目的:分析即时检测（POCT）技术筛查宫颈癌及癌前病变的准确性。方法:2020年9月，在山西省襄垣县建立的“自我采样”队列和“医生采样”队列中，采用简单随机抽样的方法从两队列人群中抽取研究对象，分别纳入197和273名。由研究对象自己或妇科医生分别采集宫颈脱落细胞标本并进行检测，采用POCT检测人乳头状瘤病毒（HPV），检测阳性者直接行阴道镜检查；同时采用 careHPV及常规PCR检测HPV，对POCT检测阴性但 careHPV或常规PCR检测任一阳性者再次进行阴道镜检查和活检。以组织病理学诊断为金标准，绘制受试者工作特征（ROC）曲线，计算灵敏度、特异度，比较POCT与 careHPV及常规PCR筛查宫颈癌及癌前病变的准确性。 结果:470名对象的年龄 M（ Q1， Q3）为51（45，57）岁。将组织病理学诊断宫颈上皮内瘤变2级及以上病变（CIN2+）作为疾病终点，基于自我采样方式的POCT检测的灵敏度及特异度分别为100.00%（95% CI：56.56%~100.00%）、28.95%（95% CI：22.97%~35.76%），POCT HPV16/18检测的灵敏度与POCT检测相同，特异度增加至89.47%（95% CI：84.30%~93.08%）；与 careHPV和常规PCR相比，自我采样POCT HPV16/18检测的AUC最佳，为0.947（95% CI：0.910~0.985）。基于医生采样方式的POCT检测的灵敏度及特异度分别为100.00%（95% CI：64.57%~100.00%），55.85%（95% CI：49.83%~61.70%）；POCT HPV16/18检测的灵敏度降低至71.43%（95% CI：35.90%~91.76%），特异度增加至92.45%（95% CI：88.63%~95.06%）。基于自我采样方式的POCT HPV16/18检测的AUC和医生采样方式差异没有统计学意义（0.947比0.819， P=0.217）。 结论:POCT HPV16/18检测灵敏度和特异度较高，是基于人群的宫颈癌筛查可选择的有效方法。

目的:分析并对比基于体外核酸杂交捕获原理的HPV检测技术(careHPV)和实时荧光PCR HPV检测技术(PCR HPV)在新疆地区适龄妇女宫颈癌初级筛查中的应用效果.方法:纳入2018 年新疆塔城地区1943 例25～64 岁有性生活史的女性,收集宫颈脱落细胞标本行HPV检测(包括careHPV和PCR HPV),任一阳性者转阴道镜行病理学诊断.比较两种HPV检测技术的一致率,分析检测结果不一致HPV阳性者的HPV型别分布.以病理确诊的子宫颈上皮内瘤变2 级及以上(CIN2+)病变为金标准,比较care-HPV、PCR HPV(14 种)和PCR HPV(18 种)3 种初筛方法的灵敏度、特异度、阳性预测值、阴性预测值.结果:针对14 种高危HPV型别,careHPV和PCR HPV的一致率为95.16%,Kappa值为0.715.careHPV和PCR HPV检测14 种高危型别均阳性妇女共126 例,其中HPV 16 型感染率最高,占18.25%(23 例);其次是HPV 51 型,占 12.70%(16 例);绝大多数是单一型别感染.在careHPV检测中,医生采样和自行采样组的高危型HPV阳性率分别为8.90%和9.83%,差异有统计学意义(P=0.006),而PCR HPV检测14 种高危型别阳性率在两组间差异无统计学意义(P=0.144).PCR HPV 检测的灵敏度最高,为88.89(95%CI为74.37～100),其次为careHPV,其灵敏度为 83.33(95%CI为 66.12～100);careHPV检测的特异度和阳性预测值最高,分别为91.79%和8.67%,PCR HPV检测的阴性预测值较高.结论:careHPV检测与PCR HPV检测一致率较高,在宫颈癌初级筛查方面,两种HPV检测方法均得到了很好的效果,且两种检测方法有其不同的优势,应根据不同地区的卫生资源,适当选择检测方法,运用于筛查及临床诊断中.

