Genital Health of Trans-males on Testosterone

项目摘要/摘要： 变性人群中宫颈癌和肛门癌的患病率明显高于顺性别人群 人，但生殖器免疫微环境可能阐明癌症的潜在生物学机制 该人群的发展仍然没有特点。 跨性别男性 (TM) 出生时被指定为女性，但实际上却是男性，并且通常长期服用高剂量药物 睾酮（T）。高水平的 T 与顺性别患浸润性宫颈癌的风险增加有关 女性 (CF) 和顺性别肛门拭子中检测人乳头瘤病毒 (HPV) 16/18 DNA 的风险增加 男男性行为者 (MSM)。然而，对于 T 的影响，我们的知识存在严重差距。 TM 中宫颈和肛门免疫微环境的影响。易感性的潜在机制 与 HPV 相关的生殖器癌症的发生可能包括高风险基因型和失调的存在 免疫微环境。 本提案的目标是评估高危 HPV 患病率并表征生殖器粘膜免疫 TM on T 的颈部和肛门区室的微环境。生成的数据将为临床提供有价值的信息 这些信息使我们能够评估 T 的使用，特别是 T 升高的水平是否会影响生殖器免疫 失调、HPV 感染和 HPV 基因型（高风险与低风险）。 我们通过惠特曼临床研究总监戈德斯坦博士拥有独特的接触这一人群的机会 Walker Health (WWH)，华盛顿特区，积极参与跨性别健康研究，并共同 此项提案的调查员。我们建议招募 50 名在 T 上工作至少 2 年的 TM 并进行比较 由 50 名种族和年龄相匹配的 CF 组成的小组，他们没有接受任何激素治疗或避孕措施。宫颈和肛门 将收集拭子样本并分析 HR-HPV 基因型、炎症和先天性生物标志物 保护的免疫生物标志物。 美国国立卫生研究院 (National Institutes of Health) 对资助跨性别研究的兴趣日益浓厚，这一点可以从 PAR-20-054 标题为“变性人：艾滋病毒和性传播感染的免疫、预防和治疗”。我们是独一无二的 凭借我们在该领域的经验以及接触这一弱势群体的机会，我们准备对这一 PAR 做出回应。 对本研究获得的数据的评估将为我们提供基线病毒学和免疫学信息 并促进进一步研究了解该人群中 HPV 相关癌症的机制。

Project Summary/Abstract: The prevalence of cervical and anal canceris significantly higher in the transgender populationrelative to cisgender people, yet the genital immune microenvironment that may elucidate underlying biological mechanisms of cancer development in this population remains uncharacterized. Transgender males (TM) are assigned female at birth but identify as male, and often are on long-term high doses of testosterone (T). High levels of T have been linked to greater risk of invasive cervical carcinoma in cisgender females (CF) and increased risk for detecting Human papilloma virus (HPV) 16/18 DNA in anal swabs in cisgender males who have sex with men (MSM). However, a critical gap in our knowledge exists regarding the effects of T on the cervical and anal immune microenvironment in TM. Potential mechanisms underlying susceptibility of developing HPV-associated genital cancers can include the presence of high-risk genotypes and dysregulated immune microenvironment. This goal of this proposal is to evaluate high risk HPV prevalence and characterize the genital mucosal immune microenvironment in cervical and anal compartments of TM on T. Data generated will provide valuable clinical information that would allow us to evaluate if T use, and specifically the level of T elevation, impacts genital immune dysregulation, HPV infection and HPV genotype (high vs low risk). We have unique access to this population through Dr. Goldstein, the Director of Clinical Research at Whitman Walker Health (WWH), Washington DC, who is actively involved in transgender health research and a co- investigator on this proposal. We propose to recruit 50 TM who are on T for at least 2 years and a comparison group of 50 race- and age-matched CF who are not on any hormonal therapy or contraceptives. Cervical and anal swab samples will be collected and analyzed for HR-HPV genotypes, biomarkers of inflammation and innate immune biomarkers of protection. There is a growing interest in the National Institutes of Health to fund transgender research as evidenced by the PAR-20-054 titled “Transgender People: Immunity, Prevention, and Treatment of HIV and STIs”. We are uniquely poised to respond to this PAR by virtue of our experience in the field and access to this vulnerable population. Assessment of data obtained fromthis study will provide us with baseline virological and immunological information and spur further research in understanding mechanisms in HPV-associated cancers in this population.