Human papillomavirus in men who have sex with men, transgender women and people living with HIV in Pakistan

Abstract

Background: Anal infection with human papillomavirus (HPV) and associated anal squamous intraepithelial lesions (ASIL), are more prevalent among men who have sex with men (MSM) particularly among MSM and transgender women living with HIV The high prevalence of HIV among MSM and transgender women in Pakistan is a significant health concern and access to screening and health-seeking is often delayed due to stigmatization and discrimination. Anal Papanicolaou (Pap) screening may have utility in the identification of these lesions and is a cost- effective modality for anal cancer prevention among MSM, but no such data are available for Pakistan. Similarly, neither HPV vaccination nor anal-cytology screening is implemented in Pakistan. To design HPV associated health interventions, HPV knowledge and positive attitudes towards uptake of HPV prevention is crucial. This thesis aimed to assess the burden of HPV and HPV related precancerous lesions in Pakistan, to explore knowledge, attitudes and perceived self- risk for HPV and associated illnesses, and to understand the policy perspective and health systems’ capacity and readiness to integrate an HPV preventive care model into existing HIV care and treatment program in Pakistan.

Methods: Cross-sectional studies (paper I and II) were conducted between March 2016 to November 2017 at a sexual health centre run by a local community-based organization and the the center for HIV treatment in Karachi to estimate burden of anal type-specific HPV infection and anal intraepithelial lesions. We recruited 320 MSM and transgender women aged ≥ 18-years who reported anal sex in the preceding 6 months. Anal samples negative for β globin or with insufficient biological material for cytological analyses were excluded. We collected two anal samples for liquid-based cytology and HPV type testing by PCR. Socio-demographic and behavioural data were collected through face-to face interviews. The prevalence of HPV16 DNA infection, ASIL and associated risk factors were analysed through Cox regression for prevalence ratios (PR) and corresponding 95% confidence intervals (CIs).

Study III was conducted between March to August 2019 and recruited 48 MSM and transgender women for focus group discussions from community-based organization. For study IV a total of 18 key informants, at different levels of seniority, were recruited from governmental and non- governmental organizations, high-level infectious disease healthcare managers, and United Nations Program representatives were recruited. Both qualitative studies employed content analysis to identify the manifest and latent themes.

Results: In study I, we observed a 65.1% of overall HPV-DNA prevalence and was higher in participants living with HIV as compared to HIV negative (87% versus 48%; 𝝌2p=<0.001). Likewise, in study II, almost 35% of the study participants had ASIL. ASIL was significantly more common among those living with HIV than in HIV negative ((50/118) 42.4%; vs. (43/153) 28.1%) (p = <0.001). HPV16 was the most common oncogenic HPV type found both in the anal canal (35.1%) and in anal lesions (35.5%), again individuals living with HIV had the highest burden. HIV-status (Prevalence ratio (PR) 2.81; 95% confidence interval (CI) 2.16-3.82) and never-condom-use (PR:3.08; 95% CI 1.69-5.60)) were independently associated with prevalence of “Anal-HPV16 infection” whereas, any HR-HPV type (PR 3.04; 95% CI 1.75-5.26), concurrent sexually transmitted infection (STI) (PR 2.13; CI (1.28–3.55)) and HIV+/HPV+ coinfection (PR 1.75; CI (1.07-2.88)) remained independently associated with ASIL in the multivariate model.

Study III identified three themes in the focus group discussions. 1) Knowledge and risk perceptions about STIs and HPV, 2) Beliefs and attitudes towards HPV prevention, 3) Participant’s recommendations for HPV vaccination and anal Pap screening. The overall knowledge of HPV was poor though, and none of the participants had heard about HPV prevention including vaccination and anal Pap screening for men but expressed a positive attitude towards prevention. In study IV, participants unanimously favoured integration of HPV preventive services into the existing HIV program, but also identified several service delivery barriers including shortage of trained workforce, limited capacity of information technology, lack of supplies needed for screening, lack of financing, and lack of services that could meet the needs of these key-populations.

Conclusions: The findings of this thesis reaffirm the high burden of HPV and associated anal precancerous lesions in MSM and transgender women living with HIV. Current findings support anal Pap-smear HPV screening for this particular group and vaccination efforts for future generations. Educational interventions should be culturally tailored to address the knowledge gaps among key-populations. Moreover, integration of anal cancer screening is dependent on political will, financing, anti-stigma and discrimination interventions, and health system efficiency.