人乳头瘤病毒及其疫苗研究进展

Introduction to human papillomavirus and vaccines

人乳头瘤病毒(human papillomavirus,HPV)是一类能够感染皮肤和黏膜的DNA病毒.到目前为止,已有100多个已知的HPV型别,其中至少有13个型别可以引起宫颈癌,而且与其他生殖器癌和头颈部肿瘤相关,这些型别被称为"高危型".两个最常见的高危型是HPV16和HPV18,可以引起大约70%左右的宫颈癌.HPV(尤其是HPV6和HPV11)还可以引起生殖器疣,这是一种外生殖器很常见的良性病变,发生率很高.HPV感染是高度传染的,尤其在性生活刚开始的时候,传染性最高.大部分人都会在他们一生的某个时间感染HPV.除了HPV感染以外,引起宫颈癌发生的因素主要还有免疫抑制、多胎生育、初次分娩年龄小、吸烟、长期使用激素类避孕药以及合并感染沙眼衣原体或单纯疱疹病毒等.HPV疫苗来自于病毒样颗粒(virus-like particles,VLPs),通过重组技术来制作完成.它们不含有任何活的生物制品或DNA,因此没有传染性.2006年,美国默克公司生产的四价疫苗(包含有HPV6,11,16和18的VLP)首先获得美国FDA颁发的营业执照;随后,英国葛兰素公司生产的二价疫苗(只包含有HPV16和18的VLP)也在全球许多国家获得营业执照.这些疫苗主要是为了保护人群不感染疫苗中包括的HPV型别及发生相关的疾病,但对于已经感染的人群,疫苗没有任何治疗作用.疫苗在几乎所有被接种的人群中都可以诱导很高的血清抗体水平,而且耐受性很好.疫苗接种组在注射部位发生的副作用比对照组常见,但严重副作用(serious adverse event,SAE)

Human papillomavirus （HPV） is the DNA virus that infects skin or mucosal cells. There are more than 100 known HPV genotypes, at least 13 of which cause cancer of the cervix and are associated with other anogenital cancers and cancers of the head and neck; they are called ＂high-risk＂ genotypes. The two most common genotypes （genotypes 16 and 18） cause appro- ximately 70% of all cervical cancers. HPV （especially genotypes 6 and 11） also causes genital warts, a common benign condition of the external genitalia that causes significant morbidity. HPV is highly transmissible, with peak incidence of infection soon after the beginning of sexual activity. Most people acquire the infection at some time in their life. Factors contributing to development of cervical cancer after HPV infection include immune suppression, multiparity, early age at first delivery, cigarette smoking, long-term use of hormonal contraceptives, and co-infection with Chlamydia trachomatis or Herpes simplex virus. HPV vaccines are prepared from virus-like particles （VLPs）, produced by recombinant technology. They do not contain any live biological product or DNA, so are non-infectious. A quadrivalent vaccine produced by Merck Company, containing VLPs related to HPV genotypes 6, 11, 16 and 18, was firstly licensed in 2006, and a bivalent vaccine produced by GSK company, containing VLPs related to HPV genotypes 16 and 18, was licensed afterwards. The vaccines are designed to prevent infection and disease due to their respective genotypes, and are not designed to treat persons who have already been infected with them. HPV vaccines induce high levels of serum antibodies in virtually all vaccinated individuals and are generally well tolerated. Adverse events at the injection site occur more often in vaccine recipients than controls, but the incidence of serious adverse events （SAEs） was not significantly higher among vaccine recipients in any of the trials.