HPVoice: A Single-Blind Three-Arm RCT on Social Media Communication Strategies Among Adolescents in Tuscany, Italy

Introduction Cervical cancer is the first cancer potentially eliminable through widespread HPV vaccination. In Italy, despite free access, vaccine coverage among adolescents remains low. Psychological factors and cognitive biases can influence vaccine decisions and contribute to vaccine hesitancy (VH). While social media offer new avenues for health communication, their effectiveness in reducing VH is uncertain. This study investigates the impact of Instagram-based communication strategies on adolescents’ HPV knowledge and VH.Methods A three-arm randomized controlled trial was conducted in 22 high school classes in Tuscany, Italy, involving 526 students. Classes were assigned to one of three Instagram accounts: a neutral control, an information-based, or a bias-aware information. After three weeks (T2), students completed a follow-up survey, followed by an in-class lesson. Surveys were administered at baseline (T1), post-intervention (T2), and three-month follow-up (T3).Results The final analysis included 301 students (mean age 15.2, 74% female). At T1, VH and knowledge scores were low (mean VH = 40%; knowledge score = 27%), and 47.9% reported likely seeking information from sexual and reproductive services. No significant changes in VH or knowledge were found at T2 overall. However, in students with low information avoidance (IA), the info-based page reduced VH significantly compared to the control (-6.9%, p = 0.009). In contrast, among high-IA students, the same intervention increased VH (estimate: +8.9%, p = 0.002). Willingness to seek information increased in the info group among low-IA students (+1.639 vs. control, p = 0.034). At T3, we measured the impact of an in-person lecture on students’ HPV and HPV vaccination literacy. A significant increase of knowledge compared to T1 is observed despite the smaller sample collected.Conclusion Social media campaigns alone may not effectively reduce VH in adolescents and can even backfire among high-IA individuals. Future strategies should incorporate personalized, bias-aware messaging and interactive tools to address VH and improve HPV vaccine uptake more effectively.