{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T13:16:42Z","timestamp":1791465402271,"version":"4.3.4"},"reference-count":100,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"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;amp; Neck"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>In patients with locally advanced, non\u2010metastatic oropharyngeal squamous cell carcinoma (OPSCC), surgery\u2010based and nonsurgical treatment approaches have not been adequately compared in randomized Phase III clinical trials. Current clinical guidelines recommend various surgical and nonsurgical strategies across disease stages for both p16\u2010negative and p16\u2010positive OPSCC, without clearly favoring a single approach.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This review summarizes the available evidence relevant to clinical decision\u2010making between primary surgical and primary nonsurgical treatment approaches in patients with non\u2010metastatic OPSCC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We reviewed studies evaluating tumor control across different treatment modalities, with emphasis on the highest\u2010quality available evidence and post\u2010treatment quality of life (QoL). Outcomes were discussed in relation to disease extent (early\u2010stage vs. locally advanced) and treatment approaches. Emerging therapeutic strategies with the potential to improve the efficacy\u2010to\u2010toxicity ratio were also reviewed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In the absence of Phase III randomized trials in non\u2010metastatic OPSCC, the most informative comparative data derive from studies employing propensity score matching to reduce selection bias. These analyses suggest that survival outcomes are largely comparable between surgery\u2010based and nonsurgical approaches in both p16\u2010positive and p16\u2010negative OPSCC. With respect to post\u2010treatment QoL, surgery alone is generally associated with the lowest toxicity burden, whereas surgery followed by adjuvant (chemo)radiotherapy and definitive (chemo)radiotherapy demonstrate broadly comparable, albeit modality\u2010specific, toxicity and QoL profiles. p16\u2010positive status is consistently associated with more favorable post\u2010treatment QoL. De\u2010escalation strategies in p16\/HPV\u2010associated OPSCC, as well as emerging modalities such as immune checkpoint inhibitors, proton therapy, and adaptive radiotherapy, may influence future treatment paradigms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In the absence of clear differences in oncologic efficacy between primary surgical and nonsurgical approaches, treatment selection should be guided primarily by anticipated toxicity and its impact on QoL, within the context of multidisciplinary assessment and patient preferences. The influence of treatment costs in the decision\u2010making process varies across healthcare systems, reflecting differences in the valuation and financing of health interventions. The role of emerging treatment strategies in OPSCC will need to be defined through prospective, disease\u2010specific clinical trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hed.70356","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T05:41:18Z","timestamp":1782193278000},"page":"2541-2556","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Non\u2010Metastatic Squamous Cell Carcinoma of the Oropharynx: Primary Surgery or (Chemo)radiotherapy?"],"prefix":"10.1002","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0445-112X","authenticated-orcid":false,"given":"Primo\u017e","family":"Strojan","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology Institute of Oncology Ljubljana  Ljubljana Slovenia"},{"name":"Faculty of Medicine University of Ljubljana  Ljubljana Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avraham","family":"Eisbruch","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"June","family":"Corry","sequence":"additional","affiliation":[{"name":"Division Radiation Oncology GenesisCare Radiation Oncology, St. Vincent's Hospital Melbourne  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5540-4796","authenticated-orcid":false,"given":"Sandra","family":"Nuyts","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Radiotherapy, Department of Oncology KU Leuven  Leuven Belgium"},{"name":"Department of Radiation Oncology University Hospitals Leuven  Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pim","family":"de Graaf","sequence":"additional","affiliation":[{"name":"Department of Radiology and Nuclear Medicine Amsterdam UMC Location Vrije Universiteit Amsterdam  Amsterdam the Netherlands"},{"name":"Cancer Center Amsterdam, Imaging and Biomarkers  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0481-156X","authenticated-orcid":false,"given":"Luiz P.","family":"Kowalski","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Surgery and Otorhinolaryngology A.C. Camargo Cancer Center  S\u00e3o Paulo Brazil"},{"name":"Department of Head and Neck Surgery Universidade de S\u00e3o Paulo Medical School  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan J.","family":"Beitler","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Winship Cancer Institute of Emory University  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1721-0680","authenticated-orcid":false,"given":"Sweet Ping","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Austin Health  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William M.","family":"Mendenhall","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology University of Florida  Gainesville Florida USA"},{"name":"University of Florida Health Cancer Center  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4050-9106","authenticated-orcid":false,"given":"M. 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