EPIDEMIOLOGY OF HPV-RELATED SCSC IN TRANSPLANT PATIENTS

___^__^^_ HPV相关癌症可能与免疫抑制有关的观察使我们关注这一点。 对长期接受强免疫抑制药物的人群进行竞争性更新 时间，即，肾脏和心脏器官移植患者（OTR）。这些患者的发病率很高， 可能是HPV相关的癌症，鳞状细胞皮肤癌（SCSC）。如果我们不做移植手术 人群是研究免疫抑制对HPV感染影响的最佳模型， HPV和SCSC之间的关联，因为移植患者现在的移植寿命更长， SCSC患病率随着移植后时间的推移而急剧增加，这些患者通常具有多个 侵袭性SCSC肿瘤，并且SCSC将最终影响大多数移植患者。在这个项目中 我们提出了两项互补但独立的基于人群的研究，以探讨HPV在肾功能损害中的作用。 和心脏OTR。我们提出的第一项研究是一项巢式病例对照研究，将能够评估1）如果 存在与SCSC风险增加相关的高危属β HPV类型; 2）是否 移植前HPV抗体预测SCSC;以及3）如果患者风险因素数据（包括日光浴史） 暴露、皮肤类型、眼睛颜色、药物使用和其他暴露）， 与属β HPV类型的测量相结合，可以预测哪些患者的HPV感染风险增加。 SCSC。第二项研究是一项纵向研究，旨在探索HPV感染的动力学， 从移植前的样本开始，在2年的时间内重复收集样本。所有患者 在2008年和2009年移植谁是当地居民将被邀请参加。在这 纵向研究，我们将评估1）是否HPV DNA类型的数量，抗体反应，或病毒 持续性随着移植后时间的推移而增加，以及2）细胞介导的细胞因子水平变化的影响， 免疫力对HPV感染状态的影响（通过HPV的各种标志物测量）。我们的HPV项目 项目组有跨学科合作的长期记录，我们计划开发一个新的 我们的工作方向，采用最近开发的实验室技术，具体研究 属β HPV类型。我们的研究可能有助于更全面地了解属的作用 SCSC中的β HPV类型以及免疫抑制在HPV活化中的作用。如果一个强有力的联系， 可以验证特定的HPV类型和SCSC，可能有证据表明HPV的临床试验 疫苗来改变OTR中SCSC的风险。 本研究将研究鳞状细胞皮肤癌的风险及其与人类的关系。 乳头瘤病毒在高危人群中。如果在这项研究和其他类似的研究中能够显示出明确的联系，未来 这项工作可以探索在不同人群中预防和治疗这种类型的皮肤癌。

___^__^^_ 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.