Scientific article
English

Mouse model of postsurgical primary tumor recurrence and regional lymph node metastasis progression in HPV-related head and neck cancer

Published inInternational journal of cancer, vol. 142, no. 12, p. 2518-2528
Publication date2018-06-15
First online date2018-01-21
Abstract

HPV-positive head and neck squamous cell carcinoma (HNSCC) is increasingly frequent. Management is particularly debated in the case of postsurgical high-risk 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-E6/E7-expressing cancer cells into the submental region of the floor-of-the-mouth. 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 (>90%) within the first 2-3 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-bearing mice were transplanted into naïve 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-positive HNSCC mouse model of postsurgical local recurrence and regional and distant metastasis progression suitable for preclinical studies.

Keywords
  • HNSCC
  • HPV
  • Metastasis
  • Minimal residual disease
  • Mouse model
  • Recurrence
  • Surgery
  • Animals
  • Disease Models, Animal
  • Disease Progression
  • Lymphatic Metastasis / pathology
  • Mice
  • Mice, Inbred C57BL
  • Neoplasm Recurrence, Local / pathology
  • Papillomavirus Infections / complications
  • Squamous Cell Carcinoma of Head and Neck / pathology
Affiliation entities Not a UNIGE publication
Research groups
Citation (ISO format)
MERMOD, Maxime et al. Mouse model of postsurgical primary tumor recurrence and regional lymph node metastasis progression in HPV-related head and neck cancer. In: International journal of cancer, 2018, vol. 142, n° 12, p. 2518–2528. doi: 10.1002/ijc.31240
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Article (Published version)
accessLevelRestricted
Identifiers
ISSN of the journal0020-7136
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