Alteraciones Genotóxicas, Citotóxicas e Inflamatorias de la Mucosa Oral Causadas por el Uso de Cigarrillos Electrónicos: Revisión Sistemática de la Literatura
DOI:
https://doi.org/10.32635/2176-9745.RBC.2026v72n3.5536Palabras clave:
Sistemas Electrónicos de Liberación de Nicotina, Genotoxicidad, Carcinogénesis, Inflamación, Neoplasias de la BocaResumen
Introducción: El aumento del uso de cigarrillos electrónicos (vapeadores) se ha identificado como un nuevo problema de salud pública. Objetivo: Identificar evidencias sobre los efectos del vapeo en el daño celular y tisular, así como las vías carcinogénicas relacionadas con el cáncer de cabeza y cuello y el cáncer oral. Método: Revisión sistemática con búsqueda en las bases de datos PubMed, LILACS, SciELO y Cochrane, dentro del período de diez años (2014-2024). Los descriptores fueron: e-cigarretes, vaping, oral cancer, squamous carcinoma e head & neck cancer. Se incluyeron y analizaron catorce estudios originales in vitro e in vivo que investigaron alteraciones a nivel molecular y clínico derivadas de la exposición y el consumo de vapeadores. Los estudios se clasificaron según el riesgo de sesgo mediante las herramientas OHAT y ROBINS-E. Resultados: Los hallazgos se agruparon según el predominio de efectos genotóxicos y citotóxicos, así como alteraciones en las vías inflamatorias, la progresión celular y las lesiones tisulares en la mucosa oral. Los resultados in vitro e in vivo mostraron daños en el ADN, formación de micronúcleos, reducción de la viabilidad celular, aumento de LDH y ROS, activación de vías oncogénicas como NF-κB y STAT3, y vías inflamatorias (aumento de interleucinas) y vías de progresión (fenotipo de transición epitelio-mesenquimal). Conclusión: En conjunto, los hallazgos demuestran que los cigarrillos electrónicos son capaces de activar vías carcinogénicas en células de cabeza y cuello y mucosa oral, además de activar y acelerar procesos inflamatorios, creando un microambiente favorable para la iniciación, promoción y progresión neoplásica, y reforzando la necesidad de realizar más estudios clínicos e investigar las vías específicas de este agente.
Descargas
Citas
Jorge M. Popularidade de cigarro eletrônico entre jovens preocupa estudiosos, que temem danos à saúde bucal e novo estímulo à dependência de nicotina. Jornal Unesp [Internet]. 2023 maio 4; [acesso 2025 fev 10]. Disponível em: https://jornal.unesp.br/2023/05/04/popularidade-de-cigarro-eletronico-entre-jovens-preocupa-estudiosos-que
Ministério da Saúde (BR) [Internet]. Brasília, DF: MS; [sem data]. Narguilé e cigarro eletrônico: modismo entre jovens, 2018 maio 3; [acesso 2025 fev 10]. Disponível em: https://www.gov.br/saude/pt-br/assuntos/saude-brasil/eu-quero-parar-de-fumar/noticias/2018/narguile-e-cigarro-eletronico-modismo-entre-jovens
Gotts J, Jordt S, McConnell R, et al. What are the respiratory effects of e-cigarettes? BMJ. 2019;366:l5275. doi: https://doi.org/10.1136/bmj.l5275 Erratum in: BMJ. 2019;367:l5980. doi: https://doi.org/10.1136/bmj.l5980 DOI: https://doi.org/10.1136/bmj.l5275
Tzortzi A, Kapetanstrataki M, Evangelopoulou V, et al. A systematic literature review of e-cigarette-related illness and injury: not just for the respirologist. Int J Environ Res Public Health. 2020;17(7):2248. doi: https://doi.org/10.3390/ijerph17072248 DOI: https://doi.org/10.3390/ijerph17072248
Tang M, Tang Y. Can electronic-cigarette vaping cause cancer? J Cancer Biol. 2021;2(3):68-70. doi: https://doi.org/10.46439/cancerbiology.2.027 DOI: https://doi.org/10.46439/cancerbiology.2.027
University of York. Centre for Reviews and Dissemination [Internet]. New York: University of York; 2019. PROSPERO - International prospective register of systematic reviews. 2023. [acesso 2025 ago 31]. Disponível em: https://www.crd.york.ac.uk/PROSPERO/
Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol. 2009;62:1006-12. doi: https://doi.org/10.1016/j.jclinepi.2009.06.005 DOI: https://doi.org/10.1016/j.jclinepi.2009.06.005
National Toxicology Program. OHAT risk of bias rating tool for human and animal studies [Internet]. Research Triangle Park: National Institute of Environmental Health Sciences; 2015. [acesso 2026 maio 18]. Disponível em: https://ntp.niehs.nih.gov/sites/default/files/ntp/ohat/pubs/riskofbiastool_508.pdf
