{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:12:13Z","timestamp":1791245533247,"version":"4.1.0"},"reference-count":35,"publisher":"American Medical Association (AMA)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Otolaryngol Head Neck Surg"],"published-print":{"date-parts":[[2026,1,1]]},"abstract":"\n Importance<\/jats:title>\n \n Although not included in the eighth edition of the\n American Joint Committee on Cancer Staging System<\/jats:italic>\n , there is growing evidence suggesting that imaging-based extranodal extension (iENE) is associated with worse outcomes in HPV-associated oropharyngeal carcinoma (OPC). Key challenges with iENE include the lack of standardized criteria, reliance on radiological expertise, and interreader variability.\n <\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To develop an artificial intelligence (AI)\u2212driven pipeline for lymph node segmentation and iENE classification using pretreatment computed tomography (CT) scans, and to evaluate its association with oncologic outcomes in HPV-positive OPC.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n \n This was a single-center cohort study conducted at a tertiary oncology center in Montreal, Canada, of adult patients with HPV-positive cN\n +<\/jats:sup>\n OPC treated with up-front (chemo)radiotherapy from January 2009 to January 2020. Participants were followed up until January 2024. Data analysis was performed from March 2024 to April 2025.\n <\/jats:p>\n <\/jats:sec>\n \n Exposures<\/jats:title>\n Pretreatment planning CT scans along with lymph node gross tumor volume segmentations performed by expert radiation oncologists were extracted. For lymph node segmentation, an nnU-Net model was developed. For iENE classification, radiomic and deep learning feature extraction methods were compared.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n iENE classification accuracy was assessed against 2 expert neuroradiologist evaluations using area under the receiver operating characteristic curve (AUC). Subsequently, the association of AI-predicted iENE with oncologic outcomes\u2014ie, overall survival (OS), recurrence-free survival (RFS), distant control (DC), and locoregional control (LRC)\u2014was assessed.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Among 397 patients (mean [SD] age, 62.3 [9.1] years; 80 females [20.2%] and 317 males [79.8%]), AI-iENE classification using radiomics achieved an AUC of 0.81. Patients with AI-predicted iENE had worse 3-year OS (83.8% vs 96.8%), RFS (80.7% vs 93.7%), and DC (84.3% vs 97.1%), but similar LRC. AI-iENE had significantly higher Concordance indices than radiologist-assessed iENE for OS (0.64 vs 0.55), RFS (0.67 vs 0.60), and DC (0.79 vs 0.68). In multivariable analysis, AI-iENE remained independently associated with OS (adjusted hazard ratio [aHR], 2.82; 95% CI, 1.21-6.57), RFS (aHR, 4.20; 95% CI, 1.93-9.11), and DC (aHR, 12.33; 95% CI, 4.15-36.67), adjusting for age, tumor category, node category, and number of lymph nodes.<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n This single-center cohort study found that an AI-driven pipeline can successfully automate lymph node segmentation and iENE classification from pretreatment CT scans in HPV-associated OPC. Predicted iENE was independently associated with worse oncologic outcomes. External validation is required to assess generalizability and the potential for implementation in institutions without specialized imaging expertise.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamaoto.2025.3225","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T16:30:20Z","timestamp":1759249820000},"page":"7","source":"Crossref","is-referenced-by-count":11,"title":["Artificial Intelligence Model for Imaging-Based Extranodal Extension Detection and Outcome Prediction in Human Papillomavirus\u2212Positive Oropharyngeal Cancer"],"prefix":"10.1001","volume":"152","author":[{"given":"Gabriel S.","family":"Dayan","sequence":"first","affiliation":[{"name":"Division of Otolaryngology\u2013Head and Neck Surgery, Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al (CHUM), Universit\u00e9 de Montr\u00e9al, Quebec, Canada"},{"name":"Research Center of CHUM, Universit\u00e9 de Montr\u00e9al, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gautier","family":"H\u00e9nique","sequence":"additional","affiliation":[{"name":"Research Center of CHUM, Universit\u00e9 de Montr\u00e9al, Quebec, Canada"},{"name":"Department of Computer and Software Engineering, Polytechnique Montr\u00e9al, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Houda","family":"Bahig","sequence":"additional","affiliation":[{"name":"Research Center of CHUM, Universit\u00e9 de Montr\u00e9al, Quebec, Canada"},{"name":"Division of Radiation Oncology, Department of Radiology, Radiation Oncology and Nuclear Medicine, CHUM, Universit\u00e9 de Montr\u00e9al, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristoff","family":"Nelson","sequence":"additional","affiliation":[{"name":"Division of Radiology, Department of Radiology, Radiation Oncology and