{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T12:29:41Z","timestamp":1784291381445,"version":"3.55.0"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T00:00:00Z","timestamp":1729555200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T00:00:00Z","timestamp":1729555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"name":"Wisconsin Head and Neck SPORE","award":["P50 CA278595"],"award-info":[{"award-number":["P50 CA278595"]}]},{"name":"Wisconsin Head and Neck SPORE","award":["P50 CA278595"],"award-info":[{"award-number":["P50 CA278595"]}]},{"name":"Wisconsin Head and Neck SPORE","award":["P50 CA278595"],"award-info":[{"award-number":["P50 CA278595"]}]},{"name":"Wisconsin Head and Neck SPORE","award":["P50 CA278595"],"award-info":[{"award-number":["P50 CA278595"]}]},{"name":"Wisconsin Head and Neck SPORE","award":["P50 CA278595"],"award-info":[{"award-number":["P50 CA278595"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Head and Neck Pathol"],"DOI":"10.1007\/s12105-024-01707-5","type":"journal-article","created":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T09:03:30Z","timestamp":1729587810000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Uncommon and Challenging Phenotypes of High-Risk Human Papillomavirus-Associated Head and Neck Carcinomas Revealed by High-Throughput Studies"],"prefix":"10.1007","volume":"18","author":[{"given":"Alex P.","family":"Tannenbaum","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taja","family":"Lozar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changxue","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Schumacher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athena","family":"Golfinos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huy Q.","family":"Dinh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Taylor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randall J.","family":"Kimple","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul M.","family":"Harari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul F.","family":"Lambert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo V.","family":"Lloyd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,10,22]]},"reference":[{"issue":"9","key":"1707_CR1","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1093\/jnci\/92.9.709","volume":"92","author":"ML Gillison","year":"2000","unstructured":"Gillison ML, Koch WM, Capone RB, Spafford M, Westra WH, Wu L et al (2000) Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst 92(9):709\u2013720","journal-title":"J Natl Cancer Inst"},{"issue":"2","key":"1707_CR2","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1097\/PAS.0b013e3182698673","volume":"37","author":"JA Bishop","year":"2013","unstructured":"Bishop JA, Guo TW, Smith DF, Wang H, Ogawa T, Pai SI, Westra WH (2013) Human papillomavirus-related carcinomas of the sinonasal tract. Am J Surg Pathol 37(2):185\u2013192","journal-title":"Am J Surg Pathol"},{"issue":"1","key":"1707_CR3","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1007\/s12105-024-01670-1","volume":"18","author":"T Abi-Saab","year":"2024","unstructured":"Abi-Saab T, Lozar T, Chen Y, Tannenbaum AP, Geye H, Yu M et al (2024) Morphologic spectrum of HPV-associated Sinonasal Carcinomas. Head Neck Pathol 18(1):67","journal-title":"Head Neck Pathol"},{"issue":"4","key":"1707_CR4","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1093\/jnci\/djn011","volume":"100","author":"C Fakhry","year":"2008","unstructured":"Fakhry C, Westra WH, Li S, Cmelak A, Ridge JA, Pinto H et al (2008) Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancer Inst 100(4):261\u2013269","journal-title":"J Natl Cancer Inst"},{"issue":"2","key":"1707_CR5","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1002\/ijc.33514","volume":"149","author":"IH Nauta","year":"2021","unstructured":"Nauta IH, Heideman DAM, Brink A, van der Steen B, Bloemena E, Koljenovic S et al (2021) The unveiled reality of human papillomavirus as risk factor for oral cavity squamous cell carcinoma. Int J Cancer 149(2):420\u2013430","journal-title":"Int J Cancer"},{"issue":"8","key":"1707_CR6","doi-asserted-by":"publisher","first-page":"982","DOI":"10.1007\/s10147-023-02327-9","volume":"28","author":"H Shigeishi","year":"2023","unstructured":"Shigeishi H (2023) Association between human papillomavirus and oral cancer: