{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:19:53Z","timestamp":1791476393135,"version":"4.3.4"},"reference-count":31,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2022,2,9]],"date-time":"2022-02-09T00:00:00Z","timestamp":1644364800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2022,6]]},"abstract":"\n Background<\/jats:title>\n New ultrasensitive methods for detecting residual disease after surgery are needed in human papillomavirus\u2013associated oropharyngeal squamous cell carcinoma (HPV+OPSCC).<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n To determine whether the clearance kinetics of circulating tumor human papillomavirus DNA (ctHPVDNA) is associated with postoperative disease status, a prospective observational study was conducted in 33 patients with HPV+OPSCC undergoing surgery. Blood was collected before surgery, postoperative days 1 (POD 1), 7, and 30 and with follow\u2010up. A subcohort of 12 patients underwent frequent blood collections in the first 24\u00a0hours after surgery to define early clearance kinetics. Plasma was run on custom droplet digital polymerase chain reaction (ddPCR) assays for HPV genotypes 16, 18, 33, 35, and 45.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n In patients without pathologic risk factors for recurrence who were observed after surgery, ctHPVDNA rapidly decreased to <1\u00a0copy\/mL by POD 1 (n\u00a0=\u00a08\/8). In patients with risk factors for macroscopic residual disease, ctHPVDNA was markedly elevated on POD 1 (>350\u00a0copies\/mL) and remained elevated until adjuvant treatment (n\u00a0=\u00a03\/3). Patients with intermediate POD 1 ctHPVDNA levels (1.2\u201058.4 copies\/mL) all possessed pathologic risk factors for microscopic residual disease (n\u00a0=\u00a09\/9). POD 1 ctHPVDNA levels were higher in patients with known adverse pathologic risk factors such as extranodal extension >1\u00a0mm (\n P<\/jats:italic>\n \u00a0=\u00a0.0481) and with increasing lymph nodes involved (\n P<\/jats:italic>\n \u00a0=\u00a0.0453) and were further associated with adjuvant treatment received (\n P<\/jats:italic>\n \u00a0=\u00a0.0076). One of 33 patients had a recurrence that was detected by ctHPVDNA 2\u00a0months earlier than clinical detection.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n POD 1 ctHPVDNA levels are associated with the risk of residual disease in patients with HPV+OPSCC undergoing curative intent surgery and thus could be used as a personalized biomarker for selecting adjuvant treatment in the future.<\/jats:p>\n <\/jats:sec>\n \n Lay Summary<\/jats:title>\n \n \n \n Human papillomavirus\u2013associated oropharyngeal squamous cell carcinoma (HPV+OPSCC) is increasing at epidemic proportions and is commonly treated with surgery.<\/jats:p>\n <\/jats:list-item>\n \n This report describes results from a study examining the clearance kinetics of circulating tumor HPV DNA (circulating tumor human papillomavirus DNA [ctHPVDNA]) following surgical treatment of HPV+OPSCC.<\/jats:p>\n <\/jats:list-item>\n \n We found that ctHPVDNA levels 1\u00a0day after surgery are associated with the risk of residual disease in patients with HPV+OPSCC and thus could be used as a personalized biomarker for selecting adjuvant treatment in the future.<\/jats:p>\n <\/jats:list-item>\n \n These findings are the first to demonstrate the potential utility of ctHPVDNA in patients with HPV+OPSCC undergoing surgery.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/cncr.34109","type":"journal-article","created":{"date-parts":[[2022,2,9]],"date-time":"2022-02-09T14:44:46Z","timestamp":1644417886000},"page":"2193-2204","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":88,"title":["Cell\u2010free human papillomavirus DNA kinetics after surgery for human papillomavirus\u2013associated oropharyngeal cancer"],"prefix":"10.1002","volume":"128","author":[{"given":"Connor J.","family":"O'Boyle","sequence":"first","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery Massachusetts Eye and Ear Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Siravegna","sequence":"additional","affiliation":[{"name":"Harvard Medical School Boston Massachusetts"},{"name":"Massachusetts General Hospital Cancer Center Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shohreh","family":"Varmeh","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery Massachusetts Eye and Ear Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Queenan","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery Massachusetts Eye and Ear Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexa","family":"Michel","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital Cancer Center Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim Chang Sing","family":"Pang","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery Massachusetts Eye and Ear Boston Massachusetts"},{"name":"Vrije Universiteit of Amsterdam Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jarrod","family":"Stein","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery Massachusetts Eye and Ear Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia C.","family":"Thierauf","sequence":"additional","affiliation":[{"name":"Department of Pathology Massachusetts General Hospital Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter M.","family":"Sadow","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery Massachusetts Eye and Ear Boston Massachusetts"},{"name":"Harvard Medical School Boston Massachusetts"},{"name":"Department of Pathology Massachusetts General Hospital Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William C.","family":"Faquin","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery Massachusetts Eye and Ear Boston Massachusetts"},{"name":"Harvard Medical School Boston Massachusetts"},{"name":"Department of Pathology Massachusetts General Hospital Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medicine Brigham and Women's Hospital Boston Massachusetts"},{"name":"Department of Neurology Brigham and Women's Hospital Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel G.","family":"Deschler","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery Massachusetts Eye and Ear Boston Massachusetts"},{"name":"Harvard Medical School Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin S.","family":"Emerick","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery Massachusetts Eye and Ear Boston Massachusetts"},{"name":"Harvard Medical School Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Varvares","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery Massachusetts Eye and Ear Boston Massachusetts"},{"name":"Harvard Medical School Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1052-0734","authenticated-orcid":false,"given":"Jong C.","family":"Park","sequence":"additional","affiliation":[{"name":"Harvard Medical School Boston Massachusetts"},{"name":"Division of Hematology\u2010Oncology Department of Medicine Massachusetts General Hospital Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Clark","sequence":"additional","affiliation":[{"name":"Harvard Medical School Boston Massachusetts"},{"name":"Division of Hematology\u2010Oncology Department of Medicine Massachusetts General Hospital Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annie W.","family":"Chan","sequence":"additional","affiliation":[{"name":"Harvard Medical School Boston Massachusetts"},{"name":"Department of Radiation Oncology Massachusetts General Hospital Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul M.","family":"Busse","sequence":"additional","affiliation":[{"name":"Harvard Medical School Boston Massachusetts"},{"name":"Division of Hematology\u2010Oncology Department of Medicine Massachusetts General Hospital Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan B.","family":"Corcoran","sequence":"additional","affiliation":[{"name":"Harvard Medical School Boston Massachusetts"},{"name":"Massachusetts General Hospital Cancer Center Boston Massachusetts"},{"name":"Division of Hematology\u2010Oncology Department of Medicine Massachusetts General Hospital Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2629-2289","authenticated-orcid":false,"given":"Lori J.","family":"Wirth","sequence":"additional","affiliation":[{"name":"Harvard Medical School Boston Massachusetts"},{"name":"Division of Hematology\u2010Oncology Department of Medicine Massachusetts General Hospital Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derrick 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