JPHI Journal of Public Health International 2641-4538 Open Access Pub United States JPHI-22-4335 10.14302/issn.2641-4538.jphi-22-4335 research-article The Risk of Oropharyngeal Cancer from E-Cigarette Use: An Urgent Public Health Concern Lee Cameron Y. S. 1 2 3 * Suzuki Jon B. 4 Private Practice in Oral, Maxillofacial and Reconstructive Surgery. Aiea, Hawaii 96701 Clinical Professor of Surgery, Department of Periodontology/Oral Implantology Kornberg School of Dentistry. Temple University, Philadelphia, PA 19140. Professor Emeritus. Departments of Periodontology/Oral Implantology and Microbiology/Immunology. Temple University School of Dentistry and Medicine. Temple University. Philadelphia, PA 19140 Corresponding author Sasho Stoleski 1 Ss. Cyril and Methodius University, Faculty of Medicine Skopje, Macedonia Cameron Y. S. Lee (DMD, MD, PhD, MPH, MSEd), Private Practice in Oral, Maxillofacial and Reconstructive Surgery. Aiea, Hawaii 96701, Clinical Professor of Surgery, Department of Periodontology/Oral Implantology, Kornberg School of Dentistry. Temple University, Philadelphia, PA 19140. clee555294@aol.com

Co-author credentials: Jon B. Suzuki (DDS, PhD, MBA).

The authors have declared that no competing interests exist.

 04 11 2022 5 4 1 4 03 10 2022 08 10 2022 04 11 2022 © 2022 Cameron Y. S. Lee, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This article is available from http://openaccesspub.org/jphi/article/1879

It is estimated that over 47 million people use tobacco products, mostly in the form of combustible (smokable) tobacco cigarettes. Thirteen to 50% of smokers also use electronic cigarettes (also known as e-cigarettes or vaping). Use of tobacco is the primary preventable cause of death and risk factor for lung, head, neck, and oropharyngeal cancer. Electronic cigarettes are a $10 billion dollar industry and has the potential to surpass the tobacco cigarette market. E-cigarette use is a public health concern because of the health issues of vaping and the limited amount of scientific research to support the safety of e-cigarette use.

The authors of this paper want to create awareness that use of e-cigarettes is not a safer alternative to smoking tobacco cigarettes as e-cigarettes contain known carcinogens that may lead to development of oropharyngeal cancer.

 tobacco cigarette lung head neck and oropharyngeal cancer Introduction

It is estimated that over 47 million people use tobacco products, mostly in the form of combustible (smokable) tobacco cigarettes.1Thirteen to 50% of smokers also use electronic cigarettes (also known as e-cigarettes or vaping).2,3Use of tobacco is the primary preventable cause of death and risk factor for lung, head, neck, and oropharyngeal cancer.4,5Cigarette smoke contains over seven hundred chemicals, including 60-70 known carcinogens. It is the combustible byproducts that lead to chronic tobacco-related disease and deaths after decades of smoking.6Compared to nonsmokers, the risk of developing lung cancer is twenty-five times greater. Cessation of smoking before age 40 decreases the risk of death by 90% from tobacco-related disease.7

Smoking is highest in adults aged 25- 64 years and it is estimated that 480,000 die annually from this social habit.8Oropharyngeal cancer is the sixth most common malignancy in the world.9The 5-year survival rate is approximately 75-83% due to high rates of recurrence with over 10,000 deaths per year in the United States.10,11The prevalence is highest in the following groups: people of color, individuals of low income and low education level, persons on Medicaid, disability benefits, uninsured and those with depression and anxiety.12

Electronic cigarettes are a $10 billion dollar industry and has the potential to surpass the tobacco cigarette market.13E-cigarette use is a public health concern because of the health issues of vaping and the limited amount of scientific research to support the safety of e-cigarette use.14

The authors of this paper want to create awareness that use of e-cigarettes is not a safer alternative to smoking tobacco cigarettes, as e-cigarettes contain known carcinogens that may lead to development of oropharyngeal cancer.

