{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:16:04Z","timestamp":1787314564443,"version":"build-2736575974"},"reference-count":53,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T00:00:00Z","timestamp":1766102400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T00:00:00Z","timestamp":1766361600000},"content-version":"vor","delay-in-days":3,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004047","name":"Karolinska Institute","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004047","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The incidence of human papillomavirus-positive (HPV\n                    <jats:sup>+<\/jats:sup>\n                    ) head and neck cancer (HNC), particularly oropharyngeal squamous cell carcinoma (OPSCC), is rising globally. Although radio- or chemo-radiotherapy yields better outcomes for patients with HPV\n                    <jats:sup>+<\/jats:sup>\n                    tumors compared to those with HPV-negative tumors, these treatments do not cure all cases and are associated with significant side effects. This underscores the need for more personalized therapy. To help individualize treatment, we evaluated the presence of cell-free HPV DNA (cfHPV-DNA) in plasma collected before, during, and after therapy in patients with HPV\n                    <jats:sup>+<\/jats:sup>\n                    HNC and correlated cfHPV-DNA levels with clinical characteristics, HPV genotype, and treatment response. 267 longitudinal plasma samples were collected from 83 patients with HPV\n                    <jats:sup>+<\/jats:sup>\n                    HNC\/cancer of unknown primary, at diagnosis\/recurrence, during treatment and follow-ups, and tested for cfHPV-DNA with droplet digital PCR assaying for HPV16, 18, 33 or 35.39. 76\/81 (93.8%) eligible diagnostic or recurrence samples tested positive for cfHPV-DNA, while a diagnostic sample was unavailable\/or had inadequate cfDNA in 2\/83 cases. cfHPV-DNA levels declined in most patients by 3\u20134 weeks post-radiotherapy initiation and became undetectable (fast responders) in approximately 30% of cases. By 3\u20136 months post-treatment, most patients had no detectable cfHPV-DNA. To date, no new recurrences have been documented, although two patients were unresponsive to therapy. Most HPV\n                    <jats:sup>+<\/jats:sup>\n                    OPSCC patients were cfHPV-DNA-positive at diagnosis and cleared their cfHPV-DNA upon treatment, but the speed of clearance varied depending on tumor sub-site, patient characteristics and treatment. The data suggest that follow-up with cfHPV-DNA is a promising clinical approach and should be expanded to include more patients and longer time periods.\n                  <\/jats:p>","DOI":"10.1038\/s41598-025-33345-4","type":"journal-article","created":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T20:32:57Z","timestamp":1766176377000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Circulating cell free HPVDNA in HPV positive head and neck cancer reveals fast responders and early peakers during treatment"],"prefix":"10.1038","volume":"15","author":[{"given":"Mark","family":"Zupancic","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeleine","family":"Birgersson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ourania N.","family":"Kostopoulou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Marklund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rusana","family":"Bark","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Signe","family":"Friesland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Jylh\u00e4","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Tham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"N\u00e4sman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Sivars","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Dalianis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,19]]},"reference":[{"key":"33345_CR1","unstructured":"IARC Monographs on the Evaluation of carcinogenic risk to humans. Lyon, France: International Agency for Research on Cancer.  (accessed 04 July 2021). (2007)."},{"key":"33345_CR2","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1093\/jnci\/92.9.709","volume":"92","author":"ML Gillison","year":"2000","unstructured":"Gillison, M. L. et al. Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J. Natl. Cancer Inst. 92, 709\u2013720 (2000).","journal-title":"J. Natl. Cancer Inst."},{"key":"33345_CR3","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1002\/1097-0215(20000520)89:3<300::AID-IJC14>3.0.CO;2-G","volume":"89","author":"H Mellin","year":"2000","unstructured":"Mellin, H., Friesland, S., Lewensohn, R., Dalianis, T. & Munck-Wikland, E. Human papillomavirus (HPV) DNA in tonsillar cancer: clinical correlates, risk of relapse, and survival. Int. J. Cancer. 89, 300\u2013304 (2000).","journal-title":"Int. J. Cancer"},{"key":"33345_CR4","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1002\/ijc.20490","volume":"112","author":"L Dahlgren","year":"2004","unstructured":"Dahlgren, L., Dahlstrand, H. M. & Lindquist, D. Human papillomavirus is more common in base of tongue than in mobile tongue cancer and is a favorable prognostic factor in base of tongue cancer patients. Int. J. Cancer. 112, 1015\u20131019 (2004).","journal-title":"Int. J. Cancer"},{"key":"33345_CR5","doi-asserted-by":"publisher","first-page":"1429","DOI":"10.1002\/cncr.22963","volume":"110","author":"EM Sturgis","year":"2007","unstructured":"Sturgis, E. M. & Cinciripini, P. M. Trends in head and neck cancer incidence in relation to smoking prevalence: an emerging epidemic of human papillomavirus-associated cancers? Cancer 110, 1429\u20131435 (2007).","journal-title":"Cancer"},{"key":"33345_CR6","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1200\/JCO.2007.14.1713","volume":"26","author":"AK Chaturvedi","year":"2008","unstructured":"Chaturvedi, A. K., Engels, E. A., Anderson, W. F. & Gillison, M. L. Incidence trends for human papillomavirus-related and -unrelated oral squamous cell carcinomas in the united States. J. Clin. Oncol. 26, 612\u2013619 (2008).","journal-title":"J. Clin. Oncol."},{"issue":"4B","key":"33345_CR7","first-page":"2077","volume":"28","author":"M Romanitan","year":"2008","unstructured":"Romanitan, M. et al. Human papillomavirus frequency in oral and oropharyngeal cancer in Greece. Anticancer Res. 28 (4B), 2077\u20132080 (2008).","journal-title":"Anticancer Res."},{"key":"33345_CR8","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1002\/ijc.24339","volume":"125","author":"A Nasman","year":"2009","unstructured":"Nasman, A. et al. Incidence of human papillomavirus (HPV) positive tonsillar carcinoma in Stockholm, sweden: an epidemic of viral-induced carcinoma? Int. J. Cancer. 125, 362\u2013366 (2009).","journal-title":"Int. J. Cancer"},{"key":"33345_CR9","doi-asserted-by":"publisher","first-page":"e85","DOI":"10.1016\/j.oraloncology.2009.03.010","volume":"45","author":"BJ Braakhuis","year":"2009","unstructured":"Braakhuis, B. J., Visser, O. & Leemans, C. R. Oral and oropharyngeal cancer in the Netherlands between 1989 and 2006: increasing incidence, but not in young adults. Oral Oncol. 45, e85\u2013e89 (2009).","journal-title":"Oral Oncol."},{"key":"33345_CR10","doi-asserted-by":"publisher","first-page":"4294","DOI":"10.1200\/JCO.2011.36.4596","volume":"29","author":"AK Chaturvedi","year":"2011","unstructured":"Chaturvedi, A. K. et al. Human papillomavirus and rising oropharyngeal cancer incidence in the united States. J. Clin. Oncol. 29, 4294\u20134301 (2011).","journal-title":"J. Clin. Oncol."},{"key":"33345_CR11","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1002\/lary.24296","volume":"124","author":"AY Chen","year":"2014","unstructured":"Chen, A. Y., Zhu, J. & Fedewa, S. Temporal trends in oropharyngeal cancer treatment and survival: 1998\u20132009. Laryngoscope 124, 131\u2013138 (2014).","journal-title":"Laryngoscope"},{"key":"33345_CR12","doi-asserted-by":"publisher","first-page":"1583","DOI":"10.1002\/hed.25585","volume":"41","author":"L Haeggblom","year":"2019","unstructured":"Haeggblom, L. et al. Changes in incidence and of human papillomavirus in tonsillar and base of tongue cancer during 2000\u20132016 in the Stockholm region and Sweden. Head Neck. 41, 1583\u20131590 (2019).","journal-title":"Head Neck"},{"key":"33345_CR13","doi-asserted-by":"publisher","first-page":"2169","DOI":"10.1002\/ijc.35099","volume":"155","author":"BB Lauritzen","year":"2024","unstructured":"Lauritzen, B. B. et al. Epidemiological trends and survival of oropharyngeal cancer in a high HPV-prevalent area: A Danish population-based study from 2000 to 2020. Int. J. Cancer. 