Combustible tobacco use has reached historic lows, demonstrating the importance of proven strategies to reduce smoking since publication of the 1964 Surgeon General's report. In contrast, the use of electronic nicotine delivery systems (ENDS), specifically e-cigarettes, has grown to alarming rates and threatens to hinder progress against tobacco use. A major concern is ENDS use by youth and adults who never previously used tobacco. While ENDS emit fewer carcinogens than combustible tobacco, preliminary evidence links ENDS use to DNA damage and inflammation, key steps in cancer development. Furthermore, high levels of nicotine can also increase addiction, raise blood pressure, interfere with brain development, and suppress the immune system. The magnitude of long-term health risks will remain unknown until longitudinal studies are completed. ENDS have been billed as a promising tool for combustible tobacco cessation, but further evidence is needed to assess their potential efficacy for adults who smoke. Of concern, epidemiological studies estimate that approximately 15% to 42% of adults who use ENDS have never used another tobacco product, and another 36% to 54% “dual use” both ENDS and combustible tobacco. This policy statement details advances in science related to ENDS and calls for urgent action to end predatory practices of the tobacco industry and protect public health. Importantly, we call for an immediate ban on all non-tobacco-flavored ENDS products that contain natural or synthetic nicotine to reduce ENDS use by youth and adults who never previously used tobacco. Concurrently, evidence-based treatments to promote smoking cessation and prevent smoking relapse to reduce cancer incidence and improve public health remain top priorities for our organizations. We also recognize there is an urgent need for research to understand the relationship between ENDS and tobacco-related disparities.

In 2015, the American Association for Cancer Research (AACR) and the American Society of Clinical Oncology (ASCO) published a joint policy statement describing a rapidly growing epidemic of electronic nicotine delivery systems (ENDS), including e-cigarettes, and policies to address this trend (1). The 2015 statement sought to balance curtailing youth use while remaining optimistic that ENDS could be a less harmful alternative to combustible tobacco cigarettes for adult smokers. As detailed in the following sections, youth ENDS use has further increased since the 2015 statement while evidence remains insufficient to show ENDS are more effective than current smoking cessation strategies. Additionally, several major health authorities have determined that the current evidence base is lacking in supporting ENDS as tobacco cessation aids, including the U.S. Surgeon General (2); the National Academies of Science, Engineering, and Medicine (NASEM; ref. 3); the U.S. Preventive Services Task Force (USPSTF; ref. 4); and the National Comprehensive Cancer Network, a coalition of 31 leading cancer centers (5). At the time of this writing, no ENDS manufacturer has applied to the U.S. Food and Drug Administration (FDA) Center for Drug Evaluation and Research (CDER) for an Investigational New Drug (IND) application, a prerequisite to run a tobacco cessation clinical trial. The AACR and ASCO are publishing the present statement to detail advances in scientific understanding of the ENDS epidemic, strengthen recommendations to protect public health, promote evidence-based tobacco cessation across all groups, and highlight areas where more research is needed.

Carcinogens from combustible tobacco products are very harmful to health, contributing to nearly half a million deaths each year in the United States and more than 8 million deaths per year globally (6, 7). The process of burning creates a large amount of carcinogens, such as benzo[a]pyrene, that are inhaled in smoke from traditional cigarettes (8). The first ENDS were introduced to the U.S. market in 2006 as a way to deliver nicotine to users without burning tobacco (9). Instead of burning tobacco, ENDS use electricity to power a heating element that aerosolizes an e-liquid, containing a solvent (e.g., propylene glycol or glycerin); nicotine; flavors; and other additives. Some ENDS products can result in rapid delivery of a similar amount of nicotine as modern American cigarettes, which contribute to high addiction potentials (10, 11).

