{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T19:39:57Z","timestamp":1790019597655,"version":"4.0.1"},"reference-count":30,"publisher":"American Medical Association (AMA)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Otolaryngol Head Neck Surg"],"published-print":{"date-parts":[[2025,3,1]]},"abstract":"Importance<\/jats:title>Given the favorable overall prognosis of human papillomavirus (HPV)\u2013related oropharyngeal squamous cell carcinoma (OPSCC) and the morbidity of increased adjuvant therapy associated with positive surgical margins, large-scale studies on the accuracy of frozen sections in predicting final surgical margin status in HPV-related OPSCC are imperative. Final surgical margin status is the definitive assessment of tumor clearance as determined through surgeon-pathologist collaboration based on permanent analysis of frozen section margins, main specimens, and supplemental resections.<\/jats:p><\/jats:sec>Objectives<\/jats:title>To assess the accuracy and testing properties of intraoperative frozen section histology (IFSH) in assessing final surgical margin status in patients undergoing transoral surgery for HPV-related OPSCC.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>This retrospective, single-institution cohort study was conducted at the Washington University in Saint Louis School of Medicine and included 299 patients who underwent transoral surgery for HPV-related OPSCC between January 2015 and December 2021 who were identified using an institutional cancer registry. Forty-five patients were excluded due to piecemeal resections, no frozen sections sent during surgery, unknown primaries, or no residual tumor identified during surgery after a diagnostic biopsy. Pathology reports of patients with at least 1 margin assessed by IFSH were reviewed. The data were analyzed between January and February 2024.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>The accuracy of IFSH for individual margins and overall final surgical margin status was evaluated through calculating sensitivity, specificity, positive predictive values, and negative predictive values from 1482 margins from 254 patients.<\/jats:p><\/jats:sec>Results<\/jats:title>Of 254 participants, 29 (11.4%) were female, and the mean (SD) age was 60.7 (9.4) years. IFSH demonstrated an accuracy of 97.1%, sensitivity of 72.2%, and specificity of 99.1% for individual margins compared with final pathology results of the same tissue. However, IFSH had a sensitivity of only 21.7% in determining the overall final surgical margin status, with 18 patients (7.1%) having at least 1 positive margin undetected intraoperatively. Positive final surgical margin status was associated with worse disease-specific survival (hazard ratio, 3.26; 95% CI, 1.05-10.13) and higher rates of locoregional recurrence (hazard ratio, 5.02; 95% CI, 1.25-20.19), while no definitive conclusion can be made about the prognostic effect of final tumor specimen histopathology status due to imprecision in the effect size estimates.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>The study results suggest that despite high accuracy for individual margins, IFSH has limitations in predicting final surgical margin status in HPV-related OPSCC, particularly for base of tongue primaries and deep margins. However, IFSH remains important for guiding intraoperative reresection and is associated with improved oncologic outcomes.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamaoto.2024.4869","type":"journal-article","created":{"date-parts":[[2025,1,23]],"date-time":"2025-01-23T16:32:13Z","timestamp":1737649933000},"page":"253","source":"Crossref","is-referenced-by-count":9,"title":["Use of Intraoperative Frozen Section to Assess Surgical Margins in HPV-Related Oropharyngeal Carcinoma"],"prefix":"10.1001","volume":"151","author":[{"given":"Salma","family":"Ramadan","sequence":"first","affiliation":[{"name":"Department of Otolaryngology\/Head and Neck Surgery, Washington University in St Louis School of Medicine, St Louis, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Bellas","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\/Head and Neck Surgery, Washington University in St Louis School of Medicine, St Louis, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaid","family":"Al-Qurayshi","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\/Head