Julian PT, Higgins RL, Morgan AA, et al. A tool to assess risk of bias in non-randomized follow-up studies of exposure effects (ROBINS-E). Environ Inter. 2024;186(108602):1-7. doi: https://doi.org/10.1016/j.envint.2024.108602 DOI: https://doi.org/10.1016/j.envint.2024.108602
Santos CMC, Pimenta CAM, Nobre MRC. The PICO strategy for the research question construction and evidence search. Rev Latino-Am Enfermagem. 2007;15(3):508-11. doi: https://doi.org/10.1590/S0104-11692007000300023 DOI: https://doi.org/10.1590/S0104-11692007000300023
Guedes Pinto T, Magalhães F, Renno A, et al. Does waterpipe smoke induce genotoxicity (DNA damage) in mammalian cells in vivo? A systematic review. Toxicol Mech Methods. 2025;35(3):240-9. doi: https://doi.org/10.1080/15376516.2024.2411381 DOI: https://doi.org/10.1080/15376516.2024.2411381
Hamad S, Brinkman M, Tsai Y, et al. Pilot study to detect genes involved in dna damage and cancer in humans: potential biomarkers of exposure to e-cigarette aerosols. Genes (Basel). 2021;12(3):448. doi: https://doi.org/10.3390/genes12030448 DOI: https://doi.org/10.3390/genes12030448
Tellez C, Juri D, Phillips L, et al. Cytotoxicity and genotoxicity of e-cigarette generated aerosols containing diverse flavoring products and nicotine in oral epithelial cell lines. Toxicol Sci. 2021;179(2):220-8. doi: https://doi.org/10.1093/toxsci/kfaa174 DOI: https://doi.org/10.1093/toxsci/kfaa174
Guo J, Ikuemonisan J, Hatsukami D, et al. Liquid chromatography-nanoelectrospray ionization-high-resolution tandem mass spectrometry analysis of apurinic/apyrimidinic sites in oral cell dna of cigarette smokers, e-cigarette users, and nonsmokers. Chem Res Toxicol. 2021;34(12):2540-8. doi: https://doi.org/10.1021/acs.chemrestox.1c00308 DOI: https://doi.org/10.1021/acs.chemrestox.1c00308
Tommasi S, Caliri A, Caceres A, et al. Deregulation of biologically significant genes and associated molecular pathways in the oral epithelium of electronic cigarette users. Int J Mol Sci. 2019;20(3):738. doi: https://doi.org/10.3390/ijms20030738 DOI: https://doi.org/10.3390/ijms20030738
Manyanga J, Ganapathy V, Bouharati C, et al. Electronic cigarette aerosols alter the expression of cisplatin transporters and increase drug resistance in oral cancer cells. Sci Rep. 2021;11(1):1821. doi: https://doi.org/10.1038/s41598-021-81148-0 DOI: https://doi.org/10.1038/s41598-021-81148-0
Kumar V, Abbas A, Fausto N, editores. Robbins & Cotran patologia: bases patológicas das doenças. 7. ed. Rio de Janeiro: Elsevier; 2005.
Omaiye E, McWhirter K, Luo W, et al. High-nicotine electronic cigarette products: toxicity of juul fluids and aerosols correlates strongly with nicotine and some flavor chemical concentrations. Chem Res Toxicol. 2019;32(6):1058-69. doi: https://doi.org/10.1021/acs.chemrestox.8b00381 DOI: https://doi.org/10.1021/acs.chemrestox.8b00381
Pandarathodiyil A, Ramanathan A, Garg R, et al. Lactate dehydrogenase levels in the saliva of cigarette and e-cigarette smokers (vapers): a comparative analysis. Asian Pac J Cancer Prev. 2021;22(10):3227-35. doi: https://doi.org/10.31557/APJCP.2021.22.10.3227 DOI: https://doi.org/10.31557/APJCP.2021.22.10.3227
Yu V, Rahimy M, Korrapati A, et al. Electronic cigarettes induce DNA strand breaks and cell death independently of nicotine in cell lines. Oral Oncol. 2016;52:58-65. doi: https://doi.org/10.1016/j.oraloncology.2015.10.018 DOI: https://doi.org/10.1016/j.oraloncology.2015.10.018
Tsai K, Hirschi Budge K, Lepre A, et al. Cell invasion, RAGE expression, and inflammation in oral squamous cell carcinoma (OSCC) cells exposed to e-cigarette flavoring. Clin Exp Dent Res. 2020;6(6):618-25. doi: https://doi.org/10.1002/cre2.314 DOI: https://doi.org/10.1002/cre2.314
Robin H, Trudeau C, Robbins A, et al. Inflammation and invasion in oral squamous cell carcinoma cells exposed to electronic cigarette vapor extract. Front Oncol. 2022;12:e917862. doi: https://doi.org/10.3389/fonc.2022.917862 DOI: https://doi.org/10.3389/fonc.2022.917862
Lima J, Macedo C, Barbosa G, et al. E-liquid alters oral epithelial cell function to promote epithelial to mesenchymal transition and invasiveness in preclinical oral squamous cell carcinoma. Sci Rep. 2023;13(1):3330. doi: https://doi.org/10.1038/s41598-023-30016-0] DOI: https://doi.org/10.1038/s41598-023-30016-0