Objective:CareHPV is a human papillomavirus (HPV) DNA test for low-resource settings (LRS).This study assesses optimum triage strategies for careHPV-positive women in LRS.Methods:A total of 2,530 Chinese women were concurrently screened for cervical cancer with visual inspection with acetic acid (VIA),liquid-based cytology and HPV testing by physician-and self-collected careHPV,and physician-collected Hybrid Capture 2 (HC2).Screen-positive women were referred to colposcopy with biopsy and endocervical curettage as necessary.HPV-positivity was defined as ≥1.0 relative light units/cutoff (RLU/CO) for both careHPV and HC2.Primary physician-HC2,physician-careHPV and self-careHPV and in sequential screening with cytology,VIA,or increased HPV test-posidvity performance,stratified by age,were assessed for cervical intraepithelial neoplasia (CIN) grade 2/3 or worse (CIN2/3+) detection.Results:The sensitivities and specificities of primary HPV testing for CIN2+ were:83.8％,88.1％ for physiciancareHPV;72.1％,88.2％ for self-careHPV;and 97.1％,86.0％ for HC2.Physician-careHPV test-positive women with ⅥA triage had a sensitivity of 30.9％ for CIN2+ versus 80.9％ with cytology triage.Self-careHPV testpositive women with ⅥA triage was 26.5％ versus 66.2％ with cytology triage.The sensitivity of HC2 test-positive women with ⅥA triage was 38.2％ versus 92.6％ with cytology triage.The sensitivity ofphysician-careHPV testing for CIN2+ decreased from 83.8％ at ≥1.0 RLU/CO to 72.1％ at ≥10.00 RLU/CO,while the sensitivity of selfcareHPV testing decreased from 72.1％ at ≥1.0 RLU/CO to 32.4％ at ≥10.00 RLU/CO;similar trends were seen with age-stratification.Conclusions:ⅥA and cytology triage improved specificity for CIN2/3 than no triage.Sensitivity with ⅥAtriage was unsuitable for a mass-screening program.ⅥA provider training might improve this strategy.Cytology triage could be feasible where a high-quality cytology program exists.Triage of HPV test-positive women by increased test positivity cutoff adds another LRS triage option.

To compare the performance of visual inspection with acetic acid and with Lugol's iodine (VIA/VILI), cytology and careHPV DNA assay in rural China performed by local health providers. Eligible women living in rural areas in Xinmi County, Henan Province were invited to participate in cervical cancer screening program. Enrolled women were randomized into 3 intervention arms, screened by VIA/VILI, pap smears, and careHPV assay respectively. Women had positive primary screening results were referred to colposcopy and/or biopsy.All the clinical and lab work was performed by local health providers. The final diagnoses of histopathology were based on the diagnosing of a senior histopathology expert from Cancer Hospital, Chinese Academy of Medical Sciences. Questionnaires about the knowledge and attitudes towards the HPV and the screening program of the health providers at village clinics were collected. Finally, 894 women had careHPV DNA test, 552 underwent VIA/ VILI and 547 had Pap smears. The positive rates for careHPV assay, VIA/VILI and Pap smears were 10. 6％, 18. 1％, and 4. 9％ respectively (χ2 = 48. 647, P < 0.001). The overall CIN2 + detection rate was 0. 5％, the CIN2 + detection rate for the three arms were not significantly different even that of careHPV was higher than the other arms (0. 7％ for careHPV assay, 0. 5％ for VIA/ VILI, 0. 2％ for pap smear, χ2 = 1. 648, P = 0. 439). The knowledge of the health providers about HPV, HPV assay in screening was unsatisfactory. However, their attitudes about implementing HPV assay into the national program were positive. Implementing careHPV assay in low resource settings and performed by simply trained lab personnel is possible. Education for implementing HPV assay in local health providers is needed.

目的 探讨care HPV及HC2(Hybrid Capture 2)高危型HPV-DNA检测在意义不明的非典型鳞状细胞(atypical squamous cells of undetermined significance,ASC-US)患者分流中的应用及意义.方法 2016年6月-2017年8月间新疆医科大学附属肿瘤医院就诊的120例ASC-US女性进行care、HC2 HPV检测及阴道镜下宫颈活检.结果 全部的病例中,病理活检为鳞状细胞癌4例,CINⅡ以上病变检出率为23.33％ (28/120);HC2高危型HPV-DNA检测阳性组与阴性组高级别病变检出率分别为37.7％和3.9％(P＜0.01);care HPV阳性组与阴性组的高级别病变检出率分别为37.5％和7.1％ (P ＜0.01);HC2与care HPV的Kappa值为0.815,有较好的一致性;以组织病理诊断为金标准,HC2及care HPV检测预测高级别病变的敏感度、特异度、阳性预测值、阴性预测值分别为92.9％、53.3％、37.7％、96.1％;85.7％、56.5％、37.5％、92.9％;HC2和care HPV检测在ROC曲线下面积分别0.731、0.711,2种方法ROC曲线下面积基本相近.结论 高危型HPV检测技术对ASC-US患者有很高的检测效果,此类患者中care及HC2 HPV检测的一致性高,均可预测CINⅡ以上病变及浸润癌,可提高诊断率,临床上可以推广.

