Epidemiologic Impact of HPV Vaccination

描述（申请人提供）：预防性人乳头瘤病毒（HPV）疫苗的广泛实施可大幅降低宫颈癌和其他HPV相关疾病的发病率和死亡率。在社区环境中引入疫苗后，有关HPV流行病学趋势的信息对于评估HPV免疫接种计划的进展和人口影响以及为计划和政策决策提供数据至关重要。因此，我们在一个社区广泛引入疫苗之前（2007年;未接种疫苗）和之后三年（2010年; 59%接种疫苗），对约800名13 - 26岁的年轻女性进行了试点HPV监测研究。我们发现：1）所有女性中疫苗型HPV的患病率大幅下降（58%），2）群体保护的证据（即未接种疫苗的女性中疫苗型HPV的患病率下降49%），以及3）可能的类型替代证据（即接种疫苗的女性中非疫苗型HPV的患病率增加25%）。该提案的总体目标是通过确定疫苗类型HPV的变化，表征群体保护，并调查HPV疫苗引入后前九年内可能的类型替代，进一步表征HPV疫苗引入对男性和女性的社区影响。我们将追求以下三个具体目标：（1）确定年轻女性和男性中疫苗型HPV的流行趋势，以a）评估HPV疫苗在社区中引入的流行病学影响，以及B）探索遗传相关HPV类型的流行变化;（2）确定未接种疫苗的年轻女性和男性中疫苗型HPV的流行趋势，为了a）表征和B）检查社区引入疫苗后的畜群保护机制;和（3）确定接种疫苗和未接种疫苗的年轻男女中非疫苗型HPV的流行趋势，为了a）调查和B）检查HPV类型替换的替代（例如统计学）解释。我们计划采用以下方法实现总体目标：我们将在另外两项监测研究中招募13 - 26岁女性（N = 400）和男性（N = 400）的不同样本（总N = 1600），并检查所有四个时间点女性的疫苗接种率和HPV患病率（2007年，2010年，2013年和2016年）和两个时间点（2013年和2016年）。这项研究具有创新性，因为1）它是第一项提供关于在男性和女性中引入HPV疫苗后前九年内疫苗类型HPV，群体保护和类型替代变化的经验数据的研究; 2）这些数据可能会改变目前疫苗开发中的研究和临床实践范式; 3）研究计划采用新的概念、方法和手段来探索畜群保护和类型替代的机制。拟议的研究意义重大，因为它将有助于描述HPV免疫接种计划的社区影响，并提供对计划和政策决策至关重要的数据，以最大限度地提高HPV疫苗接种对公共卫生的影响。

DESCRIPTION (provided by applicant): Widespread implementation of prophylactic human papillomavirus (HPV) vaccines could substantially decrease morbidity and mortality from cervical cancer and other HPV-related diseases. Information about epidemiologic trends in HPV after vaccine introduction in community settings is essential in order to assess the progress and population impact of HPV immunization programs, and to provide data for programmatic and policy decisions. Thus, we conducted pilot HPV surveillance studies among ~800 13-26 year-old young women, before (2007; none vaccinated) and three years after (2010; 59% vaccinated) widespread vaccine introduction in a community. We found: 1) a substantial decline in vaccine-type HPV prevalence among all women (58%), 2) evidence for herd protection (i.e. a decline of 49% in vaccine-type HPV among unvaccinated women), and 3) possible evidence for type-replacement (i.e. an increase of 25% in the prevalence of non- vaccine-type HPV among vaccinated women). The overall objective of this proposal is to further characterize the community-level impact of HPV vaccine introduction, in men as well as women, by determining changes in vaccine-type HPV, characterizing herd protection, and investigating possible type replacement during the first nine years after HPV vaccine introduction. We will pursue the following three specific aims: (1) Determine trends in vaccine-type HPV prevalence among young women and men to a) assess the epidemiologic impact of HPV vaccine introduction in the community, and b) explore changes in the prevalence of genetically-related HPV types; (2) Determine trends in vaccine-type HPV prevalence among unvaccinated young women and men, in order to a) characterize and b) examine mechanisms for herd protection after vaccine introduction in the community; and (3) Determine trends in non-vaccine-type HPV prevalence among vaccinated and unvaccinated young women and men, in order to a) investigate and b) examine alternative (e.g. statistical) explanations for HPV type-replacement. We plan to accomplish the overall objective using the following approach: we will enroll diverse samples of 13-26 year-old women (N=400) and men (N=400) in two additional surveillance studies (total N=1600), and examine vaccination rates and HPV prevalence at all four time points in women (2007, 2010, 2013, and 2016) and two time points in men (2013 and 2016). The proposed research is innovative because 1) it is the first study to provide empirical data concerning changes in vaccine-type HPV, herd protection, and type replacement during the first nine years after HPV vaccine introduction in both men and women; 2) the data could shift current research and clinical practice paradigms in vaccine development; and 3) the research plan utilizes novel concepts, approaches and methodologies to explore mechanisms of herd protection and type-replacement. The proposed research is significant, because it will help to characterize the community-level impact of HPV immunization programs and provide data that are essential for programmatic and policy decisions to maximize the public health impact of HPV vaccination.