Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy.
Department of Human Sciences, Society and Health, University of Cassino and Southern Lazio, Cassino, Italy.
Int J Womens Health. 2014 Dec 3;6:999-1010. doi: 10.2147/IJWH.S50365. eCollection 2014.
In this paper, we review the published evidence about the long-term efficacy of the available human papillomavirus (HPV) vaccines and their safety profile. Two prophylactic HPV vaccines - bivalent (bHPV) and quadrivalent (qHPV) - are now available, and vaccination programs are being widely implemented, primarily targeting adolescent girls. Efficacy has been widely demonstrated for both vaccines. Since the risk of HPV exposure potentially persists throughout a woman's sexual life, vaccine duration of protection is critical to overall effectiveness. Interpreting the results of long-term efficacy studies for the two HPV vaccines can be puzzling, due to the heterogeneity of studies, different methods used in the assessment of immunogenicity, histopathological and virological end points, and statistical power issues. Moreover, an immunologic correlate of protection has not yet been established, and it is unknown whether higher antibody levels will really result in a longer duration of protection. Disease prevention remains the most important measure of long-term duration of vaccine efficacy. To date, the longest follow-up of an HPV vaccine has been 9.4 years for the bHPV vaccine. Long-term follow-up for qHPV vaccine goes up to 8 years. The vaccine continues to be immunogenic and well tolerated up to 9 years following vaccination. All randomized controlled clinical trials of the bHPV and the qHPV vaccines provide evidence of an excellent safety profile. The most common complaint reported is pain in the injection site, which is self-limiting and spontaneously resolved. The incidence of systemic adverse events (AEs), serious AEs, and discontinuations due to a serious AE reported in clinical studies are similar between the two vaccines and their control groups. In particular, no increased risk of autoimmune disease has been shown among HPV-vaccinated subjects in long-term observation studies. As these are crucial topics in HPV vaccination, it is important to establish systems for continued monitoring of vaccine immunogenicity, efficacy, and safety over time.
本文综述了现有关于可获得的人乳头瘤病毒（HPV）疫苗的长期疗效及其安全性的研究证据。目前已有两种预防性 HPV 疫苗——二价（bHPV）和四价（qHPV）——可供使用，并且疫苗接种计划正在广泛实施，主要针对青少年女孩。这两种疫苗的疗效都得到了广泛证实。由于 HPV 暴露的风险可能会持续存在于女性的整个性生活中，因此疫苗的保护持续时间对于整体效果至关重要。由于研究的异质性、免疫原性评估方法的不同、组织病理学和病毒学终点以及统计学效力问题，解读这两种 HPV 疫苗的长期疗效研究结果可能会令人困惑。此外，尚未确定保护的免疫相关性，也不知道更高的抗体水平是否真的会导致更长的保护持续时间。疾病预防仍然是衡量疫苗长期疗效的最重要措施。迄今为止，bHPV 疫苗的最长随访时间为 9.4 年。qHPV 疫苗的长期随访时间长达 8 年。疫苗在接种后 9 年内仍保持免疫原性和良好耐受性。bHPV 和 qHPV 疫苗的所有随机对照临床试验都提供了安全性良好的证据。报告的最常见的不良反应是注射部位疼痛，这种疼痛是自限性的，会自行缓解。在临床试验中报告的 bHPV 和 qHPV 疫苗及其对照组的全身不良事件（AE）、严重 AE 和因严重 AE 而停药的发生率相似。特别是，在长期观察研究中，HPV 疫苗接种者没有显示出自身免疫性疾病风险增加。由于这些是 HPV 疫苗接种的关键问题，因此建立系统以随着时间的推移持续监测疫苗的免疫原性、疗效和安全性非常重要。
