{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T16:28:06Z","timestamp":1793982486722,"version":"4.8.0"},"reference-count":24,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T00:00:00Z","timestamp":1670457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Center for Advancing Translational Sciences of the National Institutes of Health","award":["UL1TR002733"],"award-info":[{"award-number":["UL1TR002733"]}]},{"name":"National Center for Advancing Translational Sciences of the National Institutes of Health","award":["R01CA255344"],"award-info":[{"award-number":["R01CA255344"]}]},{"name":"Pelotonia Institute of Immuno-Oncology (PIIO)","award":["UL1TR002733"],"award-info":[{"award-number":["UL1TR002733"]}]},{"name":"Pelotonia Institute of Immuno-Oncology (PIIO)","award":["R01CA255344"],"award-info":[{"award-number":["R01CA255344"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Purpose\/Objective(s): Microbiome has been shown to affect tumorigenesis by promoting inflammation. However, the association between the upper aerodigestive microbiome and head and neck squamous cell carcinoma (HNSCC) is not well established. Hypoxia is a modifiable factor associated with poor radiation response. Our study analyzed the HNSCC tumor samples from The Cancer Genome Atlas (TCGA) to investigate the relationship between different HNSCC tumor subsites, hypoxia, and local tumor microbiome composition. Results: A total of 357 patients were included [Oral cavity (OC) = 226, Oropharynx (OPx) = 53, and Larynx\/Hypopharynx (LHPx) = 78], of which 12.8%, 71.7%, and 10.3%, respectively, were HPV positive. The mean (SD) hypoxia scores were 30.18 (11.10), 24.31 (14.13), and 29.53 (12.61) in OC, OPx, and LHPx tumors, respectively, with higher values indicating greater hypoxia. The hypoxia score was significantly higher for OC tumors compared to OPx (p = 0.044) and LHPx (p = 0.002). There was no significant correlation between hypoxia and HPV status. Pseudomonas sp. in OC, Actinomyces sp. and Sulfurimonas sp. in OPx, and Filifactor, Pseudomonas and Actinomyces sp. in LHPx had the strongest association with the hypoxia score. Materials\/Methods: Tumor RNAseq samples from TCGA were processed, and the R package \u201ctmesig\u201d was used to calculate gene expression signature, including the Buffa hypoxia (BH) score, a validated hypoxia signature using 52 hypoxia-regulated genes. Microbe relative abundances were modeled with primary tumor location and a high vs. low tertile BH score applying a gamma-distributed generalized linear regression using the \u201cstats\u201d package in R, with adjusted p-value &lt; 0.05 considered significant. Conclusions: In our study, oral cavity tumors were found to be more hypoxic compared to other head and neck subsites, which could potentially contribute to their radiation resistance. For each subsite, distinct microbial populations were over-represented in hypoxic tumors in a subsite-specific manner. Further studies focusing on an association between microbiome, hypoxia, and patient outcomes are warranted.<\/jats:p>","DOI":"10.3390\/ijms232415531","type":"journal-article","created":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T02:51:56Z","timestamp":1670467916000},"page":"15531","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Association between Tumor Microbiome and Hypoxia across Anatomic Subsites of Head and Neck Cancers"],"prefix":"10.3390","volume":"23","author":[{"given":"Aastha","family":"Dhakal","sequence":"first","affiliation":[{"name":"The Ohio State University College of Medicine, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rituraj","family":"Upadhyay","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3374-4909","authenticated-orcid":false,"given":"Caroline","family":"Wheeler","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Hoyd","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vidhya","family":"Karivedu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauricio E.","family":"Gamez","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Mayo Clinic, Rochester, MN 55901, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sasha","family":"Valentin","sequence":"additional","affiliation":[{"name":"Department of Dentistry, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meade","family":"Vanputten","sequence":"additional","affiliation":[{"name":"Department of Dentistry, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9515-0498","authenticated-orcid":false,"given":"Priyanka","family":"Bhateja","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9399-3608","authenticated-orcid":false,"given":"Marcelo","family":"Bonomi","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Konieczkowski","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujith","family":"Baliga","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1733-9644","authenticated-orcid":false,"given":"Darrion L.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Grecula","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dukagjin M.","family":"Blakaj","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas C.","family":"Denko","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8604-4757","authenticated-orcid":false,"given":"Sachin R.","family":"Jhawar","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2314-6435","authenticated-orcid":false,"given":"Daniel","family":"Spakowicz","sequence":"additional","affiliation":[{"name":"Pelotonia Institute for Immuno-Oncology, The Ohio State University Comprehensive Cancer Center\u2014Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/s41572-020-00224-3","article-title":"Head and neck squamous cell carcinoma","volume":"6","author":"Johnson","year":"2020","journal-title":"Nat. Rev. Dis. Primer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1038\/s41588-018-0318-2","article-title":"Molecular landmarks of tumor hypoxia across cancer types","volume":"51","author":"Bhandari","year":"2019","journal-title":"Nat. Genet."},{"key":"ref_3","first-page":"20180047","article-title":"HPV, hypoxia and radiation response in head and neck cancer","volume":"92","author":"Ostheimer","year":"2019","journal-title":"Br. J. 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