Oral HPV-Related Epithelial Proliferation during Fingolimod Therapy: First Case Report and Review of the Literature

Abstract Fingolimod, an immunomodulatory agent used in the treatment of multiple sclerosis, has been associated with an increased risk of human papillomavirus (HPV)-related mucocutaneous lesions due to its immunosuppressive effects. We report the first documented case of oral mucosal HPV-related epithelial proliferation in a patient undergoing long-term fingolimod therapy. A 36-year-old male presented with multiple mildly papillomatous gingival lesions, during ongoing fingolimod (Gilenya ® ) therapy for eight years. Histopathologic examination revealed parakeratinized stratified squamous epithelium with acanthosis, papillary projections supported by fibrovascular cores, and koilocytosis. HPV DNA testing demonstrated the presence of low-risk HPV types 6/11. The clinical presentation, histopathologic features, and supporting laboratory findings, in the context of long-term immunomodulatory therapy, were consistent with an HPV-related epithelial proliferation potentially associated with fingolimod use. This case expands the anatomic spectrum of HPV-associated epithelial proliferations as a potential adverse effect of fingolimod therapy in patients with multiple sclerosis, broadening clinical awareness beyond the reported cutaneous and anogenital presentations.