and Neck Surgery, Washington University in St Louis School of Medicine, St Louis, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\/Head and Neck Surgery, Washington University in St Louis School of Medicine, St Louis, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Zolkind","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\/Head and Neck Surgery, Washington University in St Louis School of Medicine, St Louis, Missouri"},{"name":"Rob Ebert and Greg Stubblefield Head and Neck Tumor Center at Siteman Cancer Center, Washington University in St Louis School of Medicine, St Louis, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrik","family":"Pipkorn","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\/Head and Neck Surgery, Washington University in St Louis School of Medicine, St Louis, Missouri"},{"name":"Rob Ebert and Greg Stubblefield Head and Neck Tumor Center at Siteman Cancer Center, Washington University in St Louis School of Medicine, St Louis, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela L.","family":"Mazul","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, University of Pittsburgh, Pittsburgh, Pennsylvania"},{"name":"UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Alex","family":"Harbison","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\/Head and Neck Surgery, Washington University in St Louis School of Medicine, St Louis, Missouri"},{"name":"Rob Ebert and Greg Stubblefield Head and Neck Tumor Center at Siteman Cancer Center, Washington University in St Louis School of Medicine, St Louis, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan S.","family":"Jackson","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\/Head and Neck Surgery, Washington University in St Louis School of Medicine, St Louis, Missouri"},{"name":"Rob Ebert and Greg Stubblefield Head and Neck Tumor Center at Siteman Cancer Center, Washington University in St Louis School of Medicine, St Louis, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sidharth V.","family":"Puram","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\/Head and Neck Surgery, Washington University in St Louis School of Medicine, St Louis, Missouri"},{"name":"Rob Ebert and Greg Stubblefield Head and Neck Tumor Center at Siteman Cancer Center, Washington University in St Louis School of Medicine, St Louis, Missouri"},{"name":"Department of Genetics, Washington University in St Louis School of Medicine, St Louis, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"1 Pt 1","key":"ooi240100r1","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1288\/00005537-199301000-00012","article-title":"Implications of positive surgical margins.","volume":"103","author":"Jacobs","year":"1993","journal-title":"Laryngoscope"},{"issue":"2","key":"ooi240100r2","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1159\/000527369","article-title":"Specimen-based resection margins and local control during transoral robotic surgery for oropharyngeal HPV-mediated squamous cell carcinoma.","volume":"85","author":"Magliocca","year":"2023","journal-title":"ORL J Otorhinolaryngol Relat Spec"},{"issue":"5","key":"ooi240100r3","doi-asserted-by":"publisher","first-page":"1132","DOI":"10.1002\/lary.30275","article-title":"Positive deep initial incision margin affects outcomes in TORS for HPV+ oropharynx cancer.","volume":"133","author":"Kejner","year":"2023","journal-title":"Laryngoscope"},{"key":"ooi240100r4","doi-asserted-by":"publisher","first-page":"E1794","DOI":"10.1002\/hed.24319","article-title":"Surgical management of oropharyngeal squamous cell carcinoma: survival and functional outcomes.","volume":"38","author":"Kumar","year":"2016","journal-title":"Head Neck"},{"key":"ooi240100r5","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.oraloncology.2019.09.017","article-title":"A systematic review and meta-analysis of margins in transoral surgery for oropharyngeal carcinoma.","volume":"98","author":"Gorphe","year":"2019","journal-title":"Oral Oncol"},{"issue":"8","key":"ooi240100r6","doi-asserted-by":"publisher","first-page":"1768","DOI":"10.1002\/lary.25899","article-title":"Refining the utility and role of Frozen section in head and neck squamous cell carcinoma