Article(id=1249045357762646787, tenantId=1146029695717560320, journalId=1249024326687572039, issueId=1249045357167055618, articleNumber=null, orderNo=null, doi=10.12354/j.issn.1000-8179.2025.20250757, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1749139200000, receivedDateStr=2025-06-06, revisedDate=1751212800000, revisedDateStr=2025-06-30, acceptedDate=null, acceptedDateStr=null, onlineDate=1775725219431, onlineDateStr=2026-04-09, pubDate=1753804800000, pubDateStr=2025-07-30, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1775725219431, onlineIssueDateStr=2026-04-09, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1775725219431, creator=13701087609, updateTime=1775725219431, updator=13701087609, issue=Issue{id=1249045357167055618, tenantId=1146029695717560320, journalId=1249024326687572039, year='2025', volume='52', issue='14', pageStart='703', pageEnd='756', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=1, specialIssue=null, createTime=1775725219287, creator=13701087609, updateTime=1775725486224, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1249046476882649278, tenantId=1146029695717560320, journalId=1249024326687572039, issueId=1249045357167055618, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1249046476882649279, tenantId=1146029695717560320, journalId=1249024326687572039, issueId=1249045357167055618, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=703, endPage=726, ext={EN=ArticleExt(id=1249045358056248071, articleId=1249045357762646787, tenantId=1146029695717560320, journalId=1249024326687572039, language=EN, title=Expert consensus on combined screening for common cancers (2025 edition), columnId=1249045357993333510, journalTitle=Chinese Journal of Clinical Oncology, columnName=Guidelines and Consensus, runingTitle=null, highlight=null, articleAbstract=

Malignant tumors (commonly referred to as cancers) represent a major global public health challenge and contribute substantially to the global disease burden. Early screening plays a crucial role in improving detection rates, enabling timely intervention, and enhancing patient survival. However, current cancer screening guidelines primarily focus on site-specific screening, which may not fully address the need for comprehensive early detection. A scientifically rational, multi-cancer screening approach offers several advantages: it optimizes the use of biological samples, reduces the time burden for participants, enhances the efficiency and comprehensiveness of screening, and minimizes overall expenses. Moreover, this approach facilitates rational allocation of healthcare resources, ultimately helping to reduce the societal burden of cancer. To address gap, the Cancer Epidemiology Committee of the China Anti-Cancer Association has developed the Expert Consensus on Combined Screening for Common Cancers. This consensus integrates multidisciplinary expertise and synthesizes the latest domestic and international researches on cancer screening, early detection, and treatment of prevalent malignancies. Drawing upon China’s unique demographic and healthcare context and practical screening experiences, the consensus provides evidence-based recommendations on target populations, screening technologies, and procedural workflows for multi-cancer screening. These guidelines align with the principles and methodologies established by the World Health Organization (WHO), aiming to enhance the effectiveness of combined cancer screening in China, improve early detection rates, and provide a scientific foundation for national cancer prevention and control strategies.

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Kexin Chen; E-mail:
; Wanqing Chen; E-mail:
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恶性肿瘤(或称癌症)是影响居民健康的重大公共卫生问题,造成严重的全球疾病负担。早期筛查能够大幅度提高癌症的早诊早治率,提升癌症生存率。然而,当前癌症筛查指南均只关注单一癌症类型。通过科学合理的常见癌症联合筛查,不仅能优化利用生物样本资源,提高受检者依从性,节省时间成本,增强癌症筛查的全面性和有效性,还能有效降低筛查成本、合理配置医疗资源,减少癌症综合疾病负担。《中国常见癌症联合筛查专家共识》由中国抗癌协会肿瘤流行病学专业委员会发起,组织多学科专家,整合多种常见癌症筛查与早诊早治领域的国内外研究进展,同时考虑中国国情和癌症筛查的实际经验,依据世界卫生组织推荐的指南制定原则和方法完成证据评估。本共识针对常见癌症联合筛查过程中的筛查人群、技术、流程等给出了基于证据的推荐,旨在提升常见癌症联合筛查与早诊早治效果,为中国的癌症防控提供科学依据。

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陈可欣 
陈万青 
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J Adv Nurs, 2010, 66(1):191-200., articleTitle=null, refAbstract=null)], funds=null, companyList=[AuthorCompany(id=1249045358886720278, tenantId=1146029695717560320, journalId=1249024326687572039, articleId=1249045357762646787, xref=1, ext=[AuthorCompanyExt(id=1249045358899303191, tenantId=1146029695717560320, journalId=1249024326687572039, articleId=1249045357762646787, companyId=1249045358886720278, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1Department of Epidemiology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin 300060, China), AuthorCompanyExt(id=1249045358907691800, tenantId=1146029695717560320, journalId=1249024326687572039, articleId=1249045357762646787, companyId=1249045358886720278, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1天津医科大学肿瘤医院流行病学研究室,国家恶性肿瘤临床医学研究中心(天津市300060))]), AuthorCompany(id=1249045358958023449, tenantId=1146029695717560320, journalId=1249024326687572039, articleId=1249045357762646787, xref=2, ext=[AuthorCompanyExt(id=1249045358970606362, tenantId=1146029695717560320, journalId=1249024326687572039, articleId=1249045357762646787, companyId=1249045358958023449, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2Office of Early Diagnosis and Early Treatment of Cancer, National Cancer Center/National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China), AuthorCompanyExt(id=1249045358974800667, tenantId=1146029695717560320, journalId=1249024326687572039, articleId=1249045357762646787, companyId=1249045358958023449, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2国家癌症中心,国家肿瘤临床医学研究中心,中国医学科学院北京协和医学院肿瘤医院癌症早诊早治办公室)]), AuthorCompany(id=1249045359046103837, tenantId=1146029695717560320, journalId=1249024326687572039, articleId=1249045357762646787, xref=3, ext=[AuthorCompanyExt(id=1249045359092241182, tenantId=1146029695717560320, journalId=1249024326687572039, articleId=1249045357762646787, companyId=1249045359046103837, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=3Peking University Cancer Hospital (Inner Mongolia Campus)/Affiliated Cancer Hospital of Inner Mongolia Medical University, Inner Mongolia Cancer Center, Inner Mongolia 010020, China), AuthorCompanyExt(id=1249045359096435487, tenantId=1146029695717560320, journalId=1249024326687572039, articleId=1249045357762646787, companyId=1249045359046103837, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=3北京大学肿瘤医院内蒙古医院,内蒙古医科大学附属肿瘤医院,内蒙古癌症中心)])], figs=[ArticleFig(id=1249045368235823206, tenantId=1146029695717560320, journalId=1249024326687572039, articleId=1249045357762646787, language=EN, label=null, caption=null, figureFileSmall=ueph3GrOOjiGxYlnvDLWIQ==, figureFileBig=9LXppz3hHihWDEYZE4KdMg==, tableContent=null), ArticleFig(id=1249045368307126376, tenantId=1146029695717560320, journalId=1249024326687572039, articleId=1249045357762646787, language=CN, label=图1, caption=常见恶性肿瘤联合筛查流程示意图

注:AI为人工智能

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项目内容
证据质量分级
 高(A)非常有把握:观察值接近真实值
 中(B)对观察值有中等把握:观察值有可能接近真实值,但亦有可能差别很大
 低(C)对观察值的把握有限:观察值可能与真实值有较大差别
 极低(D)对观察值几乎无把握:观察值与真实值可能有极大差别
推荐强度分级
 强(1)明确显示干预措施利大于弊或弊大于利
 弱(2)利弊不确定或无论质量高低的证据均显示利弊相当
), ArticleFig(id=1249045368550396013, tenantId=1146029695717560320, journalId=1249024326687572039, articleId=1249045357762646787, language=CN, label=表1, caption=

证据质量分级以及推荐强度分级

, figureFileSmall=null, figureFileBig=null, tableContent=
项目内容
证据质量分级
 高(A)非常有把握:观察值接近真实值
 中(B)对观察值有中等把握:观察值有可能接近真实值,但亦有可能差别很大
 低(C)对观察值的把握有限:观察值可能与真实值有较大差别
 极低(D)对观察值几乎无把握:观察值与真实值可能有极大差别
推荐强度分级
 强(1)明确显示干预措施利大于弊或弊大于利
 弱(2)利弊不确定或无论质量高低的证据均显示利弊相当
), ArticleFig(id=1249045368630087791, tenantId=1146029695717560320, journalId=1249024326687572039, articleId=1249045357762646787, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
恶性肿瘤类型a吸烟[34-35]饮酒[36-37]超重/肥胖[38]糖尿病[39]高血压[45-47]高血脂[48]缺乏体力活动[41-42]不健康饮食[43-44]
注:a主要参考ICD10编码顺序排序;b鼻腔、鼻咽、口腔、下咽和喉部的恶性肿瘤;c口腔、咽、喉部的恶性肿瘤;d食管腺癌;e胃贲门癌;f绝经后乳腺癌;g子宫内膜癌;h髓样白血病。
头颈部癌bcc
食管癌dd
胃癌ee
结直肠癌
肝癌
胆囊癌
胰腺癌
肺癌
乳腺癌f
子宫颈癌
子宫体癌ggg
卵巢癌
前列腺癌
肾癌
输尿管癌
膀胱癌
脑膜瘤
甲状腺癌
非霍奇金淋巴瘤
多发性骨髓瘤
白血病h
合计1761313531313
), ArticleFig(id=1249045368722362481, tenantId=1146029695717560320, journalId=1249024326687572039, articleId=1249045357762646787, language=CN, label=表2, caption=

有相对充分证据支持的共性危险因素与相关恶性肿瘤定性关联汇总表

, figureFileSmall=null, figureFileBig=null, tableContent=
恶性肿瘤类型a吸烟[34-35]饮酒[36-37]超重/肥胖[38]糖尿病[39]高血压[45-47]高血脂[48]缺乏体力活动[41-42]不健康饮食[43-44]
注:a主要参考ICD10编码顺序排序;b鼻腔、鼻咽、口腔、下咽和喉部的恶性肿瘤;c口腔、咽、喉部的恶性肿瘤;d食管腺癌;e胃贲门癌;f绝经后乳腺癌;g子宫内膜癌;h髓样白血病。
头颈部癌bcc
食管癌dd
胃癌ee
结直肠癌
肝癌
胆囊癌
胰腺癌
肺癌
乳腺癌f
子宫颈癌
子宫体癌ggg
卵巢癌
前列腺癌
肾癌
输尿管癌
膀胱癌
脑膜瘤
甲状腺癌
非霍奇金淋巴瘤
多发性骨髓瘤
白血病h
合计1761313531313
), ArticleFig(id=1249045368789471347, tenantId=1146029695717560320, journalId=1249024326687572039, articleId=1249045357762646787, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
肿瘤类型指南推荐高危人群定义
注:Hp为幽门螺杆菌;BMI为体质指数;HPV为人乳头瘤病毒;HBV为乙型肝炎病毒;HCV为丙型肝炎病毒;HIV为人类免疫缺陷病毒。
肺癌年龄≥50岁,且符合以下任意一项者:(1)吸烟包年数≥20包年,包括曾经吸烟≥20包年,但戒烟不足15年。注:吸烟包年数=每天吸烟的包数(每包20支)×吸烟年数;(2)与吸烟人群共同生活或同室工作≥20年;(3)患有慢性阻塞性肺疾病;(4)有职业暴露史(石棉、氡、铍、铬、镉、镍、硅、煤烟和煤烟尘等)至少1年;(5)有一级亲属(父母、子女以及兄弟姐妹)确诊肺癌
乳腺癌符合下列任意一条:(1)具备以下任意一项:①一级亲属有乳腺癌或卵巢癌史;②至少2位二级亲属 50岁前患乳腺癌或卵巢癌;③自身或至少1位一级亲属携带已知BRCA1/2基因致病性遗传突变。(2)具备以下任意一项者:①月经初潮年龄≤12岁;②绝经年龄>55岁;③有乳腺活检史或乳腺良性疾病手术史,或病理证实的乳腺(小叶或导管)不典型增生病史;④使用“雌孕激素联合”的激素替代治疗不少于半年:⑤45岁后乳腺X线检查提示乳腺实质(或乳房密度)类型为不均匀致密型或致密型。(3)具备以下任意两项者:①无哺乳史或哺乳时间<4个月;②无活产史(含从未生育、流产、死胎)或初次活产年龄≥30岁;③使用“雌激素”的激素替代治疗不少于半年;④流产(含自然流产和人工流产)≥2次
食管癌年龄≥45岁,且符合以下任意一项者:(1)居住于食管癌高发地区(以县级行政区为单位界定,以2000年中国人口结构为标准的年龄标化发病率>15/10万);(2)父母、子女以及兄弟姐妹等一级亲属中有食管癌病史;(3)热烫饮食、高盐饮食、腌制食品、吸烟、重度饮酒等不良饮食习惯和生活方式;(4)患有慢性食管炎、Barrett食管、食管憩室、贲门失弛缓症、反流性食管炎、食管良性狭窄等疾病;(5)有食管的癌前病变诊疗史
胃癌年龄≥45岁,且符合以下任意一项者:(1)居住于胃癌高发地区(以县级行政区为单位界定,以2000年中国人口结构为标准的年龄标化发病率>20/10万);(2)父母、子女以及兄弟姐妹等一级亲属中有胃癌病史;(3)尿素呼气试验、血清Hp抗体、粪便Hp抗原检测任一阳性;(4)吸烟、重度饮酒、高盐饮食、腌制食品等不良生活方式和饮食习惯;(5)患有慢性萎缩性胃炎、胃溃疡、胃息肉、手术后残胃、肥厚性胃炎、恶性贫血等疾病
肝癌符合以下条件之一者:(1)各种原因(包括酒精性肝病、代谢相关脂肪性肝病)所致的肝硬化患者;(2)HBV或(和)HCV慢性感染且年龄≥40岁者
结直肠癌(1)散发性结直肠癌高风险人群。综合年龄、性别、一级亲属结直肠癌家族史、吸烟和BMI,对散发性结直肠癌风险进行评分,原则如下:①年龄:≤49岁(0分),50~59岁(1分),≥60岁(2分);②性别:女性(0分),男性(1分);③吸烟史:无(0分),有(1分);④BMI:<23 kg/m2(0分),≥23 kg/m2(1分);⑤一级亲属(父母、子女以及兄弟姐妹)确诊结直肠癌:无(0分),有(1分;其中,如有1个一级亲属<60岁时被确诊为结直肠癌,或者2个一级亲属确诊结直肠癌4分)。以上各项累计评分≥4分者,认定为高风险人群。(2)遗传性结直肠癌高风险人群,具有林奇综合征或患有家族性腺瘤性息肉病等的人群
前列腺癌预期寿命 10 年以上且符合下列条件之一的男性:(1)年龄≥60岁;(2)年龄≥45岁且有前列腺癌家族史;(3)携带 BRCA2 基因突变且年龄≥40岁
宫颈癌暂无明确定义,但宫颈癌危险因素包括:高危型HPV持续感染及其他高危因素:(1)有宫颈癌等疾病相关家族史;(2)性生活过早;(3)过早生育(18周岁以前);(4)正在接受免疫抑制剂治疗;(5)多个性伴或性伴有多个性伴;(6)HIV感染;(7)患有其他性传播疾病;(8)吸烟、吸毒者
), ArticleFig(id=1249045370341363829, tenantId=1146029695717560320, journalId=1249024326687572039, articleId=1249045357762646787, language=CN, label=表3, caption=

