Boilesen Ditte Rahbæk, Nielsen Karen Nørgaard, Holst Peter Johannes
Centre for Medical Parasitology, Institute for Immunology, University of Copenhagen, 2200 Copenhagen, Denmark.
InProTher APS, 2200 Copenhagen, Denmark.
Vaccines (Basel). 2021 Nov 1;9(11):1262. doi: 10.3390/vaccines9111262.
Human papillomavirus (HPV) infection is the cause of the majority of cervical cancers and head and neck cancers worldwide. Although prophylactic vaccines and cervical cancer screening programs have shown efficacy in preventing HPV-associated cervical cancer, cervical cancer is still a major cause of morbidity and mortality, especially in third world countries. Furthermore, head and neck cancer cases caused by HPV infection and associated mortality are increasing. The need for better therapy is clear, and therapeutic vaccination generating cytotoxic T cells against HPV proteins is a promising strategy. This review covers the current scene of HPV therapeutic vaccines in clinical development and discusses relevant considerations for the design of future HPV therapeutic vaccines and clinical trials, such as HPV protein expression patterns, immunogenicity, and exhaustion in relation to the different stages and types of HPV-associated lesions and cancers. Ultimately, while the majority of the HPV therapeutic vaccines currently in clinical testing target the two HPV oncoproteins E6 and E7, we suggest that there is a need to include more HPV antigens in future HPV therapeutic vaccines to increase efficacy and find that especially E1 and E2 could be promising novel targets.
人乳头瘤病毒（HPV）感染是全球大多数宫颈癌和头颈癌的病因。尽管预防性疫苗和宫颈癌筛查计划已显示出预防HPV相关宫颈癌的功效，但宫颈癌仍是发病和死亡的主要原因，尤其是在第三世界国家。此外，由HPV感染引起的头颈癌病例和相关死亡率正在上升。显然需要更好的治疗方法，而产生针对HPV蛋白的细胞毒性T细胞的治疗性疫苗是一种很有前景的策略。这篇综述涵盖了临床开发中HPV治疗性疫苗的现状，并讨论了未来HPV治疗性疫苗设计和临床试验的相关考虑因素，例如与不同阶段和类型的HPV相关病变及癌症有关的HPV蛋白表达模式、免疫原性和耗竭情况。最终，虽然目前大多数处于临床试验阶段的HPV治疗性疫苗都靶向两种HPV癌蛋白E6和E7，但我们建议未来的HPV治疗性疫苗有必要纳入更多HPV抗原以提高疗效，并发现尤其是E1和E2可能是很有前景的新靶点。
