Genital Health of Trans-males on Testosterone

项目摘要/摘要： 变性人中宫颈癌和肛门癌的患病率明显高于顺性人 人类，但生殖器免疫微环境可能阐明癌症潜在的生物学机制 这一人群的发展仍然没有特征。 变性人男性(TM)在出生时被指定为女性，但被认定为男性，并且经常长期服用高剂量 睾丸素(T)。T水平高与顺性人患浸润性宫颈癌的风险更高有关 女性(CF)和顺性人群肛拭子中HPV 16/18DNA的检测风险增加 与男性发生性关系的男性(MSM)。然而，关于T的影响，我们的知识中存在一个关键的缺口 TM患者宫颈和肛门免疫微环境的研究。潜在的易感性机制 发生HPV相关生殖器癌可能包括存在高危基因类型和调节失调。 免疫微环境。 这项建议的目标是评估高危HPV的流行率，并表征生殖器粘膜免疫 TM on T的颈部和肛门室的微环境数据将为临床提供有价值的数据 这些信息将使我们能够评估T的使用，特别是T升高的水平是否会影响生殖器免疫 调节失调、HPV感染和HPV基因型别(高风险与低风险)。 我们通过惠特曼临床研究总监戈尔茨坦博士获得了接触这一人群的独特途径 沃克健康(WWH)，华盛顿特区，积极参与变性人健康研究和联合 这项提案的调查员。我们建议招聘50名在T工作至少2年的TM，并进行比较 50名没有接受任何激素治疗或避孕的种族和年龄匹配的CF组。宫颈和肛门 拭子样本将被收集并分析HR-HPV基因类型、炎症和先天感染的生物标志物 免疫生物标志物的保护。 美国国立卫生研究院资助变性人研究的兴趣越来越大，这一点从 PAR-20-054题为“变性人：艾滋病毒和性传播疾病的免疫、预防和治疗”。我们独一无二 凭借我们在实地的经验和接触这一弱势群体的机会，我们准备对这一标准做出反应。 对这项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 并推动在了解这一人群中HPV相关癌症机制方面的进一步研究。

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.