Assessing the Effectiveness of HPV Vaccination Uptake Interventions among gbMSM: A Systematic Review Protocol

Introduction

Human papillomavirus (HPV) is the most prevalent sexually transmitted infection (STI) globally (Ejaz et al., 2022). Due to the association of the HPV virus with cervical cancer, HPV is often conceptualised through the lens of women’s sexual health (Chidobem et al., 2022). However, HPV is a sexually transmitted virus affecting all genders and there are more than 200 different HPV types. High-risk types can cause infections that are a major risk factor for oropharyngeal, anal, and penile cancers (Hafeez et al., 2017; Lee Mortensen & Larsen, 2010). Low-risk types can cause genital warts, the most common sexually transmitted disease, which can have effects on a physiological and psychological level for individuals. In the USA, the anal HPV infection prevalence is estimated to be greater than 80% among gbMSM. In addition, the high-risk oncogenic HPV types, 18 and 16, which are responsible for cervical cancer in females, also cause approximately 92% of anal cancers, 63% of penile cancers, and 89% of oropharyngeal and oral cavity cancers in males. Furthermore, incidences of HPV-cancers among gbMSM are 20 times greater compared to heterosexual men (Naidu & Polonijo, 2023).

HPV vaccines are effective and safe regardless of sex when following recommended guidelines (Kjaer et al., 2020; Markowitz et al., 2020; Shiko et al., 2020; Villa et al., 2020). Today, there are three HPV prophylactic recombinant vaccines that are being marketed, which are available on a global level, and have been licensed by the US Food and Drug Administration. These are Cervarix which protects against HPV types 18 and 16 that cause cervical cancer; Gardasil which protects against HPV types 11 and 6, which cause anogenital warts, in addition to HPV types’ 16 and 18; and Gardasil 9 which protects against the HPV types covered by Gardasil and Cervarix and additionally protect against HPV types 31, 33, 45, 52 and 58. There is still no protection coverage for many cancer-causing high-risk HPV types such as 35, 39, 51, 56, 59, 66, and 68 (Koyalta et al., 2021; Nyide et al., 2025).

Various countries initiated the extension of HPV vaccination to gbMSM, including the USA, Canada, England, Scotland and Ireland. Since 2018, gbMSM aged 18-45 in Ireland, have had access to a free three-dose HPV vaccination through sexual health clinics, yet vaccine uptake remains low (Comer et al., 2024). This may in part be due to the fact that despite the incidence and prevalence rates of HPV infection and HPV-related cancers among gbMSM are greater compared to heterosexual men, evidence consistently suggests low levels of knowledge and awareness of HPV among gbMSM (Nadarzynski et al., 2017). It has been argued that this is a result of the gendered nature of the discourse surrounding HPV infections and this is evident through the vaccination programs, the vaccination marketing, and the policy implementations focusing on cervical cancer prevention (Chidobem et al., 2022; Mamo, 2023). Not only is this not aligned with research evidence but it also highlights gender-related biases often leading to an inequitable programmatic emphasis on vaccines for young women and girls (Chido-Amajuoyi et al., 2019; Daley et al., 2017; Dykens et al., 2023) which might negatively impact public awareness of disease inequities and HPV vaccination in males, in particular gbMSM (Okoli et al., 2025).

That said, HPV vaccination uptake among gbMSM is likely also constrained by various psychological, social and systemic factors as outlined by the socio-ecological model of vaccination (Nadarzynski et al., 2021), which provides a comprehensive framework for understanding the multiple and interacting levels that influence vaccine acceptability, initiation, and completion among men who have sex with men (MSM). This model is comprised of five levels -individual, interpersonal, healthcare provider, organizational, and broader community and policy environment- each of which can serve either as a facilitator or as a barrier of vaccination (Nadarzynski et al., 2021). At the individual level, personal motivation to initiate and/or complete the vaccination process is shaped by factors such as disclosure of sexual behaviors and orientation to healthcare providers, existing knowledge of both HPV and HPV vaccination, socioeconomic status, risk perception and perceived efficacy and vaccine importance, sexual health service utilization and anticipated regret, as well as expectations of stigma and discrimination (Nadarzynski et al., 2021). At the interpersonal level, peer and family health education about men who have sex with men and accessibility to LGBT community networks have a significant impact in normalizing health behaviors and shaping vaccination attitudes (Nadarzynski et al., 2021). The healthcare provider level is critical in that vaccine recommendation by a healthcare provider, vaccination benefits awareness, and cultural sensitivity toward gender and sexual minorities are particularly important predictors of vaccination initiation (Nadarzynski et al., 2021). At the organizational and practice setting level, factors such as culturally sensitive educational resources for patients, reminder systems and non-discrimination policies related to gender identity and sexual orientation, and training standards for health professionals on LGBT health disparities help with the vaccination routine care establishment (Nadarzynski et al., 2021). Finally, community environment and the national, state, and local policy environment levels help with the vaccination access establishment and the associated structural conditions, as in the targeted health promotion campaigns, health centers focusing on sexual health of MSM locally, public vaccination financing, and coordination and financing of sexual health services (Nadarzynski et al., 2021). The interventions that we plan to evaluate in the planned systematic review could potentially address any of these factors.

Given the high prevalence of HPV infection, the disproportionate cancer burden among gbMSM, and the persistently low levels of vaccine uptake despite policy inclusion, there is an urgent need for systematic evidence on effective interventions to increase HPV vaccination coverage in this population. While prior studies have examined individual predictors of uptake and general population strategies, no synthesis has specifically appraised interventions targeting gbMSM through a socio-ecological lens. This systematic review and meta-analysis will appraise the effectiveness of HPV vaccination uptake interventions among gbMSM. This review will therefore address a critical gap in the literature by evaluating the effectiveness of HPV vaccination uptake interventions among gbMSM and categorizing them according to their ecological level of influence as outlined in the socio-ecological model of vaccination by Nadarzynski et al. (2021). Ultimately, the findings will inform future research, practice, and policy by identifying promising strategies that address the complex determinants of vaccine uptake in this underserved group.

Materials and methods

This review will be conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (Page et al., 2021) and recommendations from the Methodological Expectations of Cochrane Interventions Reviews (MECIR) (Higgins et al., 2023). The protocol for this systematic review has been registered with PROSPERO under registration number CRD420251141517 (Kelapostolou et al., 2025b). This protocol has been developed in line with the PRISMA-P guidelines (see Appendix A) (Shamseer et al., 2015).

The PICOS Framework (Population, Intervention, Comparison, Outcome, Study design) was used for the formulation of the current systematic review’s research questions, as well as to ensure the inclusion of all relevant components (Richardson et al., 1995).

The research questions are:

Conclusions

This systematic review and meta-analysis will appraise the effectiveness of HPV vaccination uptake interventions among gbMSM globally. By assessing the effectiveness of existing interventions, evidence-based intervention strategies will be identified based on evidence synthesis. Best practices guiding healthcare practitioners, policy makers, and community stakeholders will be highlighted to implement targeted strategies aiming to enhance HPV vaccination uptake and prevent HPV-related health inequalities in gbMSM.