{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T13:10:05Z","timestamp":1779282605026,"version":"3.51.4"},"reference-count":18,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100005713","name":"Technische Universit\u00e4t M\u00fcnchen","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005713","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Transl Med"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Human papillomavirus (HPV) is a major etiological factor in a subset of head and neck squamous cell carcinomas (HNSCC), particularly in the oropharynx, and reliable detection is critical for prognosis and treatment decisions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We applied droplet digital PCR (ddPCR) assays targeting HPV16 oncogenes (E6, E7) and the non-oncogenic gene E2 to tumor tissue, blood plasma, and oral rinse samples from 58 HNSCC patients. Results were compared with p16\n                      <jats:sup>INK4a<\/jats:sup>\n                      immunohistochemistry (IHC). A cohort of 44 non-cancer controls was included. Longitudinal monitoring was performed in 33 patients with serial liquid biopsies.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      ddPCR identified 41% of patients as HPV16-positive in tumor tissue, with higher specificity than p16\n                      <jats:sup>INK4a<\/jats:sup>\n                      IHC, which yielded 10 likely false positives. Baseline liquid biopsy results were highly concordant with tissue findings, and all 44 controls tested negative. Both blood plasma and oral rinse performed reliably, though oral rinse may be particularly well suited for HPV-related HNSCC due to direct mucosal shedding. In longitudinal analyses, all initially HPV-positive patients showed HPV clearance after surgery. In two cases, loss of clearance (i.e. re-detection of HPV DNA in plasma and oral rinse) preceded clinically confirmed progression, with lead times of 87 and 122\u2009days.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      ddPCR-based HPV testing provides high diagnostic specificity compared with p16\n                      <jats:sup>INK4a<\/jats:sup>\n                      IHC and allows minimally invasive monitoring. Plasma and oral rinse represent complementary liquid biopsy sources, with oral rinse offering particular advantages for mucosal tumors. Longitudinal testing revealed early molecular recurrence, supporting its potential as a prognostic tool. While promising, the use of liquid biopsy\u2013based HPV detection for screening at-risk but undiagnosed populations remains exploratory and requires further evaluation in larger cohorts.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12967-026-08248-1","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T07:45:04Z","timestamp":1779176704000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Blood plasma and oral rinse liquid profiling for human papillomavirus in head and neck cancer \u2013 Unmasking false-positive p16 tissue cases and tracking disease dynamics"],"prefix":"10.1186","volume":"24","author":[{"given":"Matthias","family":"Mack","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Romina","family":"Roesch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jakob","family":"Rinecker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabian","family":"St\u00f6gbauer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Krippgans","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus","family":"Nieberler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katharina","family":"P\u00fcchler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cecilia","family":"Garcia-Perez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramona","family":"Secci","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Jacob","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole","family":"Pfarr","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katja","family":"Steiger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolin","family":"Mogler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Wollenberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00fcrgen","family":"Ruland","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irina A.","family":"Kerle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus","family":"Wirth","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0253-9056","authenticated-orcid":false,"given":"Christof","family":"Winter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,5,19]]},"reference":[{"issue":"3","key":"8248_CR1","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3322\/caac.21834","volume":"74","author":"F Bray","year":"2024","unstructured":"Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. 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Sampling, biobanking, patient data collection, and analyses were performed in accordance with the Declaration of Helsinki and after approval by the local Institutional Review Board (Technical University of Munich).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"694"}}