a literature review. Int J Clin Oncol 28(8):982\u2013989","journal-title":"Int J Clin Oncol"},{"issue":"35","key":"1707_CR7","doi-asserted-by":"publisher","first-page":"3930","DOI":"10.1200\/JCO.2013.54.5228","volume":"32","author":"CH Chung","year":"2014","unstructured":"Chung CH, Zhang Q, Kong CS, Harris J, Fertig EJ, Harari PM et al (2014) p16 protein expression and human papillomavirus status as prognostic biomarkers of nonoropharyngeal head and neck squamous cell carcinoma. J Clin Oncol 32(35):3930\u20133938","journal-title":"J Clin Oncol"},{"issue":"3","key":"1707_CR8","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1007\/s12105-009-0126-1","volume":"3","author":"RD Chernock","year":"2009","unstructured":"Chernock RD, El-Mofty SK, Thorstad WL, Parvin CA, Lewis JS (2009) Jr. HPV-related nonkeratinizing squamous cell carcinoma of the oropharynx: utility of microscopic features in predicting patient outcome. Head Neck Pathol 3(3):186\u2013194","journal-title":"Head Neck Pathol"},{"issue":"8","key":"1707_CR9","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.1097\/PAS.0000000000000650","volume":"40","author":"DD Gondim","year":"2016","unstructured":"Gondim DD, Haynes W, Wang X, Chernock RD, El-Mofty SK, Lewis JS (2016) Jr. Histologic typing in Oropharyngeal squamous cell carcinoma: a 4-Year prospective practice study with p16 and high-risk HPV mRNA testing correlation. Am J Surg Pathol 40(8):1117\u20131124","journal-title":"Am J Surg Pathol"},{"issue":"Suppl 1","key":"1707_CR10","doi-asserted-by":"publisher","first-page":"S41","DOI":"10.1007\/s12105-012-0373-4","volume":"6","author":"RD Chernock","year":"2012","unstructured":"Chernock RD (2012) Morphologic features of conventional squamous cell carcinoma of the oropharynx: \u2018keratinizing\u2019 and \u2018nonkeratinizing\u2019 histologic types as the basis for a consistent classification system. Head Neck Pathol 6(Suppl 1):S41\u2013S47","journal-title":"Head Neck Pathol"},{"issue":"2","key":"1707_CR11","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1001\/jamaoncol.2016.3067","volume":"3","author":"G D\u2019Souza","year":"2017","unstructured":"D\u2019Souza G, Westra WH, Wang SJ, van Zante A, Wentz A, Kluz N et al (2017) Differences in the prevalence of human papillomavirus (HPV) in Head and Neck squamous cell cancers by sex, race, anatomic Tumor Site, and HPV Detection Method. JAMA Oncol 3(2):169\u2013177","journal-title":"JAMA Oncol"},{"issue":"5","key":"1707_CR12","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1097\/PAS.0000000000002204","volume":"48","author":"S Bhardwaj","year":"2024","unstructured":"Bhardwaj S, Gitman M, Ramirez JD, Paniz-Mondolfi A, Westra WH (2024) Reappraisal of p16 for determining HPV Status of Head and Neck Carcinomas arising in HPV hotspots. Am J Surg Pathol 48(5):581\u2013587","journal-title":"Am J Surg Pathol"},{"issue":"5","key":"1707_CR13","doi-asserted-by":"publisher","first-page":"559","DOI":"10.5858\/arpa.2017-0286-CP","volume":"142","author":"JS Lewis Jr","year":"2018","unstructured":"Lewis JS Jr., Beadle B, Bishop JA, Chernock RD, Colasacco C, Lacchetti C et al (2018) Human papillomavirus testing in Head and Neck carcinomas: Guideline from the College of American Pathologists. Arch Pathol Lab Med 142(5):559\u2013597","journal-title":"Arch Pathol Lab Med"},{"issue":"4","key":"1707_CR14","doi-asserted-by":"publisher","first-page":"1251","DOI":"10.1007\/s12105-022-01463-4","volume":"16","author":"SA Rasmussen","year":"2022","unstructured":"Rasmussen SA, Lewis JS Jr., Mirabello L, Bass S, Yeager M, Corsten MJ, Bullock MJ (2022) A case of HPV-Associated Oropharyngeal squamous cell carcinoma with Block-Like, partial loss of p16 expression. Head Neck Pathol 16(4):1251\u20131256","journal-title":"Head Neck Pathol"},{"issue":"4","key":"1707_CR15","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1007\/s12105-022-01467-0","volume":"16","author":"JS Lewis Jr","year":"2022","unstructured":"Lewis JS Jr., Smith MH, Wang X, Tong F, Mehrad M, Lang-Kuhs KA (2022) Human Papillomavirus-Associated oral cavity squamous cell carcinoma: an entity with distinct morphologic and clinical features. Head Neck Pathol 16(4):1073\u20131081","journal-title":"Head Neck Pathol"},{"issue":"5","key":"1707_CR16","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1097\/PAS.0000000000001433","volume":"44","author":"LM