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Management is particularly debated in the case of postsurgical high\u2010risk features, that is, positive surgical margins and extracapsular spread (ECS). In this increasingly complex emerging framework of HNSCC treatment, representative preclinical models are needed to support future clinical trials and advances in personalized medicine. Here, we present an immunocompetent mouse model based on the implantation of mouse tonsil epithelial HPV16\u2010E6\/E7\u2010expressing cancer cells into the submental region of the floor\u2010of\u2010the\u2010mouth. Primary tumors were found to replicate the patterns of human HNSCC local invasion and lymphatic dissemination. To study disease progression after surgery, tumors were removed likely leaving behind residual disease. Surgical resection of tumors was followed by a high rate of local recurrences (&gt;90%) within the first 2\u20133 weeks. While only 50% of mice had lymph node metastases (LNM) at time of primary tumor excision, all mice with recurrent tumors showed evidence of LNM. To study the consecutive steps of LNM progression and distant metastasis development, LNs from tumor\u2010bearing mice were transplanted into na\u00efve recipient mice. Using this approach, transplanted LNs were found to recapitulate all stages and relevant histological features of regional metastasis progression, including ECS and metastatic spread to the lungs. Altogether, we have developed an immunocompetent HPV\u2010positive HNSCC mouse model of postsurgical local recurrence and regional and distant metastasis progression suitable for preclinical studies.<\/jats:p>","DOI":"10.1002\/ijc.31240","type":"journal-article","created":{"date-parts":[[2018,1,4]],"date-time":"2018-01-04T07:47:23Z","timestamp":1515052043000},"page":"2518-2528","source":"Crossref","is-referenced-by-count":34,"title":["Mouse model of postsurgical primary tumor recurrence and regional lymph node metastasis progression in <scp>HPV<\/scp>\u2010related head and neck cancer"],"prefix":"10.1002","volume":"142","author":[{"given":"Maxime","family":"Mermod","sequence":"first","affiliation":[{"name":"Department of Otolaryngology \u2013 Head and Neck Surgery CHUV, University of Lausanne Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agn\u00e8s","family":"Hiou\u2010Feige","sequence":"additional","affiliation":[{"name":"Department of 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