中国常见恶性肿瘤筛查指南及规范推荐的恶性肿瘤高危人群定义汇总表

, figureFileSmall=null, figureFileBig=null, tableContent=
肿瘤类型指南推荐高危人群定义
注:Hp为幽门螺杆菌;BMI为体质指数;HPV为人乳头瘤病毒;HBV为乙型肝炎病毒;HCV为丙型肝炎病毒;HIV为人类免疫缺陷病毒。
肺癌年龄≥50岁,且符合以下任意一项者:(1)吸烟包年数≥20包年,包括曾经吸烟≥20包年,但戒烟不足15年。注:吸烟包年数=每天吸烟的包数(每包20支)×吸烟年数;(2)与吸烟人群共同生活或同室工作≥20年;(3)患有慢性阻塞性肺疾病;(4)有职业暴露史(石棉、氡、铍、铬、镉、镍、硅、煤烟和煤烟尘等)至少1年;(5)有一级亲属(父母、子女以及兄弟姐妹)确诊肺癌
乳腺癌符合下列任意一条:(1)具备以下任意一项:①一级亲属有乳腺癌或卵巢癌史;②至少2位二级亲属 50岁前患乳腺癌或卵巢癌;③自身或至少1位一级亲属携带已知BRCA1/2基因致病性遗传突变。(2)具备以下任意一项者:①月经初潮年龄≤12岁;②绝经年龄>55岁;③有乳腺活检史或乳腺良性疾病手术史,或病理证实的乳腺(小叶或导管)不典型增生病史;④使用“雌孕激素联合”的激素替代治疗不少于半年:⑤45岁后乳腺X线检查提示乳腺实质(或乳房密度)类型为不均匀致密型或致密型。(3)具备以下任意两项者:①无哺乳史或哺乳时间<4个月;②无活产史(含从未生育、流产、死胎)或初次活产年龄≥30岁;③使用“雌激素”的激素替代治疗不少于半年;④流产(含自然流产和人工流产)≥2次
食管癌年龄≥45岁,且符合以下任意一项者:(1)居住于食管癌高发地区(以县级行政区为单位界定,以2000年中国人口结构为标准的年龄标化发病率>15/10万);(2)父母、子女以及兄弟姐妹等一级亲属中有食管癌病史;(3)热烫饮食、高盐饮食、腌制食品、吸烟、重度饮酒等不良饮食习惯和生活方式;(4)患有慢性食管炎、Barrett食管、食管憩室、贲门失弛缓症、反流性食管炎、食管良性狭窄等疾病;(5)有食管的癌前病变诊疗史
胃癌年龄≥45岁,且符合以下任意一项者:(1)居住于胃癌高发地区(以县级行政区为单位界定,以2000年中国人口结构为标准的年龄标化发病率>20/10万);(2)父母、子女以及兄弟姐妹等一级亲属中有胃癌病史;(3)尿素呼气试验、血清Hp抗体、粪便Hp抗原检测任一阳性;(4)吸烟、重度饮酒、高盐饮食、腌制食品等不良生活方式和饮食习惯;(5)患有慢性萎缩性胃炎、胃溃疡、胃息肉、手术后残胃、肥厚性胃炎、恶性贫血等疾病
肝癌符合以下条件之一者:(1)各种原因(包括酒精性肝病、代谢相关脂肪性肝病)所致的肝硬化患者;(2)HBV或(和)HCV慢性感染且年龄≥40岁者
结直肠癌(1)散发性结直肠癌高风险人群。综合年龄、性别、一级亲属结直肠癌家族史、吸烟和BMI,对散发性结直肠癌风险进行评分,原则如下:①年龄:≤49岁(0分),50~59岁(1分),≥60岁(2分);②性别:女性(0分),男性(1分);③吸烟史:无(0分),有(1分);④BMI:<23 kg/m2(0分),≥23 kg/m2(1分);⑤一级亲属(父母、子女以及兄弟姐妹)确诊结直肠癌:无(0分),有(1分;其中,如有1个一级亲属<60岁时被确诊为结直肠癌,或者2个一级亲属确诊结直肠癌4分)。以上各项累计评分≥4分者,认定为高风险人群。(2)遗传性结直肠癌高风险人群,具有林奇综合征或患有家族性腺瘤性息肉病等的人群
前列腺癌预期寿命 10 年以上且符合下列条件之一的男性:(1)年龄≥60岁;(2)年龄≥45岁且有前列腺癌家族史;(3)携带 BRCA2 基因突变且年龄≥40岁
宫颈癌暂无明确定义,但宫颈癌危险因素包括:高危型HPV持续感染及其他高危因素:(1)有宫颈癌等疾病相关家族史;(2)性生活过早;(3)过早生育(18周岁以前);(4)正在接受免疫抑制剂治疗;(5)多个性伴或性伴有多个性伴;(6)HIV感染;(7)患有其他性传播疾病;(8)吸烟、吸毒者
), ArticleFig(id=1249045370442027127, tenantId=1146029695717560320, journalId=1249024326687572039, articleId=1249045357762646787, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
肿瘤类型推荐人群起止年龄(岁)主要筛查方法筛查间隔建议缩短筛查间隔的人群
注:PSA为前列腺特异性抗原;a:MLH1/MSH2突变引起的林奇综合征的高风险人群接受结肠镜筛查的起始年龄为20~25岁或比家族中最年轻患者发病年龄提前2~5年。MSH6/PMS2突变引起的林奇综合征的高风险人群接受结肠镜筛查的起始年龄为30~35岁或比家族中最年轻患者发病年龄提前2~5年。家族性腺瘤息肉病家系中的高风险人群从10岁开始接受结肠镜筛查,每年做1次结肠镜,并且持续终生。b:中国前列腺癌筛查与早诊早治指南(2022,北京)推荐的前列腺癌筛查目标人群定义见表3;同时,前列腺癌筛查停止时间推荐意见:(1)PSA 检测水平<1.0 ng/mL的60岁及以上男性停止筛查;(2)年龄≥75岁的男性结合个人健康状况选择是否停止筛查;(3)预期寿命<10年者停止筛查;c:不耐受或不依从结肠镜方法者,可选择免疫法或化学法的大便潜血检测、乙状结肠镜、结肠CT成像、多靶点粪便DNA检测等替代方法;-为无数据。
肺癌高风险人群50~74肺部低剂量CT每年1次(1)检出的实性结节或者部分实性结节的实性成分平均长径≥6 mm且<15 mm,或者非实性结节平均长径≥8 mm且<15 mm者,3个月后复查,并根据结果决定下一轮复查时间。(2)检出的实性结节、部分实性结节的实性成分或者非实性结节平均长径≥15 mm,如无法排除恶性结节,建议正规抗炎治疗后1~3个月复查,并根据结果决定下一轮复查时间。
乳腺癌一般风险≥45乳腺超声和(或)钼靶1~2年1次-
高风险人群≥40乳腺MRI每年1次-
食管癌高风险人群45~74上消化道内镜5年1次(1)低级别上皮内瘤变者每1~3年进行1次内镜检查。(2)低级别上皮内瘤变合并内镜下高危因素或病变长径>1 cm者每年接受1次内镜检查,持续5年。(3)Barrett食管患者伴低级别上皮内瘤变,每6~12个月进行1次内镜检查;Barrett食管患者无异型增生,每3~5年进行1次内镜检查
胃癌高风险人群45~74上消化道内镜5年1次局限于胃窦或胃体的萎缩性胃炎或肠上皮化生患者,每3年进行1次内镜检查。萎缩累及胃底或全胃,每年进行1次内镜检查。低级别上皮内瘤变每年进行1次内镜检查。高级别上皮内瘤变每3~6个月进行1次内镜检查
肝癌高风险人群40~74超声联合甲胎蛋白每年1次
结直肠癌散发性高风险人群40~74a
结肠镜或大便潜血检查等c5~10年1次(1)长径≥ l cm的腺瘤,绒毛结构≥25%的腺瘤,伴高级别上皮内瘤变的其他病变:应在治疗后1年内再次复查结肠镜,如无异常发现,后续结肠镜复查间隔可延长至3年。(2)其他腺瘤:应在诊断治疗后3年内再次复查结肠镜,如无异常发现,后续结肠镜复查间隔可延长至5年。(3)其他肠道良性病变:因结直肠癌风险增加并不明显,可视同一般人群处理。结肠镜复查间隔可为10年。(4)炎症性肠病,如溃疡性结肠炎、克罗恩病:明确诊断后每2年复查结肠镜。如筛查中发现高级别上皮内瘤变应在治疗后每年复查结肠镜。
遗传性高风险人群
前列腺癌高风险人群b前列腺
特异抗原
2年1次-
宫颈癌一般风险人群25~64高危型HPV
检测
5年1次-
宫颈细胞学
检查
3年1次-
), ArticleFig(id=1249045370504941689, tenantId=1146029695717560320, journalId=1249024326687572039, articleId=1249045357762646787, language=CN, label=表4, caption=

中国特定恶性肿瘤筛查指南及规范的核心筛查建议汇总

, figureFileSmall=null, figureFileBig=null, tableContent=
肿瘤类型推荐人群起止年龄(岁)主要筛查方法筛查间隔建议缩短筛查间隔的人群
注:PSA为前列腺特异性抗原;a:MLH1/MSH2突变引起的林奇综合征的高风险人群接受结肠镜筛查的起始年龄为20~25岁或比家族中最年轻患者发病年龄提前2~5年。MSH6/PMS2突变引起的林奇综合征的高风险人群接受结肠镜筛查的起始年龄为30~35岁或比家族中最年轻患者发病年龄提前2~5年。家族性腺瘤息肉病家系中的高风险人群从10岁开始接受结肠镜筛查,每年做1次结肠镜,并且持续终生。b:中国前列腺癌筛查与早诊早治指南(2022,北京)推荐的前列腺癌筛查目标人群定义见表3;同时,前列腺癌筛查停止时间推荐意见:(1)PSA 检测水平<1.0 ng/mL的60岁及以上男性停止筛查;(2)年龄≥75岁的男性结合个人健康状况选择是否停止筛查;(3)预期寿命<10年者停止筛查;c:不耐受或不依从结肠镜方法者,可选择免疫法或化学法的大便潜血检测、乙状结肠镜、结肠CT成像、多靶点粪便DNA检测等替代方法;-为无数据。
肺癌高风险人群50~74肺部低剂量CT每年1次(1)检出的实性结节或者部分实性结节的实性成分平均长径≥6 mm且<15 mm,或者非实性结节平均长径≥8 mm且<15 mm者,3个月后复查,并根据结果决定下一轮复查时间。(2)检出的实性结节、部分实性结节的实性成分或者非实性结节平均长径≥15 mm,如无法排除恶性结节,建议正规抗炎治疗后1~3个月复查,并根据结果决定下一轮复查时间。
乳腺癌一般风险≥45乳腺超声和(或)钼靶1~2年1次-
高风险人群≥40乳腺MRI每年1次-
食管癌高风险人群45~74上消化道内镜5年1次(1)低级别上皮内瘤变者每1~3年进行1次内镜检查。(2)低级别上皮内瘤变合并内镜下高危因素或病变长径>1 cm者每年接受1次内镜检查,持续5年。(3)Barrett食管患者伴低级别上皮内瘤变,每6~12个月进行1次内镜检查;Barrett食管患者无异型增生,每3~5年进行1次内镜检查
胃癌高风险人群45~74上消化道内镜5年1次局限于胃窦或胃体的萎缩性胃炎或肠上皮化生患者,每3年进行1次内镜检查。萎缩累及胃底或全胃,每年进行1次内镜检查。低级别上皮内瘤变每年进行1次内镜检查。高级别上皮内瘤变每3~6个月进行1次内镜检查
肝癌高风险人群40~74超声联合甲胎蛋白每年1次
结直肠癌散发性高风险人群40~74a
结肠镜或大便潜血检查等c5~10年1次(1)长径≥ l cm的腺瘤,绒毛结构≥25%的腺瘤,伴高级别上皮内瘤变的其他病变:应在治疗后1年内再次复查结肠镜,如无异常发现,后续结肠镜复查间隔可延长至3年。(2)其他腺瘤:应在诊断治疗后3年内再次复查结肠镜,如无异常发现,后续结肠镜复查间隔可延长至5年。(3)其他肠道良性病变:因结直肠癌风险增加并不明显,可视同一般人群处理。结肠镜复查间隔可为10年。(4)炎症性肠病,如溃疡性结肠炎、克罗恩病:明确诊断后每2年复查结肠镜。如筛查中发现高级别上皮内瘤变应在治疗后每年复查结肠镜。
遗传性高风险人群
前列腺癌高风险人群b前列腺
特异抗原
2年1次-
宫颈癌一般风险人群25~64高危型HPV
检测
5年1次-
宫颈细胞学
检查
3年1次-
), ArticleFig(id=1249045370580439163, tenantId=1146029695717560320, journalId=1249024326687572039, articleId=1249045357762646787, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
癌症类型筛查方法人群来源g灵敏度(%)特异度(%)文献h
注:LDCT为低剂量螺旋CT;NLST为美国国家肺部筛查试验;FIT为免疫法粪便隐血试验;PG为胃蛋白酶原;G-17为胃泌素-17;HP-Ab为幽门螺杆菌抗体;AFP为甲胎蛋白;DCP(PIVKA-Ⅱ)为异常凝血酶原,又称维生素K拮抗剂Ⅱ;PSA为前列腺特异性抗原;HPV为人乳头瘤病毒;CIN为宫颈上皮内瘤样病变;a:高危人群;b:BRCA1/2携带者;c:癌前病变;d:结直肠癌和进展期腺瘤联合;e:早期肝癌的灵敏度为47.0%;f:CIN 3+为结局;g:Meta分析人群来源于至少3个国家;h:由于Meta分析的原始参考文献过多,因此,此处仅引用Meta分析所在指南作为参考文献。
肺癌LDCT中国98.178.2[62]
LDCT美国93.873.4
LDCTMeta分析>90.028.0~100.0
乳腺癌乳腺X线Meta分析80.096.0[55]
乳腺X线aMeta分析55.094.0
乳腺超声Meta分析68.898.9
乳腺X线联合超声Meta分析96.292.6
乳腺X线联合超声aMeta分析93.292.9
乳腺核磁Meta分析82.392.2
乳腺核磁bMeta分析78.393.8
结直肠癌CT结肠镜Meta分析95.098.0[60]
CT结肠镜cMeta分析88.095.0
FITMeta分析83.090.0
FITcMeta分析36.092.0
粪便FIT-DNA d美国+加拿大92.342.4
胃癌PGMeta分析57.0~69.073.0~85.0[57]
MG7-AgMeta分析73.091.0
PG+G-17+HP-AbMeta分析78.092.0
窄带成像放大内镜Meta分析87.096.0
磁控胶囊内镜Meta分析87.0
色素内镜Meta分析90.082.0
肝癌腹部超声Meta分析84.0 e[58]
AFPMeta分析39.0~65.076.0~94.0
DCP(PIVKA-Ⅱ)Meta分析42.0~54.083.0~86.0
食管鳞癌前列腺癌普通白光内镜中国49.397.4[56]
窄带成像放大内镜中国79.597.9
Lugol 染色内镜法国100.066.0
PSA中国89.0~100 13~77[61]
宫颈癌高危型HPV检测f中国97.585.1[92]
细胞学检测f中国87.994.7
醋酸视觉检查f中国54.689.9
), ArticleFig(id=1249045370702073981, tenantId=1146029695717560320, journalId=1249024326687572039, articleId=1249045357762646787, language=CN, label=表5, caption=

