{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T13:41:32Z","timestamp":1780926092409,"version":"3.54.1"},"reference-count":41,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T00:00:00Z","timestamp":1674604800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fonds National de la Recherche Scientifique","award":["40007250"],"award-info":[{"award-number":["40007250"]}]},{"name":"Helmholtz International Graduate School of the DKFZ","award":["40007250"],"award-info":[{"award-number":["40007250"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Head and neck squamous cell carcinomas (HNSCC) caused by infections with high-risk human papillomaviruses (HPV) are responsible for an increasing number of head and neck cancers, particularly in the oropharynx. Despite the significant biological differences between HPV-driven and HPV-negative HNSCC, treatment strategies are similar and not HPV targeted. HPV-driven HNSCC are known to be more sensitive to treatment, particularly to radiotherapy, which is at least partially due to HPV-induced immunogenicity. The development of novel therapeutic strategies that are specific for HPV-driven cancers requires tumor models that reflect as closely as possible the characteristics and complexity of human tumors and their response to treatment. Current HPV-positive cancer models lack one or more hallmarks of their human counterpart. This study presents the development of a new HPV16 oncoprotein-dependent tumor model in MHC-humanized mice, modeling the major biologic features of HPV-driven tumors and presenting HLA-A2-restricted HPV16 epitopes. Furthermore, this model was developed to be orthotopic (base of tongue). Thus, it also reflects the correct tumor microenvironment of HPV-driven HNSCC. The cancer cells are implanted in a manner that allows the exact control of the anatomical location of the developing tumor, thereby homogenizing tumor growth. In conclusion, the new model is suited to study HPV16-specific therapeutic vaccinations and other immunotherapies, as well as tumor-targeted interventions, such as surgery or radiotherapy, or a combination of all these modalities.<\/jats:p>","DOI":"10.3390\/pathogens12020188","type":"journal-article","created":{"date-parts":[[2023,1,26]],"date-time":"2023-01-26T01:30:30Z","timestamp":1674696630000},"page":"188","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Development of an Orthotopic HPV16-Dependent Base of Tongue Tumor Model in MHC-Humanized Mice"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2266-8621","authenticated-orcid":false,"given":"Christoph","family":"Schifflers","sequence":"first","affiliation":[{"name":"Immunotherapy and Immunoprevention, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"},{"name":"Cell Biology Research Unit (URBC)\u2013Namur Research Institute for Life Sciences (NARILIS), University of Namur, 5000 Namur, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9077-635X","authenticated-orcid":false,"given":"Samantha","family":"Zottnick","sequence":"additional","affiliation":[{"name":"Immunotherapy and Immunoprevention, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"},{"name":"Molecular Vaccine Design, German Center for Infection Research, Partner Site Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3437-6738","authenticated-orcid":false,"given":"Jonas D.","family":"F\u00f6rster","sequence":"additional","affiliation":[{"name":"Immunotherapy and Immunoprevention, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"},{"name":"Molecular Vaccine Design, German Center for Infection Research, Partner Site Heidelberg, 69120 Heidelberg, Germany"},{"name":"Faculty of Biosciences, Heidelberg University, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4028-1391","authenticated-orcid":false,"given":"Sebastian","family":"Kruse","sequence":"additional","affiliation":[{"name":"Immunotherapy and Immunoprevention, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"},{"name":"Molecular Vaccine Design, German Center for Infection Research, Partner Site Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2890-6475","authenticated-orcid":false,"given":"Ruwen","family":"Yang","sequence":"additional","affiliation":[{"name":"Viral Transformation Mechanisms, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8450-653X","authenticated-orcid":false,"given":"Hendrik","family":"Wiethoff","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"Helmholtz-University Group Cell Plasticity and Epigenetic Remodeling, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Bozza","sequence":"additional","affiliation":[{"name":"DNA Vector Laboratory, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Hoppe-Seyler","sequence":"additional","affiliation":[{"name":"Molecular Therapy of Virus-Associated Cancers, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"Heikenw\u00e4lder","sequence":"additional","affiliation":[{"name":"Chronic Inflammation and Cancer, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard P.","family":"Harbottle","sequence":"additional","affiliation":[{"name":"DNA Vector Laboratory, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9169-1294","authenticated-orcid":false,"given":"Carine","family":"Michiels","sequence":"additional","affiliation":[{"name":"Cell Biology Research Unit (URBC)\u2013Namur Research Institute for Life Sciences (NARILIS), University of Namur, 5000 Namur, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5865-0714","authenticated-orcid":false,"given":"Angelika B.","family":"Riemer","sequence":"additional","affiliation":[{"name":"Immunotherapy and Immunoprevention, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"},{"name":"Molecular Vaccine Design, German Center for Infection Research, Partner Site Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3235","DOI":"10.1200\/JCO.2015.61.6995","article-title":"Epidemiology of Human Papillomavirus-Positive Head and Neck Squamous Cell Carcinoma","volume":"33","author":"Gillison","year":"2015","journal-title":"J. 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