Epidemiologic Impact of HPV Vaccination

项目摘要 预防性人类乳头瘤病毒(HPV)疫苗的引入有可能大幅减少 肛门癌和口咽癌的发病率和死亡率。然而，疫苗临床试验的数据 无法预测疫苗在“真实世界”社区环境中的有效性，以及引入9价疫苗(在 2015年增加2价和4价疫苗以及2016年减少剂量计划(从3剂减少到2剂)可能会 进一步修改疫苗效力。疫苗引进的影响可以高效和准确地 通过评估疫苗有效性、羊群保护、交叉保护的HPV监测研究进行评估 (在基因上与疫苗类型相关的HPV类型减少)，以及类型替换(非疫苗- 由于疫苗种类减少而导致的HPV类型)。我们之前在女性中进行了4项HPV监测研究 (2006-2017)，男性2人(2013-2017)。在女性中，我们发现了疫苗有效性的证据(但是 1剂与3剂的有效性较低)、羊群保护和交叉保护；没有证据表明类型- 替代；以及未接种疫苗的妇女中非疫苗型HPV意外增加。在男人中，我们 发现了疫苗有效性和羊群保护的初步证据。继续调查，通过 拟议的更新对于实现以下目标至关重要：1)评估9价疫苗的效果 引入和减少给药计划对有效性的影响，2)阐明牛群保护的长期趋势， 3)识别交叉保护减弱或出现类型替换的信号，以及4)确定机制 用于未接种疫苗的妇女中非疫苗类型HPV的增加。具体目标是：1)确定长期- 接种疫苗的妇女中4价HPV流行率的长期趋势和9价HPV流行率的新趋势(2006- 2023年)和男性(2013-2023年)，以评估HPV疫苗的有效性，以及在未接种疫苗的女性和男性中 评估羊群保护；2)评估接种疫苗数量的差异影响 疫苗类型HPV，按年龄；3)确定接种疫苗的妇女中非疫苗类型HPV流行的趋势 和男性，以检查持久的交叉保护和新兴类型替代；以及3)探索生物学 以及未接种疫苗的妇女中非疫苗类型HPV增加的行为机制。我们的方法 将招募1600名女性和男性参加另外两项监测研究，以表征 在女性(2006-2023年，N=2400)和男性(2013-2023年)总共6个时间段内接种疫苗 2023年，N=1,600)。这项拟议的研究具有创新性，因为由此产生的数据可能会改变当前的研究 和疫苗接种和病毒学领域的临床实践范例，研究计划利用新的 探索驱动HPV趋势的机制的概念、方法和新方法。建议数 研究意义重大，因为这些数据将为以下方面提供关键证据：1)接种疫苗与宫颈癌 筛查方案；2)公共卫生宣传和降低风险咨询；3)成本效益 分析和政策决策：这些将有助于减少HPV相关癌症造成的差异和死亡率。

Project Summary Introduction of prophylactic human papillomavirus (HPV) vaccines has the potential to dramatically decrease morbidity and mortality from anogenital and oropharyngeal cancers. However, data from vaccine clinical trials cannot predict vaccine effectiveness in “real-world” community settings, and introduction of a 9-valent (in addition to a 2- and 4-valent) vaccine in 2015 and reduced dosing schedules (from 3 to 2 doses) in 2016 could further modify vaccine effectiveness. The impact of vaccine introduction can be efficiently and accurately evaluated by HPV surveillance studies that assess vaccine effectiveness, herd protection, cross-protection (decrease in HPV types genetically related to vaccine types), and type replacement (increase in non-vaccine- type HPV due to a reduction in vaccine types). We previously conducted 4 HPV surveillance studies in women (2006-2017) and 2 in men (2013-2017). Among women, we found evidence for vaccine effectiveness (but lower effectiveness with 1 vs. 3 doses), herd protection, and cross-protection; no evidence for type- replacement; and an unexpected increase in non-vaccine-type HPV in unvaccinated women. Among men, we found preliminary evidence for vaccine effectiveness and herd protection. Continued investigation through the proposed renewal is essential to achieve the following objectives: 1) assess the effects of 9-valent vaccine introduction and reduced dosing schedules on effectiveness, 2) elucidate long-term trends in herd protection, 3) identify signals of diminished cross-protection or emerging type-replacement, and 4) determine mechanisms for increases in non-vaccine-type HPV in unvaccinated women. The specific aims are to: 1) determine long- term trends in 4-valent - and emerging trends in 9-valent - HPV prevalence among vaccinated women (2006- 2023) and men (2013-2023) to assess HPV vaccine effectiveness, and among unvaccinated women and men to assess herd protection; 2) assess the differential impact of the number of vaccine doses received on vaccine-type HPV, by age; 3) determine trends in non-vaccine-type HPV prevalence among vaccinated women and men, to examine for persistent cross-protection and emerging type replacement; and 3) explore biological and behavioral mechanisms for the increase in non-vaccine-type HPV in unvaccinated women. Our approach will be to enroll 1,600 women and men in two additional surveillance studies, to characterize the impact of vaccine introduction across a total of 6 time periods in women (2006-2023, N=2,400) and 4 in men (2013- 2023, N=1,600). The proposed research is innovative because the resulting data could shift current research and clinical practice paradigms in the areas of vaccination and virology, and the research plan utilizes novel concepts, approaches and new methodologies to explore mechanisms driving HPV trends. The proposed research is significant because the data will provide key evidence for: 1) vaccination and cervical cancer screening programs; 2) public health communications and risk-reduction counseling; and 3) cost-effectiveness analysis and policy decisions: these will help to reduce disparities and mortality due to HPV-related cancers.