基于中国常见恶性肿瘤筛查指南及规范汇总的恶性肿瘤推荐筛查方法准确性信息

, figureFileSmall=null, figureFileBig=null, tableContent=
癌症类型筛查方法人群来源g灵敏度(%)特异度(%)文献h
注:LDCT为低剂量螺旋CT;NLST为美国国家肺部筛查试验;FIT为免疫法粪便隐血试验;PG为胃蛋白酶原;G-17为胃泌素-17;HP-Ab为幽门螺杆菌抗体;AFP为甲胎蛋白;DCP(PIVKA-Ⅱ)为异常凝血酶原,又称维生素K拮抗剂Ⅱ;PSA为前列腺特异性抗原;HPV为人乳头瘤病毒;CIN为宫颈上皮内瘤样病变;a:高危人群;b:BRCA1/2携带者;c:癌前病变;d:结直肠癌和进展期腺瘤联合;e:早期肝癌的灵敏度为47.0%;f:CIN 3+为结局;g:Meta分析人群来源于至少3个国家;h:由于Meta分析的原始参考文献过多,因此,此处仅引用Meta分析所在指南作为参考文献。
肺癌LDCT中国98.178.2[62]
LDCT美国93.873.4
LDCTMeta分析>90.028.0~100.0
乳腺癌乳腺X线Meta分析80.096.0[55]
乳腺X线aMeta分析55.094.0
乳腺超声Meta分析68.898.9
乳腺X线联合超声Meta分析96.292.6
乳腺X线联合超声aMeta分析93.292.9
乳腺核磁Meta分析82.392.2
乳腺核磁bMeta分析78.393.8
结直肠癌CT结肠镜Meta分析95.098.0[60]
CT结肠镜cMeta分析88.095.0
FITMeta分析83.090.0
FITcMeta分析36.092.0
粪便FIT-DNA d美国+加拿大92.342.4
胃癌PGMeta分析57.0~69.073.0~85.0[57]
MG7-AgMeta分析73.091.0
PG+G-17+HP-AbMeta分析78.092.0
窄带成像放大内镜Meta分析87.096.0
磁控胶囊内镜Meta分析87.0
色素内镜Meta分析90.082.0
肝癌腹部超声Meta分析84.0 e[58]
AFPMeta分析39.0~65.076.0~94.0
DCP(PIVKA-Ⅱ)Meta分析42.0~54.083.0~86.0
食管鳞癌前列腺癌普通白光内镜中国49.397.4[56]
窄带成像放大内镜中国79.597.9
Lugol 染色内镜法国100.066.0
PSA中国89.0~100 13~77[61]
宫颈癌高危型HPV检测f中国97.585.1[92]
细胞学检测f中国87.994.7
醋酸视觉检查f中国54.689.9
), ArticleFig(id=1249045370806931582, tenantId=1146029695717560320, journalId=1249024326687572039, articleId=1249045357762646787, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
联合筛查
模式
推荐筛查
癌症组合
高危人群定义推荐筛查方法
核心建议GRADE分级核心建议GRADE分级
注:PG为胃蛋白酶原;HP为幽门螺杆菌;FIT为粪便隐血试验;APCS为亚太结直肠癌筛查;MCED为多癌症早期检测。
基于激素依赖性
恶性肿瘤的联合
筛查模式
乳腺癌、前列腺癌、卵巢癌和子宫内
膜癌
(1)激素依赖性恶性肿瘤家族史;
(2)性激素水平异常升高;
(3)明确的高遗传风险;
(4)存在明显升高体内激素水平
的风险相关因素;
其中(1)、(2)、(3)满足任意2条,
且同时满足(4)
证据质量:中
推荐强度:弱
指南推荐的影像学检查+下述
辅助性检查:
(1)连续3次监测体内性激素;
(2)必要时BRCA1和BRCA2
基因检测
证据质量:中
推荐强度:弱
基于同一系统常见
恶性肿瘤的联合筛
查模式
食管癌、胃癌和结直肠癌等消化系统
常见恶性肿瘤
(1)消化系统常见恶性肿瘤家族史;
(2)≥2种慢性胃肠道疾病史;
(3)≥2种消化系统常见恶性肿瘤的危险因素
证据质量:强
推荐强度:强
消化道内镜检查+下述辅助性检查:
(1)PG+HP联合的改进ABC风险
评估;
(2)FIT+APCS评分联合评估
证据质量:中
推荐强度:强
基于共性危险因素
的恶性肿瘤联合筛
查模式
吸烟相关恶性肿瘤、肥胖相关恶性肿
瘤等(表2
(1)≥2种恶性肿瘤共性上游危险
因素 (表2);
(2)≥2种恶性肿瘤共性中游危险
因素;
(3)≥2种恶性肿瘤特异性的危险
因素
证据质量:中
推荐强度:弱
指南推荐的影像学检查+下述辅助性检查:
(1)6个月内连续3次炎性相关指标监测;
(2)6个月内连续3次糖脂代谢指标检测
证据质量:弱
推荐强度:弱
基于慢病共存的
恶性肿瘤联合筛
查模式
糖尿病相关恶性
肿瘤、肥胖相关
恶性肿瘤等(表2
(1)≥2种恶性肿瘤共性上游危险
因素 (表2);
(2)≥2种恶性肿瘤共性中游危险
因素;
(3)≥2种恶性肿瘤特异性的危险
因素;
(4)心脑血管疾病史
证据质量:中
推荐强度:弱
胸部CT检查+下述辅助性检查:
(1)6个月内连续3次炎性相关指标监测;
(2)6个月内连续3次糖脂代谢指标检测;
(3)6个月内连续3次血压指标检测
证据质量:弱
推荐强度:弱
基于地区性高发
恶性肿瘤的联合
筛查模式
地区性发病率前
5位的常见恶性
肿瘤
(1)≥2种癌症共性上游危险因素
表2);
(2)≥2种癌症共性中游危险因素;
(3)≥2种癌症特异性的危险因素;
(4)极高风险人群:3种特异性危险因素均存在≥2种恶性肿瘤危险因素
证据质量:强
推荐强度:强
指南推荐的影像学检查+下述辅助性检查:
(1)目前恶性肿瘤相关肿瘤标志物和致癌性病原体检测;
(2)极高风险居民可推荐MCED或多组学检测方法
证据质量:中
推荐强度:弱
), ArticleFig(id=1249045370907594880, tenantId=1146029695717560320, journalId=1249024326687572039, articleId=1249045357762646787, language=CN, label=表6, caption=

常见恶性肿瘤不同联合筛查模式的核心推荐内容

, figureFileSmall=null, figureFileBig=null, tableContent=
联合筛查
模式
推荐筛查
癌症组合
高危人群定义推荐筛查方法
核心建议GRADE分级核心建议GRADE分级
注:PG为胃蛋白酶原;HP为幽门螺杆菌;FIT为粪便隐血试验;APCS为亚太结直肠癌筛查;MCED为多癌症早期检测。
基于激素依赖性
恶性肿瘤的联合
筛查模式
乳腺癌、前列腺癌、卵巢癌和子宫内
膜癌
(1)激素依赖性恶性肿瘤家族史;
(2)性激素水平异常升高;
(3)明确的高遗传风险;
(4)存在明显升高体内激素水平
的风险相关因素;
其中(1)、(2)、(3)满足任意2条,
且同时满足(4)
证据质量:中
推荐强度:弱
指南推荐的影像学检查+下述
辅助性检查:
(1)连续3次监测体内性激素;
(2)必要时BRCA1和BRCA2
基因检测
证据质量:中
推荐强度:弱
基于同一系统常见
恶性肿瘤的联合筛
查模式
食管癌、胃癌和结直肠癌等消化系统
常见恶性肿瘤
(1)消化系统常见恶性肿瘤家族史;
(2)≥2种慢性胃肠道疾病史;
(3)≥2种消化系统常见恶性肿瘤的危险因素
证据质量:强
推荐强度:强
消化道内镜检查+下述辅助性检查:
(1)PG+HP联合的改进ABC风险
评估;
(2)FIT+APCS评分联合评估
证据质量:中
推荐强度:强
基于共性危险因素
的恶性肿瘤联合筛
查模式
吸烟相关恶性肿瘤、肥胖相关恶性肿
瘤等(表2
(1)≥2种恶性肿瘤共性上游危险
因素 (表2);
(2)≥2种恶性肿瘤共性中游危险
因素;
(3)≥2种恶性肿瘤特异性的危险
因素
证据质量:中
推荐强度:弱
指南推荐的影像学检查+下述辅助性检查:
(1)6个月内连续3次炎性相关指标监测;
(2)6个月内连续3次糖脂代谢指标检测
证据质量:弱
推荐强度:弱
基于慢病共存的
恶性肿瘤联合筛
查模式
糖尿病相关恶性
肿瘤、肥胖相关
恶性肿瘤等(表2
(1)≥2种恶性肿瘤共性上游危险
因素 (表2);
(2)≥2种恶性肿瘤共性中游危险
因素;
(3)≥2种恶性肿瘤特异性的危险
因素;
(4)心脑血管疾病史
证据质量:中
推荐强度:弱
胸部CT检查+下述辅助性检查:
(1)6个月内连续3次炎性相关指标监测;
(2)6个月内连续3次糖脂代谢指标检测;
(3)6个月内连续3次血压指标检测
证据质量:弱
推荐强度:弱
基于地区性高发
恶性肿瘤的联合
筛查模式
地区性发病率前
5位的常见恶性
肿瘤
(1)≥2种癌症共性上游危险因素
表2);
(2)≥2种癌症共性中游危险因素;
(3)≥2种癌症特异性的危险因素;
(4)极高风险人群:3种特异性危险因素均存在≥2种恶性肿瘤危险因素
证据质量:强
推荐强度:强
指南推荐的影像学检查+下述辅助性检查:
(1)目前恶性肿瘤相关肿瘤标志物和致癌性病原体检测;
(2)极高风险居民可推荐MCED或多组学检测方法
证据质量:中
推荐强度:弱
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常见恶性肿瘤联合筛查专家共识(2025版)
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陈可欣 1 , 陈万青 2 , 黄育北 1 , 吕章艳 1 , 宋方方 1 , 夏昌发 2 , 许永杰 2 , 杨雷 3 , 盛超 1 , 张雅聪 1 , 王鹏 1 , 张芸萌 1 , 吉雨婷 1 , 李净净 1 , 李文轩 1 , 吴婕 1 , 金千韵 1 , 宋丰举 1 , 常见恶性肿瘤联合筛查专家共识制定专家组 , 常见恶性肿瘤联合筛查专家共识制定工作组
中国肿瘤临床 | 指南与共识 2025,52(14): 703-726
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中国肿瘤临床 | 指南与共识 2025, 52(14): 703-726
常见恶性肿瘤联合筛查专家共识(2025版)
全屏
陈可欣1 , 陈万青2 , 黄育北1, 吕章艳1, 宋方方1, 夏昌发2, 许永杰2, 杨雷3, 盛超1, 张雅聪1, 王鹏1, 张芸萌1, 吉雨婷1, 李净净1, 李文轩1, 吴婕1, 金千韵1, 宋丰举1, 常见恶性肿瘤联合筛查专家共识制定专家组, 常见恶性肿瘤联合筛查专家共识制定工作组
作者信息
  • 1天津医科大学肿瘤医院流行病学研究室,国家恶性肿瘤临床医学研究中心(天津市300060)
  • 2国家癌症中心,国家肿瘤临床医学研究中心,中国医学科学院北京协和医学院肿瘤医院癌症早诊早治办公室
  • 3北京大学肿瘤医院内蒙古医院,内蒙古医科大学附属肿瘤医院,内蒙古癌症中心

通讯作者:

陈万青 
Expert consensus on combined screening for common cancers (2025 edition)
Kexin Chen1 , Wanqing Chen2 , Yubei Huang1, Zhangyan Lyu1, Fangfang Song1, Changfa Xia2, Yongjie Xu2, Lei Yang3, Chao Sheng1, Yacong Zhang1, Peng Wang1, Yunmeng Zhang1, Yuting Ji1, Jingjing Li1, Wenxuan Li1, Jie Wu1, Qianyun Jin1, Fengju Song1, Expert Group for the Expert Consensus on Combined Screening for Common Cancers, Working Group for the Expert Consensus on Combined Screening for Common Cancers
Affiliations
  • 1Department of Epidemiology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin 300060, China
  • 2Office of Early Diagnosis and Early Treatment of Cancer, National Cancer Center/National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
  • 3Peking University Cancer Hospital (Inner Mongolia Campus)/Affiliated Cancer Hospital of Inner Mongolia Medical University, Inner Mongolia Cancer Center, Inner Mongolia 010020, China
出版时间: 2025-07-30 doi: 10.12354/j.issn.1000-8179.2025.20250757
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恶性肿瘤(或称癌症)是影响居民健康的重大公共卫生问题,造成严重的全球疾病负担。早期筛查能够大幅度提高癌症的早诊早治率,提升癌症生存率。然而,当前癌症筛查指南均只关注单一癌症类型。通过科学合理的常见癌症联合筛查,不仅能优化利用生物样本资源,提高受检者依从性,节省时间成本,增强癌症筛查的全面性和有效性,还能有效降低筛查成本、合理配置医疗资源,减少癌症综合疾病负担。《中国常见癌症联合筛查专家共识》由中国抗癌协会肿瘤流行病学专业委员会发起,组织多学科专家,整合多种常见癌症筛查与早诊早治领域的国内外研究进展,同时考虑中国国情和癌症筛查的实际经验,依据世界卫生组织推荐的指南制定原则和方法完成证据评估。本共识针对常见癌症联合筛查过程中的筛查人群、技术、流程等给出了基于证据的推荐,旨在提升常见癌症联合筛查与早诊早治效果,为中国的癌症防控提供科学依据。

恶性肿瘤  /  联合筛查  /  早诊早治  /  共识

Malignant tumors (commonly referred to as cancers) represent a major global public health challenge and contribute substantially to the global disease burden. Early screening plays a crucial role in improving detection rates, enabling timely intervention, and enhancing patient survival. However, current cancer screening guidelines primarily focus on site-specific screening, which may not fully address the need for comprehensive early detection. A scientifically rational, multi-cancer screening approach offers several advantages: it optimizes the use of biological samples, reduces the time burden for participants, enhances the efficiency and comprehensiveness of screening, and minimizes overall expenses. Moreover, this approach facilitates rational allocation of healthcare resources, ultimately helping to reduce the societal burden of cancer. To address gap, the Cancer Epidemiology Committee of the China Anti-Cancer Association has developed the Expert Consensus on Combined Screening for Common Cancers. This consensus integrates multidisciplinary expertise and synthesizes the latest domestic and international researches on cancer screening, early detection, and treatment of prevalent malignancies. Drawing upon China’s unique demographic and healthcare context and practical screening experiences, the consensus provides evidence-based recommendations on target populations, screening technologies, and procedural workflows for multi-cancer screening. These guidelines align with the principles and methodologies established by the World Health Organization (WHO), aiming to enhance the effectiveness of combined cancer screening in China, improve early detection rates, and provide a scientific foundation for national cancer prevention and control strategies.

