Genotoxic, Cytotoxic, and Inflammatory Alterations of the Oral Mucosa Caused by the Use of Electronic Cigarettes: Literature Systematic Review
DOI:
https://doi.org/10.32635/2176-9745.RBC.2026v72n3.5536Keywords:
Electronic Nicotine Delivery Systems, Genotoxicity, Carcinogenesis, Inflammation, Mouth NeoplasmsAbstract
Introduction: The increased use of electronic cigarettes (vapes) has been identified as a new public health problem. Objective: To find evidence on the effects of vaping on the establishment of cellular and tissue damage and to identify carcinogenic pathways related to head and neck cancer and oral cancer. Method: Systematic review research in the PubMed, LILACS, SciELO, and Cochrane databases, with a ten-year time frame (2014-2024). Descriptors: e-cigarettes, vaping, oral cancer, squamous carcinoma, and head & neck cancer. Fourteen original in vitro and in vivo studies that investigated alterations at the molecular and clinical level resulting from exposure to and consumption of vapes were included and analyzed. The studies were classified according to the risk of bias using the OHAT and ROBINS-E tools. Results: Findings were grouped by the predominance of genotoxic and cytotoxic effects, as well as alterations in inflammatory pathways and cell progression and tissue lesions in the oral mucosa. In vitro and in vivo results showed DNA damage, micronucleus formation, reduced cell viability, increased LDH and ROS, activation of oncogenic pathways such as NF-κB and STAT3, and inflammatory pathways (increased interleukins) and progression pathways (epithelial-mesenchymal transition phenotype). Conclusion: Together, the findings demonstrate that vapes are capable of activating carcinogenic pathways in head and neck cells and oral mucosa. In addition, we consider activating and accelerating inflammatory processes, creating a microenvironment favorable to neoplastic initiation, promotion, and progression. These findings highlight the need for more robust clinical studies and mechanistic investigations focused on agent-speciftradic pathways.
Downloads
References
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
Downloads
Published
How to Cite
Issue
Section
License
Os direitos morais e intelectuais dos artigos pertencem aos respectivos autores, que concedem à RBC o direito de publicação.

This work is licensed under a Creative Commons Attribution 4.0 International License.