Rooper","year":"2020","unstructured":"Rooper LM, Windon MJ, Hernandez T, Miles B, Ha PK, Ryan WR et al (2020) HPV-positive squamous cell carcinoma of the larynx, oral cavity, and hypopharynx: clinicopathologic characterization with Recognition of a Novel Warty variant. Am J Surg Pathol 44(5):691\u2013702","journal-title":"Am J Surg Pathol"},{"issue":"5","key":"1707_CR17","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1097\/PAS.0000000000000800","volume":"41","author":"AM Mills","year":"2017","unstructured":"Mills AM, Dirks DC, Poulter MD, Mills SE, Stoler MH (2017) HR-HPV E6\/E7 mRNA in situ hybridization: Validation Against PCR, DNA in situ hybridization, and p16 immunohistochemistry in 102 samples of Cervical, Vulvar, Anal, and Head and Neck Neoplasia. Am J Surg Pathol 41(5):607\u2013615","journal-title":"Am J Surg Pathol"},{"key":"1707_CR18","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.oraloncology.2016.02.008","volume":"55","author":"LM Rooper","year":"2016","unstructured":"Rooper LM, Gandhi M, Bishop JA, Westra WH (2016) RNA in-situ hybridization is a practical and effective method for determining HPV status of oropharyngeal squamous cell carcinoma including discordant cases that are p16 positive by immunohistochemistry but HPV negative by DNA in-situ hybridization. Oral Oncol 55:11\u201316","journal-title":"Oral Oncol"},{"key":"1707_CR19","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.humpath.2019.05.006","volume":"90","author":"R Randen-Brady","year":"2019","unstructured":"Randen-Brady R, Carpen T, Jouhi L, Syrjanen S, Haglund C, Tarkkanen J et al (2019) In situ hybridization for high-risk HPV E6\/E7 mRNA is a superior method for detecting transcriptionally active HPV in oropharyngeal cancer. Hum Pathol 90:97\u2013105","journal-title":"Hum Pathol"},{"issue":"9","key":"1707_CR20","doi-asserted-by":"publisher","first-page":"944","DOI":"10.1097\/01.MP.0000085760.74313.DD","volume":"16","author":"L Ai","year":"2003","unstructured":"Ai L, Stephenson KK, Ling W, Zuo C, Mukunyadzi P, Suen JY et al (2003) The p16 (CDKN2a\/INK4a) tumor-suppressor gene in head and neck squamous cell carcinoma: a promoter methylation and protein expression study in 100 cases. Mod Pathol 16(9):944\u2013950","journal-title":"Mod Pathol"},{"issue":"3","key":"1707_CR21","doi-asserted-by":"publisher","first-page":"e13","DOI":"10.1093\/nar\/gkad1167","volume":"52","author":"PL Baldoni","year":"2024","unstructured":"Baldoni PL, Chen Y, Hediyeh-Zadeh S, Liao Y, Dong X, Ritchie ME et al (2024) Dividing out quantification uncertainty allows efficient assessment of differential transcript expression with edgeR. Nucleic Acids Res 52(3):e13","journal-title":"Nucleic Acids Res"},{"issue":"12","key":"1707_CR22","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","volume":"15","author":"MI Love","year":"2014","unstructured":"Love MI, Huber W, Anders S (2014) Moderated estimation of Fold change and dispersion for RNA-seq data with DESeq2. Genome Biol 15(12):550","journal-title":"Genome Biol"},{"issue":"18","key":"1707_CR23","doi-asserted-by":"publisher","first-page":"2847","DOI":"10.1093\/bioinformatics\/btw313","volume":"32","author":"Z Gu","year":"2016","unstructured":"Gu Z, Eils R, Schlesner M (2016) Complex heatmaps reveal patterns and correlations in multidimensional genomic data. Bioinformatics 32(18):2847\u20132849","journal-title":"Bioinformatics"},{"issue":"12","key":"1707_CR24","doi-asserted-by":"publisher","first-page":"1646","DOI":"10.1038\/modpathol.2017.71","volume":"30","author":"MA Lerman","year":"2017","unstructured":"Lerman MA, Almazrooa S, Lindeman N, Hall D, Villa A, Woo SB (2017) HPV-16 in a distinct subset of oral epithelial dysplasia. Mod Pathol 30(12):1646\u20131654","journal-title":"Mod Pathol"},{"issue":"3","key":"1707_CR25","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, Taberna M, von Buchwald C, Tous S, Brooks J, Mena M et al (2023) Prognostic implications of p16 and HPV discordance in oropharyngeal cancer (HNCIG-EPIC-OPC): a multicentre, multinational, individual patient data analysis. Lancet Oncol 24(3):239\u2013251","journal-title":"Lancet Oncol"},{"issue":"7","key":"1707_CR26","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1111\/pin.12930","volume":"70","author":"M Rokutan-Kurata","year":"2020","unstructured":"Rokutan-Kurata M, Minamiguchi S, Kataoka