳞状上皮内病变(HSIL⁺)为终点事件，计算不同筛查方案的敏感性、特异性、阳...

Effectiveness of Different Testing Strategies Applied for Cervical Cancer Screening in Shuangliu District,Chengdu City

  Objective  To evaluate the clinical value of different combination strategies of high-risk HPV (hr-HPV) testing and Thinprep cytology test (TCT), a cervical cytology test, for cervical cancer screening, especially for high or higher-grade squamous intraepithelial lesion (HSIL+) in Shuangliu District, Chengdu City.   Methods  The study is a population-based randomized clinical trial. Women aged 35 to 65 years meeting the inclusion criteria were enrolled for the study. At the baseline screening conducted in the first year, the participants were randomly assigned to either cytology test or hr-HPV testing at a ratio of 1∶2. If the paticipants had positive results for the baseline hr-HPV test, they would then undergo either cytology test or colposcopy by random assignment. After 24 months, all participants were called back, and combined screening of cytology test and hr-HPV test were performed. Women who had negative results at baseline screening and who entered and completed the third-year follow-up were selected as the subjects of the study. Based on the aforementioned testing findings, the related data were extracted and four different screening protocols were simulated: 1) combined TCT and hr-HPV screening, with referral for colposcopy when there was positive results for either one of the two; 2) combined TCT and hr-HPV screening, with referral for colposcopy when both tests had positive results at the same time; 3) TCT was done for preliminary screening and those who were found to be positive would then undergo hr-HPV test for triage purpose, with subsequent referral made for colposcopy if the hr-HPV results were positive; 4) hr-HPV was done for preliminary screening and those who were found to be positive would then undergo TCT, with subsequent referral made for colposcopy if TCT results were positive. With the detection of HSIL+ on histological examination as the endpoint event, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under curve (AUC) of different combination screening models were calculated.   Results  A total of 3102 women were screened, and 2967 women were included in the statistical analysis in this study. Among the 2967 women, 979 were randomized to cytology and 1988 to hr-HPV genotyping. For prescreening, the positive rate of the cytology group was 5.6% (55/979), with of HSIL+ positive rate being 0.2% (2/979), while the positive rate of the hr-HPV group was 7.5% (149/1988), with HSIL+ positive rate being 0.9% (18/1988). After 24 months, 2456 women were called back and were given cervical cytology test and hr-HPV test at the same time. Among them, the positive rate of the cytology group was 3.2% (78/2456), while the positive rate of hr-HPV group was 8.7% (215/2456). The overall positive rate of HSIL+ was 0.69%(17/2456). Women with a negative baseline hr-HPV had a lower incidence of HSIL+ lesions in the long term. The strategy of cervical cytology screening combined with hr-HPV test for triage purpose is the best method, with a sensitivity of 88.9%, a specificity of 58.3%, a PPV of 44.4%, a NPV of 93.3%, and an AUC of 0.736, P=0.039 (95% CI: 0.555-0.917).  Conclusion  This randomized clinical trial from Shuangliu District, Chengdu City shows that the sensitivity of hr-HPV testing is better than that of cytology test, and the prevalence of HSIL+ in women with negative baseline hr-HPV results is lower than that of women with negative baseline cytology results. The screening program of TCT for prescreening plus subsequent hr-HPV test for triage purpose shows better value for the detection of HSIL+.