Tobacco would likely not be the top public health issue without the highly addictive properties of nicotine when delivered rapidly. Every time someone consumes nicotine, the brain releases the neurotransmitter dopamine, which provides a sense of pleasure or satisfaction (12). Primarily due to the pharmacology of nicotine, over time, tobacco users become dependent on nicotine to feel pleasure and stave off withdrawal symptoms (13). This rewiring of brain circuitry is especially of concern for the developing brains of youth (14). Nicotine can also harm health by raising blood pressure (15) and suppressing immune function (16). Strong evidence from clinical trials examining very low nicotine cigarettes demonstrates that reducing nicotine to less addictive levels could effectively decrease smoking rates by reducing initiation and increasing cessation of cigarette use (17–21). In 2018, the FDA issued a proposed rule to lower the level of nicotine in cigarettes to nonaddictive or minimally addictive levels (22), but at the time of writing this rule has not advanced. While the present statement focuses on policies related to ENDS, additional regulations to reduce the addictiveness and appeal of combustible tobacco are also highly important.

The following sections outline updates since our previous statement related to the evidence of biological effects from ENDS that can contribute to cancer risk, use trends, effective tobacco cessation efforts, and ENDS regulations. The data support strong, urgent action to reduce ENDS use among youth and adults who never previously used tobacco. Because of the wide use of non-tobacco-flavored ENDS among these groups, we recommend an immediate ban on all non-tobacco-flavored ENDS products that contain natural or synthetic nicotine. However, if non-tobacco-flavored ENDS are reviewed and approved by FDA CDER to increase cessation efficacy, the AACR and ASCO would welcome these as cessation therapies at that time. At the same time, new tobacco regulations should be structured to avoid any increases in combustible tobacco use, including smoking initiation and relapse. The following sections describe the evidence by which we based our recommendations.

ENDS expose users to carcinogens

The cancer-causing potential of ENDS is inferred from the currently available studies investigating the presence of carcinogens, human biomarkers of carcinogenesis, and animal and cell culture experiments. Carcinogens in ENDS can include four classes of chemicals, namely tobacco-specific nitrosamines; metals; volatile organic compounds; and polycyclic aromatic hydrocarbons. Table 1 highlights several recent reports comparing carcinogens and metabolites in urine or saliva samples from ENDS users and those who never used tobacco. The data show that at least 12 carcinogens are significantly elevated in ENDS users compared with nontobacco users, but that their levels were generally lower than the levels of carcinogens seen in smokers and dual users (Table 1; refs. 23–26). Unfortunately, the data are limited by a small number of studies that compared ENDS users with nonusers, and each study reported a different set of carcinogens. Separate studies further characterized carcinogens in ENDS aerosols and found that the power and temperature of devices greatly influences the amount of toxic metals and volatile organic compounds emitted (27–30). Therefore, additional studies are needed for a more thorough and comprehensive understanding of the carcinogen load experienced by ENDS users. Nevertheless, the results of ENDS use investigated to date clearly indicate that vaping exposes the user to carcinogens and therefore likely increases long-term cancer risk, but for most carcinogens at levels far lower than from smoking combustible tobacco cigarettes.

Table 1.

Carcinogens significantly increased in ENDS users compared with nonusers.

