{
    "abstract": "Extranodal extension on radiology(iENE) is reported in single-centre studies to be negatively prognostic in Human papillomavirus-mediated oropharyngeal cancer (HPV+OPC) and is a major eligibility criterion for surgical treatment. However, studies report widely varying sensitivities, specificities and interobserver correlation. In this research the prognostic power, sensitivity and specificity of iENE in HPV+OPC in real-world practice are determined.\nA retrospective cohort of 821 consecutive subjects with p16+OPC, treated with surgery and/or chemoradiotherapy(CRT), from 13 multinational secondary hospitals in nine countries between 1/1/1999 and 12/31/2020 was analysed. The main outcomes were sensitivity, specificity and overall survival(OS). Assessors were blinded to outcomes.\n638 were included in the final analysis. 109/394(27.7%) with no iENE had ENE on histopathology(pENE), and 109/192(56.8%) of patients with pENE were misclassified as having no iENE. iENE sensitivity and specificity were 44.5%(95%CI: 37.8-51.4%) and 87.6%(95%CI: 84.1-90.6%) respectively, and varied significantly between centres. Negative predictive value was 75.3% (95% CI 72.3-77.5%). Subgroup analyses showed significantly increased sensitivity and specificity if patients had both CT and MRI: 84.6%(95%CI: 65.1-95.6%, p<0.001) and 94.5%(95%CI: 82.3-99.4%, p=0.022) respectively, compared to only CT or MRI alone. Specialist radiologists showed better specificities (89.14%(85.69-91.99%) vs 46.67%(21.27-73.41%), p<0.001) and similar sensitivities to non-specialists. On multivariable analysis, iENE positivity was not a statistically significant independent predictor of OS (adjusted hazards ratio(aHR) 1.50(95%CI: 0.97-2.32, p=0.071)) or disease-free survival (aHR 1.41(95%CI 0.95-2.09), p=0.089). Two proposals for amended TNM staging did not yield large improvements.\nIn current real-world practice, iENE showed widely varying and modest accuracy, and was not independently prognostic of outcomes in HPV+OPC. iENE accuracy and prognostic power increased significantly by using combined CT and MRI scanning, experienced head and neck radiologists and more inclusive diagnostic criteria. Validated consensus diagnostic criteria and protocols are urgently needed to enhance the clinical utility of iENE. Until then, clinicians should be cautious about making treatment decisions based on iENE.",
    "authors": [
        {
            "affiliation": "Institute of Head and Neck Studies and Education, University of Birmingham, B15 2TT, UK. Electronic address: h.mehanna@bham.ac.uk.",
            "firstname": "Professor Hisham",
            "initials": "PH",
            "lastname": "Mehanna"
        },
        {
            "affiliation": "Institute of Head and Neck Studies and Education, University of Birmingham, B15 2TT, UK.",
            "firstname": "Ahmad K",
            "initials": "AK",
            "lastname": "Abou-Foul"
        },
        {
            "affiliation": "Department of Radiation Oncology, Stephenson Cancer Centre, University of Oklahoma Health Sciences Centre, Oklahoma City, Oklahoma, USA.",
            "firstname": "Christina",
            "initials": "C",
            "lastname": "Henson"
        },
        {
            "affiliation": "Institute of Head and Neck Studies and Education, University of Birmingham, B15 2TT, UK. Electronic address: c.a.kristunas@bham.ac.uk.",
            "firstname": "Caroline",
            "initials": "C",
            "lastname": "Kristunas"
        },
        {
            "affiliation": "Institute of Head and Neck Studies and Education, University of Birmingham, B15 2TT, UK.",
            "firstname": "Paul C",
            "initials": "PC",
            "lastname": "Nankivell"
        },
        {
            "affiliation": "Department of Radiation Oncology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.",
            "firstname": "Lachlan",
            "initials": "L",
            "lastname": "McDowell"
        },
        {
            "affiliation": "Department of Otolaryngology-Head and Neck Surgery, Amsterdam University Medical Centre, Cancer Centre Amsterdam, Amsterdam, The Netherlands.",
            "firstname": "Professor C Ren\u00e9",
            "initials": "PCR",
