HPV16 is sufficient to induce squamous cell carcinoma specifically in the tongue base in transgenic mice

• DOI: 10.1002/path.5387
• Publication Date: 2020-01-29T07:45:42Z
• Authors: Verónica F Mestre; Beatriz Medeiros‐...; Diogo Estêvão; Fátima Casaca; Sandra Silva; Ana Félix; Fernanda Silva; Bruno Colaço; Fernanda Seixas; Margarida MSM Bastos; Carlos Lopes; Rui Medeiros; Paula A Oliveira; Rui M Gil da Costa
• Keywords: Lingual papilla; Malignant Transformation; Major duodenal papilla

Abstract Head and neck squamous cell carcinomas (HNSCCs) associated with human papillomavirus (HPV) occur specifically in the tonsils tongue base, but reasons for this specificity remain unknown. We studied distribution of oral pharyngeal lesions HPV16‐transgenic mice where expression all HPV16 early genes is targeted to keratinising epithelia by cytokeratin 14 ( Krt14 ) gene promoter. At 30 weeks age, 100% developed low‐ high‐grade intraepithelial dysplasia at multiple sites. Twenty per cent animals invasive cancers that remarkably were restricted association circumvallate papilla. The maintained CK14 (KRT14) E6 E7 oncogenes, displayed deregulated proliferation up‐regulation p16 INK4A . Malignant poorly differentiated destroyed musculature. hypothesised base area might contain a transformation zone similar those observed cervix anus, explaining why HPV‐positive target specifically. Immunohistochemistry two markers, CK7 (KRT7) p63 (TP63), revealed squamocolumnar junction terminal duct von Ebner's gland, composed + luminal cells basal cells. Dysplastic retained diffuse only scattered positivity CK7. Site‐specific HPV‐induced carcinogenesis may be explained presence This mouse model reproduces key morphological molecular features HNSCC, providing unique vivo tool basic translational research. © 2020 Pathological Society Great Britain Ireland. Published John Wiley & Sons, Ltd.