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.

基因型 16 作为致癌人乳头瘤病毒 (HPV) 原型的发现引发了四分之一个世纪的实验室和流行病学研究，证明了其在宫颈癌和其他几种肛门生殖器癌和口咽癌中的必要但不充分的病因学作用。早期病毒引起的免疫偏差可能导致持续的亚临床感染，从而带来进展为癌症的风险。通过细胞学和/或 HPV 筛查对宫颈癌进行有效的二级预防取决于在普通人群中定期和广泛使用，但在资源匮乏的地区覆盖率不足。主要衣壳抗原 L1 可以自组装成具有高度免疫原性和保护性的空病毒样颗粒 (VLP)，这一发现导致多种基于 VLP 的预防性 HPV 疫苗获得许可，用于预防宫颈癌。许多国家正在对青春期女性实施疫苗接种计划，但其影响很大程度上取决于人口覆盖率，并通过群体免疫来改善。本综述考虑了如何利用我们对 HPV 感染的病毒学和免疫学的不断扩展的知识来改进疫苗技术和提供此类预防策略，以最大限度地减少 HPV 相关疾病，包括将涵盖致癌类型的 HPV 疫苗纳入标准多靶点儿科疫苗。