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Background: Human papillomavirus (HPV) vaccination is a proven and effective tool for preventing several types of #Cancers, yet vaccination rates among young adults remain suboptimal, particularly among those not enrolled in 4-year colleges. This population can be more difficult to reach due to fewer established institutional touchpoints, limited engagement with campus-based health services, and greater variability in access to preventive care. At the same time, social media has become a dominant source of information for young adults, with TikTok (ByteDance) emerging as one of the most widely used platforms. Approximately 41% of TikTok’s users are between the ages of 16 and 24 years, making it a potentially important channel for public health communication. However, little is known about how noncollege young adults perceive HPV-related content on TikTok, or how influencers themselves view their role in communicating about vaccination. Objective: This study explored the perspectives of young adults and TikTok influencers regarding the dissemination and reception of HPV vaccine information on TikTok. The goal was to assess the potential of leveraging influencers as trusted messengers for this hard-to-reach population. Methods: Researchers conducted 5 focus groups with noncollege young adults, stratified by gender and vaccination status. Each group included 5-8 participants, resulting in a total of 34 individuals. Participants who reported being extremely hesitant about the HPV vaccine were excluded to focus on those more receptive to information. In parallel, researchers recruited 9 TikTok influencers who reached audiences aged 18-25 years and conducted in-depth individual interviews. Influencers represented a diverse mix of identities, follower counts, and content genres, providing varied perspectives on engagement with health-related topics. Results: Across the focus groups, young adults described regularly encountering or actively seeking health-related information online, with TikTok emerging as a primary or supplementary source for some. However, very few participants reported seeing content specifically related to HPV vaccination. Despite this gap, most expressed openness to such content if it was delivered in a relatable, authentic manner and included concise, relevant facts. Influencers echoed the importance of authenticity, emphasizing that their credibility is grounded in genuine connections with their audiences. Many described frequent, meaningful exchanges with followers about sensitive issues, suggesting comfort in addressing health topics. Influencers noted that they would be willing to share HPV-related content under certain conditions, including alignment with existing content, personal relevance, or participation in a structured campaign or partnership. Conclusions: Findings suggest that TikTok may be a promising platform to engage noncollege young adults in HPV vaccination messaging. The strong parasocial relationships influencers maintain with their audiences could position them as effective messengers on sensitive health topics. Strategic collaborations with influencers, coupled with carefully crafted, authentic content, may help bridge communication gaps and support increased awareness of HPV vaccination in this underserved population.

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