{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T13:08:48Z","timestamp":1772716128693,"version":"3.50.1"},"reference-count":39,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,18]],"date-time":"2022-12-18T00:00:00Z","timestamp":1671321600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Although the prognosis of tonsillar cancer (human papillomavirus-positive oropharyngeal squamous cell carcinoma) is improving, disease control failure (distant metastasis) still occurs in some cases. We explored whether several 18F-fluorodeoxyglucose (FDG) positron-emission tomography (PET) parameters can predict metastasis. We retrospectively reviewed the medical records of 55 patients with tonsil squamous cell carcinoma who underwent pretreatment 18F-FDG positron-emission tomography\/computed tomography (PET\/CT) followed by primary surgery. During the follow-up period, systemic metastases were found in 7 of the 55 patients. The most common sites were the lungs (33%), bone (22%), brain\/skull base (22%), small bowel (11%), and liver (11%). Pathologically, P53 mutation was less common in patients with systemic metastasis (41.7% vs. 14.3%, p = 0.054) than without systemic metastasis. In terms of PET parameters, the metabolic tumor volume (MTV2.5) and total lesion glycolysis (TLG2.5) values were lower in the primary tumor, and higher in the metastatic lymph nodes, of human papillomavirus (HPV)-positive compared to HPV-negative patients (all p &lt; 0.05). The MTV2.5, TLG2.5, and tumor\u2013to\u2013liver uptake ratio were 36.07 \u00b1 54.24 cm3, 183.46 \u00b1 298.62, and 4.90 \u00b1 2.77, respectively, in the systemic metastasis group, respectively; all of these values were higher than those of the patients without systemic metastasis (all p &lt; 0.05). The MTV2.5 value was significantly different between the groups even when the values for the primary tumor and metastatic lymph nodes were summed (53.53 \u00b1 57.78 cm3, p = 0.036). The cut-off value, area under the curve (95% confidence interval), sensitivity, and specificity of MTV2.5 for predicting systemic metastasis were 11.250 cm3, 0.584 (0.036\u20130.832), 0.571, and 0.565, respectively. The MTV2.5 of metastatic lymph nodes and summed MTV2.5 values of the primary tumor and metastatic lymph nodes were significantly higher in tonsillar cancer patients with than without systemic metastases. We suggest PET\/CT scanning for pre-treatment cancer work-up and post-treatment surveillance to consider additional systemic therapy in patients with a high risk of disease control failure.<\/jats:p>","DOI":"10.3390\/cancers14246242","type":"journal-article","created":{"date-parts":[[2022,12,19]],"date-time":"2022-12-19T08:41:41Z","timestamp":1671439301000},"page":"6242","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Predictive Value of 18F-Fluorodeoxyglucose Positron-Emission Tomography Metabolic and Volumetric Parameters for Systemic Metastasis in Tonsillar Cancer"],"prefix":"10.3390","volume":"14","author":[{"given":"Jooin","family":"Bang","sequence":"first","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Seoul St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1089-6261","authenticated-orcid":false,"given":"Hye Lim","family":"Park","sequence":"additional","affiliation":[{"name":"Division of Nuclear Medicine, Department of Radiology, Eunpyeong St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ie Ryung","family":"Yoo","sequence":"additional","affiliation":[{"name":"Division of Nuclear Medicine, Department of Radiology, Seoul St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyun-Il","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Seoul St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geun-Jeon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Seoul St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong-Il","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Seoul St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang-Yeon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Seoul St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1920","DOI":"10.1080\/21645515.2019.1600985","article-title":"HPV-related oropharyngeal cancer: A review on burden of the disease and opportunities for prevention and early detection","volume":"15","author":"Timbang","year":"2019","journal-title":"Hum. Vaccin. Immunother."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.3390\/v7031332","article-title":"Human papillomavirus and tonsillar and base of tongue cancer","volume":"7","author":"Ramqvist","year":"2015","journal-title":"Viruses"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.1002\/cncr.29323","article-title":"Surgical salvage improves overall survival for patients with HPV-positive and HPV-negative recurrent locoregional and distant metastatic oropharyngeal cancer","volume":"121","author":"Guo","year":"2015","journal-title":"Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.oraloncology.2013.10.007","article-title":"Distant metastasis in p16-positive oropharyngeal squamous cell carcinoma: A critical analysis of patterns and