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The report describes the first documented oral case of HPV-related epithelial proliferation during long-term fingolimod treatment. A 36-year-old man developed multiple mildly papillomatous gingival lesions after eight years of fingolimod (Gilenya®) therapy. Histopathology showed parakeratinized stratified squamous epithelium with acanthosis, papillary projections with fibrovascular cores, and koilocytosis. Low-risk HPV types 6/11 were detected, supporting an association potentially related to fingolimod use. The authors expand the anatomic spectrum of HPV-associated epithelial proliferations as a possible adverse effect.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/oral-hpv-related-epithelial-proliferation-during-fingolimod-therapy-first-case-report-and-review-of-the-literature/468119/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/oral-hpv-related-epithelial-proliferation-during-fingolimod-therapy-first-case-report-and-review-of-the-literature/468119.png","ImageObject",300,407,{"name":92,"@type":93},"Noah","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-27","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":34},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What treatment and risk factor are discussed in this case report?","Question",{"text":112,"@type":113},"The patient was receiving long-term fingolimod (Gilenya®) for multiple sclerosis, and the report discusses its immunosuppressive effect as a potential risk factor for HPV-related lesions.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What oral findings and biopsy results were observed?",{"text":117,"@type":113},"The patient had multiple mildly papillomatous gingival lesions. Biopsy showed parakeratinized stratified squamous epithelium with acanthosis, finger-like epithelial projections with fibrovascular cores, and koilocytosis.",{"name":119,"@type":110,"acceptedAnswer":120},"Which HPV types were detected, and how were they tested?",{"text":121,"@type":113},"HPV DNA testing demonstrated low-risk HPV types 6/11. 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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.  \nKeywords Multiple sclerosis · Fingolimod · Gilenya · HPV · Human papilloma virus · Oral  \nIntroduction  \nMultiple sclerosis (MS) is a chronic autoimmune demyelinating disorder of the central nervous system. Disease-modifying therapies (DMTs) are widely used in relapsing-remitting MS to reduce relapse frequency and delay disability progression. Fingolimod, an oral sphingosine-1-phosphate (S1P) receptor modulator, is one such DMT approved for the treatment of relapsing forms of MS. It functions by sequestering naïve and central memory T cells in lymph nodes, thereby reducing peripheral lymphocyte circulation and exerting systemic immunosuppressive effects [1] .  \n􀀍 Kittiphoj Tikkhanarak [kittiphoj-tikkhanarak@uiowa.edu](kittiphoj-tikkhanarak@uiowa.edu)  \n1 Department of Oral Pathology, Radiology and Medicine, College of Dentistry, The University of Iowa, Iowa City, IA, USA  \n2 Greenfield Dental, Greenfield, IA, USA  \nWhile fingolimod effectively controls MS activity [1], it has been associated with an increased risk of opportunistic infections and virus-related complications, including herpes virus infections, cryptococcosis, histoplasmosis, progressive multifocal leukoencephalopathy, hepatitis C reactivation, and Kaposi sarcoma [2] . Moreover, fingolimod has been implicated in the development of human papillomavirus (HPV)-associated lesions [3–7] . Although such lesions have been documented in the cutaneous and anogenital regions of patients undergoing fingolimod therapy, no prior cases have described involvement of the oral mucosa. Herein, we present the first reported case of oral mucosal HPV-related epithelial proliferation in a patient undergoing long-term fingolimod (Gilenya®) therapy.  \nCase presentation  \nA 36-year-old male presented with numerous painless gingival lesions. He had a known history of multiple sclerosis and had been receiving fingolimod (Gilenya®, Novartis Pharmaceuticals Corp., East Hanover, NJ, USA) therapy for eight years. On intraoral examination, multiple sessile and  \npedunculated mucosal-colored lesions with a mildly papillomatous surface were noted along the labial aspects of both maxillary and mandibular gingiva (Fig. 1a), as well asthe lingual anterior and posterior right mandibular gingi","cbCaijAaqu4ZAjW7","https://ap.wps.com/l/cbCaijAaqu4ZAjW7","pdf",2117009,"English","# Abstract\n# Introduction\n# Case presentation\n## Histopathologic and molecular findings","[{\"question\":\"What treatment and risk factor are discussed in this case report?\",\"answer\":\"The patient was receiving long-term fingolimod (Gilenya®) for multiple sclerosis, and the report discusses its immunosuppressive effect as a potential risk factor for HPV-related lesions.\"},{\"question\":\"What oral findings and biopsy results were observed?\",\"answer\":\"The patient had multiple mildly papillomatous gingival lesions. Biopsy showed parakeratinized stratified squamous epithelium with acanthosis, finger-like epithelial projections with fibrovascular cores, and koilocytosis.\"},{\"question\":\"Which HPV types were detected, and how were they tested?\",\"answer\":\"HPV DNA testing demonstrated low-risk HPV types 6/11. High-risk HPV type 16 and p16 immunohistochemistry were negative, and additional PCR-based genotyping on FFPE tissue found no high-risk types including 16, 18, 31, 33, 45, or 58.\"}]","Oral HPV-Related Epithelial Proliferation during Fingolimod Therapy - First Case Report and Review of the Literature | PDF",1790773776,18]