Genital Health of Trans-males on Testosterone

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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.