155, 2169\u20132179 (2024).","journal-title":"Int. J. Cancer"},{"key":"33345_CR14","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1016\/j.molonc.2007.08.005","volume":"1","author":"D Lindquist","year":"2007","unstructured":"Lindquist, D. et al. Human papillomavirus is a favourable prognostic factor in tonsillar cancer and its oncogenic role is supported by the expression of E6 and E7. Mol. Oncol. 1, 350\u2013355 (2007).","journal-title":"Mol. Oncol."},{"key":"33345_CR15","doi-asserted-by":"publisher","first-page":"2892","DOI":"10.1002\/ijc.25625","volume":"128","author":"P Attner","year":"2011","unstructured":"Attner, P. et al. Human papillomavirus and survival in patients with base of tongue cancer. Int. J. Cancer. 128, 2892\u20132897 (2011).","journal-title":"Int. J. Cancer"},{"key":"33345_CR16","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1038\/s41571-022-00603-7","volume":"19","author":"M Lechner","year":"2022","unstructured":"Lechner, M., Liu, J., Masterson, L. & Fenton, T. R. HPV-associated oropharyngeal cancer: epidemiology, molecular biology and clinical management. Nat. Rev. Clin. Oncol. 19, 306\u2013327 (2022).","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"33345_CR17","unstructured":"Oropharyngeal Cancer. Treatment (Adult) (PDQ\u00ae)\u2013Health Professional Version. (accessed 04 July 2021); https:\/\/www.cancer.gov\/types\/head-and-neck\/hp\/adult\/oropharyngeal-treatment-pdq"},{"key":"33345_CR18","doi-asserted-by":"publisher","first-page":"873","DOI":"10.6004\/jnccn.2020.0031","volume":"18","author":"DG Pfister","year":"2020","unstructured":"Pfister, D. G. et al. Head and neck Cancers, version 2.2020, NCCN clinical practice guidelines in oncology. J. Natl. Compr. Canc Netw. 18, 873\u2013898 (2020).","journal-title":"J. Natl. Compr. Canc Netw."},{"key":"33345_CR19","doi-asserted-by":"publisher","first-page":"2138","DOI":"10.1158\/1078-0432.CCR-09-3185","volume":"16","author":"AC Nichols","year":"2010","unstructured":"Nichols, A. C. et al. Bcl2 and human papilloma virus 16 as predictors of outcome following concurrent chemoradiation for advanced oropharyngeal cancer. Clin. Cancer Res. 16, 2138\u20132146 (2010).","journal-title":"Clin. Cancer Res."},{"key":"33345_CR20","first-page":"153","volume":"32","author":"D Lindquist","year":"2012","unstructured":"Lindquist, D., Ahrlund-Richter, A., Tarjan, M., Tot, T. & Dalianis, T. Intense CD44 expression is a negative prognostic factor in tonsillar and base of tongue cancer. Anticancer Res. 32, 153\u2013161 (2012).","journal-title":"Anticancer Res."},{"key":"33345_CR21","doi-asserted-by":"publisher","first-page":"2522","DOI":"10.1016\/j.ejca.2013.03.019","volume":"49","author":"C Nordfors","year":"2013","unstructured":"Nordfors, C. et al. CD8\u2009+\u2009and CD4\u2009+\u2009tumour infiltrating lymphocytes in relation to human papillomavirus status and clinical outcome in tonsillar and base of tongue squamous cell carcinoma. Eur. J. Cancer. 49, 2522\u20132530 (2013).","journal-title":"Eur. J. Cancer"},{"key":"33345_CR22","doi-asserted-by":"publisher","first-page":"2154","DOI":"10.1158\/1078-0432.CCR-12-3572","volume":"19","author":"AB Hui","year":"2013","unstructured":"Hui, A. B. et al. Potentially prognostic MiRNAs in HPV-associated oropharyngeal carcinoma. Clin. Cancer Res. 19, 2154\u20132162 (2013).","journal-title":"Clin. Cancer Res."},{"key":"33345_CR23","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1186\/gm453","volume":"5","author":"M Lechner","year":"2013","unstructured":"Lechner, M. et al. Targeted next-generation sequencing of head and neck squamous cell carcinoma identifies novel genetic alterations in HPV\u2009+\u2009and HPV- tumors. Genome Med. 5, 49 (2013).","journal-title":"Genome Med."},{"key":"33345_CR24","doi-asserted-by":"publisher","first-page":"1793","DOI":"10.1038\/bjc.2014.87","volume":"110","author":"D Lindquist","year":"2014","unstructured":"Lindquist, D. et al. Expression of LRIG1 is associated with good prognosis and human papillomavirus status in oropharyngeal cancer. Br. J. Cancer. 