文章：

人乳头瘤病毒疫苗在癌症中的机遇和挑战

Opportunities and challenges for human papillomavirus vaccination in cancer

原文发布日期：2018-03-02

DOI: 10.1038/nrc.2018.13

类型: Review Article

开放获取: 否

要点：

1. Cervical cancer is potentially a completely preventable disease
2. The licensed vaccines are safe and highly effective against the most common human papillomavirus (HPV) types found in cervical and other anogenital cancers and are likely to prevent HPV⁺ oropharyngeal cancers
3. Implementation of HPV vaccination is lagging where it is most needed: in the poorest and most at-risk communities that lack screening programmes and have the highest rates of HIV
4. Local production of biosimilar HPV vaccines is progressing, especially in China, but acceptance of virological end points and/or immunological non-inferiority by regulators could speed access
5. The current HPV vaccines do not cover all oncogenic types, and efforts are underway to increase the breadth of protection, including targeting of L2
6. HPV vaccination affects the cost and benefits of screening by reducing the prevalence of high-grade intraepithelial neoplasia associated with vaccine-targeted types
7. Effective communication to policymakers, physicians, patients and their families of the safety and benefits of HPV vaccination is critical to promote global implementation and fully realize the potential for prevention of cervical and other HPV-related cancers
8. In current populations with a high prevalence of HPV, the application of mathematical modelling is critical to optimize cervical cancer prevention and to balance the use of limited public resources for both HPV vaccination and screening programmes

要点翻译：

1. 宫颈癌是一种可能完全可预防的疾病。
2. 已上市的疫苗对宫颈癌及其他肛门生殖器癌症中最常见的人乳头瘤病毒（HPV）类型安全有效，并可能预防HPV阳性口咽癌。
3. HPV疫苗接种在最需要的地方推进缓慢：这些最贫困、最高危的社区缺乏筛查项目且HIV感染率最高。
4. 生物类似药HPV疫苗的本地化生产正在推进（尤其在中国），但监管机构若接受病毒学终点和/或免疫学非劣效性标准可加速疫苗普及。
5. 现有HPV疫苗未覆盖所有致癌类型，目前正通过靶向L2等途径拓宽保护范围。
6. HPV疫苗接种通过降低疫苗靶向型别相关的高度上皮内瘤变患病率，影响筛查的成本与效益。
7. 向政策制定者、医生、患者及其家属有效传递HPV疫苗接种的安全性与获益，对推动全球实施、充分实现宫颈癌及其他HPV相关癌症的预防潜力至关重要。
8. 在当前HPV高感染率人群中，应用数学模型对优化宫颈癌预防、平衡HPV疫苗接种与筛查项目有限公共资源的使用至关重要

英文摘要：

The discovery of genotype 16 as the prototype oncogenic human papillomavirus (HPV) initiated a quarter century of laboratory and epidemiological studies that demonstrated their necessary, but not sufficient, aetiological role in cervical and several other anogenital and oropharyngeal cancers. Early virus-induced immune deviation can lead to persistent subclinical infection that brings the risk of progression to cancer. Effective secondary prevention of cervical cancer through cytological and/or HPV screening depends on regular and widespread use in the general population, but coverage is inadequate in low-resource settings. The discovery that the major capsid antigen L1 could self-assemble into empty virus-like particles (VLPs) that are both highly immunogenic and protective led to the licensure of several prophylactic VLP-based HPV vaccines for the prevention of cervical cancer. The implementation of vaccination programmes in adolescent females is underway in many countries, but their impact critically depends on the population coverage and is improved by herd immunity. This Review considers how our expanding knowledge of the virology and immunology of HPV infection can be exploited to improve vaccine technologies and delivery of such preventive strategies to maximize reductions in HPV-associated disease, including incorporation of an HPV vaccine covering oncogenic types within a standard multitarget paediatric vaccine.

摘要翻译： 

16型基因作为原型致癌人乳头瘤病毒（HPV）的发现，开启了长达25年的实验室与流行病学研究，最终证实其在宫颈及其他多种肛门生殖器与口咽癌中具有“必要但非充分”的致病作用。病毒早期诱导的免疫偏移可导致持续亚临床感染，进而带来癌变风险。细胞学和/或HPV筛查对宫颈癌的有效二级预防依赖于普通人群的定期、广泛参与，但在资源匮乏地区覆盖率不足。随后发现主要衣壳抗原L1可自组装为空病毒样颗粒（VLP），兼具高度免疫原性与保护力，由此促成多种预防性VLP-HPV疫苗获批上市，用于预防宫颈癌。目前多国已启动针对青春期女性的疫苗接种计划，其效果关键取决于人群覆盖率，并可通过群体免疫进一步提升。本文综述了如何借助不断扩充的HPV病毒学与免疫学知识，改进疫苗技术与递送策略，以最大限度降低HPV相关疾病负担，包括将覆盖致癌型别的HPV疫苗纳入标准多联儿科疫苗的可行性。

原文链接：

Opportunities and challenges for human papillomavirus vaccination in cancer