{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T00:53:21Z","timestamp":1793408001562,"version":"4.5.0"},"reference-count":35,"publisher":"American Medical Association (AMA)","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Otolaryngol Head Neck Surg"],"published-print":{"date-parts":[[2025,7,1]]},"abstract":"\n Importance<\/jats:title>\n \n A subset of\n Union for International Cancer Control<\/jats:italic>\n (\n UICC<\/jats:italic>\n )\/\n American Joint Committee on Cancer<\/jats:italic>\n (\n AJCC<\/jats:italic>\n )\n eighth edition<\/jats:italic>\n TNM stage I and II human papillomavirus\u2013positive oropharyngeal carcinoma has undesirable outcomes, which might have contributed to a lack of success in phase III deintensification trials. Refining clinical stage groups, especially in the overabundant cN1\/stage I group, has become important for treatment selection.\n <\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To assess the prognostic importance of pretreatment lymph node (LN) characteristics to optimize case distribution and outcome homogeneity within the N classification system.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This is an international multi-institutional retrospective prognostic cohort study. Analysis of human papillomavirus\u2013positive oropharyngeal carcinoma treated curatively from 4 institutions (International Collaboration of Oropharyngeal Cancer Network for N-Classification [ICON-N] dataset) provided a refined clinical staging proposal; an independent dataset (Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al [CHUM] dataset) validated the proposal. Neuroradiologists reviewed pretreatment computed tomography and\/or magnetic resonance imaging for nodal features, including presence or absence of abnormal LN(s), retropharyngeal LN, laterality, number of abnormal LN, and imaging-detected extranodal extension (iENE). Data were collected from February to May 2023, and data were analyzed from June to July 2023.<\/jats:p>\n <\/jats:sec>\n \n Exposures<\/jats:title>\n Definitive chemoradiotherapy\/radiotherapy or definitive surgery with or without postoperative chemoradiotherapy\/radiotherapy.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n \n The primary end point was overall survival. A Cox proportional hazards multivariable model was used to estimate adjusted hazard ratios (AHRs) and to derive an optimal clinical TNM stage classification (AHR-stage schema) incorporating the strongest prognostic nodal features within the\n UICC\/AJCC eighth edition<\/jats:italic>\n TNM framework after confirming the prognostication of iENE status. The performance (according to overall normalized scores and ranking) of the AHR-stage schema against the current\n UICC\/AJCC eighth edition<\/jats:italic>\n TNM staging system was evaluated for hazard consistency, hazard discrimination, prognostic importance, and sample size balance. Validation was performed in the CHUM dataset.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n The ICON-N dataset comprised 2053 patients, including 1898 (92.5%) with cN-positive disease and 155 (7.5%) with cN0 disease; a total of 298 (14.5%) were female, and the mean (SD) age was 60.6 (9.3) years. iENE-positive disease was identified in 710 of 1898 patients with cN-positive disease (37.4%). The median (range) follow-up was 5.1 (0.1-14.7) years. iENE was the strongest prognostic nodal feature in multivariable analysis; the AHR for iENE-positive vs iENE-positive disease was 2.43 (95% CI, 1.96-3.03) in the ICON-N dataset and 2.04 (95% CI, 1.28-3.23) in the CHUM dataset (n\u2009=\u2009451). Reclassifying iENE-positive cases 1 stratum higher for N categorization without altering iENE-negative cases yielded an AHR-stage schema that outperformed the current TNM staging system in disease-free and overall survival with a lower (ie, better) overall normalized score (2 vs 3).<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n In this study, reclassifying each N category 1 stratum higher for iENE-positive disease resulted in better disease-free and overall survival. The proposed new classification outperformed the currently TNM staging system in risk stratification and may facilitate future clinical trial design, outcomes research, and patient care.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamaoto.2025.0848","type":"journal-article","created":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T11:00:35Z","timestamp":1746702035000},"page":"655","source":"Crossref","is-referenced-by-count":27,"title":["A Proposal for HPV-Associated Oropharyngeal Carcinoma in the Ninth Edition Clinical TNM Classification"],"prefix":"10.1001","volume":"151","author":[{"given":"Shao Hui","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Princess Margaret Cancer Centre, University of 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