No Increased Risk of Autoimmune Diseases Following HPV Vaccination: A Systematic Review and Meta-Analysis
Filippo Alberto Ferrari,
Enrico Ciminello,
Marcello Ceccaroni,
Matteo Pavone,
Violante Di Donato,
Giorgia Perniola,
Pierluigi Benedetti Panici,
Ludovico Muzii,
Andrea Giannini,
Giuseppe Vizzielli,
Giorgio Bogani,
Giusi Santangelo
Affiliations
Filippo Alberto Ferrari
Department of Obstetrics and Gynecology, Gynecologic Oncology and Minimally Invasive Pelvic Surgery, International School of Surgical Anatomy, IRCCS “Sacro Cuore-Don Calabria” Hospital, Negrar di Valpolicella, 37024 Verona, Italy
Enrico Ciminello
Italian National Institute of Health, Viale Regina Elena 299, 00161 Rome, Italy
Marcello Ceccaroni
Department of Obstetrics and Gynecology, Gynecologic Oncology and Minimally Invasive Pelvic Surgery, International School of Surgical Anatomy, IRCCS “Sacro Cuore-Don Calabria” Hospital, Negrar di Valpolicella, 37024 Verona, Italy
Matteo Pavone
UOC Ginecologia Oncologica, Dipartimento di Scienze per la Salute della Donna e del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli, IRCCS, 00168 Rome, Italy
Violante Di Donato
Department of Gynecological, Obstetrical and Urological Sciences, “Sapienza” University of Rome, 00184 Rome, Italy
Giorgia Perniola
Department of Gynecological, Obstetrical and Urological Sciences, “Sapienza” University of Rome, 00184 Rome, Italy
Pierluigi Benedetti Panici
Department of Gynecological, Obstetrical and Urological Sciences, “Sapienza” University of Rome, 00184 Rome, Italy
Ludovico Muzii
Department of Gynecological, Obstetrical and Urological Sciences, “Sapienza” University of Rome, 00184 Rome, Italy
Andrea Giannini
Department of Gynecological, Obstetrical and Urological Sciences, “Sapienza” University of Rome, 00184 Rome, Italy
Giuseppe Vizzielli
Department of Medicine (DMED), University of Udine, 33100 Udine, Italy
Giorgio Bogani
Gynecological Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, 20133 Milano, Italy
Giusi Santangelo
Department of Gynecological, Obstetrical and Urological Sciences, “Sapienza” University of Rome, 00184 Rome, Italy
Background: HPV vaccination reduces the risk of anogenital warts, high-grade cervical intraepithelial neoplasia (CIN2+), and cervical cancer. To enhance immunogenicity, HPV vaccines include adjuvants such as toll-like receptor agonists, which may theoretically trigger autoimmune responses. However, existing data on this risk remain conflicting. This systematic review and meta-analysis assess the association between HPV vaccination and autoimmune disease onset in post-licensure controlled studies. Methods: A comprehensive literature search was conducted in Scopus, PubMed/MEDLINE, ScienceDirect, and the Cochrane Library from inception to June 2024, following PRISMA guidelines. The study protocol was registered in PROSPERO (CRD42024606834). Results: A total of 356 studies were identified, including cross-reference reviews. Fourteen met inclusion criteria for qualitative and quantitative analysis, encompassing 8,088,838 patients, of whom 2,041,865 received the HPV vaccine. Conclusions: This meta-analysis found no significant association between HPV vaccination and autoimmune disease development. However, further large-scale observational studies are needed, particularly among male recipients, as current evidence is predominantly based on female populations. Future research should also evaluate risks for specific autoimmune disorders to refine the vaccine’s safety profile.
