目的:评价阴道自取样本高危型HPV（HR-HPV）分型检测用于子宫颈癌初筛的筛查效率，并探讨以不同HR-HPV亚型组合联合医生取样本的细胞学检查或HR-HPV病毒载量检测对自取样本HR-HPV阳性者进行二次筛查的筛查效率。方法:本研究的数据来自2009年4月至2010年4月深圳市子宫颈癌筛查项目Ⅱ（SHENCCAST-Ⅱ）数据库，收集其中有自取样本的基质辅助激光解吸电离-飞行时间质谱分析（MALDI-TOF-MS）技术进行的HR-HPV分型检测结果以及医生取样本的第2代杂交捕获技术（HC-Ⅱ）检测的HR-HPV病毒载量结果、子宫颈细胞学检查结果的妇女共8 556例，转诊阴道镜检查者均有活检组织病理检查结果。分析自取样本HR-HPV分型检测作为子宫颈癌初筛方案（即方案1）时，基于其不同HR-HPV亚型组合［包括5个亚方案，即1a：HPV 16和（或）18型（HPV 16/18型）阳性；1b：HPV 16/18/58型阳性；1c：HPV 16/18/58/31/33型阳性；1d：HPV 16/18/58/31/33/52型阳性；1e：所有14种HR-HPV亚型中任一亚型阳性］的阴道镜转诊方案检出子宫颈上皮内瘤变（CIN）Ⅱ及以上病变（CIN Ⅱn +）、CIN Ⅲ及以上病变（CIN Ⅲn +）的敏感度与特异度；并以自取样本HR-HPV初筛阳性者即以方案1中的各亚方案为基础，对比分析其联合医生取样本的细胞学检查（即方案2，包括2a、2b、2c、2d、2e共5个亚方案）或HR-HPV病毒载量检测（即方案3，包括3a、3b、3c、3d共4个亚方案）作为分流指标的二次筛查方案的筛查效率。n 结果:（1）本研究纳入的8 556例妇女的年龄为（38.9±7.9）岁，自取样本检测的HR-HPV阳性率为13.77%（1 178/8 556），其中HPV 16/18型、HPV 16/18/58型、HPV 16/18/58/31/33型和HPV 16/18/58/31/33/52型组合的阳性率分别为3.16%（270/8 556）、5.14%（440/8 556）、6.66%（570/8 556）和9.81%（839/8 556）。医生取样本的HR-HPV病毒载量≥10相对光单位/临床阈值（RLU/CO）者占8.87%（759/8 556），细胞学结果≥未明确诊断意义的不典型鳞状上皮细胞（ASCUS）者占12.05%（1 031/8 556）。（2）方案1中，所有14种HR-HPV亚型中任一亚型阳性者（即方案1e）行阴道镜检查对检出CIN Ⅱn +、CIN Ⅲn +的敏感度在所有方案（包括3个方案共14个亚方案）中最高（分别为92.70%、94.33%），但是特异度和阳性预测值（PPV）在所有方案中最低（特异度分别为88.44%、87.58%，PPV分别为18.34%、11.29%），且阴道镜检查率在所有方案中最高（为13.77%）。方案1的其他亚方案（即方案1a、1b、1c、1d）中，检出CIN Ⅱn +、CIN Ⅲn +的特异度方案1a最高，分别为97.92%、97.69%，其他亚方案也较高，均达90%以上；但敏感度方案1d最高（分别为88.41%、92.20%）。（3）HPV 16/18型阳性者直接行阴道镜检查（即方案1a），非HPV 16/18型阳性者行医生取样本细胞学检查或HR-HPV病毒载量检测，细胞学结果达到阈值（≥ASCUS，即方案2a）或病毒载量达到阈值（≥10 RUL/CO，即方案3a）者行阴道镜检查，其阴道镜转诊率低，而筛查CIN Ⅱn +、CIN Ⅲn +的敏感度和特异度则较高。若在此两个二次筛查方案基础上，首先根据自取样本HR-HPV分型检测结果，依次增加另外4种HR-HPV亚型（即HPV 58、31、33和52型）阳性者行阴道镜检查，再以细胞学检查或病毒载量检测结果进行二次分流，筛查CIN Ⅱn +、CIN Ⅲn +的敏感度也相应提高。n 结论:以自取样本HR-HPV分型检测为子宫颈癌初筛方案，以及其联合细胞学检查或病毒载量检测进行二次筛查的方案，可以在筛查CIN Ⅱn +、CIN Ⅲn +的敏感度、特异度以及阴道镜检查率之间获得较好的平衡；将HPV 58、31、33、52型纳入HPV 16/18型阳性的初筛分流指标，并联合细胞学检查或病毒载量检测的序贯二次筛查，可进一步提高筛查效率。n “,”Objective:To evaluate the efficacy of high-risk HPV (HR-HPV) genotyping with vaginal self-sampling in primary screening and combining cytology or viral load for HR-HPV positive as secondary screening strategies.Methods:The data referring to HR-HPV genotyping of self-collected sample with mass array matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF-MS), HR-HPV viral load of physician-collected sample with hybrid capture Ⅱ (HC-Ⅱ), liquid-based cytology and histology of 8 556 women were from Shenzhen cervical cancer screening trial Ⅱ (SHENCCAST-Ⅱ) conducted between April 2009 and April 2010. The data were reanalyzed to determine the sensitivity and specificity to cervical intraepithelial neoplasia (CIN) of grade 2 or worse (CIN Ⅱn +), CIN of grade 3 or worse (CIN Ⅲn +) when HR-HPV genotyping