            "lastname": "Leemans"
        },
        {
            "affiliation": "Department of Head and Neck Oncology and Surgery, Netherlands Cancer Institute, Antoni van Leeuwenhoek, Amsterdam, The Netherlands.",
            "firstname": "Professor Michiel Wm",
            "initials": "PMW",
            "lastname": "van-den-Brekel"
        },
        {
            "affiliation": "Department of Otorhinolaryngology, Head and Neck Surgery & Audiology, Copenhagen University Hospital, Rigshospitalet, Denmark.",
            "firstname": "Professor Christian",
            "initials": "PC",
            "lastname": "von-Buchwald"
        },
        {
            "affiliation": "Department of Otorhinolaryngology, Head and Neck Surgery & Audiology, Copenhagen University Hospital, Rigshospitalet, Denmark.",
            "firstname": "Kathrine Kronberg",
            "initials": "KK",
            "lastname": "Jakobsen"
        },
        {
            "affiliation": "Department of Otorhinolaryngology, Head and Neck Surgery & Audiology, Copenhagen University Hospital, Rigshospitalet, Denmark.",
            "firstname": "Christian",
            "initials": "C",
            "lastname": "Gr\u00f8nh\u00f8j"
        },
        {
            "affiliation": "Department of Otorhinolaryngology, Head and Neck Surgery & Audiology, Copenhagen University Hospital, Rigshospitalet, Denmark.",
            "firstname": "Jacob H\u00f8ygaard",
            "initials": "JH",
            "lastname": "Rasmussen"
        },
        {
            "affiliation": "Department of Surgery, Nebraska Methodist Hospital and Methodist Women's Hospital, Creighton University, Omaha, Nebraska, USA.",
            "firstname": "Professor William M",
            "initials": "PWM",
            "lastname": "Lydiatt"
        },
        {
            "affiliation": "Department of Radiation Oncology, Mount Sinai Health System, New York, NY, USA.",
            "firstname": "Vishal",
            "initials": "V",
            "lastname": "Gupta"
        },
        {
            "affiliation": "Department of Radiology, University of PIttsburgh, Pittsburgh, Pennsylvania, USA.",
            "firstname": "Professor Barton F",
            "initials": "PBF",
            "lastname": "Branstetter"
        },
        {
            "affiliation": "Department of Otorhinolaryngology, Head and Neck Surgery, Medical Faculty, University Hospital of Cologne, Cologne, Germany.",
            "firstname": "Professor Jens Peter",
            "initials": "PJP",
            "lastname": "Klussmann"
        },
        {
            "affiliation": "Department of Otolaryngology, Head & Neck Surgery, Technical University Munich (MRI TUM), Munich, Germany.",
            "firstname": "Professor Barbara",
            "initials": "PB",
            "lastname": "Wollenberg"
        },
        {
            "affiliation": "Department of Otolaryngology, Head & Neck Surgery, Technical University Munich (MRI TUM), Munich, Germany.",
            "firstname": "Benedikt",
            "initials": "B",
            "lastname": "Schmidl"
        },
        {
            "affiliation": "Department of Otolaryngology-Head and Neck Surgery, University Clinic of the University Hospital Zurich, University of Zurich, Zurich, Switzerland.",
            "firstname": "Martina A",
            "initials": "MA",
            "lastname": "Broglie"
        },
        {
            "affiliation": "Department of Otolaryngology-Head and Neck Surgery, Amsterdam University Medical Centre, Cancer Centre Amsterdam, Amsterdam, The Netherlands.",
            "firstname": "Jan-Jaap",
            "initials": "JJ",
            "lastname": "Hendrickx"
        },
        {
            "affiliation": "University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.",
            "firstname": "Daniel R",
            "initials": "DR",
            "lastname": "Awad"
        },
        {
            "affiliation": "Department Clinical Oncology, Leeds Cancer Centre, Leeds, UK.",
            "firstname": "Professor Robin",
            "initials": "PR",
            "lastname": "Prestwich"
        },
        {
            "affiliation": "Service d'Imagerie, Hopital Europ\u00e9en Georges PompidouAPHP, Universit\u00e9 Paris Cit\u00e9, Paris, France.",
