{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T08:48:54Z","timestamp":1784018934225,"version":"3.55.0"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2019,3,6]],"date-time":"2019-03-06T00:00:00Z","timestamp":1551830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Juvenile-onset recurrent respiratory papillomatosis (JO-RRP) is a human papilloma virus-mediated progressive benign neoplasm that affects children and young adults. Primary management consists of regular surgical debulking to maintain airway patency and vocal function. Like condyloma acuminata, JO-RRP is associated with immune dysregulation, and T cells isolated from papillomas express an anergic phenotype. Therefore, we hypothesized that programmed death protein 1 axis inhibition could stabilize tumor growth.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Materials and Methods<\/jats:title>\n                  <jats:p>We treated two patients with refractory JO-RRP using nivolumab, with the primary objective of assessing clinical activity. We explored baseline papilloma features using immunohistochemistry and comprehensive genomic profiling.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Both patients experienced symptomatic improvement, and interval laryngoscopies revealed a reduction in papillomatosis burden. One patient has not required subsequent surgical debridement for almost 2\u2009years. On pathologic examination of pretreatment papillomas from both cases, infiltrating T cells were evident in the papilloma stroma, and papilloma programmed death ligand 1 expression was absent. Papilloma mutational load ranged between three and six mutations per megabase for each case. From on-treatment biopsy tissue, a higher amount of intraepithelial T cells and programmed death ligand 1 expression were detected in the papilloma.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Nivolumab appears to have promising activity in JO-RRP, and further clinical investigation with more patients in clinical trials is warranted.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1634\/theoncologist.2018-0505","type":"journal-article","created":{"date-parts":[[2019,3,6]],"date-time":"2019-03-06T19:51:31Z","timestamp":1551901891000},"page":"829-835","source":"Crossref","is-referenced-by-count":13,"title":["Clinical Activity of Nivolumab for Human Papilloma Virus-Related Juvenile-Onset Recurrent Respiratory Papillomatosis"],"prefix":"10.1093","volume":"24","author":[{"given":"Ben C.","family":"Creelan","sequence":"first","affiliation":[{"name":"Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Usman","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Morsani College of Medicine, University of South Florida, Tampa, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank J.","family":"Kaszuba","sequence":"additional","affiliation":[{"name":"Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farah K.","family":"Khalil","sequence":"additional","affiliation":[{"name":"Department of Anatomic Pathology, H. 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