{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T01:18:16Z","timestamp":1784855896979,"version":"3.55.0"},"reference-count":26,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,4,16]],"date-time":"2020-04-16T00:00:00Z","timestamp":1586995200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["CA210807, CA022443, DE026787, DC009401, DC004336, DC018184"],"award-info":[{"award-number":["CA210807, CA022443, DE026787, DC009401, DC004336, DC018184"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Human head and neck cancers that develop from the squamous cells of the oropharynx (Oropharyngeal Squamous Cell Carcinomas or OPSCC) are commonly associated with the papillomavirus infection. A papillomavirus infection-based mouse model of oropharyngeal tumorigenesis would be valuable for studying the development and treatment of these tumors. We have developed an efficient system using the mouse papillomavirus (MmuPV1) to generate dysplastic oropharyngeal lesions, including tumors, in the soft palate and the base of the tongue of two immune-deficient strains of mice. To maximize efficiency and safety during infection and endoscopy, we have designed a nose cone for isoflurane-induced anesthesia that takes advantage of a mouse\u2019s need to breathe nasally and has a large window for oral manipulations. To reach and infect the oropharynx efficiently, we have repurposed the Greer Pick allergy testing device as a virus delivery tool. We show that the Pick can be used to infect the epithelium of the soft palate and the base of the tongue of mice directly, without prior scarification. The ability to induce and track oropharyngeal papillomavirus-induced tumors in the mouse, easily and robustly, will facilitate the study of oropharyngeal tumorigenesis and potential treatments.<\/jats:p>","DOI":"10.3390\/v12040450","type":"journal-article","created":{"date-parts":[[2020,4,16]],"date-time":"2020-04-16T13:01:39Z","timestamp":1587042099000},"page":"450","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["A Mouse Model of Oropharyngeal Papillomavirus-Induced Neoplasia Using Novel Tools for Infection and Nasal Anesthesia"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4838-4731","authenticated-orcid":false,"given":"Andrea","family":"Bilger","sequence":"first","affiliation":[{"name":"McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6540-3834","authenticated-orcid":false,"given":"Renee E.","family":"King","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Wisconsin, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josh P.","family":"Schroeder","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Wisconsin, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jared T.","family":"Piette","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Wisconsin, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis A.","family":"Hinshaw","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Wisconsin, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew D.","family":"Kurth","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Wisconsin, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronnie W.","family":"AlRamahi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Wisconsin, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew V.","family":"Barthel","sequence":"additional","affiliation":[{"name":"McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ella T.","family":"Ward-Shaw","sequence":"additional","affiliation":[{"name":"McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darya","family":"Buehler","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6911-3116","authenticated-orcid":false,"given":"Kristyn S.","family":"Masters","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Wisconsin, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan L.","family":"Thibeault","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Wisconsin, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul F.","family":"Lambert","sequence":"additional","affiliation":[{"name":"McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,16]]},"reference":[{"key":"ref_1","unstructured":"(2019, December 20). How Many Cancers Are Linked with HPV Each Year?, Available online: https:\/\/www.cdc.gov\/cancer\/hpv\/statistics\/cases.htm."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1002\/path.4656","article-title":"Model systems of human papillomavirus-associated disease","volume":"238","author":"Doorbar","year":"2016","journal-title":"J. Pathol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1146\/annurev-virology-100114-054908","article-title":"Transgenic Mouse Models of Tumor Virus Action","volume":"3","author":"Lambert","year":"2016","journal-title":"Annu. Rev. Virol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"6308","DOI":"10.1158\/1078-0432.CCR-17-3535","article-title":"Loss of Function of Canonical Notch Signaling Drives Head and Neck Carcinogenesis","volume":"24","author":"Nyman","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1177\/0300985810377186","article-title":"Novel laboratory mouse papillomavirus (MusPV) infection","volume":"48","author":"Ingle","year":"2011","journal-title":"Vet. Pathol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Cladel, N.M., Budgeon, L.R., Balogh, K.K., Cooper, T.K., Hu, J., and Christensen, N.D. (2015). A Novel Pre-Clinical Murine Model to Study the Life Cycle and Progression of Cervical and Anal Papillomavirus Infections. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0120128"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Uberoi, A., Yoshida, S., Frazer, I.H., Pitot, H.C., and Lambert, P.F. (2016). Role of Ultraviolet Radiation in Papillomavirus-Induced Disease. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005664"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Sundberg, J.P., Stearns, T.M., Joh, J., Proctor, M., Ingle, A., Silva, K.A., Dadras, S.S., Jenson, A.B., and Ghim, S. (2014). Immune status, strain background, and anatomic site of inoculation affect mouse papillomavirus (MmuPV1) induction of exophytic papillomas or endophytic trichoblastomas. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0113582"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"00180-19","DOI":"10.1128\/mBio.00180-19","article-title":"A Novel In Vivo Infection Model To Study Papillomavirus-Mediated Disease of the Female Reproductive Tract","volume":"10","author":"Spurgeon","year":"2019","journal-title":"mBio"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.virol.2015.10.030","article-title":"Mouse papillomavirus MmuPV1 infects oral mucosa and preferentially targets the base of the tongue","volume":"488","author":"Cladel","year":"2016","journal-title":"Virology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.pvr.2017.05.002","article-title":"Time to change perspectives on HPV in oropharyngeal cancer. A systematic review of HPV prevalence per oropharyngeal sub-site the last 3 years","volume":"4","author":"Haeggblom","year":"2017","journal-title":"Papillomavirus Res. Amst. Neth."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"E55","DOI":"10.1093\/ilar.53.1.55","article-title":"Mice anesthesia, analgesia, and care, Part I: Anesthetic considerations in preclinical research","volume":"53","author":"Gargiulo","year":"2012","journal-title":"ILAR J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1038\/nm1598","article-title":"Genital transmission of HPV in a mouse model is potentiated by nonoxynol-9 and inhibited by carrageenan","volume":"13","author":"Roberts","year":"2007","journal-title":"Nat. Med."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Uberoi, A. (2017). MmuPV1 L1- cytokeratin dual immunofluorescence using home-based tyramide signal amplification. Protocols.io.","DOI":"10.17504\/protocols.io.i8cchsw"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.jmoldx.2011.08.002","article-title":"RNAscope: A novel in situ RNA analysis platform for formalin-fixed, paraffin-embedded tissues","volume":"14","author":"Wang","year":"2012","journal-title":"J. Mol Diagn."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.jaci.2005.03.035","article-title":"Immunotherapy Committee of the American Academy of Allergy, Asthma and Immunology Comparison of test devices for skin prick testing","volume":"116","author":"Carr","year":"2005","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1006\/scbi.1999.0141","article-title":"Human papillomavirus life cycle: Active and latent phases","volume":"9","author":"Stubenrauch","year":"1999","journal-title":"Semin. Cancer Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"476","DOI":"10.5946\/ce.2015.48.6.476","article-title":"Narrow Band Imaging: Technology Basis and Research and Development History","volume":"48","author":"Gono","year":"2015","journal-title":"Clin. Endosc."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1002\/cncr.20482","article-title":"Squamous cell carcinoma in situ at oropharyngeal and hypopharyngeal mucosal sites","volume":"101","author":"Muto","year":"2004","journal-title":"Cancer"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"E2358","DOI":"10.1002\/hed.24300","article-title":"Narrow band imaging for the diagnosis of head and neck squamous cell carcinoma: A systematic review","volume":"38","author":"Cosway","year":"2016","journal-title":"Head Neck"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s41199-018-0039-3","article-title":"HPV-driven oropharyngeal cancer: Current knowledge of molecular biology and mechanisms of carcinogenesis","volume":"3","author":"Pan","year":"2018","journal-title":"Cancers Head Neck"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Mestre, V.F., Medeiros-Fonseca, B., Est\u00eav\u00e3o, D., Casaca, F., Silva, S., F\u00e9lix, A., Silva, F., Cola\u00e7o, B., Seixas, F., and Bastos, M.M. (2020). HPV16 is sufficient to induce squamous cell carcinoma specifically in the tongue base in transgenic mice. J. Pathol.","DOI":"10.1002\/path.5387"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.pvr.2019.04.005","article-title":"Refining our understanding of cervical neoplasia and its cellular origins","volume":"7","author":"Doorbar","year":"2019","journal-title":"Papillomavirus Res. Amst. Neth."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e50056","DOI":"10.7554\/eLife.50056","article-title":"Sexual transmission of murine papillomavirus (MmuPV1) in Mus musculus","volume":"8","author":"Spurgeon","year":"2019","journal-title":"eLife"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"355","DOI":"10.3389\/fonc.2019.00355","article-title":"Mucosal and Cutaneous Human Papillomavirus Infections and Cancer Biology","volume":"9","author":"Gheit","year":"2019","journal-title":"Front. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.oraloncology.2017.07.028","article-title":"Current mouse models of oral squamous cell carcinoma: Genetic and chemically induced models","volume":"73","author":"Ishida","year":"2017","journal-title":"Oral Oncol."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/12\/4\/450\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T14:09:11Z","timestamp":1760364551000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/12\/4\/450"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,16]]},"references-count":26,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2020,4]]}},"alternative-id":["v12040450"],"URL":"https:\/\/doi.org\/10.3390\/v12040450","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,16]]}}}