outcomes","volume":"50","author":"Sinha","year":"2014","journal-title":"Oral Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"102592","DOI":"10.1016\/j.amjoto.2020.102592","article-title":"The association of smoking and outcomes in HPV-positive oropharyngeal cancer: A systematic review","volume":"41","author":"Chen","year":"2020","journal-title":"Am. J. Otolaryngol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1002\/hed.23850","article-title":"HPV-related oropharyngeal cancer: Risk factors for treatment failure in patients managed with primary transoral robotic surgery","volume":"38","author":"Kaczmar","year":"2016","journal-title":"Head Neck"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"E805","DOI":"10.1002\/hed.24105","article-title":"Matted nodes: High distant-metastasis risk and a potential indication for intensification of systemic therapy in human papillomavirus-related oropharyngeal cancer","volume":"38","author":"Vainshtein","year":"2016","journal-title":"Head Neck"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1001\/jamaoncol.2017.3852","article-title":"Association of Quantitative Metastatic Lymph Node Burden With Survival in Hypopharyngeal and Laryngeal Cancer","volume":"4","author":"Ho","year":"2018","journal-title":"JAMA Oncol"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1093\/annonc\/mdy490","article-title":"Quantitative lymph node burden as a \u2018very-high-risk\u2019 factor identifying head and neck cancer patients benefiting from postoperative chemoradiation","volume":"30","author":"Zumsteg","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1002\/hed.21361","article-title":"Future of the TNM classification and staging system in head and neck cancer","volume":"32","author":"Takes","year":"2010","journal-title":"Head Neck"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"5861","DOI":"10.1158\/1078-0432.CCR-08-3290","article-title":"Metabolic tumor volume of [18F]-fluorodeoxyglucose positron emission tomography\/computed tomography predicts short-term outcome to radiotherapy with or without chemotherapy in pharyngeal cancer","volume":"15","author":"Chung","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"870319","DOI":"10.3389\/fonc.2022.870319","article-title":"18F-Fluorodeoxyglucose Positron Emission Tomography of Head and Neck Cancer: Location and HPV Specific Parameters for Potential Treatment Individualization","volume":"12","author":"Zschaeck","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1097\/MNM.0b013e328346f02c","article-title":"Early prediction of local control in head and neck cancer after chemoradiotherapy by FDG-PET","volume":"32","author":"Hoshikawa","year":"2011","journal-title":"Nucl. Med. Commun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"163","DOI":"10.2967\/jnmt.119.233353","article-title":"Revisiting Weight-Normalized SUV and Lean-Body-Mass-Normalized SUV in PET Studies","volume":"48","author":"Sarikaya","year":"2020","journal-title":"J. Nucl. Med. Technol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"122S","DOI":"10.2967\/jnumed.108.057307","article-title":"From RECIST to PERCIST: Evolving Considerations for PET response criteria in solid tumors","volume":"50","author":"Wahl","year":"2009","journal-title":"J. Nucl. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1002\/hed.22904","article-title":"Prognostic value of 18F-FDG PET\/CT in patients with squamous cell carcinoma of the tonsil: Comparisons of volume-based metabolic parameters","volume":"35","author":"Moon","year":"2013","journal-title":"Head Neck"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1002\/hed.23296","article-title":"Preoperative 18F-FDG PET\/CT and high-risk HPV in patients with oropharyngeal squamous cell carcinoma","volume":"36","author":"Joo","year":"2014","journal-title":"Head Neck"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"105239","DOI":"10.1016\/j.oraloncology.2021.105239","article-title":"Pre-treatment PET\/MRI based FDG and DWI imaging parameters for predicting HPV status and tumor response to chemoradiotherapy in primary oropharyngeal squamous cell carcinoma (OPSCC)","volume":"116","author":"Freihat","year":"2021","journal-title":"Oral Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"E1613","DOI":"10.1002\/hed.24287","article-title":"Tumor volume as a predictor of survival in human papillomavirus-positive oropharyngeal cancer","volume":"38","author":"Davis","year":"2016","journal-title":"Head Neck"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1002\/hed.24711","article-title":"Predictors of distant metastasis in human papillomavirus-associated oropharyngeal cancer","volume":"39","author":"Weller","year":"2017","journal-title":"Head Neck"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.tranon.2015.03.001","article-title":"Significance of lymph node metastasis in cancer dissemination of head and neck cancer","volume":"8","author":"Cho","year":"2015","journal-title":"Transl. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3396","DOI":"10.1245\/s10434-009-0659-2","article-title":"The role of lymph node metastasis in the systemic dissemination of breast cancer","volume":"16","author":"Nathanson","year":"2009","journal-title":"Ann. Surg. Oncol."