malignant tumor  /  combined screening  /  early detection and treatment  /  consensus
陈可欣, 陈万青, 黄育北, 吕章艳, 宋方方, 夏昌发, 许永杰, 杨雷, 盛超, 张雅聪, 王鹏, 张芸萌, 吉雨婷, 李净净, 李文轩, 吴婕, 金千韵, 宋丰举, 常见恶性肿瘤联合筛查专家共识制定专家组, 常见恶性肿瘤联合筛查专家共识制定工作组. 常见恶性肿瘤联合筛查专家共识(2025版). 中国肿瘤临床, 2025 , 52 (14) : 703 -726 . DOI: 10.12354/j.issn.1000-8179.2025.20250757
Kexin Chen, Wanqing Chen, Yubei Huang, Zhangyan Lyu, Fangfang Song, Changfa Xia, Yongjie Xu, Lei Yang, Chao Sheng, Yacong Zhang, Peng Wang, Yunmeng Zhang, Yuting Ji, Jingjing Li, Wenxuan Li, Jie Wu, Qianyun Jin, Fengju Song, Expert Group for the Expert Consensus on Combined Screening for Common Cancers, Working Group for the Expert Consensus on Combined Screening for Common Cancers. Expert consensus on combined screening for common cancers (2025 edition)[J]. Chinese Journal of Clinical Oncology, 2025 , 52 (14) : 703 -726 . DOI: 10.12354/j.issn.1000-8179.2025.20250757
恶性肿瘤是影响全球居民健康的重大公共卫生问题,它不仅是导致全球大多数国家居民导致过早死亡的主要原因,也是全球疾病负担的重要影响因素。有适宜的筛查手段,并有效实施筛查才能够显著提高恶性肿瘤的早诊率和生存率。然而,当前的恶性肿瘤筛查指南均多只关注单一癌种类型。通过科学合理的常见恶性肿瘤联合筛查,不仅能提升恶性肿瘤筛查的全面性和有效性,同时能节约医疗资源,减轻恶性肿瘤的综合疾病负担,提高受检者的依从性。因此,为了推进我国常见恶性肿瘤联合筛查工作的规范化、均质化和优质化,由中国抗癌协会肿瘤流行病学专业委员会发起,天津医科大学肿瘤医院成立中国常见恶性肿瘤(即我国发病率前10的癌种)联合筛查专家共识制定专家组,联合肿瘤学、内镜学、外科学、病理学、临床检验学、流行病学、循证医学、卫生经济学和卫生管理学等多学科专家,基于WHO推荐的指南制定原则和方法[1],采用系统综述的方法汇总当前国内外恶性肿瘤筛查相关高级别证据,结合我国恶性肿瘤发病特征,制定常见恶性肿瘤联合筛查专家共识(2025版,简称“共识”)。以期为我国常见恶性肿瘤联合筛查与早诊早治的规范开展提供参考。
本共识证据素材来源于课题组前期基于国内外恶性肿瘤筛查相关高级别证据的系统综述汇总。评价过程由2人(均为副研究员)独立完成,若存在分歧,则由更资深的研究员共同讨论解决。共识工作组基于证据评价小组提供的国内外证据,同时考虑我国筛查人群的特点、当前国情和干预措施的成本和利弊后,拟定初步的筛查关键问题推荐意见,并采用推荐分级评估、制定及评价(Grading of Recommendations Assessment Development and Evaluation,GRADE)的方法对证据质量和推荐意见进行分级(表1)。
1. 中国恶性肿瘤的疾病负担
2022年,我国恶性肿瘤新发和死亡病例数分别约为482.5万例和257.4万例,分别占全球恶性肿瘤新发和死亡例数的24.2%和26.4%[2]。然而,我国人口占全球的18.3%,初步提示我国当前同时面临严重的恶性肿瘤发病及死亡负担[3]。我国发病例数前5位的高发癌种(肺癌、结直肠癌、甲状腺癌、肝癌和胃癌)占我国恶性肿瘤总发病人数的57.42%;死亡例数前5位的癌种(肺癌、肝癌、胃癌、结直肠癌和食管癌)占我国同期恶性肿瘤总死亡人数的67.50%[3]。2022年,我国总体恶性肿瘤的粗发病率和年龄标准化发病率(age-standardized incidence rate,ASIR)分别为341.75/10万和201.61/10万;粗死亡率和年龄标准化死亡率(age-standardized mortality rate,ASMR)分别为182.34/10万和96.47/10万[2]。2000~2018年期间,我国恶性肿瘤的ASIR以年平均1.4%的速度在快速增长,其中女性恶性肿瘤发病率的年均增长速度明显快于男性(2.6%和0.3%);我国恶性肿瘤ASMR以年平均1.3%的速度在快速下降,女性恶性肿瘤死亡率下降速度也快于男性(1.3%和1.2%)[2]
2008~2021年期间,我国绝大多数常见恶性肿瘤的5年相对生存率均有明显改善,其中肺癌的改善最为显著[4]。2019~2021年,我国恶性肿瘤患者的总体5年相对生存率为45.9%,最高的是甲状腺癌(93.6%),5年相对生存率超过70%的其他癌种依次是睾丸癌(82.7%)、乳腺癌(82.4%)、膀胱癌(74.1%)、前列腺癌(73.9%)和子宫体癌(70.8%)[4]。但与欧美国家相比,除胃癌和食管癌外,我国多数恶性肿瘤患者5年生存率仍偏低,其主要原因是我国恶性肿瘤筛查起步较晚,导致早期癌的比例明显较低。2016~2017年,我国Ⅰ期恶性肿瘤的总体比例不足20%,而同期美国早期癌的比例为35.5%,比我国高出15%[5]
恶性肿瘤不仅给人们带来了严重的疾病负担,同时还给全球造成了大量直接和间接的经济负担。2020~2050年,全球恶性肿瘤经济负担预期约为25.2万亿美元,占全球国内生产总值(gross domestic product,GDP)的0.55%[6]。2017年,我国居民恶性肿瘤总费用高达3 048.4亿元人民币,占医疗总费用的5.8%;调整消费者价格指数后,恶性肿瘤患者医疗费用从2008年的633.0亿元增加至2017年的2495.6亿元;年平均增加15.2%[7]。该数据提示,我国当前的肿瘤防控不仅面临着严重的疾病负担,同时面临着沉重的经济负担,而且未来还将持续面临不断增长的双重负担[3]
2. 常见恶性肿瘤联合筛查的意义
在人口老龄化和其他环境因素的多重影响下,未来30年内,全球恶性肿瘤的发病数预期将再升高将近1倍[8]。开展人群筛查,提高恶性肿瘤的早期发现和早期诊断,被认为是目前降低肿瘤疾病负担和经济负担的最有效措施之一[9]。大量观察性研究和干预性研究均提示,不同类型恶性肿瘤的筛查能降低大约20%~57%的恶性肿瘤死亡,而且不同时期、不同研究的结论几乎一致[10-14]。即使是接受一次性的肺部低剂量CT筛查或上消化道内镜筛查,也能显著降低人群31%的肺癌死亡和57%的上消化道癌死亡风险[15-16]。基于相应证据,国内外不同国家分别制定了不同恶性肿瘤的筛查指南。如美国癌症协会和美国预防医学工作组分别推荐对肺癌、结直肠癌、乳腺癌和子宫颈癌等4种恶性肿瘤进行人群筛查。我国自2020年之后先后制定了针对8种恶性肿瘤的筛查指南。然而,当前几乎所有国内外恶性肿瘤筛查指南均多只针对单一癌种筛查。随着近年来泛癌多组学研究的不断深入,不断有研究发现,不同恶性肿瘤之间存在诸多的共性危险因素(如吸烟、饮酒、不健康饮食和缺乏锻炼等)和共性遗传基础,同时存在广泛的共性早期代谢改变和蛋白表达异常基础[17-19]。然而,单一癌种筛查很难避免具有共性危险因素或遗传背景的其他恶性肿瘤的死亡。更为重要的是,对于人口众多、人群分布较广、社会资源相对缺乏、医疗卫生资源相对不足的国家或地区而言,在同一人群中分别针对不同癌种开展独立筛查,容易造成有限筛查资源的重复投入,从而造成潜在浪费。通过科学合理的常见恶性肿瘤联合筛查,扩大筛查癌种,不仅能提升恶性肿瘤筛查的全面性和有效性,提高筛查依从性和覆盖率,同时能减少不必要的医疗资源浪费,更有效地配置医疗资源,减少多种恶性肿瘤的总体疾病负担,预期更加符合我国国情。
3. 全球恶性肿瘤联合筛查的现状
国内外已有不少大规模人群的多种常见恶性肿瘤联合筛查干预研究。例如,美国国家癌症研究所(National Cancer Institute,NCI)设计并主导的前列腺癌、肺癌、结直肠癌和卵巢癌筛查随机对照试验(prostate,lung,colorectal,and ovarian randomized trial,PLCO)[20-21],美国疾病与预防控制中心开展的国家乳腺癌和子宫颈癌早期检测计划(national breast and cervical cancer early detection program,NBCCEDP)[22],法国伊泽尔省实施的大规模乳腺癌、子宫颈癌和结直肠癌筛查计划[23],以及美国的乳腺癌、子宫颈癌和结直肠癌联合筛查(population based research optimizingscreening through personalized regimens,PROSPR)[24]。我国是目前开展多种恶性肿瘤联合筛查项目最多、覆盖人群最广的国家,包括全国“两癌”(宫颈癌和乳腺癌)筛查项目、全国多中心的淮河流域癌症早诊早治项目(食管癌、胃癌和肝癌联合筛查)、城市癌症早诊早治项目(肺癌、乳腺癌、肝癌、上消化道癌和结直肠癌联合筛查)和农村癌症早诊早治项目(肺癌、食管癌、胃癌、肝癌、结直肠癌和鼻咽癌联合筛查),以及在某些地区开展的多种恶性肿瘤联合筛查项目,如天津市的常见癌症联合筛查试验研究(Chinese colorectal,breast,lung,liver,and stomach cancer screening trial,C-BLAST)[25]和中国台湾地区的肝癌、结直肠癌、乳腺癌、子宫颈癌和口腔癌筛查研究(Keelung community-based integrated screening,KCIS)[26]
上述研究分别从不同层面探索了多种恶性肿瘤联合筛查的可行性、潜在收益和筛查优化方向。如基于PLCO研究的二次分析结果显示,常见恶性肿瘤联合筛查不仅显著降低男性12%的目标癌种联合死亡风险,而且能降低全人群9%的全癌死亡和11%的全因死亡风险[27]。NBCCEDP研究提示,联合筛查能显著降低没有保险的、低收入女性的乳腺癌和子宫颈癌死亡率,并能显著改善该类女性的生活质量。法国伊泽尔省的研究提示,子宫颈癌与乳腺癌联合筛查,能提高50~69岁女性宫颈涂片的筛查参与率。PROSPR研究通过对筛查参与率、及时诊断率和恶性肿瘤检出率等指标的分析提示个性化优化筛查方案能系统地确定需要改进的筛查流程步骤。KCIS研究则提示基于社区的恶性肿瘤联合筛查计划,不仅能够同时发现多种疾病的早期患者,而且提高了筛查依从性。
除了上述大规模人群筛查干预研究,近年来,基于液体活检技术的多癌种联合筛查探索性研究受到了广泛关注,其中最受关注的是基于血液样本的多癌症早期检测(multi-cancer early detection,MCED)技术[28]。不同于传统的联合筛查研究中每一种筛查方法均只针对一种癌种,MCED技术通过检测循环游离DNA(cell-free DNA,cfDNA)中的恶性肿瘤特异性生物标志物(如甲基化模式、DNA片段化和基因突变等),能够非侵入性地同时能够检测多癌种,包括目前尚无有效筛查方法的恶性肿瘤类型(如胰腺癌、卵巢癌等)。由于其对恶性肿瘤检出的相对特异性,MCED技术也被认为是目前最具潜力的常见恶性肿瘤联合筛查方法。如CancerSEEK测试可以准确检测出处于不同发展阶段的8种不同的癌种[29]。基于血小板RNA谱的高度特异性的泛癌种血液检测涵盖了18种不同的肿瘤类型,并可以相对准确地定位原发性肿瘤[30]。有研究人员进一步论证了通过整合高通量检测技术和机器学习方法,可以提高MCED检测的准确性,并扩大现有筛查计划的可及性[31]。研究人员提出基于cfDNA甲基化测序结果的MCED检测不仅对早期恶性肿瘤具有出色的灵敏度,对于食管癌、肝癌和卵巢癌等恶性肿瘤的联合特异性更是高达99.1%[32]。有学者则提出了适合在中低收入国家进行广泛癌种筛查的常见恶性肿瘤联合检测方法[33]。所有这些研究都为MCED的大规模人群推广奠定了较好的基础。
4.当前恶性肿瘤联合筛查的局限性
尽管恶性肿瘤联合筛查在早期发现和降低多种恶性肿瘤相关死亡率方面展现出巨大潜力,但仍存在明显的不足,限制了其广泛应用和效果优化,具体包括:(1)缺乏高级别的联合筛查效果评价证据。虽然目前已有不少的大规模人群恶性肿瘤联合筛查干预研究,但绝大多数研究并非高级别证据的随机对照试验研究(randomized controlled trial,RCT)。即使是基于RCT设计的PLCO研究,原始研究设计并没有针对4种恶性肿瘤联合筛查效果的评估设计,而是分别针对单一癌种类型的设计与评价。(2)缺乏系统的安全性评估。不同于单一癌种的筛查,联合筛查除了能预期降低多种恶性肿瘤的联合疾病负担,同时也可能因为多重恶性肿瘤筛查阳性而带来更多的潜在风险,比如多重筛查阳性是否会显著增加心理健康问题的风险,同时导致更多的过度检查、过度诊断和过度治疗。(3)缺乏统一规范。虽然目前单一癌种筛查均有相对规范统一的指南,但针对多种恶性肿瘤的联合筛查,目前尚缺乏统一规范的指南或专家共识。随着常见恶性肿瘤联合筛查需求的不断增加,类似MCED检测的常见恶性肿瘤联合筛查新产品将会不断涌现。截至2024年7月,美国NCI早期筛查研究网络显示,MCED注册研究已有17项,每一项研究评价的MCED技术均不一样[28]。为了防止MCED技术及其衍生的常见恶性肿瘤联合筛查过程挤兑有限的医疗卫生资源,制定统一规范的常见恶性肿瘤联合筛查专家共识,指导常见恶性肿瘤联合筛查实践,尤为必要。
(一)联合筛查的推荐原则
常见恶性肿瘤联合筛查的基本原则包括:(1)因地制宜。不同恶性肿瘤的高发年龄、危险因素及筛查方法均存在明显差异,同时不同地区的社会文化背景千差万别。因此,不推荐采用“一刀切”的方法进行统一的常见恶性肿瘤联合筛查。(2)资源适配。不同地区的经济发展水平和医疗卫生资源也存在显著差异,因此,常见恶性肿瘤联合筛查必须同时遵循资源适配的基本原则。(3)求同存异。虽然不同恶性肿瘤的筛查存在诸多差异,但常见恶性肿瘤联合筛查的关键在于最大化求同存异,以便最大化优化资源配置,以真正达到联合筛查的目的。
