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

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.