{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T23:45:41Z","timestamp":1793403941780,"version":"4.5.0"},"reference-count":34,"publisher":"SAGE Publications","issue":"11","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["DNA and Cell Biology"],"published-print":{"date-parts":[[2026,11,1]]},"abstract":"<jats:p>Head and neck squamous cell carcinoma (HNSCC) presents a significant global health challenge, characterized by late-stage diagnosis and high rates of locoregional recurrence. Traditional tissue biopsy, while considered the gold standard, is invasive and often fails to capture the spatial and temporal heterogeneity of the tumor. Liquid biopsy has emerged as a transformative, noninvasive paradigm for molecular diagnostics, leveraging circulating biomarkers found in blood and saliva. This systematic review critically evaluates current evidence regarding the diagnostic accuracy, prognostic value, and molecular validity of circulating tumor cells, circulating tumor DNA (ctDNA), and the transcriptomic landscape of coding and noncoding RNAs (miRNAs, lncRNAs, and circRNAs) in HNSCC. Our review highlights the specificity of ctDNA for monitoring minimal residual disease, particularly in human papillomavirus- and Epstein-Barr virus-driven malignancies, where viral kinetics serve as sensitive biomarkers for recurrence. Furthermore, we explore the utility of \u201cSaliva-Exosomics,\u201d suggesting that salivary exosomes may offer high sensitivity for early-stage oral cavity lesions due to anatomical proximity. The review also synthesizes data on novel RNA species, such as tumor-educated platelets and circular RNAs, which act as stable systemic biosensors. Despite promising results, significant heterogeneity in isolation protocols and detection platforms (e.g., next-generation sequencing vs. digital PCR) remains a barrier to widespread clinical implementation. We conclude that integrating multianalyte liquid biopsies into clinical practice holds the potential to personalize therapeutic strategies, improve survival outcomes, and redefine the standard of care in head and neck oncology.<\/jats:p>","DOI":"10.1177\/10445498261475085","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T09:14:14Z","timestamp":1785921254000},"page":"527-534","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Liquid Biopsy in Head and Neck Squamous Cell Carcinoma: A Systematic Review of the Scientific Literature"],"prefix":"10.1177","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-1418-2562","authenticated-orcid":false,"given":"Tabata","family":"Briaunys Milan","sequence":"first","affiliation":[{"name":"Head and Neck Department, Institute of Cancer Dr. Arnaldo Vieira de Carvalho (ICAVC), S\u00e3o Paulo, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cailaine","family":"Garcia Pereira","sequence":"additional","affiliation":[{"name":"Head and Neck Department, Institute of Cancer Dr. Arnaldo Vieira de Carvalho (ICAVC), S\u00e3o Paulo, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Pereira de Souza","sequence":"additional","affiliation":[{"name":"Head and Neck Department, Institute of Cancer Dr. Arnaldo Vieira de Carvalho (ICAVC), S\u00e3o Paulo, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo","family":"Soares Schalch","sequence":"additional","affiliation":[{"name":"Head and Neck Department, Institute of Cancer Dr. Arnaldo Vieira de Carvalho (ICAVC), S\u00e3o Paulo, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"De Cicco","sequence":"additional","affiliation":[{"name":"Head and Neck Department, Institute of Cancer Dr. Arnaldo Vieira de Carvalho (ICAVC), S\u00e3o Paulo, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"key":"e_1_3_2_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2017.07.004"},{"key":"e_1_3_2_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2015.09.018"},{"key":"e_1_3_2_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3007094"},{"key":"e_1_3_2_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14122858"},{"key":"e_1_3_2_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics8020031"},{"key":"e_1_3_2_7_1","first-page":"1120000","article-title":"Liquid biopsy in head and neck cancer: Current evidence and future perspectives","volume":"13","author":"Economopoulou P","year":"2023","unstructured":"Economopoulou P, , Kotsantis I, , Kyrodimos E, et al. Liquid biopsy in head and neck cancer: Current evidence and future perspectives. Front Oncol 2023;13:1120000.","journal-title":"Front Oncol"},{"issue":"4","key":"e_1_3_2_8_1","first-page":"1395","article-title":"Liquid biopsy and PCR-free ultrasensitive detection systems in oncology (review)","volume":"53","author":"Finotti A","year":"2018","unstructured":"Finotti A, , Allegretti M, , Gasparello J, et al. Liquid biopsy and PCR-free ultrasensitive detection systems in oncology (review). Int J Oncol 2018;53(4):1395\u20131434.","journal-title":"Int J Oncol"},{"issue":"9","key":"e_1_3_2_9_1","first-page":"1280","article-title":"Circulating tumor DNA as a marker of therapeutic efficacy in head and neck cancer","volume":"10","author":"Galot R","year":"2020","unstructured":"Galot R, , Le Tourneau C, , Guigay J, et al. Circulating tumor DNA as a marker of therapeutic efficacy in head and neck cancer. 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Mol Cancer 2023;22(1):50\u201368.","journal-title":"Mol Cancer"},{"key":"e_1_3_2_17_1","first-page":"3089","article-title":"Circulating tumor cells in patients with head and neck squamous cell carcinoma: A feasibility study on the correlation of cytological and molecular findings with clinical parameters","volume":"279","author":"Linxweiler M","year":"2022","unstructured":"Linxweiler M, , K\u00f6rner S, , Wemmert S, et al. Circulating tumor cells in patients with head and neck squamous cell carcinoma: A feasibility study on the correlation of cytological and molecular findings with clinical parameters. 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