110, 1793\u20131800 (2014).","journal-title":"Br. J. Cancer"},{"key":"33345_CR25","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1016\/j.ejca.2013.11.010","volume":"50","author":"MM Rietbergen","year":"2014","unstructured":"Rietbergen, M. M. et al. Cancer stem cell enrichment marker CD98: a prognostic factor for survival in patients with human papillomavirus-positive oropharyngeal cancer. Eur. J. Cancer. 50, 765\u2013773 (2014).","journal-title":"Eur. J. Cancer"},{"key":"33345_CR26","doi-asserted-by":"publisher","first-page":"14416","DOI":"10.18632\/oncotarget.14796","volume":"8","author":"K Oguejiofor","year":"2017","unstructured":"Oguejiofor, K. et al. Distinct patterns of infiltrating CD8\u2009+\u2009T cells in HPV\u2009+\u2009and CD68 macrophages in HPV- oropharyngeal squamous cell carcinomas are associated with better clinical outcome but PD-L1 expression is not prognostic. Oncotarget 8, 14416\u201314427 (2017).","journal-title":"Oncotarget"},{"key":"33345_CR27","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.oraloncology.2017.03.007","volume":"68","author":"C Bersani","year":"2017","unstructured":"Bersani, C. et al. A model using concomitant markers for predicting outcome in human papillomavirus positive oropharyngeal cancer. Oral Oncol. 68, 53\u201355 (2017).","journal-title":"Oral Oncol."},{"key":"33345_CR28","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.ejca.2017.02.018","volume":"77","author":"AK Hess","year":"2017","unstructured":"Hess, A. K. et al. MiR-200b and miR-155 as predictive biomarkers for the efficacy of chemoradiation in locally advanced head and neck squamous cell carcinoma. Eur. J. Cancer. 77, 3\u201312 (2017).","journal-title":"Eur. J. Cancer"},{"key":"33345_CR29","doi-asserted-by":"publisher","first-page":"35339","DOI":"10.18632\/oncotarget.15240","volume":"8","author":"C Bersani","year":"2017","unstructured":"Bersani, C. et al. Targeted sequencing of tonsillar and base of tongue cancer and human papillomavirus positive unknown primary of the head and neck reveals prognostic effects of mutated FGFR3. Oncotarget 8, 35339\u201335350 (2017).","journal-title":"Oncotarget"},{"key":"33345_CR30","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.oraloncology.2018.04.021","volume":"82","author":"C Bersani","year":"2018","unstructured":"Bersani, C. et al. MicroRNA-155, -185 and \u2013\u2009193b as biomarkers in human papillomavirus positive and negative tonsillar and base of tongue squamous cell carcinoma. Oral Oncol. 82, 8\u201316 (2018).","journal-title":"Oral Oncol."},{"key":"33345_CR31","doi-asserted-by":"publisher","first-page":"1672","DOI":"10.1038\/s41416-018-0107-9","volume":"118","author":"C Gronhoj","year":"2018","unstructured":"Gronhoj, C. et al. Development and external validation of nomograms in oropharyngeal cancer patients with known HPV-DNA status: a European multicentre study (OroGrams). Br. J. Cancer. 118, 1672\u20131681 (2018).","journal-title":"Br. J. Cancer"},{"key":"33345_CR32","doi-asserted-by":"publisher","first-page":"1601","DOI":"10.21037\/atm-20-2984","volume":"8","author":"MP Strohl","year":"2020","unstructured":"Strohl, M. P., Wai, K. C. & Ha, P. K. De-intensification strategies in HPV-related oropharyngeal squamous cell carcinoma-a narrative review. Ann. Transl Med. 8, 1601 (2020).","journal-title":"Ann. Transl Med."},{"key":"33345_CR33","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1093\/jnci\/djz224","volume":"112","author":"BT Beaty","year":"2020","unstructured":"Beaty, B. T. et al. PIK3CA mutation in HPV-Associated OPSCC patients receiving deintensified chemoradiation. J. Natl. Cancer Inst. 112, 855\u2013858 (2020).","journal-title":"J. Natl. Cancer Inst."},{"key":"33345_CR34","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1111\/joim.20088","volume":"297","author":"M Zupancic","year":"2025","unstructured":"Zupancic, M., Kostopoulou, O. N., Marklund, L. & Dalianis, T. Therapeutic options for human papillomavirus-positive tonsil and base of tongue cancer. J. Intern. Med. 297, 608\u2013629 (2025).","journal-title":"J. Intern. Med."