Increase compared with nonusers
Class of carcinogenName of carcinogenMetabolite analyzedENDS UsersDual usersSmokersSample sizeRef
Tobacco-specific nitrosamines 4-(N-Nitrosomethylamino)-a-(3-pyridyl)-1-butanone 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol 431% 28,412% 21,996% 5097 23  
 4-(N-Nitrosomethylamino)-a-(3-pyridyl)-1-butanone 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol 75% N/A 3,100% 57 26  
 N'-Nitrosonornicotine N/A 80% 513% 514% 4985 23  
 N'-Nitrosonornicotine (saliva) N/A 5,740% N/A 37,700% 59 26  
Metals Cadmium N/A 30% 88% 86% 5091 23  
 Lead N/A 23% 42% 36% 5105 23  
Polycyclic aromatic hydrocarbons 2-Naphthylamine N/A 29% N/A N/A 23 24  
Volatile organic compounds Acrylonitrile N‐Acetyl‐S‐(2‐cyanoethyl)‐L‐cysteine 201% 11,018% 9,322% 4,877 23  
 Acrylonitrile N‐Acetyl‐S‐(1‐cyano‐2‐hydroxyethyl)‐L‐cysteine 30% 1,242% 1,066% 4,877 23  
 N,N-Dimethylformamide N‐Acetyl‐S‐(N-methylcarbamoyl)‐L‐cysteine 46% 424% 359% 4,844 23  
 Acrylamide N-Acetyl-S-(2-carbamoylethyl)-L-cysteine 95% 583% N/A 103 25  
 Propylene oxide 2-Hydroxy-Propyl Methacrylate 89% 94% N/A 103 25  
 Crotonaldehyde N-Acetyl-S-(3-hydroxypropyl-1-methyl)-L-cysteine 48% 85% N/A 103 25  
 Acrolein 3-hydroxypropyl mercapturic acid 32% 128% N/A 103 25  
 ortho-Toluidine N/A 133% N/A N/A 22 24  
Increase compared with nonusers
Class of carcinogenName of carcinogenMetabolite analyzedENDS UsersDual usersSmokersSample sizeRef
Tobacco-specific nitrosamines 4-(N-Nitrosomethylamino)-a-(3-pyridyl)-1-butanone 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol 431% 28,412% 21,996% 5097 23  
 4-(N-Nitrosomethylamino)-a-(3-pyridyl)-1-butanone 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol 75% N/A 3,100% 57 26  
 N'-Nitrosonornicotine N/A 80% 513% 514% 4985 23  
 N'-Nitrosonornicotine (saliva) N/A 5,740% N/A 37,700% 59 26  
Metals Cadmium N/A 30% 88% 86% 5091 23  
 Lead N/A 23% 42% 36% 5105 23  
Polycyclic aromatic hydrocarbons 2-Naphthylamine N/A 29% N/A N/A 23 24  
Volatile organic compounds Acrylonitrile N‐Acetyl‐S‐(2‐cyanoethyl)‐L‐cysteine 201% 11,018% 9,322% 4,877 23  
 Acrylonitrile N‐Acetyl‐S‐(1‐cyano‐2‐hydroxyethyl)‐L‐cysteine 30% 1,242% 1,066% 4,877 23  
 N,N-Dimethylformamide N‐Acetyl‐S‐(N-methylcarbamoyl)‐L‐cysteine 46% 424% 359% 4,844 23  
 Acrylamide N-Acetyl-S-(2-carbamoylethyl)-L-cysteine 95% 583% N/A 103 25  
 Propylene oxide 2-Hydroxy-Propyl Methacrylate 89% 94% N/A 103 25  
 Crotonaldehyde N-Acetyl-S-(3-hydroxypropyl-1-methyl)-L-cysteine 48% 85% N/A 103 25  
 Acrolein 3-hydroxypropyl mercapturic acid 32% 128% N/A 103 25  
 ortho-Toluidine N/A 133% N/A N/A 22 24  

Note: The table lists carcinogens identified by Goniewicz and colleagues (23), Fuller and colleagues (24), Rubinstein and colleagues (25), and Bustamante an colleagues (26), to be elevated in the urine (or saliva where noted) of adults who use ENDS products compared with adults who do not use any tobacco products. All listed carcinogens are rated “Possibly Carcinogenic” (Group 2B) to “Carcinogenic to Humans” (Group 1) by the International Agency for Research on Cancer (31). “ENDS Users” refers to exclusive ENDS use. “Smokers” refers to exclusive combustible cigarette use. “Dual Users” refers to people who use both ENDS and combustible cigarettes.