            "firstname": "Dr Anne-Laure",
            "initials": "DA",
            "lastname": "Gaultier"
        },
        {
            "affiliation": "Department of Medical Oncology, Head and Neck Cancer Unit/Drug Development Program, Institut Catal\u00e0 d'Oncologia (ICO) L\u00b4Hospitalet, Barcelona, Spain.",
            "firstname": "Marc",
            "initials": "M",
            "lastname": "Oliva"
        },
        {
            "affiliation": "Department of Head and Neck Oncology, Tata Memorial Centre, Mumbai, India.",
            "firstname": "Professor Sudhir",
            "initials": "PS",
            "lastname": "Nair"
        },
        {
            "affiliation": "School of Medicine, University of New South Wales, Sydney, New South Wales, Australia.",
            "firstname": "Dr Anthony",
            "initials": "DA",
            "lastname": "Noor"
        },
        {
            "affiliation": "Department of Otolaryngology, Head & Neck Surgery, Royal Adelaide Hospital, South Australia, Australia.",
            "firstname": "Professor Suren",
            "initials": "PS",
            "lastname": "Krishnan"
        },
        {
            "affiliation": "Department of Clinical Oncology, Leeds Cancer Centre, University of Leeds, UK.",
            "firstname": "Zsuzsanna",
            "initials": "Z",
            "lastname": "Iyizoba-Ebozue"
        },
        {
            "affiliation": "Institute for Head and Neck Studies and Education, University of Birmingham, UK.",
            "firstname": "Mantegh",
            "initials": "M",
            "lastname": "Sethi"
        },
        {
            "affiliation": "Department of Otolaryngology-Head and Neck Surgery, Amsterdam University Medical Centre, Cancer Centre Amsterdam, Amsterdam, The Netherlands.",
            "firstname": "Irene H",
            "initials": "IH",
            "lastname": "Nauta"
        },
        {
            "affiliation": "Department of Biostatistics and Epidemiology, Stephenson Cancer Centre, University of Oklahoma Health Sciences Centre, Oklahoma City, Oklahoma, USA.",
            "firstname": "Professor Daniel",
            "initials": "PD",
            "lastname": "Zhao"
        },
        {
            "affiliation": "Department of Radiation Oncology, University of California, Department of Otolaryngology-Head and Neck Surgery, San Francisco, USA.",
            "firstname": "Professor Sue S",
            "initials": "PSS",
            "lastname": "Yom"
        }
    ],
    "conclusions": null,
    "copyrights": "Copyright \u00a9 2025. Published by Elsevier Inc.",
    "doi": "10.1016/j.ijrobp.2025.04.003",
    "journal": "International journal of radiation oncology, biology, physics",
    "keywords": [
        "Human papillomavirus",
        "extracapsular extension",
        "extranodal extension",
        "head and neck cancer",
        "radiology",
        "squamous cell carcinoma"
    ],
    "methods": null,
    "publication_date": "2025-04-27",
    "pubmed_id": "40286939",
    "results": "638 were included in the final analysis. 109/394(27.7%) with no iENE had ENE on histopathology(pENE), and 109/192(56.8%) of patients with pENE were misclassified as having no iENE. iENE sensitivity and specificity were 44.5%(95%CI: 37.8-51.4%) and 87.6%(95%CI: 84.1-90.6%) respectively, and varied significantly between centres. Negative predictive value was 75.3% (95% CI 72.3-77.5%). Subgroup analyses showed significantly increased sensitivity and specificity if patients had both CT and MRI: 84.6%(95%CI: 65.1-95.6%, p<0.001) and 94.5%(95%CI: 82.3-99.4%, p=0.022) respectively, compared to only CT or MRI alone. Specialist radiologists showed better specificities (89.14%(85.69-91.99%) vs 46.67%(21.27-73.41%), p<0.001) and similar sensitivities to non-specialists. On multivariable analysis, iENE positivity was not a statistically significant independent predictor of OS (adjusted hazards ratio(aHR) 1.50(95%CI: 0.97-2.32, p=0.071)) or disease-free survival (aHR 1.41(95%CI 0.95-2.09), p=0.089). Two proposals for amended TNM staging did not yield large improvements.",
    "title": "Accuracy and prognosis of extranodal extension on radiologic imaging in HPV+ oropharyngeal cancer.",
    "xml": "<Element 'PubmedArticle' at 0x788504b00770>"
}