Ganesan S, Dabdoub S, Nagaraja H, et al. Adverse effects of electronic cigarettes on the disease-naive oral microbiome. Sci Adv. 2020;6(22):eaaz0108. doi: https://doi.org/10.1126/sciadv.aaz0108 DOI: https://doi.org/10.1126/sciadv.aaz0108
Escobar Y, Morrison C, Chen Y, et al. Differential responses to e-cig generated aerosols from humectants and different forms of nicotine in epithelial cells from nonsmokers and smokers. Am J Physiol Lung Cell Mol Physiol. 2021;320(6):L1064-73. doi: https://doi.org/10.1152/ajplung.00525.2020 DOI: https://doi.org/10.1152/ajplung.00525.2020
Bardellini E, Amadori F, Conti G, et al. Oral mucosal lesions in electronic cigarettes consumers versus former smokers. Acta Odontol Scand. 2018;76(3):226-8. doi: https://doi.org/10.1080/00016357.2017.1406613 DOI: https://doi.org/10.1080/00016357.2017.1406613
Al-Otaibi H, Baqasi A, Alhadrami H. Genotoxicity and mutagenicity assessment of electronic cigarette liquids. Ann Thorac Med. 2024;19(3):222-7. doi: https://doi.org/10.4103/atm.atm_59_24 DOI: https://doi.org/10.4103/atm.atm_59_24
Jitareanu A, Agoroaei L, Aungurencei O, et al. Electronic cigarettes’ toxicity: from periodontal disease to oral cancer. Appl Sci. 2021;11(20):9742. doi: https://doi.org/10.3390/app11209742 DOI: https://doi.org/10.3390/app11209742
Anda S, Sugimoto H, Yamada T, et al. Mechanisms of e-cigarette vape-induced epithelial cell damage. Cells. 2023;12(21):2552. doi: https://doi.org/10.3390/cells12212552 DOI: https://doi.org/10.3390/cells12212552
Silva A, Moreira J. Sais de nicotina e nicotina sintética: novos desafios para um velho problema. Rev Bras Cancerol. 2022;68(4):e-202846. Disponível em: https://doi.org/10.32635/2176-9745.RBC.2022v68n4.2846 DOI: https://doi.org/10.32635/2176-9745.RBC.2022v68n4.2846
Jelic M, Mandic A, Maricic S, et al. Oxidative stress and its role in cancer. J Cancer Res Ther. 2021;17(1):22-28. doi: https://doi.org/10.4103/jcrt.jcrt_862_16 DOI: https://doi.org/10.4103/jcrt.JCRT_862_16
Li J, Tan J, Wang T, et al. cGAS-ISG15-RAGE axis reprogram necroptotic microenvironment and promote lymphatic metastasis in head and neck cancer. Exp Hematol Oncol. 2024;13(1):63. doi: https://doi.org/10.1186/s40164-024-00531-5 DOI: https://doi.org/10.1186/s40164-024-00531-5
Plemmenos G, Tzimogianni V, Fili C, et al. Contributing role of high mobility group box 1 signaling in oral cancer development and therapy. Life (Basel). 2023;13(7):1577. doi: https://doi.org/10.3390/life13071577 DOI: https://doi.org/10.3390/life13071577
Liu C, Wu K, Li C, et al. SPP1⁺ macrophages promote head and neck squamous cell carcinoma progression by secreting TNF-α and IL-1β. J Exp Clin Cancer Res. 2024;43(1):177. doi: https://doi.org/10.1186/s13046-024-03255-w DOI: https://doi.org/10.1186/s13046-024-03255-w
Xu Q, Ma H, Chang H, et al. The interaction of interleukin-8 and PTEN inactivation promotes the malignant progression of head and neck squamous cell carcinoma via the STAT3 pathway. Cell Death Dis. 2020;11(5):405. doi: https://doi.org/10.1038/s41419-020-2627-5 DOI: https://doi.org/10.1038/s41419-020-2627-5
Španko M, Strnadová K, Pavlíček A, et al. IL-6 in the ecosystem of head and neck cancer: possible therapeutic perspectives. Int J Mol Sci. 2021;22(20):11027. doi: https://doi.org/10.3390/ijms222011027 DOI: https://doi.org/10.3390/ijms222011027
Wallis SP, Stafford ND, Greenman J. Clinical relevance of immune parameters in the tumor microenvironment of head and neck cancers. Head Neck. 2015;37(3):449-59. doi: https://doi.org/10.1002/hed.23736 DOI: https://doi.org/10.1002/hed.23736
Pérez-Jardón A, Carvalho BFDC, Chamorro-Petronacci CM, et al. Impact of electronic nicotine delivery systems on oral mucosa: a cytopathological and molecular study. J Oral Pathol Med. 2026;55(3):331-9. doi: https://doi.org/10.1111/jop.70095 DOI: https://doi.org/10.1111/jop.70095
Publicado
Cómo citar
Número
Sección
Licencia
Os direitos morais e intelectuais dos artigos pertencem aos respectivos autores, que concedem à RBC o direito de publicação.
Esta obra está bajo una licencia internacional Creative Commons Atribución 4.0.