Nuclear Medicine, CHUM, Universit\u00e9 de Montr\u00e9al, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Coralie","family":"Brodeur","sequence":"additional","affiliation":[{"name":"Research Center of CHUM, Universit\u00e9 de Montr\u00e9al, Quebec, Canada"},{"name":"Department of Computer and Software Engineering, Polytechnique Montr\u00e9al, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Apostolos","family":"Christopoulos","sequence":"additional","affiliation":[{"name":"Division of Otolaryngology\u2013Head and Neck Surgery, Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al (CHUM), Universit\u00e9 de Montr\u00e9al, Quebec, Canada"},{"name":"Research Center of CHUM, Universit\u00e9 de Montr\u00e9al, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edith","family":"Filion","sequence":"additional","affiliation":[{"name":"Division of Radiation Oncology, Department of Radiology, Radiation Oncology and Nuclear Medicine, CHUM, Universit\u00e9 de Montr\u00e9al, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phuc-Felix","family":"Nguyen-Tan","sequence":"additional","affiliation":[{"name":"Division of Radiation Oncology, Department of Radiology, Radiation Oncology and Nuclear Medicine, CHUM, Universit\u00e9 de Montr\u00e9al, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"O\u2019Sullivan","sequence":"additional","affiliation":[{"name":"Research Center of CHUM, Universit\u00e9 de Montr\u00e9al, Quebec, Canada"},{"name":"Division of Radiation Oncology, Department of Radiology, Radiation Oncology and Nuclear Medicine, CHUM, Universit\u00e9 de Montr\u00e9al, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tareck","family":"Ayad","sequence":"additional","affiliation":[{"name":"Division of Otolaryngology\u2013Head and Neck Surgery, Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al (CHUM), Universit\u00e9 de Montr\u00e9al, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Bissada","sequence":"additional","affiliation":[{"name":"Division of Otolaryngology\u2013Head and Neck Surgery, Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al (CHUM), Universit\u00e9 de Montr\u00e9al, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Tabet","sequence":"additional","affiliation":[{"name":"Division of Otolaryngology\u2013Head and Neck Surgery, Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al (CHUM), Universit\u00e9 de Montr\u00e9al, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis","family":"Guertin","sequence":"additional","affiliation":[{"name":"Division of Otolaryngology\u2013Head and Neck Surgery, Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al (CHUM), Universit\u00e9 de Montr\u00e9al, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoine","family":"Desilets","sequence":"additional","affiliation":[{"name":"Research Center of CHUM, Universit\u00e9 de Montr\u00e9al, Quebec, Canada"},{"name":"Division of Medical Oncology, Department of Medicine, CHUM, Universit\u00e9 de Montr\u00e9al, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Kadoury","sequence":"additional","affiliation":[{"name":"Research Center of CHUM, Universit\u00e9 de Montr\u00e9al, Quebec, Canada"},{"name":"Department of Computer and Software Engineering, Polytechnique Montr\u00e9al, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Letourneau-Guillon","sequence":"additional","affiliation":[{"name":"Research Center of CHUM, Universit\u00e9 de Montr\u00e9al, Quebec, Canada"},{"name":"Division of Radiology, Department of Radiology, Radiation Oncology and Nuclear Medicine, CHUM, Universit\u00e9 de Montr\u00e9al, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"4","key":"ooi250064r1","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/S1470-2045(15)00560-4","article-title":"Development and validation of a staging system for HPV-related oropharyngeal cancer by the International Collaboration on Oropharyngeal Cancer Network for Staging (ICON-S): a multicentre cohort study.","volume":"17","author":"O\u2019Sullivan","year":"2016","journal-title":"Lancet Oncol"},{"issue":"10","key":"ooi250064r3","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1002\/hed.20279","article-title":"Defining risk levels in locally advanced head and neck cancers: a comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (# 9501).","volume":"27","author":"Bernier","year":"2005","journal-title":"Head Neck"},{"issue":"19","key":"ooi250064r4","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1056\/NEJMoa032641","article-title":"Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer.","volume":"350","author":"Bernier","year":"2004","journal-title":"N Engl J Med"},{"issue":"19","key":"ooi250064r5","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.1056\/NEJMoa032646","article-title":"Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck.","volume":"350","author":"Cooper","year":"2004","journal-title":"N Engl J Med"},{"issue":"4","key":"ooi250064r6","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1177\/0194599820951176","article-title":"Prognostic significance of extranodal extension in HPV-mediated oropharyngeal carcinoma: a systematic review and meta-analysis.","volume":"164","author":"Benchetrit","year":"2021","journal-title":"Otolaryngol Head Neck Surg"},{"key":"ooi250064r7","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.radonc.2021.10.018","article-title":"Prognostic importance of radiologic extranodal extension in nasopharyngeal carcinoma treated in a Canadian cohort.","volume":"165","author":"Chin","year":"2021","journal-title":"Radiother Oncol"},{"key":"ooi250064r8","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.radonc.2019.10.011","article-title":"Prognostic importance of radiologic extranodal extension in HPV-positive oropharyngeal carcinoma and its potential role in refining TNM-8 cN-classification.","volume":"144","author":"Huang","year":"2020","journal-title":"Radiother Oncol"},{"key":"ooi250064r9","doi-asserted-by":"crossref","DOI":"10.1016\/j.oraloncology.2020.105167","article-title":"Prognostic value of clinical and radiologic extranodal extension and their role in the 8th edition TNM cN classification for HPV-negative oropharyngeal carcinoma.","volume":"114","author":"Pilar","year":"2021","journal-title":"Oral Oncol"},{"issue":"7","key":"ooi250064r10","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1001\/jamaoto.2025.0848","article-title":"A proposal for HPV-associated oropharyngeal carcinoma in the ninth edition clinical TNM classification.","volume":"151","author":"Huang","year":"2025","journal-title":"JAMA Otolaryngol Head Neck Surg"},{"issue":"11","key":"ooi250064r12","doi-asserted-by":"crossref","first-page":"2361","DOI":"10.1002\/hed.27130","article-title":"Augmenting inter-rater concordance of radiologic extranodal extension in HPV-positive oropharyngeal carcinoma: a multicenter study.","volume":"44","author":"Hoebers","year":"2022","journal-title":"Head Neck"},{"key":"ooi250064r13","doi-asserted-by":"crossref","DOI":"10.1016\/j.ijrobp.2025.04.003","article-title":"Accuracy and prognosis of extranodal extension on radiologic imaging in human papillomavirus-mediated oropharyngeal cancer: a Head and Neck Cancer International Group (HNCIG) real-world study.","author":"Mehanna","year":"2025","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"ooi250064r14","doi-asserted-by":"crossref","DOI":"10.1136\/bmj-2023-078378","article-title":"TRIPOD+AI statement: updated guidance for reporting clinical prediction models that use regression or machine learning methods.","volume":"385","author":"Collins","year":"2024","journal-title":"BMJ"},{"issue":"7","key":"ooi250064r15","doi-asserted-by":"crossref","first-page":"e297","DOI":"10.1016\/S1470-2045(24)00066-4","article-title":"Criteria for the diagnosis of extranodal extension detected on radiological imaging in head and neck cancer: Head and Neck Cancer International Group consensus recommendations.","volume":"25","author":"Henson","year":"2024","journal-title":"Lancet Oncol"},{"issue":"2","key":"ooi250064r16","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/s41592-020-01008-z","article-title":"nnU-Net: a self-configuring method for deep learning-based biomedical image segmentation.","volume":"18","author":"Isensee","year":"2021","journal-title":"Nat Methods"},{"issue":"5","key":"ooi250064r17","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1016\/j.ijrobp.2019.03.047","article-title":"Radiologic extranodal extension portends worse outcome in cN+ TNM-8 stage I human papillomavirus-mediated oropharyngeal cancer.","volume":"104","author":"Billfalk-Kelly","year":"2019","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"ooi250064r18","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.radonc.2021.01.013","article-title":"Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 107 randomized trials and 19,805 patients, on behalf of MACH-NC Group.","volume":"156","author":"Lacas","year":"2021","journal-title":"Radiother Oncol"},{"issue":"1","key":"ooi250064r19","first-page":"18","article-title":"Long-term functional and quality-of-life outcomes after transoral robotic surgery in patients with oropharyngeal cancer.","volume":"144","author":"Achim","year":"2018","journal-title":"JAMA Otolaryngol Head Neck Surg"},{"issue":"3","key":"ooi250064r20","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1177\/1971400917694048","article-title":"Computed tomography detection of extracapsular spread of squamous cell carcinoma of the head and neck in metastatic cervical lymph nodes.","volume":"30","author":"Carlton","year":"2017","journal-title":"Neuroradiol J"},{"key":"ooi250064r21","doi-asserted-by":"crossref","DOI":"10.1016\/j.oraloncology.2022.105716","article-title":"Inter-rater concordance and operating definitions of radiologic nodal feature assessment in human papillomavirus-positive oropharyngeal carcinoma.","volume":"125","author":"Chin","year":"2022","journal-title":"Oral Oncol"},{"key":"ooi250064r22","doi-asserted-by":"crossref","DOI":"10.1002\/cncr.35815","article-title":"International multi-specialty expert physician preoperative identification of extranodal extension n oropharyngeal cancer patients using computed tomography: prospective