HPV-related papillary squamous cell carcinoma of the tonsil during treatment with fingolimod

Fingolimod is a commonly used treatment for highly active relapsing-remitting multiple sclerosis (MS). We describe the case of a 50-year old man on fingolimod since 2011 who presented, in April 2017, with a voluminous swelling of the left tonsil. A left tonsillectomy was performed, and histological exam disclosed a papillary squamous cell carcinoma of the palatine tonsil, with an in situ hybridization positive for human papillomavirus (HPV)-16 DNA. Neither lymph nodes involvement nor other metastases were detected. Fingolimod was stopped as a precautionary measure in May 2017, and the patient currently continues his follow up at our Department. Immunocompromised patients are at risk for developing HPV-related malignancies probably in light of the suppression of T-cell immunity, therefore an increased risk for HPV activation in MS patients treated with disease modifying therapies (DMTs) characterized by a more pronounced immunosuppressant activity cannot be excluded. Given the absence of studies on larger cohorts of MS patients exposed to DMTs, additional monitoring for HPV infection during fingolimod treatment is not currently recommended. However, vigilance for this possible association is warranted.