combining with colposcopy as primary screening strategy based on varied HR-HPV subtype (strategy 1, including 5 sub-strategies: 1a: HPV 16/18 positive; 1b: HPV 16/18/58 positive; 1c: HPV 16/18/58/31/33 positive; 1d: HPV 16/18/58/31/33/52 positive; 1e: any HR-HPV positive). The data were also compared to determine the efficacy of cytology (strategy 2, including 5 sub-strategies: 2a, 2b, 2c, 2d, 2e) or HR-HPV viral load (strategy 3, including 4 sub-strategies: 3a, 3b, 3c, 3d) of physician-collected sample as a triage with HR-HPV genotyping for self-sampling HR-HPV positives.n Results:(1) The HR-HPV positive rate was 13.77% (1 178/8 556) in the self-collected samples of 8 556 pregnant women. Of them,the prevalences of HPV 16/18, HPV 16/18/58, HPV 16/18/58/31/33 and HPV 16/18/58/31/33/52 were 3.16% (270/8 556), 5.14% (440/8 556), 6.66% (570/8 556) and 9.81% (839/8 556), respectively. The HR-HPV viral load ≥10 relative light units/control (RLU/CO) was 8.87%(759/ 8 556), while cytological results ≥atypical squamous cell of undetermined signification (ASCUS) were 12.05% (1 031/8 556). (2) The strategy 1e had the highest sensitivities for CIN Ⅱn +, CIN Ⅲn + which were 92.70% and 94.33%,respectively,among 14 sub-strategies,while the lowest specificity and positive predictive value (PPV). Meanwhile,the required colposcopy referral rates were much higher than other 13 sub-strategies (13.77%). The other 4 sub-strategies of strategy 1 (1a, 1b, 1c, 1d), strategy 1a had the highest specificities for CIN Ⅱn + and CIN Ⅲn + (97.92%, 97.69%, respectively), while 1d had the highest sensitivities for CIN Ⅱn + and CIN Ⅲn + (88.41%, 92.20%, respectively). (3) Both strategies of referring self-sampling HPV 16/18 positives for immediate colposcopy followed by triage physician-collected sample cytology (≥ASCUS) or viral load (≥10 RLU/CO) for non-HPV 16/18 positives had significantly higher sensitivity and specificity for CIN Ⅱ, CIN Ⅲn +, as well as lower referral rates (strategy 2a and 3a). Additionally, based on these two secondary screening strategies, cumulatively using the other four HR-HPV (HPV 58, 31, 33 and 52) positives as triage for immediate colposcopy showed an enhanced sensitivity.n Conclusions:Primary HR-HPV cervical cancer screening strategy based on self-sampling with triage of cytology (≥ASCUS) or viral load (≥10 RUL/CO) provides a good balance among sensitivity, specificity for CIN Ⅱn + and CIN Ⅲn + and the number of tests required, referral rates. The efficacy of HR-HPV genotyping combining cytology or viral load secondary screening strategies will have a spiral escalation when HPV 58, 31, 33, 52 are included.n