适合中国人群的宫颈癌筛查技术和效果评价的真实世界研究

Real-world research on cervical cancer screening program and effect evaluation for Chinese population

目的评价在我国不同经济水平地区的真实医疗条件中宫颈癌及癌前病变筛查干预技术的应用和效果。方法2015—2018年全国21家医院开展宫颈癌人群筛查技术的应用和效果评价。按照地理位置将全国分为7个大区，采用多阶段抽样方法每区选取2～4个两癌（宫颈癌和乳腺癌）检查项目点，基层筛查点在上级医院的指导下对临床检测指标进行评价。农村地区女性采用细胞学、人乳头状瘤病毒（HPV）检测或肉眼观察初筛，细胞学或肉眼观察初筛阳性女性直接行阴道镜检查；HPV检测初筛阳性女性行细胞学或肉眼观察分流，或直接行阴道镜检查。城市地区女性采用细胞学或HPV检测，细胞学或HPV16/18型初筛阳性女性直接行阴道镜检查，其他高危型HPV阳性行液基细胞学分流或直接阴道镜检查。入组女性在第3年采用基线的初筛技术联合筛查，阳性女性行阴道镜检查。比较各初筛组人群的筛查阳性率、人群阴道镜转诊率和宫颈鳞状上皮内瘤样病变2级及以上（CIN2＋）病变检出率。结果基线筛查中共入组63 931人。11个农村筛查点共33 823人，其中HPV组15 577人，醋酸碘染肉眼观察法（VIA/VILI）组11 157人，液基细胞学组7 089人。10个城市筛查点共30 108人，其中液基细胞学组9 907人，HPV检测组20 201人。城市和农村地区HPV阳性率分别为9.34%和12.53%，城市和农村地区细胞学异常率分别为5.63%和4.24%，农村人群VIA/VILI的初筛阳性率为12.25%。基线筛查中人群CIN2＋病变检出率为0.56%，城市和农村地区HPV组的检出率均高于液基细胞学组（均P〈0.05）。结论各个项目点均按预期完成了基线筛查任务，农村女性的HPV感染率高于城市地区。基线筛查中，采用HPV初筛对CIN2＋病变的检出优于液基细胞学。真实条件下的宫颈癌筛查效果评价为我国卫生决策者在不同地区推进宫颈癌防控工作提供证据。

ObjectiveTo evaluate the actual efficacy of cervical cancer and precancerous lesions screening approaches in real-world regions with different economic levels in China.MethodsThe demonstrative application and effect evaluation of cervical cancer screening program were conducted in 21 hospitals nationwide from 2015 to 2018. Multi-stage sampling method was adopted to divide the country into 7 large areas according to geographical location. Two to four screening sites of two types of cancer （cervical cancer and breast cancer） were selected in each area, and the grassroots screening sites were implemented under the guidance of superior hospitals. In rural areas, women were initially screened using cytology, human papillomavirus （HPV） testing and visual inspection. The women with positive cytology or visual inspection were referred for colposcopy, and the women with positive HPV infection were randomly referred for reflex cytology or visual inspection, or direct colposcopy examination. In urban areas, women were primarily randomized into cytology or HPV testing groups. The women with abnormal cytology or positive HPV 16/18 infection were directly referred for colposcopy examination, whereas the women with positive infection of the other 12 high-risk subtypes of HPV were referred for reflex cytology or colposcopy. All of recruited women would be follow-up and screened by the baseline screening techniques in the third year while the positive women underwent colposcopy examination. The positive rates, referral rates, the detection rates of grade 2 and above of cervical intraepithelial neoplasia （CIN 2＋ ） were compared.ResultsA total of 63 931 women were recruited at the baseline. Among them, 11 rural sites included 33 823 women： 15 577, 11 157 and 7 089 women were screened by HPV testing, visual inspection via acetic acid or Lugol′s iodine （VIA/VILI） and cytology, respectively. Additionally, 30 108 women were from 10 urban sites： 9 907 and 20 201 women were screened by cytology and HPV subtyping, respectively. The HPV positive rate for urban women was 9.34%, whereas that for rural women was 12.53%. The abnormal rate of cytology for urban women was 5.63%, and that for rural women was 4.24%. The positive rate of VIA/VILI in the rural women was 12.25% Furthermore, the detection rate of CIN2＋ at the baseline was 0.56%, and that was statistically higher in HPV-positive group than cytology-positive group （P〈0.05）.ConclusionsAll of screening sites completed the baseline screening tasks as expected. The prevalence of HPV infection is higher in rural women than urban women. The performance of HPV testing is better than cytology for detecting CIN2＋ cases. This real-world demonstration study provides evidences for cervical cancer prevention and control in different regions.