blinded human inter-observer performance evaluation.","author":"Sahin","year":"2025","journal-title":"Cancer"},{"issue":"5","key":"ooi250064r23","doi-asserted-by":"crossref","first-page":"3693","DOI":"10.1007\/s00330-023-09407-4","article-title":"Diagnostic performance of computed tomography features in detecting oropharyngeal squamous cell carcinoma extranodal extension.","volume":"33","author":"Tran","year":"2023","journal-title":"Eur Radiol"},{"issue":"1","key":"ooi250064r24","doi-asserted-by":"crossref","first-page":"14036","DOI":"10.1038\/s41598-018-32441-y","article-title":"Pretreatment identification of head and neck cancer nodal metastasis and extranodal extension using deep learning neural networks.","volume":"8","author":"Kann","year":"2018","journal-title":"Sci Rep"},{"issue":"12","key":"ooi250064r25","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1200\/JCO.19.02031","article-title":"Multi-institutional validation of deep learning for pretreatment identification of extranodal extension in head and neck squamous cell carcinoma.","volume":"38","author":"Kann","year":"2020","journal-title":"J Clin Oncol"},{"issue":"6","key":"ooi250064r26","doi-asserted-by":"crossref","first-page":"e360","DOI":"10.1016\/S2589-7500(23)00046-8","article-title":"Screening for extranodal extension in HPV-associated oropharyngeal carcinoma: evaluation of a CT-based deep learning algorithm in patient data from a multicentre, randomised de-escalation trial.","volume":"5","author":"Kann","year":"2023","journal-title":"Lancet Digit Health"},{"issue":"7","key":"ooi250064r27","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1001\/jamaoto.2016.0882","article-title":"Association of extracapsular spread with survival according to human papillomavirus status in oropharynx squamous cell carcinoma and carcinoma of unknown primary site.","volume":"142","author":"Kharytaniuk","year":"2016","journal-title":"JAMA Otolaryngol Head Neck Surg"},{"issue":"18","key":"ooi250064r28","doi-asserted-by":"crossref","first-page":"3302","DOI":"10.1002\/cncr.28169","article-title":"Extracapsular spread in head and neck carcinoma: impact of site and human papillomavirus status.","volume":"119","author":"Maxwell","year":"2013","journal-title":"Cancer"},{"issue":"5","key":"ooi250064r29","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1016\/j.oraloncology.2015.02.098","article-title":"High metastatic node number, not extracapsular spread or N-classification is a node-related prognosticator in transorally-resected, neck-dissected p16-positive oropharynx cancer.","volume":"51","author":"Sinha","year":"2015","journal-title":"Oral Oncol"},{"issue":"14","key":"ooi250064r30","doi-asserted-by":"crossref","first-page":"3519","DOI":"10.1002\/cncr.26671","article-title":"Extracapsular spread and adjuvant therapy in human papillomavirus-related, p16-positive oropharyngeal carcinoma.","volume":"118","author":"Sinha","year":"2012","journal-title":"Cancer"},{"issue":"13626","key":"ooi250064r31","first-page":"1","article-title":"Overview of the HECKTOR challenge at MICCAI 2022: automatic head and neck tumor segmentation and outcome prediction in PET\/CT.","volume":"13626","author":"Andrearczyk","year":"2023","journal-title":"Head Neck Tumor Chall (2022)"},{"issue":"1","key":"ooi250064r34","doi-asserted-by":"crossref","first-page":"15198","DOI":"10.1038\/s41598-019-51599-7","article-title":"Combined CT radiomics of primary tumor and metastatic lymph nodes improves prediction of loco-regional control in head and neck cancer.","volume":"9","author":"Bogowicz","year":"2019","journal-title":"Sci Rep"},{"issue":"1","key":"ooi250064r35","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/s41746-025-01693-0","article-title":"Scoping review of deep learning research illuminates artificial intelligence chasm in otolaryngology-head and neck surgery.","volume":"8","author":"Liu","year":"2025","journal-title":"NPJ Digit Med"},{"key":"ooi250064r2","volume-title":"AJCC Cancer Staging Manual","author":"Amin","year":"2018","edition":"8th ed"},{"key":"ooi250064r11","volume-title":"TNM Classification of Malignant Tumours","author":"Brierley","year":"2025","edition":"9th ed"},{"key":"ooi250064r32","volume-title":"Head and Neck Tumor Segmentation and Outcome Prediction","author":"Sun"},{"key":"ooi250064r33","volume-title":"Head and Neck Tumor Segmentation and Outcome Prediction","author":"Rebaud"}],"container-title":["JAMA Otolaryngology\u2013Head & Neck Surgery"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamaotolaryngology\/articlepdf\/2839507\/jamaotolaryngology_dayan_2025_oi_250064_1767717033.02181.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T16:01:05Z","timestamp":1767888065000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamaotolaryngology\/fullarticle\/2839507"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,1]]},"references-count":35,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamaoto.2025.3225","relation":{},"ISSN":["2168-6181"],"issn-type":[{"value":"2168-6181","type":"print"}],"subject":[],"published":{"date-parts":[[2026,1,1]]}}}