ENDS linked to DNA damage

Several reports have found that ENDS vapor or extracts cause DNA damage in cell culture either by directly changing the chemical structure of DNA or indirectly by increasing highly reactive oxygen-containing molecules (32–36). One of those reports found that potent antioxidant molecules prevented DNA damage in cell culture, confirming the contribution of reactive oxygen species (32). A limitation of some studies is that they use higher concentrations of ENDS vapor than experienced by ENDS users, but DNA damage was also found in studies that used lower concentrations. Chemical modification of DNA by ENDS extracts leads to broken DNA strands (35, 37), which must be repaired by cells, or they will die. Repairing broken DNA strands can cause mutations that predispose cells to become cancerous, depending on how the damage is repaired (38).

Furthermore, nicotine itself and ENDS extracts can inhibit DNA repair processes in cell cultures. The DNA Checkpoint is a critical cellular system that senses damage and prevents cells from making new DNA in order to prevent further damage and initiate DNA repair. Nishioka and colleagues found that nicotine overrides the DNA Checkpoint and allows cells to make DNA even when there is DNA damage (39). Base Excision Repair (BER) is a key repair mechanism for DNA that has been chemically altered; two studies found that ENDS extracts reduce the abundance of BER proteins, thus limiting the ability of cells to repair damage caused by ENDS (33, 34). It is possible inhibition of DNA repair from ENDS use could exacerbate DNA damage and related DNA mutations caused by smoking in people who dual use.

ENDS linked to inflammation and cellular replication

In addition to DNA damage, ENDS vapor could also lead to cancer by promoting inflammation and cellular replication that expands mutations caused by prior carcinogen exposure. A core hallmark of cancer is uncontrolled cellular replication (40). Several constituents in ENDS vapor can cause inflammation, as demonstrated by increased pro-inflammatory cytokines such as IL6 and CXCL8 (41–46). Wang and colleagues found that nicotine signaling in mouse lungs was a significant contributor to inflammation, and that deleting the nicotine receptor in lung cells reduced inflammation, confirming nicotine directly causes inflammation (44). However, even use of ENDS that only contained propylene glycol and vegetable glycerin had moderate pro-inflammatory effects in human lungs (43). An additional study found that ENDS users had significantly elevated levels of IL6 and CXCL8 in the blood compared with never smokers (45). IL6 is well documented to induce cell signaling pathways that promote cellular replication and transform precancerous cells into cancerous cells (47–49). Singh and colleagues also found that ENDS users had elevated levels of growth signaling molecules commonly implicated in cancer progression compared with never tobacco users, including epidermal growth factor, vascular endothelial growth factor, and hepatocyte growth factor (45). These findings suggest that ENDS vapor can promote replication of precancerous cells and therefore promote cancer-predisposing DNA mutations.

Summary

A growing body of evidence points toward a biologically plausible role for ENDS use in contributing to human carcinogenesis, based on the presence of carcinogens in ENDS aerosols; metabolites of carcinogens in human urine samples; inflammation markers in human lung swabs and blood samples; and cell culture and mouse experiments exhibiting DNA damage and inflammation. It is important to note that the evidence from biomarker studies tends to show lower carcinogen exposures in ENDS users compared with dual users and exclusive smokers of combustible tobacco, likely due to the absence of combustion-related carcinogens. Additionally, the lack of well-designed epidemiologic studies is a critical hurdle to definitively characterizing cancer risk. ENDS remain relatively new products, so it may take decades for enough exposure to occur that would enable studies with sufficient follow-up to fully characterize the associations between ENDS use and cancer. Even less is known about the harms of second-hand exposure to ENDS vapor. In contrast, the scientific evidence very clearly demonstrates smoking combustible tobacco increases the risk of being diagnosed with lung cancer by approximately 25-fold compared with never smoking (6), and is an established cause of at least 17 other human cancers (6, 50).

