{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T23:19:07Z","timestamp":1789427947792,"version":"build-2803163510"},"reference-count":47,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T00:00:00Z","timestamp":1766707200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T00:00:00Z","timestamp":1766707200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Head &amp; Neck"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Head and neck squamous cell carcinoma (HNSCC) often presents with cervical lymph node metastasis, with 1%\u20134% of cases presenting as cancer of unknown primary (CUP). CUP poses diagnostic and therapeutic challenges and is linked to poorer survival outcomes. Its incidence is expected to rise with the increasing prevalence of HPV\u2010positive HNSCC. This study evaluated the use of MRI,\n                      <jats:sup>18<\/jats:sup>\n                      F\u2010FDG PET, examination under anesthesia (EUA), and TORS\u2010assisted tonsillectomy and tongue base mucosectomy (TORS\u2010TE\/TBM) in the work\u2010up of CUP.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This single\u2010center retrospective study included 79 patients with cytologically confirmed CUP (years 2019\u20132024). HPV\u2010positive (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200951) and HPV\u2010negative (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200928) cases were evaluated separately. Primary tumor detection rates for MRI,\n                      <jats:sup>18<\/jats:sup>\n                      F\u2010FDG PET and EUA were calculated. For HPV\u2010positive tumors TORS\u2010TE\/TBM was additionally evaluated for primary tumor detection.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In HPV\u2010positive cases MRI and\n                      <jats:sup>18<\/jats:sup>\n                      F\u2010FDG PET had detection rates of 45% individually (respectively) and 53% combined. Of detected cases, 37% were identified by a single modality. Post\u2010hoc image review increased the detection rate to 63%. Subsequent imaging\u2010guided EUA had a detection rate of 68%. When TORS\u2010TE\/TBM was performed after negative EUA, tumor detection occurred in 50% of cases. Multimodal work\u2010up resulted in an over\u2010all detection rate of 75%. In contrast, HPV\u2010negative cases had a lower over\u2010all multimodal detection rate of 39%.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      MRI and\n                      <jats:sup>18<\/jats:sup>\n                      F\u2010FDG PET each play a pivotal and complimentary role for the detection of primary tumors in HNSCC CUP. Image\u2010guided EUA and, in selected cases, TORS\u2010TE\/TBM further improve detection. A multimodal approach including expert imaging interpretation is recommended for optimal tumor identification and treatment planning.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hed.70147","type":"journal-article","created":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T11:26:13Z","timestamp":1766748373000},"page":"1426-1436","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Efficacy of Multimodal Work\u2010Up of Head and Neck Squamous Cell Carcinoma Lymph Node Metastasis of Unknown Primary"],"prefix":"10.1002","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0347-1919","authenticated-orcid":false,"given":"Robin W.","family":"Jansen","sequence":"first","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery Amsterdam UMC, Vrije Universiteit Amsterdam  Amsterdam the Netherlands"},{"name":"Department of Radiology and Nuclear Medicine Amsterdam UMC, Vrije Universiteit Amsterdam  Amsterdam the Netherlands"},{"name":"Cancer Center Amsterdam, Imaging and Biomarkers  Amsterdam the Netherlands"},{"name":"Amsterdam UMC VU University Medical Center  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland M.","family":"Martens","sequence":"additional","affiliation":[{"name":"Department of Radiology and Nuclear Medicine Amsterdam UMC, Vrije Universiteit Amsterdam  Amsterdam the Netherlands"},{"name":"Cancer Center Amsterdam, Imaging and Biomarkers  Amsterdam the Netherlands"},{"name":"Amsterdam UMC VU University Medical Center  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Obaida","family":"Abdulrahman","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery Amsterdam UMC, Vrije Universiteit Amsterdam  Amsterdam the Netherlands"},{"name":"Department of Radiology and Nuclear Medicine Amsterdam UMC, Vrije Universiteit Amsterdam  Amsterdam the Netherlands"},{"name":"Amsterdam UMC VU University Medical Center  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Peferoen","sequence":"additional","affiliation":[{"name":"Cancer Center Amsterdam, Imaging and Biomarkers  Amsterdam the Netherlands"},{"name":"Amsterdam UMC VU University Medical Center  Amsterdam the Netherlands"},{"name":"Department of Pathology, Amsterdam UMC, Vrije Universiteit Amsterdam  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. Ren\u00e9","family":"Leemans","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery Amsterdam UMC, Vrije Universiteit Amsterdam  Amsterdam the Netherlands"},{"name":"Amsterdam UMC VU University Medical Center  Amsterdam the Netherlands"},{"name":"Cancer Center Amsterdam, Cancer Biology and Immunology  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerben J. 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