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实现癌症预防的潜力——实施科学的作用
Realizing the Potential of Cancer Prevention — The Role of Implementation Science
在过去二十年中，我们及其他研究者通过估算发现，若能充分运用现有科学知识，超过半数的癌症本可预防。吸烟、缺乏运动和肥胖是可干预的癌症诱因1-3。现有证据提示，通过接种人乳头瘤病毒疫苗、服用阿司匹林及使用选择性雌激素受体调节剂，以及参与癌症筛查计划，可进一步降低特定癌症的发病风险4,5。这些策略对普通人群的癌症相关结局有显著影响。50岁时戒烟可使肺癌死亡率降低62% 6，且环境和政策策略能有效提升戒烟率6-8。宫颈癌筛查可使死亡率降低95% 9，而接种人乳头瘤病毒疫苗可使死亡率降低100% 10-12，接种乙肝疫苗可使慢性肝病和肝癌相关死亡率降低90%13。这些策略对于癌症高危人群也有益处。肺癌筛查能使高危吸烟者的死亡率降低20%，输卵管卵巢切除术可使携带BRCA1/2基因突变的女性患乳腺癌和卵巢癌的风险降低14,15，选择性雌激素受体调节剂治疗能使高危女性患乳腺癌的几率降低50%16,17。对丙型肝炎病毒感染者的筛查、诊断和治疗可使其全因死亡率降低50%18。我们预防癌症的能力已显著提高。
我们对癌症预防证据的应用程度如何？
美国对癌症预防证据的应用成效尚未达到应有水平（表1）。在各类癌症预防策略中，戒烟有着最悠久的证据基础。通过环境与政策手段（如税收调控与限制性政策）降低高危行为发生率并提升戒烟治疗可及性，对人群层面的控烟工作尤为重要6-8,26。然而，目前联邦对烟草征收的消费税为1.01美元，与全世界高收入国家平均每包约3.15美元的水平相比偏低。各州在应用证据方面往往存在显著差异。例如，各州的烟草税从每包香烟17美分到4.35美元不等27。提高州和联邦层面的香烟消费税被视为降低吸烟率的关键策略，但近三分之一的州在过去十年中未提高其税率。《平价医疗法案》（Affordable Care Act，ACA）28,29曾试图解决长期存在的戒烟治疗可及性差距问题，但该法案如今面临风险。
表1. 美国癌症风险影响因素的流行情况*
* CDC表示美国疾病控制和预防中心。
† BMI表示体质指数（体重[kg]除以身高[m]的平方）。部分机构将肥胖定义为BMI≥30。
‡ 缺乏体力活动的定义为：≥18岁的人群在闲暇时间无任何体力活动。
§ 结肠癌筛查百分比是基于50~75岁人群中符合美国预防服务工作组（U.S. Preventive Services Task Force）筛查建议者。
¶ 乳腺X线检查数据来自在过去2年内接受过该项检查的≥40岁女性。
‖ 巴氏涂片（Pap）检查数据来自在过去3年内接受过该项检查的21~65岁女性。
** 这些儿童至少接种过三剂人乳头瘤病毒（HPV）疫苗。
†† 乙型肝炎病毒（HBV）疫苗接种时间为出生后3日内。
对于几乎所有已知的癌症预防策略，在证据应用方面都能看到类似差距。简而言之，美国在癌症一级预防与筛查领域仍存在系统性投入不足，且未能采取措施确保所有人群平等获益于现有的癌症预防知识。其结果是癌症发病率和死亡率居高不下30，而这本可避免。高发病率和死亡率又导致了巨大的医疗费用，并给患者及其家庭带来了沉重负担31,32。相比之下，预防措施的成本效益显著。例如，吸烟的经济成本估计每年达3000亿美元33。在马萨诸塞州，每投入1美元用于全面戒烟计划，就能获得2.12美元的投资回报34。
我们如何最大化应用现有癌症预防证据？
如果我们希望进一步应用现有癌症预防证据，就必须开展更多以癌症预防为重点的传播研究（dissemination research）和实施研究（implementation research）。传播研究的目的是系统性研究推动循证实践广泛普及的过程及影响因素35。实施研究侧重于了解在特定环境中（例如初级保健诊所或学校）成功整合循证实践的过程和因素，并评估在该环境中对这些实践进行必要调整的效果。在日益完善的方法学支持下，这两种研究路径将共同助力扭转癌症预防证据应用不足的现状。聚焦于提升人群层面癌症预防效能的传播和实施研究，可能会特别富有成效26。