resection.","volume":"126","author":"Du","year":"2016","journal-title":"Laryngoscope"},{"issue":"48","key":"ooi240100r7","doi-asserted-by":"publisher","first-page":"84320","DOI":"10.18632\/oncotarget.21035","article-title":"Therapeutic implications of tumor free margins in head and neck squamous cell carcinoma.","volume":"8","author":"Backes","year":"2017","journal-title":"Oncotarget"},{"issue":"1","key":"ooi240100r8","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1186\/s40463-021-00501-5","article-title":"Specimen oriented intraoperative margin assessment in oral cavity and oropharyngeal squamous cell carcinoma.","volume":"50","author":"Horwich","year":"2021","journal-title":"J Otolaryngol\u2013Head Neck Surg"},{"issue":"6","key":"ooi240100r9","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1016\/j.hoc.2015.07.003","article-title":"Molecular aspects of head and neck cancer therapy.","volume":"29","author":"Puram","year":"2015","journal-title":"Hematol Oncol Clin North Am"},{"issue":"2","key":"ooi240100r10","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1007\/s12105-017-0846-6","article-title":"Frozen section evaluation of margin status in primary squamous cell carcinomas of the head and neck: a correlation study of frozen section and final diagnoses.","volume":"12","author":"Layfield","year":"2018","journal-title":"Head Neck Pathol"},{"issue":"3","key":"ooi240100r11","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1002\/jso.24134","article-title":"The importance of margins in head and neck cancer.","volume":"113","author":"Baddour","year":"2016","journal-title":"J Surg Oncol"},{"issue":"10","key":"ooi240100r12","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1001\/jamaoto.2022.2131","article-title":"Use of intraoperative frozen section to assess final tumor margin status in patients undergoing surgery for oral cavity squamous cell carcinoma.","volume":"148","author":"Long","year":"2022","journal-title":"JAMA Otolaryngol Head Neck Surg"},{"issue":"11","key":"ooi240100r13","doi-asserted-by":"publisher","first-page":"952","DOI":"10.1002\/hed.20269","article-title":"Surgical margin determination in head and neck oncology: current clinical practice: the results of an International American Head and Neck Society Member Survey.","volume":"27","author":"Meier","year":"2005","journal-title":"Head Neck"},{"issue":"2","key":"ooi240100r14","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1007\/s12105-021-01385-7","article-title":"Frozen\u2014permanent section discrepancy rate in oral cavity and oropharyngeal squamous cell carcinoma.","volume":"16","author":"Serinelli","year":"2022","journal-title":"Head Neck Pathol"},{"issue":"4","key":"ooi240100r15","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1288\/00005537-198404000-00017","article-title":"Reliability of frozen section diagnosis in head and neck neoplasms.","volume":"94","author":"Remsen","year":"1984","journal-title":"Laryngoscope"},{"issue":"11","key":"ooi240100r16","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1001\/jamaoto.2022.2840","article-title":"Association of intraoperative frozen section controls with improved margin assessment during transoral robotic surgery for human papillomavirus\u2013positive oropharyngeal squamous cell carcinoma.","volume":"148","author":"Yu","year":"2022","journal-title":"JAMA Otolaryngol Head Neck Surg"},{"issue":"10","key":"ooi240100r17","doi-asserted-by":"publisher","first-page":"1555","DOI":"10.1001\/jamaoncol.2020.3172","article-title":"Comparison of survival after transoral robotic surgery vs nonrobotic surgery in patients with early-stage oropharyngeal squamous cell carcinoma.","volume":"6","author":"Nguyen","year":"2020","journal-title":"JAMA Oncol"},{"issue":"9","key":"ooi240100r18","doi-asserted-by":"publisher","first-page":"3064","DOI":"10.1002\/hed.25792","article-title":"Positive margin rates and predictors in transoral robotic surgery after federal approval: a national quality study.","volume":"41","author":"Hanna","year":"2019","journal-title":"Head Neck"},{"issue":"4","key":"ooi240100r19","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1177\/0194599817742852","article-title":"Positive margins by oropharyngeal subsite in transoral robotic surgery for T1\/T2 squamous cell carcinoma.","volume":"158","author":"Persky","year":"2018","journal-title":"Otolaryngol Head Neck