EPIDEMIOLOGY OF HPV-RELATED SCSC IN TRANSPLANT PATIENTS

_^__^_ 观察到HPV相关癌症可能与免疫抑制有关，这让我们关注这一点 长期接受强免疫抑制药物治疗的人群的竞争性更新 时间的长短，即肾和心脏器官移植患者(OTR)。这些患者的发病率很高。 可能是一种与HPV相关的癌症--鳞状细胞皮肤癌(SCSC)。我们假设移植 人群是研究免疫抑制对HPV感染影响的最佳模型 HPV和SCSC之间的关系因为移植患者现在通过移植可以活得更长， 自移植以来，SCSC的患病率随着时间的推移而急剧增加，这些患者往往具有多发性和多发性 侵袭性的SCSC肿瘤，SCSC最终会影响到大多数移植患者。在这个项目中 我们提出了两个互补但独立的基于人群的研究，以调查HPV在肾脏中的作用。 和心脏OTR。我们建议的第一项研究是嵌套式病例对照研究，将能够评估1) 有一些高危的乙型HPV类型与SCSC的风险增加有关；2)是否 移植前的HPV抗体预测SCSC；以及3)患者的危险因素数据(包括SUN病史 暴露、皮肤类型、眼睛颜色、药物使用和其他暴露)在面对面采访中收集并 结合β属HPV类型的测量，共同预测哪些患者患上HPV的风险增加 SCSC。第二项研究是一项纵向研究，旨在探索HPV感染的动力学。 在两年内重复采集样本，从移植前的样本开始。所有患者 2008年和2009年迁入的当地居民将被邀请参加。在这 纵向研究我们将评估1)HPV DNA类型的数量、抗体反应或病毒 自移植以来，持久性随时间的延长而增加；2)细胞介导性水平的变化的影响 随着时间的推移，对HPV感染状态(通过各种HPV标志物衡量)的免疫力。我们的HPV计划 项目组在跨学科协作方面有着长期的记录，我们计划开发一种新的 我们的工作方向，采用了最近开发的专门针对研究的实验室技术 人乳头瘤病毒属..我们的研究可能有助于更全面地理解属的作用。 SCSC中的β-HPV类型及免疫抑制在HPV激活中的作用。如果两者之间有很强的联系 可以验证特定的HPV类型和SCSC，可能有证据建议进行HPV临床试验 疫苗以降低OTR中SCSC的风险。 这项研究将研究鳞状细胞皮肤癌的风险及其与人类的关系 高危人群中的乳头瘤病毒。如果在这项研究和其他类似的研究中可以显示出明确的联系，未来 这项工作可以探索在不同人群中预防和治疗这种皮肤癌。

___^__^^_ The observation that HPV-related cancers may be linked to immunosuppression has led us to focus this competitive renewal on a population that is receiving strong immunosuppressive drugs for extended periods of time, i.e., renal and cardiac organ transplant patients (OTR). These patients experience a high incidence of what may be an HPV-associated cancer, squamous cell skin cancer (SCSC). We posit that transplant populations are the best model to study the effect of immunosuppression on HPV infection and the association between HPV and SCSC because transplant patients are now living longer with theirtransplants, the prevalence of SCSC sharply increases with time since transplant, these patients often have multiple and aggressive SCSC tumors, and SCSC will ultimately affect the majority of transplant patients. In this project we propose two complementary but separate population-based studies to investigate the role of HPV in renal and cardiac OTR. The first study we propose is a nested case-control study that will be able to assess 1) if there are high-risk genus beta HPV types that are associated with an increased risk of SCSC; 2) whether pre-transplant HPV antibodies predict SCSC; and 3) if patient risk factor data (including history of sun exposure, skin type, eye color, medication use, and other exposures) gathered in an in-person interview and integrated with measures of genus beta HPV types together predict which patients are at increased risk of SCSC. The second study is a longitudinal study designed to explore the kinetics of HPV infection with repeated sample collection over a 2-year period, starting with a pre-transplant sample. All patients transplanted in 2008 and 2009 who are residents of the local area will be invited to participate. In this longitudinal study we will assess 1) whether the number of HPV DNA types, antibody response, or viral persistence increases with time since transplant and 2) the effect of changes in levels of cell-mediated immunity on HPV infection status (as measured by various markers of HPV) over time. Our HPV Program Project group has a long track record of interdisciplinary collaboration, and we plan to develop a new direction for our work that employs recently developed laboratory techniques that are specific to studying genus beta HPV types.. Our studies may contribute to a more complete understanding of the role of genus beta HPV types in SCSC and the role immunosuppression plays in HPV activation. If a strong link between specific HPV types and SCSC can be verified, there may be evidence to suggest clinical trials of HPV vaccines to modify the risk of SCSC in OTR. Lay Summary: This study will examine the risk of squamous cell skin cancer and its relationship to human papillomavirus in a high-risk group. If a clear association can be shown in this study and others like it, future work could explore prevention and treatment of this type of skin cancer in different populations.