Age of Acquiring Causal Human Papillomavirus (HPV) Infections: Leveraging Simulation Models to Explore the Natural History of HPV-induced Cervical Cancer
Age of Acquiring Causal Human Papillomavirus (HPV) Infections: Leveraging Simulation Models to Explore the Natural History of HPV-induced Cervical Cancer
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DOI：
10.1093/cid/cix475
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发表时间：
2017-09-15
影响因子：
11.8
通讯作者：
Castle, Philip E.
中科院分区：
文献类型：
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作者：
Burger, Emily A.;Kim, Jane J.;Castle, Philip E.
背景虽然新的人乳头瘤病毒（HPV）感染可以发生在所有年龄，但女性获得发展为宫颈癌的“因果”HPV感染的年龄知之甚少，实际上无法观察到。我们的目的是估计在没有HPV疫苗接种或筛查的情况下，个体获得其致病性HPV感染的年龄分布，以帮助指导两者的最佳使用。使用模拟宫颈癌自然史的经验校准数学模型，我们估计了按年龄、按HPV基因型（HPV 16与其他HPV基因型）分层的致病HPV感染的累积数量，以及替代疫苗接种启动方案（即，例如，年龄9-45岁）。我们的模型预测，在所有宫颈癌中，50%和75%的女性分别在20.6岁（范围：20.1-21.1）和30.6岁（范围：29.6-31.6）时获得HPV感染。HPV 16感染在较早的年龄获得。假设对HPV 16和HPV 18感染的有效性为95%，宫颈癌终生风险的直接降低从9岁接种疫苗的妇女的55%（53-56%）到45岁接种疫苗的妇女的6%（范围：6-7%）不等。第二代疫苗也观察到类似的模式。虽然新的HPV感染和癌前病变可能发生在女性的一生中，但只有一小部分是在中年女性中获得的，并且是疫苗可预防的。我们的模拟强调了使用替代终点进行中年妇女疫苗有效性研究以指导实施政策决策的潜在局限性。
Background. Although new human papillomavirus (HPV) infections can occur at all ages, the age at which women acquire their "causal" HPV infection that develops into cervical cancer is poorly understood and practically unobservable. We aimed to estimate the age distribution at which individuals acquired their causal HPV infection in the absence of HPV vaccination or screening to help guide the optimal use of both.Methods. Using an empirically calibrated mathematical model that simulates the natural history of cervical cancer, we estimated the cumulative number of causal HPV infections by age, stratified by HPV genotype (HPV16 vs. other HPV genotypes), and the direct age-specific reduction in cancer incidence for alternative vaccination initiation scenarios (i. e., age 9-45 years).Results. Our model projected that among all cervical cancers, 50% and 75% of women acquired their causal HPV infection by ages 20.6 (range: 20.1-21.1) and 30.6 (range: 29.6-31.6) years, respectively. HPV16 infections were acquired at an earlier age. Assuming 95% efficacy against HPV16 and HPV18 infections, the direct reduction in lifetime risk of cervical cancer varied from 55% (53-56%) among women vaccinated at age 9 years to 6% (range: 6-7%) among women vaccinated at age 45 years. Similar patterns were observed for the second- generation vaccine.Conclusions. Although new HPV infections and precancers can occur throughout a woman's lifetime, only a small proportion are acquired in mid-adult women and are vaccine-preventable. Our simulations highlight the potential limitations of using surrogate endpoints for vaccine efficacy studies of mid-adult women to guide policy decisions for implementation.