{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T22:41:09Z","timestamp":1792622469628,"version":"4.5.0"},"reference-count":59,"publisher":"American Medical Association (AMA)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n Nasopharyngeal carcinoma (NPC) presents unique challenges in nonendemic regions, with varying patient characteristics and outcomes compared with endemic populations.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To fill gaps in the current understanding of NPC by focusing on a US population, comparing patient characteristics and treatment outcomes with endemic populations, and identifying key factors to inform management and follow-up protocols in Western health care settings.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This retrospective cohort study included patients with NPC treated at a single large US tertiary academic medical center from 2000 to 2023. The study analyzed patient demographics, tumor characteristics, treatment modalities, and survival outcomes. Data were analyzed from January to July 2024.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n Overall survival (OS), progression-free survival (PFS), and recurrence-free survival, stratified by patient characteristics, tumor types, Epstein-Barr virus (EBV) status, and p16 expression.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The sample included 159 adult patients with NPC (median [range] age, 53.5 [18-90] years; 117 [73.6%] male), with 23 African American patients (15.3%), 21 Asian patients (14.0%), and 106 White patients (70.7%). World Health Organization type III tumors predominated (88 patients [68.8%]), followed by type II (25 patients [19.5%]) and type I (15 patients [11.7%]). EBV positivity rates varied significantly by race (Asian: 13 patients [81.3%]; African American: 17 patients [63.0%]; White: 40 patients [47.0%];\n P<\/jats:italic>\n \u2009=\u2009.03) and WHO type (type III: 50 patients [72.5%]; type II: 10 patients [48.0%]; type I: 0 patients;\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001). p16 status, a proxy for human papillomavirus status, did not vary by race but did vary by histopathologies (type III: 12 patients [28.5%]; type II: 12 patients [63.0%]; type I: 3 patients [43.0%];\n P<\/jats:italic>\n \u2009=\u2009.04). On Kaplan-Meier curves, stratifying p16 by EBV status eliminated its assumed association with OS. Multivariate analysis revealed that increasing age (hazard ratio [HR] per 1-year increase, 1.03 [95% CI, 1.00-1.05];\n P<\/jats:italic>\n \u2009=\u2009.04) and former smoking status (HR, 2.29 [95% CI, 1.03-5.10];\n P<\/jats:italic>\n \u2009=\u2009.04) were associated with inferior OS, while WHO type III tumors were associated with better OS compared with type I (HR, 0.38 [95% CI, 0.17-0.87];\n P<\/jats:italic>\n \u2009=\u2009.02). Male sex was associated with worse PFS (HR, 5.35 [95% CI, 1.23-23.30];\n P<\/jats:italic>\n \u2009=\u2009.03). For recurrence-free survival, former smokers (HR, 25.24 [95% CI, 2.56-249.23];\n P<\/jats:italic>\n \u2009=\u2009.006), current smokers (HR, 44.97 [95% CI, 2.27-892.10];\n P<\/jats:italic>\n \u2009=\u2009.01), and patients with advanced stages (IVa\/b) (HR, 261.34 [95% CI, 3.96-17\u202f258.06];\n P<\/jats:italic>\n \u2009=\u2009.009) had significantly increased risk.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n This cohort study contributes to the evolving body of knowledge on NPC in nonendemic regions, finding a shift toward WHO type III tumors and underscoring the association of EBV status with survival outcomes, while highlighting the lack of association between human papillomavirus status and outcomes. Smoking history, advanced stage at diagnosis, male sex, and increasing age emerged as adverse factors. Notably, WHO type I tumors demonstrated particularly poor outcomes, highlighting the need for more intensive follow-up in this subgroup.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2025.1895","type":"journal-article","created":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T13:01:58Z","timestamp":1742994118000},"page":"e251895","source":"Crossref","is-referenced-by-count":25,"title":["Patient Characteristics and Treatment Outcomes of Nasopharyngeal Carcinoma in Nonendemic Regions"],"prefix":"10.1001","volume":"8","author":[{"given":"Mohammad Bilal","family":"Alsavaf","sequence":"first","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, The Ohio State University Wexner Medical Center, Columbus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Marquardt","sequence":"additional","affiliation":[{"name":"The Ohio State University College of Medicine, Columbus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moataz D.","family":"Abouammo","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, The Ohio State University Wexner Medical Center, Columbus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menglin","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Medical Oncology, The Ohio State University Wexner Medical Center, Columbus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Elguindy","sequence":"additional","affiliation":[{"name":"Division of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Grecula","sequence":"additional","affiliation":[{"name":"Division of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujith","family":"Baliga","sequence":"additional","affiliation":[{"name":"Division of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Konieczkowski","sequence":"additional","affiliation":[{"name":"Division of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emile","family":"Gogineni","sequence":"additional","affiliation":[{"name":"Division of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priyanka","family":"Bhateja","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Medical Oncology, The Ohio State University Wexner Medical Center, Columbus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James W.","family":"Rocco","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, The Ohio State University Wexner Medical Center, Columbus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew O.","family":"Old","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, The Ohio State University Wexner Medical Center, Columbus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dukagjin M.","family":"Blakaj","sequence":"additional","affiliation":[{"name":"Division of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo L.","family":"Carrau","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, The Ohio State University Wexner Medical Center, 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J, Ervik? M, Lam? F, . Global Cancer Observatory: Cancer Today. Accessed February 12, 2025. https:\/\/gco.iarc.who.int\/today"},{"key":"zoi250115r13","unstructured":"Liu? Z. Etiology and early detection of nasopharyngeal carcinoma: an epidemiological approach. Thesis. Karolinska Institutet; 2016. 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