},{"key":"33345_CR35","doi-asserted-by":"publisher","first-page":"2193","DOI":"10.1002\/cncr.34109","volume":"128","author":"CJ O\u2019Boyle","year":"2022","unstructured":"O\u2019Boyle, C. J. et al. Cell-free human papillomavirus DNA kinetics after surgery for human papillomavirus-associated oropharyngeal cancer. Cancer 128, 2193\u20132204 (2022).","journal-title":"Cancer"},{"key":"33345_CR36","doi-asserted-by":"publisher","first-page":"15777","DOI":"10.1002\/cam4.6191","volume":"12","author":"ST Ferrier","year":"2023","unstructured":"Ferrier, S. T., Tsering, T., Sadeghi, N., Zeitouni, A. & Burnier, J. V. Blood and saliva-derived ctdna is a marker of residual disease after treatment and correlates with recurrence in human papillomavirus-associated head and neck cancer. Cancer Med. 12, 15777\u201315787 (2023).","journal-title":"Cancer Med."},{"key":"33345_CR37","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.ygyno.2022.07.028","volume":"167","author":"L Sivars","year":"2022","unstructured":"Sivars, L. et al. Circulating cell-free tumor human papillomavirus DNA is a promising biomarker in cervical cancer. Gynecol. Oncol. 167, 107\u2013114 (2022).","journal-title":"Gynecol. Oncol."},{"key":"33345_CR38","doi-asserted-by":"publisher","first-page":"3914","DOI":"10.1158\/1078-0432.CCR-23-1064","volume":"29","author":"KK Jakobsen","year":"2023","unstructured":"Jakobsen, K. K. et al. Liquid biopsies with Circulating plasma HPV-DNA measurements-a clinically applicable surveillance tool for patients with hpv-positive oropharyngeal cancer. Clin. Cancer Res. 29, 3914\u20133923 (2023).","journal-title":"Clin. Cancer Res."},{"key":"33345_CR39","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1007\/s40291-024-00743-9","volume":"28","author":"A Qvick","year":"2024","unstructured":"Qvick, A. et al. Sensitive and specific droplet digital PCR assays for Circulating tumor HPV DNA: development, validation, and clinical application in HPV-associated cancers. Mol. Diagn. Ther. 28, 835\u2013845 (2024).","journal-title":"Mol. Diagn. Ther."},{"key":"33345_CR40","doi-asserted-by":"publisher","first-page":"2764","DOI":"10.1158\/1078-0432.CCR-23-3941","volume":"30","author":"L Sivars","year":"2024","unstructured":"Sivars, L. et al. Cell-free human papillomavirus DNA is a sensitive biomarker for prognosis and for early detection of relapse in locally advanced cervical cancer. Clin. Cancer Res. 30, 2764\u20132771 (2024).","journal-title":"Clin. Cancer Res."},{"key":"33345_CR41","doi-asserted-by":"publisher","first-page":"2465","DOI":"10.1002\/ijc.22980","volume":"121","author":"SJ Smeets","year":"2007","unstructured":"Smeets, S. J. et al. A novel algorithm for reliable detection of human papillomavirus in paraffin embedded head and neck cancer specimen. Int. J. Cancer. 121, 2465\u20132472 (2007).","journal-title":"Int. J. Cancer"},{"key":"33345_CR42","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/j.oraloncology.2018.01.010","volume":"78","author":"M Mena","year":"2018","unstructured":"Mena, M. et al. Double positivity for HPV-DNA\/p16(ink4a) is the biomarker with strongest diagnostic accuracy and prognostic value for human papillomavirus related oropharyngeal cancer patients. Oral Oncol. 78, 137\u2013144 (2018).","journal-title":"Oral Oncol."},{"key":"33345_CR43","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/S1470-2045(23)00013-X","volume":"24","author":"H Mehanna","year":"2023","unstructured":"Mehanna, H. et al. HNCIG-EPIC group. Prognostic implications of p16 and HPV discordance in oropharyngeal cancer (HNCIG-EPIC-OPC): a multicentre, multinational, individual patient data analysis. Lancet Oncol. 24, 239\u2013251 (2023).","journal-title":"Lancet Oncol."},{"key":"33345_CR44","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1097\/CCO.0000000000000935","volume":"35","author":"I Tinhofer","year":"2023","unstructured":"Tinhofer, I., Staudte, S. & George, S. Liquid biopsy in head neck cancer: ready for clinical routine diagnostics? Curr. Opin. Oncol. 35, 151\u2013157 (2023).","journal-title":"Curr. Opin. Oncol."},{"key":"33345_CR45","doi-asserted-by":"publisher","first-page":"3278","DOI":"10.1038\/s41598-024-53894-4","volume":"14","author":"M Tatsumi","year":"2024","unstructured":"Tatsumi, M. et al. Association of Circulating tumor HPV16DNA levels and quantitative PET parameters in patients with HPV-positive head and neck squamous cell carcinoma. Sci. Rep. 14, 3278 (2024).","journal-title":"Sci. Rep."