基于以上三大基本原则,常见恶性肿瘤联合筛查的总体推荐原则:基于常见恶性肿瘤的共性风险相关因素(包括共性遗传背景、饮食生活方式、代谢变化、炎性改变及其他共性特征)和不同癌种的特异性危险因素,共同识别常见恶性肿瘤联合筛查的高危人群;以经济有效的影像学检查方法为主要筛查方法,辅以适宜的辅助性检查,包括基于多组学数据整合的人工智能(artificial intelligence,AI)分析来共同提高常见恶性肿瘤的联合检出率;充分评估并尽可能减少联合筛查的潜在超额风险,最终降低常见恶性肿瘤的综合疾病负担(证据质量:中等,推荐强度:强)
(二)联合筛查的推荐人群
由于遗传、环境、饮食习惯和社会发展水平的不同,不同地区的高发恶性肿瘤类型及相应的发病率均存在明显差异,从而导致不同恶性肿瘤筛查的重点人群也存在明显差异。对于人口众多、人群相对分散、社会资源相对缺乏、医疗卫生资源相对不足的地区,开展全人群常见恶性肿瘤联合筛查不大现实;针对高危人群筛查,预期更加经济有效。为更好地明确恶性肿瘤联合筛查的高危人群,首先需对常见恶性肿瘤的风险相关因素进行相对统一的定义。在此基础上,高危人群的推荐原则包括:(1)明确不同目标恶性肿瘤的共性基础,包括共性危险因素、遗传背景、代谢变化、炎性改变及其他共性特征。(2)进一步明确不同癌种之间的特异性危险因素,包括恶性肿瘤特异性高遗传风险、良性疾病或癌前病变、致癌性病原体感染、激素暴露及其他特异危险因素。两者联合共同定义联合筛查的高危人群。
1. 常见恶性肿瘤的共性及特异性危险因素
目前相对公认与至少2种恶性肿瘤风险存在显著相关的共性危险因素包括:吸烟、饮酒、不健康饮食、缺乏体力活动、超重或肥胖、高血压、高脂血症、糖尿病和恶性肿瘤家族史(证据质量:中等;推荐强度:强)。如吸烟可增加包括肺癌在内的17个部位或亚部位的恶性肿瘤风险[34-35]。饮酒明确增加包括某些类型的头颈部癌种等6种恶性肿瘤风险[36-37],超重或肥胖会显著增加以消化道肿瘤为主的13种恶性肿瘤风险[38]。糖尿病则与胰腺癌等13种恶性肿瘤的发病风险存在不同程度的关联[39]。后者分别被统称为肥胖相关肿瘤和糖尿病相关肿瘤[40]。富含糖类和脂肪的高热量饮食和缺乏体力活动主要通过增加体重来升高肥胖或糖尿病相关恶性肿瘤风险;同时,不健康饮食(如加工和超加工饮食)还可通过破坏或减少维生素或微量元素等营养成分、增加炎症反应或氧化应激、抑制免疫反应等机制增加恶性肿瘤的风险[41-44]。高血压主要升高肾癌发病风险,并很可能增加乳腺癌、结肠癌、食管癌和前列腺癌等风险[45-47]。总胆固醇显著增加前列腺癌、乳腺癌和结直肠癌风险[48-49],与结直肠癌及其癌前病变之间的关系在此后多项研究中被证实[50-53]。目前有相对充分证据支持的共性危险因素与相关恶性肿瘤定性关联汇总见表2。除此之外,虽然家族史是多种恶性肿瘤特异性风险增加的关键因素,但目前已有大量证据证实不同癌种之间存在诸多的共性遗传基础[17-18]
除上述共性危险因素外,根据国家卫生健康委员会及专业机构制定的我国常见恶性肿瘤筛查指南及规范中恶性肿瘤高危人群定义(表3[54-66],不同部位恶性肿瘤存在各自相对特异性的危险因素,并可以分为以下4种:(1)恶性肿瘤特异性高遗传风险:包括恶性肿瘤特异性的家族史、致病性基因突变(如乳腺癌风险相关的BRCA1/2基因)或遗传综合征(如结直肠癌风险相关的遗传性结直肠癌综合征,包括非息肉病性和息肉病性结直肠癌综合征)。(2)恶性肿瘤特异性的良性疾病或癌前病变:包括肺癌、肝癌和胃癌风险分别相关的慢性阻塞性肺疾病、肝硬化和慢性萎缩性胃炎等,以及乳腺、宫颈、食管、胃和结直肠等部位上皮细胞的异型或不典型增生。(3)致癌性病原体感染:截至2012年,国际癌症研究署已将11种病原体归为人类1类致癌物,即致癌性病原体,包括高危型人乳头瘤病毒(human papillomavirus,HPV)-16/18、乙型肝炎病毒(hepatitis B virus,HBV)、丙型肝炎病毒(hepatitis C virus,HCV)、幽门螺杆菌(helicobacter pylori,HP)、卡波西肉瘤疱疹病毒、EB病毒、人T细胞白血病病毒1型、人类免疫缺陷病毒1型、日本血吸虫、中华肝吸虫和湄公肝吸虫[67-69](4)激素暴露及其他特异危险因素:包括乳腺癌的女性特异性生理生育风险因素(月经初潮年龄早等)、肺癌的吸烟和被动吸烟、食管癌的喜好热烫饮食和结直肠癌的过多摄入红肉和加工肉类(证据质量:中等,推荐强度:强)
2. 联合筛查的高危人群定义
适宜联合筛查恶性肿瘤的高危人群,即为至少存在2种恶性肿瘤的风险高于一般风险人群。基于该基本定义及上述适宜联合筛查恶性肿瘤的共性和特异性危险因素,可以分别采用以下两种方式来进一步完善适宜联合筛查恶性肿瘤的高危人群定义:(1)基于单一癌种独立风险评估后的综合评估;(2)基于多种癌种或全癌风险的整体评估。
(1)基于单一癌种独立风险评估后的综合评估:鉴于不同恶性肿瘤风险相关因素的共性和特异性风险相关因素,同时结合现有可获取的恶性肿瘤风险评估资源,可以进一步采用以下3种方案来完善常见恶性肿瘤联合高风险人群的定义:①基于恶性肿瘤共性和特异性危险因素数量的初步综合评估。当至少存在前述2个恶性肿瘤共性危险因素和2种恶性肿瘤特异性危险因素时,该人群即可初步定义为联合筛查的高危人群。该方案适用于无法满足指南推荐恶性肿瘤高风险人群的完整评估或恶性肿瘤风险预测模型构建的地区。②基于筛查指南推荐的不同恶性肿瘤高危人群评估后的再次评估。当满足两类恶性肿瘤高危人群指南推荐定义时,即可定义为常见恶性肿瘤联合高风险人群,该方案适用于有一定筛查资源,但无法构建完整恶性肿瘤风险预测模型的地区。③基于不同恶性肿瘤完整风险预测模型评估后的再次评估。在资源可及的情况下,可以针对不同场景分别选取目前相对成熟的单一癌种风险预测模型,进行个体化的特定恶性肿瘤风险评估[70-83]。上述任意两类恶性肿瘤的风险评估定义为高危人群时,即为相对准确的常见恶性肿瘤联合高风险人群。
(2)基于多种恶性肿瘤或全癌联合风险的整体评估:虽然目前已有大量、相对成熟的单一癌种风险预测模型用于评估特定恶性肿瘤的高危人群,但尚缺乏常见恶性肿瘤的综合风险评估模型。联合常见恶性肿瘤的共性危险因素、遗传背景、代谢变化、炎性改变及其他共性特征,完善常见恶性肿瘤联合风险的整体评估,将有助于进一步优化常见恶性肿瘤联合筛查人群。相应模型包括:①基于传统风险因素构建的常见恶性肿瘤联合风险预测模型。如基于性别特异性恶性肿瘤危险因素构建的前列腺癌、肺癌、结直肠癌和卵巢癌联合风险PLCO-CA模型[27],和基于丹麦人口电子健康记录建立的泛癌症风险时间依赖性贝叶斯Cox风险模型[84]。②基于遗传组学、代谢组学或蛋白组学等组学数据发现的恶性肿瘤风险相关标志物构建的多癌症或泛癌风险预测模型。如基于全基因组关联研究发现的癌症风险相关遗传易感位点(即单核苷酸多态性),并根据发病率加权构建的综合恶性肿瘤多基因遗传风险得分[85-86]。或基于UK Biobank的83290名参与者泛癌代谢组学分析发现与全癌风险关联最强的13种代谢物构建的全癌代谢组学得分,此类模型相比临床模型的AUC净改善在6%~15%[19]。以及基于UKB-PPP(UK biobank pharma proteomics project)队列41 931名个体蛋白组学数据分析得到与218种常见及稀有疾病最相关5种蛋白质构建的蛋白质组学标志物风险预测模型。虽然该研究尚没有多疾病、多癌种或全癌风险的综合预测模型,但前者在17种癌种的特异性预测能力与临床模型相当,在另外4种特定癌种(乳腺癌、前列腺癌、多发性骨髓瘤和非霍奇金淋巴瘤)上的预测表现显著优于临床模型,同时对前列腺癌的预测效果优于多基因风险评分(polygenic risk score,PRS)[87]
(三)联合筛查的推荐年龄
基于我国常见恶性肿瘤筛查指南及规范的推荐筛查起止年龄(表4)及国外恶性肿瘤筛查指南的筛查年龄建议[54-62,88-90],本共识对于常见恶性肿瘤联合筛查的起止年龄推荐原则如下。
1. 筛查年龄应以常见恶性肿瘤的高发年龄段为主要依据,同时结合恶性肿瘤特异性危险因素的高峰暴露年龄和年龄别特异性的生理生育特征来共同决定常见恶性肿瘤联合筛查的适宜起始年龄(证据质量:中等;推荐强度:强)。例如,高危型HPV感染是导致宫颈癌的重要病因,女性HPV感染的第1个高峰通常发生在20~24岁之间,从HPV感染到发生病变至少需要5~10年。因此,多数指南推荐子宫颈癌的筛查起始年龄为25岁或30岁,少部分国家建议是20~21岁,或在初次性生活后3年进行筛查。乳腺癌是一种激素依赖型肿瘤,怀孕、生育、哺乳和绝经等生理生育过程与女性激素的暴露水平息息相关,同时绝经后激素替代治疗也明显影响绝经后女性激素暴露水平。因此,多数国家的乳腺癌筛查指南推荐在完成女性生理生育期后并逐渐步入绝经期的45岁开始接受乳腺癌筛查,对于高风险女性则推荐适当提前至40岁开始筛查,以避免潜在的漏诊[91]。对于吸烟引起的肺癌和不良饮食习惯导致的消化道肿瘤,由于危险因素暴露通常存在较长的累积时间,因此,国内外肺癌和消化道肿瘤的筛查起始年龄通常推荐在45岁或50岁。而对于与老龄化明显相关且预后较好的恶性肿瘤,筛查起始年龄通常较晚,如我国指南推荐高风险人群从60岁之后开始进行前列腺癌筛查。
2. 联合筛查的结束年龄需综合权衡筛查的收益和潜在风险,同时兼顾筛查参与者的预期寿命和筛查意愿(证据质量:高;推荐强度:强)。根据我国常见恶性肿瘤筛查指南及规范推荐的筛查结束年龄(表4),除乳腺癌、宫颈癌和前列腺癌外,其他大部分恶性肿瘤筛查都将74岁定义为恶性肿瘤筛查的适宜结束年龄。针对乳腺癌的筛查结束年龄,目前并没有统一的结论,《中国女性乳腺癌筛查指南》推荐我国女性应在70岁之后结束乳腺癌筛查,但之后发布的《中国女性乳腺癌筛查与早诊早治指南(2021,北京)》却没有明确规定乳腺癌筛查终止年龄。《中国子宫颈癌筛查指南(一)》建议:(1)65岁以上女性,如既往有充分的阴性筛查记录,并且无宫颈上皮内瘤样病变(cervical intraepithelial neoplasia,CIN)、HPV持续感染,以及没有HPV相关疾病治疗史等高危因素,可终止筛查;(2)65岁以上女性,如从未接受过筛查,或65岁前10年无充分的阴性筛查记录,或有临床指征者,仍应持续筛查。《中国前列腺癌筛查与早诊早治指南(2022,北京)》推荐:(1)前列腺特异性抗原(prostate specific antigen,PSA)检测水平<1.0 ng/mL的60岁及以上男性停止筛查;(2)年龄≥75岁的男性结合个人健康状况选择是否停止筛查;(3)预期寿命<10年者停止筛查。
综合我国特定恶性肿瘤筛查指南及规范推荐的筛查起止年龄,针对常见癌症联合风险的高危人群,本共识推荐适宜进行常见恶性肿瘤联合筛查的年龄为45~74岁(证据质量:中,推荐强度:中)。
(四)联合筛查的推荐方法
基于我国常见恶性肿瘤筛查指南及规范推荐的不同癌种主要筛查方法(表4)及相应的准确性汇总(表5[55-62,92],本共识针对常见恶性肿瘤联合筛查方法的推荐原则包括:(1)推荐有高级别证据支持的影像学检查方法作为常见恶性肿瘤联合筛查的主要方法。(2)推荐适宜的辅助性筛查方法进一步明确常见恶性肿瘤联合筛查的高危人群。(3)在影像学筛查和多维度辅助性筛查结果基础上,推荐AI辅助的分析方法提高常见恶性肿瘤联合筛查方法的准确性。(4)目前尚不推荐在一般风险人群中采用MCED等方法进行常见恶性肿瘤的联合初筛(证据质量:中,推荐强度:强)。
1.筛查方法的选择
(1)主要筛查方法
根据我国常见恶性肿瘤筛查指南及规范推荐的不同癌种主要筛查方法(表45),本共识推荐的高级别证据支持的影像学检查方法包括:上消化道癌的上消化道内镜、结直肠癌的结直肠镜(包括乙状结肠镜和全结直肠镜)、肺癌的胸部低剂量螺旋CT(low-dose computed tomography,LDCT)、肝癌的腹部超声检查、乳腺癌的乳腺超声(包括手持的和全自动乳腺超声)和乳腺X线(证据质量:高,推荐强度:强)
(2)辅助筛查方法
①基于常规肿瘤标志物和致癌性病原体的辅助筛查方法:本共识推荐的常规肿瘤标志物和致癌性病原体辅助筛查方法包括:胃癌的HP和胃蛋白酶原(pepsinogen,PG),肝癌的HBV和甲胎蛋白(alpha-fetoprotein,AFP),前列腺癌的PSA,卵巢癌的糖类抗原125(carbohydrate antigen 125,CA125),子宫颈癌的高危型HPV核酸检测和细胞学检查,和结直肠癌的免疫法粪便隐血试验(fecal immunochemical test,FIT;证据质量:中,推荐强度:中)
如在胃癌高发区,推荐采用尿素呼气试验初筛HP感染人群,在条件允许的情况下,可联合检测PG、胃泌素-17和血清HP抗体,进一步提升胃癌筛查的准确性[57]。对于林奇综合征及遗传性弥漫性胃癌患者的家属,则推荐直接采用定期的胃镜筛查[57]。不具备高危型HPV核酸检测条件的地区,可暂时采用子宫颈细胞学检查进行过渡,联合筛查可用于医疗卫生资源充足地区、机会性筛查人群以及部分特殊人群女性的子宫颈癌筛查[63]。血清PSA检测虽是前列腺癌筛查的首选方法,但已有研究提示采用人群筛查切点值(1.4~2.7 ng/mL)[93-94],而非诊断切点值(如4 ng/mL)作为PSA筛查阳性的标准,同时结合多次PSA筛查的进展可以更有效降低前列腺癌筛查的假阳性[93]。CA125筛查卵巢癌同样应关注CA125的筛查切点值及多轮CA125筛查的进展对卵巢癌的提示作用[95]。肝癌筛查中,虽然目前已有研究提示异常凝血酶原(des-gamma-carboxy prothrombin,DCP;又称维生素K拮抗剂Ⅱ,protein induced by vitamin K absence or antagonist-Ⅱ,PIVKA-Ⅱ)的筛查准确性强于AFP,但仍缺乏大规模的人群验证[58]。此外,虽然RCT表明愈创木脂粪便潜血试验(guaiac-based fecal occult blood test,gFOBT)可以降低9%~22%结直肠癌死亡率,但由于其对结直肠癌和癌前病变的灵敏度低且受饮食和药物影响,目前多数指南明确推荐采用FIT取代gFOBT用于结直肠癌的初筛。