人乳头瘤病毒(human papillomavirus,HPV)检测试剂应根据检测目的而选择.用于宫颈癌筛查和分流侧重试剂的临床性能,经过国内外验证的试剂包括:美国凯杰公司的HC2,德国雅培公司的Abbott RT hrHPV test,美国罗氏公司的cobas 4800 HPV test,美国豪洛捷公司的APTIMAassay,中国凯杰公司的careHPV test.用于HPV感染及型别鉴定侧重试剂的分析性能,目前没有金标准,应考虑当地HPV亚型流行情况选择适宜的试剂,以避免掩盖真实感染水平.

目的 探讨和评价适合中国农村地区的子宫颈癌筛查方案.方法 本研究依托中国2015年卫生行业科研专项"适合中国农村地区的子宫颈癌筛查技术与示范研究"建立筛查人群队列,收集卫生经济学和流行病学参数,采用Treeage Pro 2011软件建立未筛查组模型和筛查组模型.通过将现场调查获得的人群筛查、诊断、治疗的相关临床资料和成本数据代入模型,以模拟中国农村妇女在采用不同筛查方案干预后子宫颈癌的发生、发展,并预测20年后的筛查效果[包括累积发病率、累积发病风险、挽救的生命年和质量调整生命年(QALY)、收益]和相应的成本费用,并进行卫生经济学评价(包括成本效果分析、成本效用分析、成本效益分析).子宫颈癌筛查方法有5种,包括醋酸或碘染色后肉眼观察(VIA/VILI)法、HPV快速筛查技术(careHPV)、液基薄层细胞学检查(TCT)、careHPV+TCT、careHPV+VIA/VILI,筛查间隔时间有3个,包括1年1次、3年1次和5年1次,共15种子宫颈癌筛查方案.结果 与未筛查组相比,15种子宫颈癌筛查方案可降低累积发病风险22.65%~51.76%.在同一筛查间隔时间,careHPV分别与TCT、VIA/VILI法比较,降低的累积发病风险、挽救的生命年、增加的QALY、收益均较高.15种子宫颈癌筛查方案的成本效果比为(0.44~3.24)万元/生命年,成本效用比为(0.15~1.01)万元/QALY,效益成本比为7.73~59.10.增量成本效果分析显示,优势方案有VIA/VILI法5年1次、VIA/VILI法3年1次、care HPV检测5年1次、careHPV检测3年1次和careHPV检测1年1次.结论 VIA/VILI法筛查经济有效,careHPV成本稍高但效果更好.对于我国农村地区建议选择careHPV检测5年1次的筛查方案.本研究为确定适合中国农村地区的子宫颈癌筛查方法提供了依据.

目的 评价宫颈癌快速筛查(CareHPV)检测的有效性,探索适合于基层妇女宫颈癌筛查的方法及方案.方法 选取2013年在江苏省盐城地区东台市唐洋镇进行宫颈癌筛查的20岁以上已婚妇女1703人,于2015年再次随访筛查,并对筛查数据进行统计分析.结果 2013年筛查显示,液基细胞学检查(TCT)结果异常者[≥非典型鳞状细胞-不能明确意义(ASC-US)]共68人,占总人数的3.99％;CareHPV检测结果异常者(>1.00RLU/CO)260人,占总人数的15.27％.2015年随访到筛查过的妇女1219例,CareHPV检测阳性178例,HPV感染率为14.60％;TCT异常22例.有阴道镜检查指征的给予活检,病理结果112例:宫颈可疑浸润癌有1例,宫颈上皮内瘤变3级(CIN3)有3例,CIN2～3有1例,CIN2有1例,CIN1有10例,慢性炎症伴鳞状上皮增生(挖空细胞、化生、萎缩等)86例,正常或慢性炎症6例,息肉1例,乳头样增生3例.2013年行CareHPV检测,2015年行CareHPV检测和TCT的受试者共1219例,根据HPV感染结果分为:持续感染组81例,非持续感染组110例,新感染组97例,无感染组931例.2013年CareHPV检测为阳性者,间隔两年HPV持续感染率为42.41％(81/191),2013年CareHPV检测为阴性者,间隔两年HPV新感染率为9.44％(97/1028);两者间的HPV感染率比较差异有统计学意义(χ2=159.350,P<0.01).间隔两年HPV清除率为57.59％(110/191).在设计的基层宫颈病变筛查方法策略中,CareHPV初筛及TCT分流有最高的阴性预测值;TCT初筛及Care分型分流有最好的阳性预测值;CareHPV初筛及TCT分流的阴性预测值(99.02％)和阳性预测值(36.36％)是综合评价适用性最优方法.结论 在江苏省基层地区开展以CareHPV检测为主的宫颈癌筛查方法,结合TCT分流,以阴道镜活检病理为准,能够有效检出≥CIN2的病变,CareHPV初筛TCT分流或CareHPV初筛CareHPV分型检测分流有很好的阴性预测值,CareHPV初筛及TCT分流是适用性最优方法.