环境和政策举措能够高效地惠及大量人群6-8。传播和实施研究有助于阐明可能在不同环境中加速实施的组织因素。例如，工作场所禁烟令和全面戒烟计划已被证明是减少成人吸烟的有效策略7，并且推动禁烟令落地的关键组织特征也已确定36,37。未来政策干预的机会可能集中在循证策略推广受阻的领域，如前文提及的消费税低的州或控烟政策执行薄弱的州。风险行为高发人群聚集的场所也需重点关注。例如，在精神健康障碍与药物滥用群体的医疗照护机构，亟需加强循证控烟干预，因为这两类人群的吸烟率远超一般人群平均水平38。仅有35%的药物滥用治疗机构实行禁烟令9，约半数机构提供戒烟咨询或药物干预40，而精神科医师仅在12%的接诊过程中向吸烟患者提供戒烟咨询41。尽管在精神卫生保健背景下实施戒烟治疗已被证明有效，但只有13个州要求酒精/药物滥用及其他心理健康相关治疗机构提供戒烟治疗服务42。治疗中心与工作场所推动禁烟政策的影响因素可能存在差异。通过传播与实施研究，结合州/联邦政策改革（如加强二手烟暴露防护、保障戒烟治疗可及性），可有效提升此类场景中禁烟令的覆盖率与综合治疗的供给水平。
提升癌症预防循证证据的应用水平，另一个重要方向是优化癌症治疗的实施环境。2014年美国卫生总监（Surgeon General）的报告得出结论，吸烟与癌症患者不良健康结局和死亡率之间存在因果关系，如果这些患者在确诊时戒烟，全因死亡率可降低30%~40%7。类比推理，若某癌症治疗中心未采用循证化疗方案，其在申请美国国立癌症研究所（National Cancer Institute）资助时将丧失竞争力。若对癌症患者的行为风险因素干预也采用同等循证标准，将有助于加速降低全美1300万癌症幸存者的死亡风险，这不仅造福患者，更能减轻其家庭与照护者的负担。传播和实施研究应着重探究在医务人员、患者、机构及政策层面阻碍循证癌症预防策略推广的制约因素。
通过在多个影响层面集中研究力量（通常通过新的和非传统的合作），也能在更大范围内实现癌症预防措施的普及。正如上述例子所表明的那样，我们既要鼓励降低风险行为的政策，也要保障循证疗法的可及性。若《平价医疗法案》被大规模废除，数百万吸烟者将难以获得或完全失去循证治疗的机会。癌症筛查服务的可及性也将下降。因此必须开辟其他获取途径。联邦医疗保险和医疗补助保险服务中心（CMS）可以利用其创新资助项目助力开发新策略，以提供筛查服务并推广循证癌症预防策略，就像它在帮助降低心血管疾病风险方面所做的那样。值得探讨的是，州级措施能否取得与CMS投资支持不同的成效？CMS资源能否用于推动各州加强循证研究的实施？与医疗领域外的机构（如学校、教堂及农业、住房等政府部门）合作能否提升相关措施的普及率？通过与美国国立卫生研究院（National Institutes of Health）及美国疾病控制与预防中心（Centers for Disease Control and Prevention）合作，可创建有针对性的研究项目以提升知识产出效益。
社会决定因素是导致癌症发病率和死亡率差异的重要原因43。为经济资源有限社区提供服务的机构（如安全网医疗中心）在确保公平获取癌症预防项目方面发挥着特殊作用。然而，由于资源有限且需求量大，将新的实践模式整合到这类组织中可能存在困难。初步研究表明，除了干预措施本身的特性外，组织或社区的某些特征（例如领导者参与变革的意愿、对变革的抵触情绪或认为现状难以容忍的看法，以及是否有正式任命的领导者）能够将采用循证实践的系统与表现较差的系统区分开来44,45。未来需要在癌症负担高且资源有限地区开展更多研究，将影响这些地区实施工作的所有因素都纳入其中46。
结论
要让整个国家真正受益于癌症研究的投入，我们必须专注于能够减少癌症预防项目实施情况差异的策略。我们需要借鉴更广泛采用预防政策的组织和社区的经验，而且需要更深入地了解能促进循证项目有效实施的社会、政治和环境因素47。为了真正实现减轻癌症负担的目标（而不只是停留在口头上），我们必须解决那些导致结局差异的实施因素，并且对癌症负担最重的人群产生最大影响。如果我们能正确实施循证预防与筛查项目并扩大覆盖范围，将在人群层面显著获益。当前许多研究仍在努力深化对癌症病因和治疗方案的认知，而通过实施现有成熟方案，立即就能切实减轻癌症负担。因此，我们需要加强相关研究的投入，帮助我们更深入理解如何运用现有知识。属于我们的“登月计划”就在眼前，只待我们去实现。
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答谢
Drs. Emmons and Colditz contributed equally to this article.
Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.
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