②基于基础生化指标的辅助筛查方法:糖脂代谢异常是多癌种的共性危险因素,其可能通过胰岛素/胰岛素样生长因子、单磷酸腺苷激活蛋白激酶、哺乳动物雷帕霉素靶蛋白及促炎细胞因子(如白介素6、肿瘤坏死因子α和环氧化酶-2等)等信号通路,调节肿瘤细胞周期,促进肿瘤细胞增殖、迁移和侵袭能力,进而促进肿瘤的发生和发展[96-99]。美国近16万人的前瞻性队列研究显示,糖尿病不仅显著增加25%的糖尿病相关恶性肿瘤风险,同时增加21%的全癌风险;其与单一癌种的风险比(HR)从结直肠癌的1.21(95%CI:1.06~1.38)到肝癌的3.39(95%CI:2.24~5.12)不等[40]。糖尿病前期个体全癌(特别是肝癌、子宫内膜癌、胃癌和结直肠癌)风险增加15%[100],乳腺癌的风险增加45%[101]。近200万人的Meta分析提示,高甘油三酯血症和高胆固醇血症分别增加18%和11%的结直肠癌风险[102]。韩国超过100万人的队列研究还支持高胆固醇血症与前列腺癌和乳腺癌等多种恶性肿瘤的发病风险显著相关[48]。UK Biobank近44万人的前瞻性队列研究观察到7种恶性肿瘤风险与系统免疫炎症指数(systemic immune-inflammation index,SII)等新型炎症指标呈正相关,与单核细胞与淋巴细胞比值(monocyte to lymphocyte ratio,MLR)呈负相关。其中,SII每增加一个标准差,结直肠癌风险增加9%[98]。6项欧洲队列组成的51万人群研究进一步支持TG与血糖的联合指标(triglyceride-glucose index,TyG)指数每增加一个标准差,不同恶性肿瘤风险增加7%~13%;而且体质指数对不同恶性肿瘤风险的影响中,TyG指数中介影响在11%~42%之间(胰腺癌:42%;直肠癌:34%;结肠癌:20%;肾癌:15%,肝癌:11%)[103]。因此,越来越多的研究提示,血糖、血脂等生化指标、血常规衍生的炎性指标,以及基于血糖和血脂衍生的胰岛素抵抗指标,均可联合用于明确常见恶性肿瘤的高危人群[98,104-106]
③基于多组学评估或液体活检的辅助筛查方法:基于不同癌种或泛癌多组学分析方法发现的新型恶性肿瘤标志物是目前备受关注的常见恶性肿瘤辅助筛查方法,这些方法可以统称为前述的MCED检测方法[28]。用于开发MCED检测的标志物种类可以概括为:(a)基因组学标志物:如循环细胞游离基因组图谱(circulating cell-free genome atlas,CCGA)亚组研究采用循环肿瘤等位基因分数来定义MCED的临床检测限[107]。其他的基因组学标志物还包括血液中cfDNA或循环肿瘤DNA的突变、拷贝数变异和DNA片段特征。(b)表观遗传学标志物:泛癌早检研究THUNDER中采用血液cfDNA甲基化方法来同时检测结直肠癌、食管癌、肝癌、肺癌、卵巢癌和胰腺癌6种肿瘤[108]。英国NHS-Galleri试验和CCGA联盟研究所采用cfDNA甲基化方法能同时检测超过50种恶性肿瘤类型[109-110]。(c)蛋白组学标志物:Olink公司的CancerSEEK技术利用血浆蛋白质组学能检测到8种未转移恶性肿瘤,包括卵巢、肝脏、胃、胰腺、食管、结直肠、肺和乳腺癌[111]。(d)代谢组学标志物:Fahrmann等[112]研究显示,基于5种代谢物标志物组合相比先前验证的蛋白质标志物组合,能显著改善早期胰腺导管癌的检出。(e)多组学数据整合标志物:清华大学研究团队通过分析cfDNA和cfRNA的4种组学和10余种变异类型,发现多组学标志物相对于单组学标志物检测恶性肿瘤的效果有所提升[113]。在多组学数据基础上,利用AI算法进行数据整合,可进一步提高恶性肿瘤筛查的准确性和效率[114]。(f)其他,如基于肿瘤干细胞的mRNA和循环肿瘤细胞的染色体畸变等同样可用于常见癌种或泛癌的联合辅助筛查[115]
2. 筛查方法的准确性
我国常见恶性肿瘤筛查指南及规范推荐筛查方法的准确性汇总详见表5。目前虽无相对统一的多癌种联合筛查方法,但不同MCED检测方法的准确性已有一定程度的探索分析。CancerSEEK技术基于1005例未转移恶性肿瘤患者的DNA突变和蛋白类标志物,对于8种恶性肿瘤检出的灵敏度从68%~98%不等;对Ⅲ期恶性肿瘤的灵敏度更高(80%);相比之下,Ⅰ期恶性肿瘤的灵敏度仅为40%;对于812名健康者的联合特异度为99.0%[111]。THUNDER研究中,基于cfDNA靶向甲基化检测6种恶性肿瘤的灵敏度为69.1%,特异度为98.9%[108]。CCGA联盟基于6 689名参与者(包括50种恶性肿瘤类型的2 482例患者和4 207例对照)的血浆cfDNA分析结果显示,在验证集中,恶性肿瘤检出的特异性为99.3%,假阳性率为0.7%。在预先指定的12种恶性肿瘤类型中,Ⅰ~Ⅲ期恶性肿瘤的灵敏度为67.3%[109]。为了降低前述病例对照研究设计所带来的偏倚,SYMPLIFY研究首次采用前瞻性研究设计的方法招募了6238名18岁及以上的有症状参与者,MCED检测在323例病例中检测到恶性肿瘤信号,其中244例被诊断为恶性肿瘤,阳性预测值为75.5%,阴性预测值为97.6%,灵敏度为66.3%,特异性为98.4%;同时灵敏度随着年龄和恶性肿瘤分期的增加而增加,从Ⅰ期的24.2%增加到Ⅳ期的95.3%[116]。随后的PATHFINDER研究进一步通过前瞻性研究招募了6662名50岁及以上没有明显恶性肿瘤相关体征或症状的成年人,MCED检测在92名参与者中(1.4%)中检测到恶性肿瘤信号,其中35名参与者确诊患有恶性肿瘤,阳性预测值为38%,阴性预测值98.6%,特异度99.1%,进一步对恶性肿瘤组织溯源的准确性达到97%[117]
3. 筛查方法的有效性
单一癌种筛查能降低20%~57%的恶性肿瘤死亡,而且不同时期、不同研究的结论几乎一致[11-14]。PLCO恶性肿瘤联合筛查能显著降低男性12%的目标恶性肿瘤联合死亡风险,而且降低全人群9%的全癌死亡和11%的全因死亡风险[27]。目前尚没有基于MCED检测并评价其对常见恶性肿瘤联合死亡或全因死亡影响的RCT研究,但基于cfDNA筛查的模型研究的结果显示,①筛查可降低50~79岁英国居民40%~50%晚期恶性肿瘤发病率和17%~21%的5年恶性肿瘤死亡率。②潜在的晚期癌发病率降低效益因癌症类型而异,MCED筛查可显著降低晚期结直肠癌等7种恶性肿瘤的发病率(50%~78%),但无助于黑色素瘤、甲状腺癌和尿路上皮癌的早期诊断。③对于早期生存率明显优于晚期生存率的恶性肿瘤包括乳腺癌等11种癌种,5年恶性肿瘤死亡率降低10%以上[118]。在美国,如果采用MCED检测进行常见恶性肿瘤联合筛查,结合监测、流行病学和终点结果数据,估计美国晚期恶性肿瘤发病率可降低78%,所有恶性肿瘤相关死亡率可降低26%[119]。如果将MCED检测固定在极低假阳性率(<1%),可以最大限度地减少伤害,从而获得高阳性预测值,且能够识别大多数致死性的恶性肿瘤[120]
4. 筛查方法的安全性
筛查的安全性是指与筛查收益相比,个体在参与筛查过程中产生的任何负面效应。由于常见恶性肿瘤联合筛查涉及更多的检测,因此,常见恶性肿瘤联合筛查很可能会比单一癌种筛查带来更多、更为明显的潜在风险,主要包括假阳性、过度诊断、辐射暴露和心理伤害等。
(1)假阳性:指实际无病但根据筛查判定为有病的情况,也即反映筛查所带来的误诊情况。假阳性是肿瘤筛查中的常见风险,需要进一步检查以明确恶性肿瘤诊断,这可能导致患者产生不良心理影响,以及为调查结果而进行的诊断程序造成的身体伤害,并且增加患者的额外医疗负担。NLST研究中,LDCT每筛查1000人,假阳性结果导致17次侵入性检查,也即每筛查59个人就会导致1个人因为假阳性结果而进行非必要的侵入性检查[11]。与每2年筛查1次相比,每年进行乳腺X线筛查的10年累积假阳性率和活检率更高(分别为61%、42%和7%、5%),对于40~49岁的女性、致密乳腺的女性和使用联合激素治疗的女性尤其如此[121]。采用PSA筛查前列腺癌的欧洲RCT研究中,有17.8%的人收到了假阳性结果。PSA异常后进行活检的男性中,有0.5%~1.6%的并发症需要住院治疗[122]。第1轮高危型HPV筛查子宫颈癌的假阳性率为6.6%~7.4%,而细胞学筛查的假阳性率为2.6%~6.5%。联合检测的假阳性率为5.8%~19.9%[13]
(2)过度诊断:筛查的过度诊断是指对不可能进展为晚期恶性肿瘤的早期肿瘤进行的诊断,也即通过筛查确诊为恶性肿瘤,但如果未进行筛查,则恶性肿瘤在参与者死亡前不会被发现的情况[123]。过度诊断不仅导致不必要的治疗和随访,还会给患者带来心理压力和焦虑。现有证据表明,LDCT筛查导致的肺癌过度诊断估计差异很大(0~67%)[11],不仅如此,LDCT筛查很可能导致大量低风险肺结节的过度诊断。使用不同方法筛查乳腺癌的过度诊断率在0~54%之间[121],而且随着年龄的增加呈现倒U型改变[124]。PSA筛查发现的前列腺癌中出现过度诊断的比例估计在20.7%~50.4%之间[122]。40岁之前甲状腺癌过度诊断的比例可能高达99%,80岁之后诊断的甲状腺癌仍有将近34%是被潜在过度诊断的[125]。虽然肝癌筛查能够在早期发现恶性肿瘤,并为患者提供肝移植等治愈性治疗,但过度诊断的风险依然存在[126]
(3)辐射风险:在恶性肿瘤筛查过程中,辐射风险是筛查副作用的一个重要考量因素。多种恶性肿瘤筛查技术,如乳腺X线摄影、胸部X线摄影、LDCT等检查,都涉及一定量的电离辐射。一项基于美国人群的研究表明,每年筛查10万名40~74岁的女性,预计会诱发125例乳腺癌病例,导致16例乳腺癌死亡[127]。乳腺X线筛查诱发乳腺癌发病和死亡的风险很可能受筛查剂量、初诊年龄和筛查频率等因素的影响,其中乳腺较大的女性患辐射诱发乳腺癌的风险可能更大[127]。NLST结果表明,LDCT筛查组的平均3年辐射暴露量为8 mSv,每2 500名筛查者中就有1人死于辐射诱发恶性肿瘤[128]
(4)其他:筛查带来的不确定性、假阳性结果以及对恶性肿瘤诊断的恐惧,都可能会导致筛查参与者产生心理焦虑等负面情绪。Meta分析结果显示,与结果正常的女性相比,得到假阳性结果的女性进行乳腺自我检查的频率更高,痛苦和焦虑水平更高[129]。内镜筛查的副作用包括内镜下穿孔和大出血,其中肠镜筛查的穿孔和大出血发生率分别为3.1/1万次和14.6/1万次[12]。CA125筛查可导致1%的女性进行疑似卵巢癌的手术,而经阴道超声检查无论是否结合CA125筛查,都会导致3%的疑似卵巢癌手术,其中3%~15%的手术出现了重大并发症[130]。每100例因筛查阳性导致的甲状腺切除术中有2.12~5.93例出现永久性甲状旁腺功能减退,同时有0.99~2.13例出现复发性喉返神经麻痹;放射性碘治疗分化型甲状腺癌与第二原发癌风险小幅增加相关,并且增加对唾液腺永久性不良反应的风险[131]
5. 筛查风险的规避措施
尽管联合筛查有以上潜在风险,基于PLCO研究的结果表明,基于偶然性筛查结果阳性(即筛查结果≤2次)的健康教育或健康行为改变,或可改变焦虑或应激等所导致的潜在心血管疾病死亡风险,进而带来潜在的保护作用[132]。因此,针对常见恶性肿瘤联合筛查所带来的潜在风险,开展必要的健康教育或健康促进,显得尤为必要。具体推荐的风险规避或干预防控措施包括:(1)知情同意和自愿参与。筛查是一把双刃剑,筛查在带来收益的同时,同样也存在潜在的风险。筛查前必须充分告知筛查的潜在风险,并获得居民的知情同意。筛查过程中,任意一项检查都必须遵循自愿参与的基本原则。(2)高危人群筛查。根据家族史、疾病史、不良的饮食生活习惯、特殊的生理生育特征等因素,制定明确的高危人群筛查方案,避免对非高危人群或无症状人群进行不必要的筛查。(3)动态风险监测。高危人群出现任意一项筛查结果阳性时,结合症状和体征,推荐适宜的动态风险监测,必要的多模态影像佐证,或合适的多组学检测。不推荐无差别的上述检查或检测。(4)健康行为促进。对于无法排除恶性肿瘤风险的高危居民或筛查阳性居民,长期规律的健康行为改变,相比过早或过于频繁的筛查,前者更值得推荐。(5)心理健康支持。不论是组织性筛查,还是机会性筛查,都推荐在筛查前组建心理健康咨询团队,以便给筛查阳性者提供心理支持和咨询服务,帮助其缓解焦虑和恐惧的不良情绪。
6. 筛查方法的成本
我国城市居民6种常见恶性肿瘤(肺、胃、食管、肝、结直肠和乳腺癌)联合筛查的支付意愿的研究表明,对于多种恶性肿瘤联合筛查服务,在免费筛查情况下,93.9%的居民选择每1~3年进行1次筛查,而在自费情况下,这一比例降至67.3%;多数居民(76.7%)对支付部分费用持积极态度,但他们的支付意愿额度有限,30.8%的居民最多愿意支付50元,只有11.2%的居民愿意支付500元以上。此外,不愿支付的主要原因包括费用难以承受(71.7%)和认为没有必要(40.4%)[133]
联合筛查的初期成本主要包括筛查检测的费用,如血液标志物、影像学和多癌种早期检测技术的花费[109]。筛查后的诊断和治疗花费因癌种的类型和分期而异。早期发现的恶性肿瘤治疗成本显著低于晚期恶性肿瘤,特别是手术、放疗或化疗的费用可以得到大幅削减。对于确诊的恶性肿瘤患者,还需要进行定期的随访和监测,这些花费主要用于防止复发或早期发现其他并发症[134]。在我国上消化道癌高发地区,内镜筛查食管癌或胃癌的增量成本效果比(incremental cost effectiveness ratio,ICER)为1343~3035美元/质量调整生命年(quality-adjusted life-years,QALY);每2年1次的筛查,相比于其他筛查频率,能够带来更多的生命年和较高的成本效益[135]。模型研究结果表明,在我国开展基于PRS分层的常见恶性肿瘤(肺、肝、胃、结直肠、食管和乳腺癌)联合筛查的综合ICER为14930美元/QALY,低于我国2022年的人均GDP水平(18364美元);其中结直肠癌筛查的ICER最低(7928美元/QALY),其次是乳腺癌(13135美元/QALY),最高是肝癌(39068美元/QALY)[136]。因此,在我国开展有组织的、基于PRS分层的常见恶性肿瘤联合筛查是经济有效的,包括除肝癌外其他5种恶性肿瘤的单独筛查也均是经济有效的,但降低PRS检测成本依然是必须的[136]。此外,基于MCED检测的模型研究结果显示,在每个QALY的支付意愿阈值为10万美元的情况下,MCED检测用于人群筛查的价格在1196美元以下时,有可能是经济有效的[137]
7. 筛查方法的人群接受度