While youth and adult use of combustible tobacco has decreased to historic lows (2), the epidemic of youth ENDS use threatens to diminish progress against nicotine addiction. The AACR and ASCO published our first ENDS statement in 2015 due to concerns regarding the almost 400% rise between 2012 and 2014 in ENDS use among U.S. high school students, according to the 2014 National Youth Tobacco Use Survey (NYTS; Fig. 1; ref. 51). The number of high school students who had used ENDS in the past 30 days increased by an additional 46% in 2020 compared with 2014 levels, to a total of 3.6 million youth (52). A separate national survey, Monitoring the Future (MTF), also found a dramatic 73% increase between 2015 and 2020 among 12th grade students who had vaped in the past 30 days (Fig. 1; ref. 53). This continued increase in the youth ENDS epidemic underscores the need for urgent action to save a generation of youth from life-long nicotine addiction.

Figure 1.

Percentage of various school age groups who vaped in the past 30 days. Blue lines indicate data from the NYTS (51, 52, 54–60), and red lines indicate data from the MTF survey (53). MTF, Monitoring the Future; NYTS, National Youth Tobacco Use Survey.

Figure 1.

Percentage of various school age groups who vaped in the past 30 days. Blue lines indicate data from the NYTS (51, 52, 54–60), and red lines indicate data from the MTF survey (53). MTF, Monitoring the Future; NYTS, National Youth Tobacco Use Survey.

Close modal

Numerous studies have clearly demonstrated that appealing flavors are key drivers of youth initiation of ENDS use, with the pharmacology of nicotine as the key driver of addiction to ENDS (61–68). The 2020 NYTS found that 82.9% of youth ENDS users used flavored products. Among high school ENDS users, 73% reported vaping fruit-flavored ENDS, 55.8% vaped mint, and 37% vaped menthol (percentages add to greater than 100 % due to use of multiple flavors by one person) (52). In comparison, the 2020 MTF found that only 2.9% of youth ENDS users vaped tobacco-flavored products (69). Youth who are offered fruit flavored ENDS by peers are 6.49-fold more likely to try ENDS compared with tobacco-flavored ENDS (61). In contrast, adults are 21-fold more likely to exclusively use tobacco-flavored ENDS compared with youth (63). Flavored ENDS follow a long history of the tobacco industry using flavors to attract youth towards nicotine by disguising the otherwise unpleasant taste of tobacco and purposefully altering perceptions of risk (61).

In February 2020, the FDA implemented restrictions on pod- or cartridge-based ENDS product flavors, except for menthol and tobacco flavors (70). The policy lacked definitions of “mint” or “menthol,” thus allowing manufacturers to simply relabel products to avoid the flavor restriction (71). Open tank and single-use ENDS were also exempted from any flavor restrictions, which left thousands of appealing flavors on the market. Consequently, youth switched to exempted products. The 2020 NYTS found that disposable products were used by 2.4% of high school ENDS users in 2019 (52), but this increased 11-fold to 26.5% in 2020. The prevalence of flavored disposable ENDS also increased among middle schoolers, with a 5-fold increase in disposable product use between 2019 and 2020 (3.0% vs. 15.2%). Flavoring chemicals and other additives of ENDS have not been studied to determine the health risks associated with inhalation. The ability to mix flavors at the point of sale also increases the difficulty of regulators to gain a complete understanding of the health impact of these chemicals in real-world use.