TR, Abiko K, Mandai M, Haga H (2020) Uterine cervical squamous cell carcinoma without p16 (CDKN2A) expression: heterogeneous causes of an unusual immunophenotype. Pathol Int 70(7):413\u2013421","journal-title":"Pathol Int"},{"issue":"12","key":"1707_CR27","doi-asserted-by":"publisher","first-page":"1319","DOI":"10.1016\/S1470-2045(14)70471-1","volume":"15","author":"C Ndiaye","year":"2014","unstructured":"Ndiaye C, Mena M, Alemany L, Arbyn M, Castellsague X, Laporte L et al (2014) HPV DNA, E6\/E7 mRNA, and p16INK4a detection in head and neck cancers: a systematic review and meta-analysis. Lancet Oncol 15(12):1319\u20131331","journal-title":"Lancet Oncol"},{"issue":"2","key":"1707_CR28","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1007\/s10006-012-0383-0","volume":"18","author":"K Kansy","year":"2014","unstructured":"Kansy K, Thiele O, Freier K (2014) The role of human papillomavirus in oral squamous cell carcinoma: myth and reality. Oral Maxillofac Surg 18(2):165\u2013172","journal-title":"Oral Maxillofac Surg"},{"issue":"1","key":"1707_CR29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.oraloncology.2012.07.002","volume":"49","author":"MW Lingen","year":"2013","unstructured":"Lingen MW, Xiao W, Schmitt A, Jiang B, Pickard R, Kreinbrink P et al (2013) Low etiologic fraction for high-risk human papillomavirus in oral cavity squamous cell carcinomas. Oral Oncol 49(1):1\u20138","journal-title":"Oral Oncol"},{"issue":"1","key":"1707_CR30","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1002\/cre2.342","volume":"7","author":"TM Soland","year":"2021","unstructured":"Soland TM, Bjerkli IH, Georgsen JB, Schreurs O, Jebsen P, Laurvik H, Sapkota D (2021) High-risk human papilloma virus was not detected in a Norwegian cohort of oral squamous cell carcinoma of the mobile tongue. Clin Exp Dent Res 7(1):70\u201377","journal-title":"Clin Exp Dent Res"},{"key":"1707_CR31","doi-asserted-by":"crossref","unstructured":"Nibu KI, Oridate N, Saito Y, Roset M, Fores Maresma M, Cuadras D et al (2024) Human papillomavirus-driven head and neck cancers in Japan during 2008\u20132009 and 2018\u20132019: the BROADEN study. Cancer Sci","DOI":"10.1111\/cas.16230"},{"key":"1707_CR32","doi-asserted-by":"crossref","unstructured":"Katirachi SK, Gronlund MP, Jakobsen KK, Gronhoj C, von Buchwald C (2023) The prevalence of HPV in oral cavity squamous cell carcinoma. Viruses. ;15(2)","DOI":"10.3390\/v15020451"},{"issue":"3","key":"1707_CR33","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/caac.21660","volume":"71","author":"H Sung","year":"2021","unstructured":"Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F (2021) Global Cancer statistics 2020: GLOBOCAN estimates of incidence and Mortality Worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71(3):209\u2013249","journal-title":"CA Cancer J Clin"}],"container-title":["Head and Neck Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12105-024-01707-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12105-024-01707-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12105-024-01707-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,8]],"date-time":"2025-01-08T15:06:30Z","timestamp":1736348790000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12105-024-01707-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,22]]},"references-count":33,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["1707"],"URL":"https:\/\/doi.org\/10.1007\/s12105-024-01707-5","relation":{},"ISSN":["1936-0568"],"issn-type":[{"value":"1936-0568","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,22]]},"assertion":[{"value":"30 August 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 September 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 October 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and\/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"}},{"value":"For this type of study informed consent is not required. This study has obtained IRB approval from University of Wisconsin and the need for informed consent was waived.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed Consent"}},{"value":"For this type of retrospective study, consent for publication is not required.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for Publication"}},{"value":"The authors declare no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"112"}}