常见恶性肿瘤联合筛查方法的人群接受度主要包括潜在目标人群的筛查参与率(或称为人群筛查率、筛查覆盖率)、高风险人群进一步影像筛查的依从性、筛查方法的可接受度及筛查流程的满意度等。WHO设定的2030年女性在35岁和45岁至少有2次宫颈癌筛查的覆盖率目标为70%。然而,2019年,全球30~49岁女性过去1年、3年和5年内接受子宫颈癌筛查的覆盖率分别为15%、28%和32%,终生至少接受1次子宫颈癌筛查的比例为36%,距离WHO的2030目标仍有相当大的差距[138-139]。2015年,我国子宫颈癌筛查的覆盖率是37%。2018~2019年,我国35~44岁女性子宫颈癌筛查覆盖率达到了43.4%,但与70%的目标仍相距甚远,农村地区和中西部地区的筛查覆盖率更低[140]。2015年,我国只有18.9%的成年女性接受乳腺癌筛查;2018~2019年,我国20岁及以上女性的乳腺癌筛查覆盖率达到22.3%[141]。然而,社会经济地位较低的女性筛查覆盖率较低,不同省份之间的乳腺癌筛查覆盖率也存在显著差异[141]
除了子宫颈癌和乳腺癌筛查,我国3项重大公共卫生服务项目(农村癌症早诊早治项目、淮河流域癌症早诊早治项目、城市癌症早诊早治项目)在全国目标人群的恶性肿瘤筛查覆盖率均相对较低,其中我国发病率前5的恶性肿瘤人群覆盖率估计低于1%[142]。2019年肝癌初筛的覆盖率在全国35~74岁人群中仅为0.09 %[58]。2012~2014年我国12个省(自治区、直辖市)开展的城市癌症早诊早治项目中所获取的97445例结直肠癌高危人群,14 949例接受了结肠镜检查,肠镜筛查的依从性为15.3%[143]。2012~2015年扩大规模的城市癌症早诊早治项目结直肠癌高危人群肠镜筛查的依从性仍只有14%[144]
相比而言,美国常见恶性肿瘤的人群筛查率明显高于我国,其中美国结直肠癌的人群筛查率从2005年的46.8%上升到了2015年的62.6%[145]。2015年,美国女性过去1年内接受乳腺X线筛查的比例为50.2%,21~64岁女性接受巴氏涂片筛查子宫颈癌的比例为81.6%,但采用低剂量CT筛查肺癌的比例同样也相对较低,仅为3.9%[145]。目前尚没有基于MCED或其他多种恶性肿瘤联合筛查的人群接受度调查,如何提高联合筛查的人群覆盖率势必面临更多的挑战。
8. 特殊人群的备选筛查方法
常见恶性肿瘤联合筛查方法的特殊性需同时考虑特殊人群对特定恶性肿瘤筛查方法的特定需求。因此,对于不能接受常规内镜检查者,可考虑使用磁控胶囊胃镜用于特殊人群的筛查,如老人、儿童和孕妇等[57]。在PSA检测过程中,我国相应指南同时建议前列腺按摩后至少1周,直肠指诊、膀胱镜检查、导尿等操作后至少48 h后,射精后至少24 h,前列腺炎消退后数周等,再检测PSA;如服用对PSA检测结果有影响的药物,在咨询专科医师后再行PSA检测[61]。对于食管癌筛查中的食管内镜选择,除了首选的Lugol染色内镜或窄带成像,条件不足者可选择普通白光内镜,有条件者可联合使用放大内镜或尝试使用AI显微内镜;不能耐受常规通道内镜者也可以经鼻内镜[56]。对于致密乳腺的一般风险人群或乳腺癌高风险人群,推荐使用乳腺X线检查联合乳腺超声进行筛查;对于BRCA1/2基因突变携带者,还可考虑使用乳腺MRI筛查[54]。结肠CT成像技术和多靶点粪便FIT-DNA检测在特定条件下可用于结直肠癌筛查,如无法完成结肠镜检查,或倾向于非侵入性筛检技术且有检测条件的受检者使用[59]。此外,针对特殊人群的筛查,不但存在筛查技术的选择问题,同时存在筛查间隔和后续管理的衍生问题,均应引起高度重视并进行充分权衡。例如,人类免疫缺陷病毒(human immunodeficiency virus,HIV)感染者恶性肿瘤筛查技术与筛查间隔的问题,特殊职业人群筛查问题等。
9. 联合筛查的筛查间隔
不同恶性肿瘤的筛查频次及筛查间隔主要根据特定恶性肿瘤从临床前期(或癌前病变)进展到临床期的平均进展时间或停留时间来确定。因此,常见恶性肿瘤联合筛查的间隔不仅需要考虑特定恶性肿瘤的平均进展时间,同时需要兼顾不同恶性肿瘤进展速度的特异性。根据我国特定恶性肿瘤筛查指南及规范的核心筛查建议(表4),我国常见恶性肿瘤的筛查推荐间隔多为1、2、3年或5年。总体上可以归纳为3类:(1)对于进展相对较快或预后相对较差的癌种,如肺癌、乳腺癌和肝癌,总体推荐每1年或2年筛查1次,以避免潜在的漏诊。(2)对于有明确癌前病变的癌种,如上消化道癌、结直肠癌和宫颈癌,如推荐的主要筛查方法未发现任何可疑病灶,总体上推荐每3~5年筛查1次,甚至可以间隔更长进行筛查。(3)对于主要筛查方法发现有明确癌前病变或可疑病灶的居民,则通常需要根据具体情况进行监测,并择机进行主动干预。如LDCT检出的实性结节或者部分实性结节的实性成分平均长径≥6 mm且<15 mm,或者非实性结节平均长径≥8 mm且<15 mm者,建议3个月后复查,并根据结果决定下一轮复查时间。其他建议缩短筛查间隔的人群详见表4
(五)联合筛查的关键管理指标
常见恶性肿瘤联合筛查结果的管理是一个多步骤、多方面的过程,主要包括以下几个关键内容:(1)筛查结果的解读与分类:对筛查中发现的异常结果进行解读,并根据其严重程度和恶性肿瘤风险进行分类。(2)基于风险评估的后续治疗和随访建议:对筛查结果阴性的个体,提供相应的健康教育和生活方式干预建议,以降低未来恶性肿瘤发生风险;对于筛查结果异常的个体,提供进一步的诊断和治疗建议。(3)随访计划:对于所有筛查对象,制定长期随访计划,以监测恶性肿瘤的发展或复发,并及时调整治疗方案。(4)信息共享与资源库建设:建立恶性肿瘤筛查资源库,包括问卷调查数据库、初步风险评估数据库、影像资料库和生物样本库,以便开展长期跟踪和定量研究。(5)质量控制:确保筛查、诊断和治疗过程的质量,包括对筛查技术的准确性、诊疗流程的规范性以及患者管理的连续性进行监控和评估。(6)健康教育与心理支持:为筛查对象提供必要的健康教育,帮助他们理解筛查结果的意义,并在需要时提供心理支持。(7)政策与指南的制定与推广:制定和推广恶性肿瘤早诊早治指南,以提高恶性肿瘤筛查的规范化水平。我国常见恶性肿瘤筛查结果的报告要求及随访管理,参考国家卫生健康委员会及专业机构制定的我国常见恶性肿瘤筛查指南及规范的相关内容。
(六)恶性肿瘤联合筛查的推荐模式
为进一步推荐常见恶性肿瘤联合筛查的实践,本共识总结提出5种联合筛查的推荐模式,包括基于激素依赖性恶性肿瘤的联合筛查模式、基于同一系统常见恶性肿瘤的联合筛查模式、基于共性危险因素的恶性肿瘤联合筛查模式、基于慢病共存的恶性肿瘤联合筛查模式和基于地区性高发癌症的联合筛查模式。常见恶性肿瘤不同联合筛查模式的核心推荐内容见表6
1. 基于激素依赖性癌种的联合筛查模式
激素依赖性恶性肿瘤是指肿瘤的发生和发展与体内性激素水平及其受体的表达密切相关的恶性肿瘤,包括乳腺癌、前列腺癌、卵巢癌和子宫内膜癌等[146-148]。此类恶性肿瘤不仅依赖于特定的激素环境,包括雌激素(雌二醇、雌三醇、雌酮)、孕激素(孕酮)和雄激素(睾酮、双氢睾酮),并且在肿瘤组织中可以发现特异性激素受体的存在,如雌激素受体和孕激素受体。此外,部分激素依赖性恶性肿瘤患者还可能存在共同的遗传基础,如BRCA1和BRCA2基因突变[149-150]。因此,这些肿瘤也被称为BRCA相关恶性肿瘤[151]
鉴于以上共同特性,推荐采用以下标准定义激素依赖性恶性肿瘤联合筛查高危人群:(1)激素依赖性恶性肿瘤家族史:至少2位一级或二级亲属患有乳腺癌、前列腺癌、卵巢癌或子宫内膜癌;或至少1位一级亲属50岁之前患有前述4类恶性肿瘤之一。(2)性激素水平异常升高:除女性生理生育期外,体内性激素(主要包括雌二醇、雌三醇、雌酮、孕酮、睾酮和双氢睾酮)水平异常升高。(3)明确的高遗传风险:至少1位一级或二级亲属携带已知的BRCA1和BRCA2基因突变。(4)存在明显升高体内激素水平的风险相关因素:如肥胖、长期规律使用雌激素相关的替代治疗或采用他莫昔芬进行乳腺癌的化学性预防等。其中(1)、(2)、(3)满足任意2条,且同时满足(4)(证据质量:中,推荐强度:弱)。
针对上述高危人群,除指南推荐的影像学检查外,同时推荐采用以下辅助性检查进一步明确激素依赖性恶性肿瘤的高危人群:(1)除女性生理生育期外,目标恶性肿瘤推荐筛查年龄段内,6个月内连续3次监测体内性激素(主要包括雌二醇、雌三醇、雌酮、孕酮、睾酮和双氢睾酮)水平,任意2项指标3次均超出正常参考值范围。(2)当至少1位一级或二级亲属明确携带BRCA1和BRCA2基因突变时,推荐进行BRCA1和BRCA2基因检测(证据质量:中,推荐强度:弱)。
2. 基于同一系统常见癌种的联合筛查模式
目前针对同一系统常见恶性肿瘤的联合筛查模式,主要是指消化系统的常见恶性肿瘤联合筛查,具体包括食管癌、胃癌和结直肠癌的联合筛查。三者联合筛查的基础包括[56-57,59,152-154]:(1)年龄:3种恶性肿瘤的风险都随年龄的增长而增加,高发年龄均在45岁以上。(2)性别:男性中3种恶性肿瘤的发病率均普遍高于女性。(3)吸烟和饮酒:两者均是3种恶性肿瘤的共同危险因素,尤其是长期吸烟和酗酒者。(4)饮食习惯:相比其他恶性肿瘤,缺乏新鲜水果和蔬菜与三者之间的关联更为明显;同时高盐饮食和腌制食品均会明显增加食管癌和胃癌的风险。(5)幽门螺杆菌感染:HP感染是胃癌的已知风险因素,近年来也有研究表明其可能与食管癌的发生有关。(6)家族史:有食管癌、胃癌或结直肠癌家族史的人群发生3种恶性肿瘤的风险均更高。(7)慢性消化系统疾病:长期反复的胃食管反流病、慢性萎缩性胃炎、肠上皮化生、低级别或高级别上皮内瘤变、胃溃疡、胃息肉、结直肠腺瘤或息肉等与三者的发生均有不同程度的关联。(8)癌前病变:三者均具有相似的癌前病变,即食管、胃和结直肠黏膜的上皮内瘤变或腺瘤样息肉等。根据病变程度可进一步分为低级别上皮内瘤变和高级别上皮内瘤变。(9)三者均以内镜为主要的影像学检查方式。
鉴于以上关联及相应恶性肿瘤的筛查指南建议,推荐年龄45岁及以上,且符合下列任意条件者定义为消化系统常见恶性肿瘤联合筛查的高危人群:(1)消化系统常见恶性肿瘤家族史:至少2位一级或二级亲属患有食管癌、胃癌或结直肠癌;或至少1位一级亲属50岁之前患有前述三类恶性肿瘤之一。(2)至少有2种慢性胃肠道疾病史:长期反复的胃食管反流病、Barrett食管、慢性萎缩性胃炎、胃溃疡、胃息肉、手术后残胃、肥厚性胃炎、结直肠腺瘤或息肉或炎症性肠病史,或既往筛查发现食管、胃和结直肠黏膜存在明显的上皮内瘤变。(3)至少有2种消化系统常见恶性肿瘤的危险因素:长期吸烟、酗酒者、高盐饮食、偏好腌制食品、蔬菜水果摄入明显偏少,或HP感染(证据质量:强,推荐强度:强)
针对高危人群,除消化道内镜检查作为推荐的主要影像学检查外,推荐采用以下辅助性检查综合评估消化道恶性肿瘤风险的高危人群:(1)PG+HP血清抗体联合检测,并根据改良的ABC风险评估方法推荐B2/C/D类人群进行内镜筛查。(2)FIT粪便隐血试验,并建议联合亚太结直肠癌筛查(Asia-Pacific Colorectal Screening,APCS)评分提高进展期结直肠肿瘤筛查的有效性(证据质量:中,推荐强度:强)。
3. 基于共性危险因素的恶性肿瘤联合筛查模式
基于既往大量流行病学证据及前述恶性肿瘤危险因素的概述,根据危险因素在恶性肿瘤发生发展自然进程中出现的时间先后顺序,恶性肿瘤相关危险因素可以简单归为三类:(1)上游危险因素:恶性肿瘤发生发展过程中最早出现的因素,包括共性上游危险因素(吸烟、饮酒、不健康饮食、缺乏体力活动和超重或肥胖等)和特异性上游危险因素(癌症特异性的高遗传风险和其他特异性危险因素等)。(2)中游危险因素:在上游危险因素累积暴露下,与恶性肿瘤发生有密切关联的非靶器官疾病、症状或体征,包括:慢性低水平炎症、免疫功能异常和代谢异常(如高血压、高脂血症、糖尿病)等。(3)下游危险因素:与恶性肿瘤早期临床改变相关的靶器官疾病、症状或体征,包括恶性肿瘤特异性的良性疾病或癌前病变。
由于不同部位恶性肿瘤的下游危险因素相对特异,共性的疾病或症状相对少见。因此,该模式中的共性危险因素特指恶性肿瘤风险相关的共性上游和中游危险因素,或其他可引起14个恶性肿瘤标志中任意一种改变的非特异性危险因素。14个恶性肿瘤标志包括:(1)8个核心特征,包括维持增殖信号、逃避生长抑制、抵抗细胞死亡、获得复制永生性、诱导血管生成、激活侵袭和转移、重编程细胞代谢和避免免疫破坏;(2)2个使能特征,包括基因组不稳定和突变和肿瘤相关炎症;(3)4个定义性特征,包括非突变性表观遗传重编程、多态性微生物组、衰老细胞和解锁表型可塑性[155]
基于上述共性危险因素和共性恶性肿瘤标志,推荐同时满足以下3条标准的人群开展基于共性危险因素的恶性肿瘤联合筛查:(1)至少暴露于2种已知的恶性肿瘤共性上游危险因素,包括吸烟、饮酒、不健康饮食、缺乏体力活动和超重或肥胖。(2)至少暴露于2种恶性肿瘤共性中游危险因素:常规炎性因子(如C反应蛋白或肿瘤坏死因子等)及衍生的炎性指标(如SII、中性粒细胞与淋巴细胞计数比值、血小板淋巴细胞比值或MLR等)异常升高6个月以上饮食控制、规律锻炼或服用药物等均无法明显改善的高血压、高脂血症和血糖异常升高(包括糖尿病前期、糖尿病、胰岛素抵抗、胰岛功能障碍或胰岛功能衰竭)且持续6个月以上。(3)至少暴露于2种恶性肿瘤特异性的危险因素,包括特异性的高遗传风险、良性疾病或癌前病变,和其他特异性危险因素(证据质量:中,推荐强度:弱)。
针对上述高危人群,除指南推荐的影像学检查外,推荐以下辅助性检查随访监测目标恶性肿瘤风险:(1)6个月内炎性相关指标(包括常规炎性因子及衍生的系统炎性指标)任意2项指标连续3次均超出参考值上限。(2)6个月内糖代谢指标(包括空腹血糖、糖化血红蛋白和TyG等胰岛素抵抗指标)和脂代谢指标(包括甘油三酯、总胆固醇、高密度脂蛋白胆固醇和低密度脂蛋白胆固醇)每类任意指标连续3次均超出参考值上限(证据质量:弱,推荐强度:弱)。
4. 基于慢病共存的恶性肿瘤联合筛查模式