},{"key":"ref_23","first-page":"1549","article-title":"Predictive Impact of Metastatic Lymph Node Burden on Distant Metastasis Across Papillary Thyroid Cancer Variants","volume":"31","author":"Ho","year":"2021","journal-title":"Thyroid"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Rich, B., Huang, J., Yang, Y., Jin, W., Johnson, P., Wang, L., and Yang, F. (2021). Radiomics Predicts for Distant Metastasis in Locally Advanced Human Papillomavirus-Positive Oropharyngeal Squamous Cell Carcinoma. Cancers, 13.","DOI":"10.3390\/cancers13225689"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.oraloncology.2017.12.013","article-title":"Prediction of distant metastasis and survival in adenoid cystic carcinoma using quantitative (18)F-FDG PET\/CT measurements","volume":"77","author":"Lim","year":"2018","journal-title":"Oral Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1097\/IGC.0b013e31829ee012","article-title":"Prognostic value of fluorine-18-fluorodeoxyglucose positron emission tomography or PET-computed tomography in cervical cancer: A meta-analysis","volume":"23","author":"Zhao","year":"2013","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Liu, J., Dong, M., Sun, X., Li, W., Xing, L., and Yu, J. (2016). Prognostic Value of 18F-FDG PET\/CT in Surgical Non-Small Cell Lung Cancer: A Meta-Analysis. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0146195"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1001\/archotol.130.12.1361","article-title":"FDG-PET Prediction of Head and Neck Squamous Cell Cancer Outcomes","volume":"130","author":"Schwartz","year":"2004","journal-title":"Arch. Otolaryngol. Head Neck Surg."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3167","DOI":"10.1007\/s00405-021-07169-7","article-title":"SUVmax for predicting regional control in oropharyngeal cancer","volume":"279","author":"Morand","year":"2022","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s13139-017-0493-6","article-title":"Current Methods to Define Metabolic Tumor Volume in Positron Emission Tomography: Which One is Better?","volume":"52","author":"Im","year":"2018","journal-title":"Nucl. Med. Mol. Imaging"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.ijrobp.2007.04.036","article-title":"Metabolic tumor burden predicts for disease progression and death in lung cancer","volume":"69","author":"Lee","year":"2007","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1002\/hed.1136","article-title":"Serial positron emission tomography scans following radiation therapy of patients with head and neck cancer","volume":"23","author":"Greven","year":"2001","journal-title":"Head Neck"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"278","DOI":"10.2967\/jnmt.119.236109","article-title":"Assessing PET Parameters in Oncologic (18)F-FDG Studies","volume":"48","author":"Sarikaya","year":"2020","journal-title":"J. Nucl. Med. Technol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"849","DOI":"10.2967\/jnumed.115.167684","article-title":"18F-FDG PET\/CT of Non-Small Cell Lung Carcinoma Under Neoadjuvant Chemotherapy: Background-Based Adaptive-Volume Metrics Outperform TLG and MTV in Predicting Histopathologic Response","volume":"57","author":"Burger","year":"2016","journal-title":"J. Nucl. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1924","DOI":"10.1016\/j.cell.2022.04.019","article-title":"Lymph node colonization induces tumor-immune tolerance to promote distant metastasis","volume":"185","author":"Zhang","year":"2022","journal-title":"Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"101977","DOI":"10.1016\/j.ctrv.2020.101977","article-title":"Biomarkers for immunotherapy response in head and neck cancer","volume":"84","author":"Gavrielatou","year":"2020","journal-title":"Cancer Treat. Rev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2455","DOI":"10.1056\/NEJMoa1200694","article-title":"Safety and Activity of Anti-PD-L1 Antibody in Patients with Advanced Cancer","volume":"366","author":"Brahmer","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1016\/j.cell.2015.08.016","article-title":"Metabolic Competition in the Tumor Microenvironment Is a Driver of Cancer Progression","volume":"162","author":"Chang","year":"2015","journal-title":"Cell"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"789014","DOI":"10.3389\/fonc.2021.789014","article-title":"Evaluation of PD-L1 Expression Level in Patients With Non-Small Cell Lung Cancer by (18)F-FDG PET\/CT Radiomics and Clinicopathological Characteristics","volume":"11","author":"Li","year":"2021","journal-title":"Front. Oncol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/24\/6242\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:43:39Z","timestamp":1760147019000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/24\/6242"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,18]]},"references-count":39,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["cancers14246242"],"URL":"https:\/\/doi.org\/10.3390\/cancers14246242","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,18]]}}}