Increase in E-Cigarette Use

Although cigarette smoking has deceased in younger age groups, e-cigarette use has steadily increased, especially students in middle (4.7 %) and high school (19.6%).15In 2019, greater than 5.3 million middle and high school students used e-cigarettes. The increase in vaping is propelled by an increase in marketing, the perceived perception that vaping is safer compared to tobacco cigarettes, introduction of new vaping devices that include prefilled cartridges and pods and the many flavors that are appealing in taste. Of the over 15,000 vaping flavor blends, menthol is one of the most popular flavors that is commonly found in peppermint, spearmint and other mint plants and is considered safe. It is used in cough drops, candy, and gums because of its cooling sensation to the oral cavity. Compared to tobacco cigarettes, menthol is found in higher concentrations in e-cigarettes and increases the nicotine effects increasing the risk of nicotine addiction and could be why students get addicted to vaping.16

 Health Risk of Nicotine

Nicotine is the major addictive compound in tobacco.17Each inhalation of cigarette smoke from a cigarette delivers to the brain 1 mg of nicotine within 7 to 30 seconds.18Most of the inhaled nicotine is metabolized into continine which is non-carcinogenic. However, inhaled nicotine is also metabolized into nitrosamines which are potent carcinogens and cause DNA damage. 17E-cigarettes contain higher amounts of nicotine compared to tobacco cigarettes and is the major component of e-cigarette smoke without having to burn tobacco. JUUL is the most common brand e-cigarette in the United States and each pod contains 5% (59mg/ml) nicotine.19

Nicotine is one of the main toxic substances in e-cigarettes and 45% released from vaping is deposited in the oral cavity.20Although there is no conclusive evidence that nicotine is involved in carcinogenesis in humans it has been shown that nicotine causes chromosomal abnormalities that results in DNA single strand breaks and mutations that could lead to cancer.21,22

 Association of Carcinogens and Oropharyngeal Cancer

Studies have shown that oral mucosa and epithelial cells of the oropharynx are the first tissue exposed to tobacco smoke and e-liquid aerosols from vaping. Chemical analysis of the components of e-cigarette aerosols has revealed the presence of many harmful environmental toxins and carcinogens such as organic compounds (e.g., formaldehyde, acetaldehyde, benzaldehyde, acetone), free radicals and heavy metals (copper, chromium, iron, lead, arsenic, lead, nickel).23,24, 25In their study evaluating 225 e-liquid fluids, Lim and Shim 26discovered the presence of formaldehyde, acetaldehyde and nitrosamines that are carcinogenic to the head and neck region. In a New Egland Journal of Medicine study, Jensen and colleagues27also discovered formaldehyde in aerosols during the vaping process. Yu et. al.28 demonstrated that the vapors from e-cigarettes induced cell apoptosis resulting in cell death and DNA single strand breaks independent of the presence of nicotine. In another study by Flach and colleagues,29vaping liquid aerosols resulted in DNA double strand breaks that increases the risk of mutations and cancer. In a study on gene regulation and cell function of oral epithelial cells, Tommasi et. al.30 observed dysregulation of genes involved in carcinogenic pathways. Based on these studies, the use of e-cigarettes is a risk factor for oropharyngeal cancer.

 Conclusion

There is a paucity of studies of oropharyngeal cancer from e-cigarette use due to the long duration of carcinogenesis and the recent introduction of e-cigarettes. The authors clearly believe that this is an urgent public health issue as there will be an exponential increase in the number of cases of oropharyngeal cancer due to the known carcinogenic components in e-cigarettes over the next few decades.