Surg"},{"issue":"10","key":"ooi240100r20","doi-asserted-by":"publisher","first-page":"2298","DOI":"10.1002\/lary.25397","article-title":"Surgical margins and primary site resection in achieving local control in oral cancer resections.","volume":"125","author":"Varvares","year":"2015","journal-title":"Laryngoscope"},{"issue":"7","key":"ooi240100r21","doi-asserted-by":"publisher","first-page":"636","DOI":"10.1001\/jamaoto.2023.1201","article-title":"Margins in stage I and II oral cavity squamous cell carcinoma: a review from the American Head and Neck Society.","volume":"149","author":"Puram","year":"2023","journal-title":"JAMA Otolaryngol Head Neck Surg"},{"issue":"1","key":"ooi240100r22","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.anl.2018.08.011","article-title":"Surgical margins in head and neck cancer: intra- and postoperative considerations.","volume":"46","author":"Thomas Robbins","year":"2019","journal-title":"Auris Nasus Larynx"},{"issue":"10","key":"ooi240100r23","doi-asserted-by":"publisher","first-page":"1034","DOI":"10.1016\/j.oraloncology.2005.06.008","article-title":"A histopathological appraisal of surgical margins in oral and oropharyngeal cancer resection specimens.","volume":"41","author":"Woolgar","year":"2005","journal-title":"Oral Oncol"},{"issue":"6","key":"ooi240100r24","doi-asserted-by":"publisher","first-page":"1500","DOI":"10.1002\/lio2.1163","article-title":"Clarification of the margin status by the multidisciplinary tumor board following transoral robotic surgery for p16 positive oropharyngeal squamous cell carcinoma.","volume":"8","author":"Parvathaneni","year":"2023","journal-title":"Laryngoscope Investig Otolaryngol"},{"issue":"2","key":"ooi240100r25","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/j.coms.2014.01.003","article-title":"Pitfalls in determining head and neck surgical margins.","volume":"26","author":"Weinstock","year":"2014","journal-title":"Oral Maxillofac Surg Clin North Am"},{"issue":"4","key":"ooi240100r26","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1002\/hed.25055","article-title":"Transoral robotic surgery for oropharyngeal carcinoma: surgical margins and oncologic outcomes.","volume":"40","author":"Moore","year":"2018","journal-title":"Head Neck"},{"issue":"3","key":"ooi240100r27","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1007\/s10900-019-00649-2","article-title":"Prevalence and correlates of cultural smokeless tobacco products among South Asian Americans in New York City.","volume":"44","author":"Han","year":"2019","journal-title":"J Community Health"},{"issue":"4","key":"ooi240100r28","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjoto.2023.103877","article-title":"Prognostic significance of extra-nodal extension and positive surgical margins in HPV positive oropharyngeal squamous cell carcinoma.","volume":"44","author":"Kaur","year":"2023","journal-title":"Am J Otolaryngol"},{"issue":"1","key":"ooi240100r29","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjoto.2020.102793","article-title":"HPV\/p16-positive oropharyngeal cancer treated with transoral robotic surgery: the roles of margins, extra-nodal extension and adjuvant treatment.","volume":"42","author":"Nichols","year":"2021","journal-title":"Am J Otolaryngol"},{"issue":"8","key":"ooi240100r30","doi-asserted-by":"publisher","first-page":"2434","DOI":"10.1002\/hed.26708","article-title":"Impact of surgical margins on local control in patients undergoing single-modality transoral robotic surgery for HPV-related oropharyngeal squamous cell carcinoma.","volume":"43","author":"Holcomb","year":"2021","journal-title":"Head Neck"}],"container-title":["JAMA Otolaryngology\u2013Head & Neck Surgery"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamaotolaryngology\/articlepdf\/2829461\/jamaotolaryngology_ramadan_2025_oi_240100_1740587377.68001.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T15:05:00Z","timestamp":1741878300000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamaotolaryngology\/fullarticle\/2829461"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,1]]},"references-count":30,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,3,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamaoto.2024.4869","relation":{},"ISSN":["2168-6181"],"issn-type":[{"value":"2168-6181","type":"print"}],"subject":[],"published":{"date-parts":[[2025,3,1]]}}}