Assuntos
Lábio/cirurgia , Cirurgia de Mohs/efeitos adversos , Retalhos Cirúrgicos/transplante , Ferida Cirúrgica/cirurgia , Idoso , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Estética , Humanos , Lábio/patologia , Neoplasias Labiais/patologia , Neoplasias Labiais/cirurgia , Masculino , Mucosa Bucal/transplante , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Ferida Cirúrgica/etiologia , Técnicas de Sutura , Resultado do TratamentoRESUMO
Cutaneous squamous cell carcinoma (cuSCC) comprises 15-20% of all skin cancers, accounting for over 700,000 cases in USA annually. Most cuSCC arise in association with a distinct precancerous lesion, the actinic keratosis (AK). To identify potential targets for molecularly targeted chemoprevention, here we perform integrated cross-species genomic analysis of cuSCC development through the preneoplastic AK stage using matched human samples and a solar ultraviolet radiation-driven Hairless mouse model. We identify the major transcriptional drivers of this progression sequence, showing that the key genomic changes in cuSCC development occur in the normal skin to AK transition. Our data validate the use of this ultraviolet radiation-driven mouse cuSCC model for cross-species analysis and demonstrate that cuSCC bears deep molecular similarities to multiple carcinogen-driven SCCs from diverse sites, suggesting that cuSCC may serve as an effective, accessible model for multiple SCC types and that common treatment and prevention strategies may be feasible.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/genética , Ceratose Actínica/patologia , Lesões Pré-Cancerosas/patologia , Neoplasias Cutâneas/genética , Animais , Carcinogênese/genética , Carcinoma de Células Escamosas/etiologia , Carcinoma de Células Escamosas/prevenção & controle , Análise Mutacional de DNA , Progressão da Doença , Feminino , Perfilação da Expressão Gênica , Genômica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Camundongos , Camundongos Pelados , Terapia de Alvo Molecular/métodos , Lesões Pré-Cancerosas/genética , Análise de Sequência de RNA , Pele/patologia , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/prevenção & controle , Raios Ultravioleta/efeitos adversos , Sequenciamento do ExomaRESUMO
Human papillomaviruses (HPVs) are frequently detected in a variety of lesions in the oral mucosa and upper respiratory tract. The pathogenesis in these areas is not as clearly elucidated as in other anatomical regions, but most experts agree that HPVs are responsible for the commonly observed benign lesions, such as squamous papillomas, verruca vulgaris and recurrent respiratory papillomatosis. Transformation of these benign lesions is well described, but it is not clear what role the virus plays, if any, in carcinogenesis. HPV types 6 and 11 are most frequently detected in oral cavity and respiratory tract lesions, though several other types have also been reported. Despite an opaque understanding of these lesions' pathogeneses, it is essential for the clinician to recognize these diseases, to provide appropriate treatment and to promote patient awareness of potential oral transmission. In this paper, we review the major HPV-associated diseases of the oral mucosa and upper respiratory tract, focusing specifically on clinical features, histopathological characteristics and disease management.
