Evidence-Based Efficacy and Recommendations for HPV Vaccination in International and National Practice

Background: Human papillomavirus (HPV) is a major causative agent of cervical cancer and other anogenital and oropharyngeal malignancies. Prophylactic vaccination against HPV has proven effective in preventing high-risk HPV infections and their associated precancerous and cancerous lesions. Objective: This article presents a comparative review of the immunogenicity, efficacy, and safety profiles of the quadrivalent (Gardasil 4) and nonavalent (Gardasil 9) HPV vaccines. It synthesizes current clinical guidelines from major health authorities and professional societies in the United States and Europe, and discusses updated national vaccination strategies, with a focus on recent policy changes in Georgia. Methods: A systematic literature search was conducted in PubMed, Cochrane Library, PMC, CDC, and Merck databases for publications from 2019 to 2025. Only peer-reviewed articles and official guidelines were included. Results: Both Gardasil 4 and Gardasil 9 demonstrate equivalent protection against HPV types 6, 11, 16, and 18. Gardasil 9 induces a stronger immune response against five additional oncogenic types (31, 33, 45, 52, 58) and shows higher immunogenicity in the 9–15 age group compared to older cohorts. Network meta-analyses confirm significant reductions in CIN2+ lesions associated with HPV 16 and 18 following vaccination. Recent WHO and ECDC guidelines increasingly favor Gardasil 9 and support simplified dose regimens, including one-dose strategies for population-wide coverage. In Georgia, HPV vaccination is now freely available to females aged 10–45 and males aged 10–26 under a revised national program. Conclusion: Gardasil 9 is the preferred vaccine for broad-spectrum HPV protection. Updated guidelines and evidence support a two-dose schedule for adolescents and a three-dose schedule for older or immunocompromised individuals. Georgia’s expanded HPV vaccination program aligns with global efforts to achieve cervical cancer elimination through equitable access and optimized vaccine strategies.