Lowy Douglas R, Schiller John T
Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
J Clin Invest. 2006 May;116(5):1167-73. doi: 10.1172/JCI28607.
Human papillomavirus (HPV) infection causes virtually all cases of cervical cancer, the second most common cause of death from cancer among women worldwide. This Review examines prophylactic HPV subunit vaccines based on the ability of the viral L1 capsid protein to form virus-like particles (VLPs) that induce high levels of neutralizing antibodies. Following preclinical research by laboratories in the nonprofit sector, Merck and GlaxoSmithKline are developing commercial versions of the vaccine. Both vaccines target HPV16 and HPV18, which account for approximately 70% of cervical cancer. The Merck vaccine also targets HPV6 and HPV11, which account for approximately 90% of external genital warts. The vaccines have an excellent safety profile, are highly immunogenic, and have conferred complete type-specific protection against persistent infection and associated lesions in fully vaccinated women. Unresolved issues include the most critical groups to vaccinate and when the vaccine's cost may be low enough for widespread implementation in the developing world, where 80% of cervical cancer occurs.
人乳头瘤病毒(HPV)感染几乎导致所有宫颈癌病例,宫颈癌是全球女性癌症死亡的第二大常见原因。本综述基于病毒L1衣壳蛋白形成能诱导高水平中和抗体的病毒样颗粒(VLP)的能力,对预防性HPV亚单位疫苗进行了研究。在非营利部门的实验室进行临床前研究之后,默克公司和葛兰素史克公司正在开发该疫苗的商业版本。两种疫苗均针对HPV16和HPV18,这两种病毒约导致70%的宫颈癌。默克公司的疫苗还针对HPV6和HPV11,这两种病毒约导致90%的外生殖器疣病例。这些疫苗具有出色的安全性,免疫原性很强,并且在完全接种疫苗的女性中已实现针对持续性感染及相关病变的完全型特异性保护。尚未解决的问题包括最关键的接种人群,以及在80%的宫颈癌病例发生的发展中世界,疫苗成本何时能低到足以广泛推广。