},{"key":"33345_CR46","doi-asserted-by":"publisher","first-page":"4682","DOI":"10.1158\/1078-0432.CCR-19-0211","volume":"25","author":"BS Chera","year":"2019","unstructured":"Chera, B. S. et al. Rapid clearance profile of plasma Circulating tumor HPV type 16 DNA during chemoradiotherapy correlates with disease control in HPV-Associated oropharyngeal cancer. Clin. Cancer Res. 25, 4682\u20134690 (2019).","journal-title":"Clin. Cancer Res."},{"key":"33345_CR47","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1158\/1078-0432.CCR-21-2338","volume":"28","author":"Y Cao","year":"2022","unstructured":"Cao, Y. et al. Early HPV ctdna kinetics and imaging biomarkers predict therapeutic response in p16\u2009+\u2009Oropharyngeal squamous cell carcinoma. Clin. Cancer Res. 28, 350\u2013359 (2022).","journal-title":"Clin. Cancer Res."},{"key":"33345_CR48","doi-asserted-by":"publisher","first-page":"1120","DOI":"10.1001\/jamaoto.2022.3282","volume":"148","author":"EM Rettig","year":"2022","unstructured":"Rettig, E. M. et al. Association of pretreatment Circulating tumor Tissue-Modified viral HPV DNA with clinicopathologic factors in HPV-Positive oropharyngeal cancer. JAMA Otolaryngol. Head Neck Surg. 148, 1120\u20131130 (2022).","journal-title":"JAMA Otolaryngol. Head Neck Surg."},{"key":"33345_CR49","doi-asserted-by":"publisher","first-page":"1126","DOI":"10.1016\/j.oraloncology.2015.09.007","volume":"51","author":"T Ramqvist","year":"2015","unstructured":"Ramqvist, T. et al. Studies on human papillomavirus (HPV) 16 E2, E5 and E7 mRNA in HPV-positive tonsillar and base of tongue cancer in relation to clinical outcome and immunological parameters. Oral Oncol. 51, 1126\u20131131 (2015).","journal-title":"Oral Oncol."},{"key":"33345_CR50","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.oraloncology.2017.03.007","volume":"68","author":"C Bersani","year":"2017","unstructured":"Bersani, C. et al. A model using concomitant markers for predicting outcome in human papillomavirus positive oropharyngeal cancer. Oral Oncol. 68, 53\u201359 (2017).","journal-title":"Oral Oncol."},{"key":"33345_CR51","doi-asserted-by":"publisher","first-page":"1376595","DOI":"10.3389\/fonc.2024.1376595","volume":"14","author":"A Kais","year":"2024","unstructured":"Kais, A. et al. Human papillomavirus Circulating tumor DNA: a diagnostic tool in squamous cell carcinoma of unknown primary-a pilot study. Front. Oncol. 14, 1376595 (2024).","journal-title":"Front. Oncol."},{"key":"33345_CR52","doi-asserted-by":"publisher","first-page":"1716","DOI":"10.1001\/jamaoncol.2023.4042","volume":"9","author":"KA Lang Kuhs","year":"2023","unstructured":"Lang Kuhs, K. A., Brenner, J. C., Holsinger, F. C. & Rettig, E. M. Circulating tumor HPV DNA for surveillance of HPV-Positive oropharyngeal squamous cell carcinoma: A narrative review. JAMA Oncol. 9, 1716\u20131724 (2023).","journal-title":"JAMA Oncol."},{"key":"33345_CR53","doi-asserted-by":"publisher","first-page":"995","DOI":"10.1002\/ijc.33287","volume":"148","author":"H Tanaka","year":"2021","unstructured":"Tanaka, H. et al. Circulating tumor HPV DNA complements PET-CT in guiding management after radiotherapy in HPV-related squamous cell carcinoma of the head and neck. Int. J. Cancer. 148, 995\u20131005 (2021).","journal-title":"Int. J. Cancer"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-33345-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-33345-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-33345-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T22:01:51Z","timestamp":1766440911000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-33345-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,19]]},"references-count":53,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["33345"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-33345-4","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,19]]},"assertion":[{"value":"18 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 December 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 December 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"44236"}}