HPV Infection, Sexually Transmitted Infections and Anal Dysplasia in the Transgender Population

Human papillomaviruses (HPV) are viruses that are widespread in the general population. They are transmitted through direct contact, mainly through sexual intercourse. According to the World Health Organization (WHO) and the International Agency for Research on Cancer (IARC), they are among the most common sexually transmitted infections in the world.

More than 150 types have been described to date. They are traditionally classified into two groups: low-risk oncogenic HPV (low-risk HPV) and high-risk oncogenic HPV (high-risk HPV). Low-risk HPV, the most prevalent being HPV6 and HPV11, is responsible for papillomas such as warts when its tropism is cutaneous and for condyloma acuminata when its tropism is more mucosal. High-risk HPV can cause cancer, the most common type associated with HPV being cervical cancer.

Nearly 100% of cervical cancers are attribuable to HPV, as are 88% of anal cancers and approximately 30% of head and neck cancers (de Martel et al., 2017). HPV types 16 and 18 together account for approximately 70% of cervical cancers worldwide. Persistent HPV infection is a key factor in the progression to carcinogenesis. Co-infections with multiple types of HPV are also a significant risk factor for progression to precancerous lesions and cancer (Trottier, 2006). Co-infection with HIV is also a risk factor for progression to anal or cervical cancer (Adebamowo et al., 2017; Clifford et al., 2016). Thus, populations at high risk of HIV exposure are also at high risk of HR-HPV infection, mainly representing men who have sex with men (MSM), sex workers (SW), and transgender people (TG).

Numerous studies have described the epidemiology of HPV infections in MSM, showing a high prevalence of HR-HPV infections between 80% and 90% in HIV-positive individuals (Nowak et al., 2016; Müller et al., 2016; Ferré et al., 2018) and a very high proportion of individuals infected with multiple HR-HPV types (approximately 85%) (Müller et al., 2016; Ferré et al., 2018). Fewer studies have been conducted in the sex worker population, showing a prevalence of HR-HPV infections between 40% and 58% (Soohoo et al., 2013; Marra et al., 2018; Menon et al., 2017; Ferré et al., 2018). In contrast, very few studies have been conducted in transgender populations. Furthermore, in some of these publications, HPVhr prevalence data are combined for the two key populations studied in these studies, MSM and TG.

The few publications focusing on a specific transgender population were conducted in South America (Peru, Argentina) and showed very high prevalence rates of HPVhr in the anal and anogenital areas, around 97% (dos Ramos Farias et al., 2011; Brown et al., 2016). A recent study of 22 TG individuals showed a high prevalence of anal dysplastic lesions, with low-grade lesions detected in 8 individuals and high-grade lesions in 3 individuals (Kobayashi et al., 2017). Given this high prevalence of 50% for anal dysplasia, the TG population appears to be at risk of developing anal dysplastic lesions, and this needs to be explored in another TG population. Furthermore, to our knowledge, no study has evaluated the concomitant prevalence of HPVhr infection in the anogenital and ENT areas in the transgender population. The Infectious and Tropical Diseases Department at Bichat-Claude Bernard Hospital is particularly involved in the follow-up of transgender people, with a large active caseload participating in clinical research projects (Pommier et al., 2019; Bertin et al., 2019; Phung et al., 2018).

The objective of this project, which is part of a broader sexual health context, is to study the prevalence of various viral and bacterial sexually transmitted infections (STIs) in the key transgender population, for which no data currently exists in France.

Research hypothesis:

HPV prevalence is higher in the transgender population than in other populations described in the literature, particularly among transgender people living with HIV.

A cross-sectional observational study is the most relevant design for meeting the research objective. The participant selection criteria will ensure high external validity. As this is an observational study, the examinations are carried out as part of routine care.

Conduct of the visit:

During the visit, the research team:

• Performs a clinical examination;
• Interviews the patient to gather information on:
• Surgery involving the genital tract, intercurrent conditions, and current treatments (particularly hormone use); Responses to a questionnaire concerning demographic characteristics and lifestyle habits (socioeconomic status, level of education, alcohol, tobacco, and drug use, prostitution, condom use, number of partners in recent months, type of sexual relations, etc.).
• Collect the following information from the medical record:
• For all individuals included: all available previous anatomo-cytopathology and proctology data in order to obtain information on a history of dysplastic lesions;
• For HIV-infected patients: immuno-virological data collected as part of care: latest plasma viral load, latest CD4 cell count, HBV serology, HCV serology, current antiretroviral (ARV) treatment, CD4 cell nadir, duration of ARV treatment, duration of plasma HIV viral load <50 copies/mL, and clinical stage.
• Prescribes and performs the following tests:
• Venous blood sample (2 dry tubes of 5 ml each): HIV serology for HIV-negative participants or those with unknown HIV serological status, and syphilis serology;
• Genital swab: swabbing of the external genitalia;
• Anal swab: swabbing of the anal canal;
• ENT sample: gargling with saline solution
• Screening for bacterial sexually transmitted infections (N gonorrhoeae, C trachomatis) carried out as part of care, therefore only if screening was performed more than 3 months ago or if clinical signs are present: urine sample, rectal swab, throat swab.

Given the study's objectives of investigating the prevalence of HPV and STI infections among transgender people, it is essential to collect data on a number of factors associated with these infections that are recognised in the literature in order to provide an accurate description of the characteristics of the study population on the one hand and of those who test positive on the other. For example, tobacco use is known to be associated with HPV infection. Similarly, drug use is also associated with chemsex and, consequently, with risky sexual behaviour associated with the occurrence of STIs. Therefore, collecting data on participants' drug use and sexual activity is essential for interpreting the biological results.

Samples will be collected from all participants for on-site biological testing. Samples will be taken as part of routine care (regular patient follow-up or consultation) and in accordance with recommendations.

The following tests will be prescribed and performed:

• A genital swab: swabbing of the external genitalia;
• An anal swab: swabbing of the anal canal;
• An ENT sample: gargling with saline solution
• A venous blood sample (2 dry tubes): HIV serology for HIV-negative participants or those with unknown HIV serological status, and syphilis serology;
• Testing for bacterial sexually transmitted infections (N gonorrhoeae, C trachomatis) carried out as part of care, therefore only if screening was performed more than 3 months ago or clinical signs are present: urine sample, rectal swab, throat swab.

The transfer of sample tubes will be carried out in accordance with the internal procedures of the investigation sites, monitored by the CMG team in charge of research management, at the latest when the research is set up at the said sites.

Statistical methods:

Individuals' characteristics will be described for all included subjects. Continuous variables will be described using mean, standard deviation, median, interquartiles values, minimal and maximal values. Qualitative variables will be described using numbers and percentages by modality. Prevalences will be described by proportion and their confidence interval will be calculated under binomial law. All statistical tests will be performed using 5% as significance level. Prevalence of high risk HPV infection in each anatomical site and the concordance of HPV types by anatomical site will be determined using Fleiss Kappa test.