 Cornelius M E Loretan C G Wang T W Tobacco product use among adults- United States 2020 MMWR Morb Mortal Wkly Rep 71 397 405 Douptcheva N Gmel G Studer J Use of electronic cigarettes among young Swiss men 2013 J Epidemiol Community Health 67 1075 1076 Al Rifai M Merchant A T Nambi V Temporal trends in e-cigarette use among U.S. adults: Behavioral risk factor surveillance system2016-2018 2020 Am J Med.133: 508 511 Fox J L Rosenzweig K E Ostroff J S The effect of smoking status on survival following radiation therapy for non-small cell lung cancer. Lung Cancer 2004 44 287 293 Cohen N Fedewa S Chen A Y Epidemiology and demographics of the head and neck cancer population. Oral Maxillofac Surg Clin North Am 2018 30 381 395 Zevin S Benowitz N L Drug interactions with tobacco smoking: an update. Clin Pharmacokinet 1999 36 425 438 Jha P Peto R Global effects of smoking, of quitting, and of taxing tobacco 2014 N Engl J Med 370 60 68 Office on Smoking and Health. The health consequences of smoking- 50 years of progress: a report of the Surgeon General. Atlanta: 2014 DHHS National Center for Chronic Disease Prevention and Health Promotion Warnakulasuriya S Global epidemiology of oral and oropharyngeal cancer. Oral Oncol 2009 45 309 316 Lindenblatt R C Martinez G L Silva L E Oral squamous cell carcinoma grading systems- analysis of the best survival predictor. J Oral Pathol Med 2012 41 34 39 D Radoi L Luce A review of risk factors for oral cavity cancer: the importance of a standardized case definition. Community Dent Oral Epidemiol 2013 41 97 109 Cornelius M E Loretan C G Wang T W Tobacco product use among adults- United States 2020 MMWR Morb Mortal Wkly Rep 71 397 405 McQueen N Partington E J Harrington K F Smoking cessation and electronic cigarette use among head and neck cancer patients. Otolaryngol Head Neck Surg 2016 154 73 79 National Academies of Sciences, Engineering and Medicine. Public health consequences of e-cigarettes; National Academies Press: 2018 Washington , DC, USA Wang T W Neff I J Park-Lee E E-cigarette use among middle and high school students- United States 2020 69 1310 1312 Barrington-Trimis J L Leventhal A M Adolescents’ of “pod mod” e-cigarettes- urgent concerns 2018 N Engl J Med 379 1099 Benowitz N L Pharmacology of nicotine: addiction, smoking-induced disease, and therapeutics. Annu Rev Pharmacol Toxicol 2009 49 57 71 Brody A L Mandelkern M A London E D Cigarette smoking saturates brain alpha 4 beta 2 nicotinic acetylcholine receptors. Arch Gen Psychiatry 2006 63 907 915 Morean M E Bold K W Kong G Adolescents’ awareness of the nicotine strength and e-cigarette status of JUUL e-cigarettes. Drug and Alcohol Depend 2019 204 107512 Kumar P Geisinger M DeLong H R Living under a cloud: electronic cigarettes and the dental patient 2020 JADA 151 155 158 Haussmann H J Fariss M W Comprehensive review of epidemiological and animal studies on the potential carcinogenic effects of nicotine per se 2016 Crit Rev Toxicol 46 701 734 Sanner T Grimsrud T K Nicotine: Carcinogenicity and effects on response to cancer treatment- a review. Front Oncol 2015 5 196 Cheng T Chemical evaluation of electronic cigarettes Tob Control 2014; 23 Suppl 2:ii 11 17 Williams M Bozhilov K Ghail S Elements including metals in the atomizer and aerosol of disposable electronic cigarettes and electronic hookahs 2017 Rubinstein M L Delucchi K Benowitz N L Adolescent exposure to toxic volatile organic chemicals from E-cigarettes. Pediatrics 2018 Lim H H Shim H S Measurement of aldehydes in replacement liquids of electronic cigarettes by headspace gas chromatography- mass spectrometry 2013 B Korean Chem 34 2691 2696 Jensen R P Luo W Pankow J F Hidden formaldehyde in e-cigarette aerosols 2015 N Engl J Med 372 392 394 Yu V Rahimy Y Korrapati A Electronic cigarettes induce DNA strand breaks and cell death independently of nicotine in cell lines. Oral Oncol 2016 52 58 65 Flach S Maniam P Manickavasagam J E-cigarettes and head and neck cancers: a systematic review of the current literature. Clin Otolaryngol 2019 44 749 756 10.1111/coa.13384 Tommasi S Caliri A W Caceres A Deregulation of biologically significant genes and associated molecular pathways in the oral epithelium of electronic cigarette users 2019 Int J Mol Sci 20 1 18