强有力的证据支持心脑血管疾病(cardiovascular and cerebrovascular disease,CCVD)和恶性肿瘤具有诸多共同的危险因素和发病机制,而且两者之间存在密切关联[156-157]。首先,吸烟、饮酒、不健康饮食、缺乏体力活动、肥胖、高血压、高脂血症和糖尿病等可改变的危险因素,不仅是CCVD的常见危险因素,同时也是多种恶性肿瘤共性的上游或中游危险因素。这些共享的危险因素揭示了为何部分群体会同时面临CCVD和恶性肿瘤的双重威胁。其次,CCVD和恶性肿瘤之间很可能存在双向影响。恶性肿瘤患者往往有更高的CCVD风险,这不仅是由于恶性肿瘤治疗相关心血管不良反应,同样也可能归因于恶性肿瘤本身和CCVD存在诸多共享的病理生理机制。同样,CCVD患者也有更高的恶性肿瘤风险,这可能与慢性炎症、氧化应激和代谢失调等共同的病理生理过程有关。比如,慢性炎症不仅促进动脉粥样硬化和心血管疾病的发展,还可能通过抑制肿瘤微环境中的免疫反应,促进肿瘤的生长和治疗抵抗。此外,CCVD和恶性肿瘤在某些影像检查上,如乳腺X线、肺部低剂量CT和心脏CT检查等,均有可能呈现出类似的病理性特征影像改变,这为两种疾病的联合筛查和联合防控提供了充分的依据,同时具有广泛的公共卫生意义。
鉴于CCVD和恶性肿瘤等慢病共存的特征及当前不同恶性肿瘤的筛查指南建议,推荐同时满足前述3条恶性肿瘤共性危险因素联合筛查入选标准及CCVD病史[既往诊断过中风(包括缺血性或出血性中风)、急性冠脉综合征(包括心肌梗死和心绞痛)或心力衰竭]共计4条入选标准的高危人群开展基于心脑血管代谢慢病共存的恶性肿瘤联合筛查(证据质量:中,推荐强度:中)。
上述高危人群,首选CT作为目标恶性肿瘤的主要影像学筛查方法,以同时评估CCVD和目标恶性肿瘤的联合发病风险。并在共性危险因素联合筛查模式推荐的辅助性检查(包括炎性指标和糖脂代谢指标监测)基础上,同时推荐6个月内连续3次的血压评估来监测慢病共病风险(证据质量:弱,推荐强度:弱)。
5. 基于地区性高发恶性肿瘤的联合筛查模式
基于地区性高发恶性肿瘤开展联合筛查,是目前最常见的联合筛查模式,包括美国的PLCO研究,我国的淮河流域癌症早诊早治项目、全国城市癌症早诊早治项目、全国农村癌症早诊早治项目和全国农村妇女两癌筛查项目,以及部分省(自治区、直辖市)自行开展的常见恶性肿瘤联合筛查项目,如C-BLAST和KCIS研究。这些项目在筛查组织上存在诸多的共性:(1)目标一致性:均以当地高发的常见癌症为目标筛查恶性肿瘤,旨在提高当地高发恶性肿瘤的早诊率和治疗率,降低恶性肿瘤死亡率,改善恶性肿瘤患者的预后和生活质量。(2)高危人群筛查:这些项目都主要针对恶性肿瘤高危人群开展筛查,以提高筛查的效果。(3)初筛联合复查的序贯筛查方式:包括HP联合PG初筛阳性后的上消化道内镜筛查胃癌、AFP或HBV表面抗原初筛阳性后的腹部超声筛查肝癌、FIT初筛阳性后的结肠镜筛查结直肠癌,和PSA初筛阳性后的MRI筛查前列腺癌,等等。(4)筛查年龄相对一致:除国家两癌筛查(子宫颈癌和乳腺癌)多推荐从35岁开始筛查外,多数项目均以40~74岁为主要的目标筛查年龄;(5)筛查间隔:虽然多数恶性肿瘤的指南推荐筛查间隔存在明显差异,但多数项目的实际执行周期多采用每年1次,以保证项目的连续性。(6)当地政府支持和多部门合作:多数项目除了国家经费支持,当地政府均在不同程度给予政策和经费的支持,同时涉及当地卫生、财政、妇联等多个部门的合作,共同推进项目的实施。(7)统一的技术培训、筛查流程和质量控制:所有项目都采用严格统一的技术培训、筛查流程和质量控制标准,从而确保筛查的准确性、数据的完整性及操作的规范性。
基于以上共性,为提高地区高发型恶性肿瘤联合筛查效果,推荐在满足前述共性危险因素联合筛查高危人群判定标准基础上,强化评估地区高发癌症(发病率前5位)的特异性危险因素(证据质量:中,推荐强度:强)。针对共性危险因素联合筛查判定标准的第3类标准,如果3种特异性危险因素(包括特异性的高遗传风险、良性疾病或癌前病变,和其他特异性危险因素)均存在至少2类恶性肿瘤危险因素暴露时,定义为极高风险人群。
针对上述高危人群,除指南推荐的影像学检查,推荐同时检测目前恶性肿瘤常规肿瘤标志物(如AFP等)和致癌性病原体(如HBV+HP等),以共同评估地区高发癌症风险针对极高风险居民,当有明确需求且条件允许情况下(包括成熟的检测条件、明确的管理规范和稳定的支持团队),获取知情同意后,可推荐MCED等多组学检测方法,进一步明确多恶性肿瘤风险(证据质量:中;推荐强度:弱)
(七)联合筛查的推荐流程
常见恶性肿瘤联合筛查的基本流程包括知情同意→风险评估→筛查检测→早诊早治→复查随访。医疗知情同意书是医务人员履行告知义务、患者行使知情同意权的关键文件,也表明患者自愿承担医疗风险[158]。履行告知义务、加强医患沟通、规范签署知情同意书是建立医患信任、防范医疗风险、处理医患矛盾的重要步骤[159-160]。因此,居民在参加常见恶性肿瘤联合筛查前,必须签署知情同意书,明确筛查目的、意义、过程、潜在收益与风险。风险评估除了采用问卷调查获取基础信息外,推荐采用一般健康状况等工具收集筛查对居民心理健康的影响[161],同时推荐癌症筛查信仰调查量表(如Cancer Beliefs about Screening Scale for Breast Cancer)了解居民对于恶性肿瘤筛查的知识、态度和行为等[162]。筛查检测需严格按照相应规范和要求来进行操作和填报,筛查高危人群的判定标准、各项检查的阳性标准和所有恶性肿瘤的病理诊断标准等,均应遵循明确的、统一的可执行早诊早治标准。所有筛查数据均应由统一筛查平台进行整合,以保证各项筛查数据的互联互通,同时方便复查随访。
除上述基础流程,常见恶性肿瘤的联合筛查需首先根据目标人群特征、资源可及性和卫生经济学先验评估结果,来综合决策选择何种联合筛查模式。据此选择联合筛查方法,包括多模态影像学检查、常规肿瘤标志物及病原体检测、基础生化指标,以及多组学评估/液体活检等不同方法的有机整合。在初步明确了恶性肿瘤所在组织/器官定位后,通过病理诊断明确癌症来源,并采用AI整合大数据分析进行综合风险分层。不同风险分层的居民分别推荐不同的诊断和随访方案。明确诊断之后,并进行综合评价分析,包括准确性评价、有效性评价、安全性评价、卫生经济学后验评价和人群可接受性评价。最终根据各项评估结果对筛查方案进行反馈,进一步优化联合筛查模式。推荐的联合筛查流程见图1
本共识聚焦于常见恶性肿瘤的联合筛查,是由多学科专家团队,遵循国际通用规范和方法制定而成。核心推荐原则是:基于常见恶性肿瘤的共性危险因素(包括共同遗传背景、饮食与生活方式、代谢变化、炎性改变及其他共性特征)和不同恶性肿瘤的特异性危险因素,共同识别常见恶性肿瘤联合筛查的高危人群。恶性肿瘤高风险人群中,在充分知晓筛查的获益与风险后,推荐以经济有效且有高级别证据支持的影像学检查为主要筛查方法,辅以适宜的辅助性检查和人工智能分析开展常见恶性肿瘤的联合筛查。不建议对一般风险人群开展无选择性的大规模组织化的常见恶性肿瘤联合筛查。本共识是国内外首部常见恶性肿瘤联合筛查专家共识,为保证共识内容的科学性和合理性,本共识工作组通过关键问题调研和筛选、证据检索与评价、专家讨论与综合等过程,最终形成了以证据为基础、平衡风险和获益、综合考虑筛查者意愿和行业专家经验的推荐意见。本共识旨在指导我国常见恶性肿瘤联合筛查实践,提高我国常见恶性肿瘤联合筛查的同质化和规范化,提升常见恶性肿瘤联合筛查的收益,以期最终降低常见恶性肿瘤的综合疾病负担,提高社会与经济效益。
值得注意的是,本共识目前仍有诸多问题亟待解决,如目前国内外尚缺乏常见恶性肿瘤不同联合筛查模式效果评价的高质量RCT研究,因而缺乏不同联合筛查模式相对有代表性的、客观的准确性评估和有效性评价数据。同时,如何避免因联合筛查所带来的潜在过度诊断和过度治疗问题,以及如何提升AI在常见恶性肿瘤联合筛查中的应用价值等等,均有待进一步的探索和完善。因此,本共识基于我国国情和现有国内外证据得出的专家推荐意见仍需在实践中检验。本工作组也将持续关注后续研究,在后续共识中进行及时更新。
共识制定专家组(以姓氏汉语拼音字母排序)
曹广文(解放军海军军医大学流行病学教研室)、陈可欣 (天津医科大学肿瘤医院流行病学研究室)、陈万青 (国家癌症中心国家肿瘤临床医学研究中心中国医学科学院北京协和医学院肿瘤医院癌症早诊早治办公室)、杜灵彬 (浙江省肿瘤医院肿瘤防治办公室)、郜恒骏 (生物芯片上海国家工程研究中心)、何忠虎(北京大学肿瘤医院遗传学研究室)、贺宇彤(河北医科大学第四医院肿瘤研究所肿瘤防治室和分析细胞室)、胡志斌(南京医科大学流行病学系)、贾卫华(中山大学肿瘤医院肿瘤防治中心肿瘤分子流行病学研究室)、李霓(国家癌症中心国家肿瘤临床医学研究中心中国医学科学院北京协和医学院肿瘤医院癌症早诊早治办公室)、潘凯枫(北京大学肿瘤医院流行病学研究室)、孙凤(北京大学公共卫生学院流行病与卫生统计学系)、王新(空军军医大学唐都医院消化内科)、项永兵(上海市肿瘤研究所流行病学研究室)、张韶凯(郑州大学附属肿瘤医院肿瘤防治研究办公室)、张涛(天津医科大学公共卫生学院流行病与卫生统计学系)、赵方辉(国家癌症中心国家肿瘤临床医学研究中心中国医学科学院北京协和医学院肿瘤医院流行病学研究室)、庄贵华(西安交通大学流行病与卫生统计学系)
共识制定专家组组长
陈可欣(天津医科大学肿瘤医院流行病学研究室)
共识制定专家组副组长
陈万青(国家癌症中心,国家肿瘤临床医学研究中心,中国医学科学院北京协和医学院肿瘤医院癌症早诊早治办公室)
共识制定工作组(按姓氏汉语拼音字母排序)
陈宏达(国家癌症中心,国家肿瘤临床医学研究中心,中国医学科学院北京协和医学院肿瘤医院癌症早诊早治办公室)、戴弘季(天津医科大学肿瘤医院流行病学研究室)、黄育北(天津医科大学肿瘤医院流行病学研究室)、金明娟(浙江大学流行病与统计学系)、姜晶(吉林大学第一医院临床流行病学研究中心)、雷林(深圳市慢性病防治中心肿瘤防控科)、李贺(国家癌症中心 国家肿瘤临床医学研究中心 中国医学科学院北京协和医学院肿瘤医院癌症早诊早治办公室)、李江(国家癌症中心,国家肿瘤临床医学研究中心,中国医学科学院北京协和医学院肿瘤医院癌症早诊早治办公室)、李文庆(北京大学肿瘤医院流行病学研究室)、梁迪(河北医科大学第四医院肿瘤研究所)、刘奔(天津医科大学肿瘤医院流行病学研究室)、刘红(天津医科大学肿瘤医院乳腺肿瘤科)、刘萌飞(北京大学肿瘤医院遗传学研究室)、刘运泳(中国医学科学院北京协和医学院肿瘤医院深圳医院科研教学部)、卢树雪(天津医科大学肿瘤医院流行病学研究室)、吕章艳(天津医科大学肿瘤医院流行病学研究室)、买合丽艳·阿不都米吉提(天津医科大学肿瘤医院流行病学研究室)、任建松(国家癌症中心,国家肿瘤临床医学研究中心,中国医学科学院北京协和医学院肿瘤医院癌症早诊早治办公室)、石菊芳(国家癌症中心,国家肿瘤临床医学研究中心,中国医学科学院北京协和医学院肿瘤医院癌症早诊早治办公室)、王飞(国家癌症中心,国家肿瘤临床医学研究中心,中国医学科学院北京协和医学院肿瘤医院癌症早诊早治办公室)、王乐(浙江省肿瘤医院肿瘤防治办公室)、王宁(北京大学肿瘤医院肿瘤防治研究办公室)、席云峰(内蒙古自治区综合疾病预防控制中心慢病科)、颜仕鹏(湖南省肿瘤医院肿瘤防治研究办公室)、张莉(中国医学科学院北京协和医学院群医学及公共卫生学院)、张敏(湖北省肿瘤医院肿瘤防治办公室)、赵雪莲(国家癌症中心,国家肿瘤临床医学研究中心,中国医学科学院北京协和医学院肿瘤医院流行病学研究室)、赵岩(辽宁省肿瘤医院肿瘤外科)、曾红梅(国家癌症中心,国家肿瘤临床医学研究中心,中国医学科学院北京协和医学院肿瘤医院全国肿瘤防治办公室)
共识制定工作组组长
黄育北(天津医科大学肿瘤医院流行病学研究室)
共识制定工作组副组长
吕章艳(天津医科大学肿瘤医院流行病学研究室)
执笔团队(按姓氏汉语拼音字母排序)
陈可欣(天津医科大学肿瘤医院流行病学研究室)、陈万青(国家癌症中心,国家肿瘤临床医学研究中心, 中国医学科学院北京协和医学院肿瘤医院癌症早诊早治办公室)、黄育北(天津医科大学肿瘤医院流行病学研究室)、吉雨婷(天津医科大学肿瘤医院流行病学研究室)、金千韵(天津医科大学肿瘤医院流行病学研究室)、李净净(天津医科大学肿瘤医院流行病学研究室)、李文轩(天津医科大学肿瘤医院流行病学研究室)、吕章艳(天津医科大学肿瘤医院流行病学研究室)、盛超(天津医科大学肿瘤医院流行病学研究室)、宋方方(天津医科大学肿瘤医院流行病学研究室)、宋丰举(天津医科大学肿瘤医院流行病学研究室) 、王鹏(天津医科大学肿瘤医院流行病学研究室)、吴婕(天津医科大学肿瘤医院流行病学研究室)、夏昌发(国家癌症中心,国家肿瘤临床医学研究中心,中国医学科学院北京协和医学院肿瘤医院癌症早诊早治办公室)、许永杰(国家癌症中心,国家肿瘤临床医学研究中心,中国医学科学院北京协和医学院肿瘤医院癌症早诊早治办公室)、杨雷(北京大学肿瘤医院内蒙古医院,内蒙古医科大学附属肿瘤医院,内蒙古癌症中心)、张雅聪(天津医科大学肿瘤医院流行病学研究室)、张芸萌(天津医科大学肿瘤医院流行病学研究室)
志谢
感谢中国抗癌协会肿瘤流行病学专委会及中国抗癌协会癌症筛查与早诊早治专委会的多位专家在本共识制定过程中提出的宝贵建议
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2025年第52卷第14期
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doi: 10.12354/j.issn.1000-8179.2025.20250757
  • 接收时间:2025-06-06
  • 首发时间:2026-04-09
  • 出版时间:2025-07-30
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  • 收稿日期:2025-06-06
  • 修回日期:2025-06-30
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    1天津医科大学肿瘤医院流行病学研究室,国家恶性肿瘤临床医学研究中心(天津市300060)
    2国家癌症中心,国家肿瘤临床医学研究中心,中国医学科学院北京协和医学院肿瘤医院癌症早诊早治办公室
    3北京大学肿瘤医院内蒙古医院,内蒙古医科大学附属肿瘤医院,内蒙古癌症中心

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2种不同金属材料的力学参数

Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)

Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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