The use of ENDS among adults has also increased in recent years, particularly among young adults. According to the Behavioral Risk Factor Surveillance System (BRFSS, N = 1,156,411), the prevalence of ENDS use increased among U.S. adults from 4.5% in 2016 to 5.4% in 2018 (72), and was 15.0% among adults under the age of 24 years. These data correspond to almost 14 million adults using ENDS in 2018. A second study analyzed data from the Population Assessment of Tobacco and Health (PATH) study (N = 30,191), which is also representative of the population of U.S. adults, and found that 6.5% of U.S. residents used ENDS in 2018 (73). Concerningly, the BRFSS study found that 42% of adult ENDS users had never previously used another tobacco product (72), and the PATH study found 15% of adult ENDS users had never used another type of tobacco product (73). While the high variability between analyses necessitates further study, the data suggest ENDS are being used by millions of adults who never previously used tobacco. In addition, approximately 36% of ENDS users in the BRFSS study and 52% in the PATH study “dual use” ENDS and combustible tobacco. A separate nation-wide survey (N = 5,989) found that 27.7% of adults who smoked also dual used ENDS in 2018 (74). Notably, dual use rates were higher in adults who wanted to quit smoking within 6 months (33.1%), compared with 18.7% of those who did not plan to quit smoking. Similar to the general population, adult patients with cancer and survivors who use ENDS are more likely to be under the age of 50 years (75, 76), but patients with cancer who use ENDS are far more likely to be current or former smokers than never smokers. As presented in Table 1, dual users continue to be exposed to similarly high levels of carcinogens as exclusive users of combustible tobacco and the current evidence of the efficacy of dual using ENDS to help quit smoking remains unclear. The evidence is clear that any combustible smoking, even one cigarette per day, has significant negative health impacts (77).

As stated in the introduction, major U.S. public health authorities have found insufficient evidence to conclude ENDS effectively help smokers quit combustible tobacco (2–5). In contrast, there is evidence that demonstrates ENDS significantly increase the likelihood youth and young adults start smoking combustible tobacco. A 2021 meta-analysis analyzed nine studies (combined baseline N = 32,286), which compared the likelihood of smoking initiation between youth ENDS users and never users (78); youth who used ENDS were 4-fold more likely to ever smoke a combustible cigarette than never users, even after accounting for potentially confounding factors. Similarly, a 2020 meta-analysis analyzed 17 studies (combined baseline N = 57,514), which compared the likelihood of smoking initiation between young adult ENDS users and never users; young adults who used ENDS were approximately three-fold more likely to ever smoke a combustible cigarette compared with never users (79). On the other hand, the nation-wide increased rates of e-cigarette use among youth is accompanied by a substantial decrease in past month smoking rates (53, 80), and the extent to which ENDS use leads to established or regular smoking to date appears to be low (81). Nonetheless, the well-documented ability of ENDS to roughly triple smoking initiation by youth and young adults is of concern and overshadows the more limited evidence suggesting the efficacy of ENDS for smoking cessation (82). As stated above, flavors are a key driver of youth initiation of ENDS, with the pharmacology of nicotine leading to addiction and continued, repetitive use. Therefore, to limit youth nicotine dependence, we recommend an immediate ban on all non-tobacco-flavored ENDS products that contain natural or synthetic nicotine, unless an ENDS product is approved by FDA CDER as a smoking cessation therapy.

Advertising has a powerful effect on youth tobacco initiation, including for ENDS. Many studies have found that advertisements from social media influencers, television, radio, print, and in retail stores significantly increases the probability that youth will start using ENDS (83–90). Additionally, a national survey (N = 4,604) found that high exposure to tobacco use during television shows more than doubled the likelihood of initiating ENDS use among youth and young adults (91). These findings demonstrate a strong link between ENDS advertising or imagery exposure and subsequent initiation. Therefore, in addition to a ban on flavors, we support efforts to prevent all forms of advertisement for nicotine products from reaching youth.

There are currently no evidence-based pharmacologic therapies to help ENDS users quit vaping (92). However, it is reasonable to conclude that lessons learned from smoking cessation could aid in treating nicotine dependence from ENDS. The 2021 USPSTF tobacco cessation recommendation concluded that the most effective treatment for tobacco use includes both FDA-approved pharmacotherapies and behavioral counseling (Fig. 2; ref.4). Additional research is critically needed to identify effective cessation therapies specifically for ENDS users. A major hurdle to assessing tobacco use in clinical research studies is the lack of standardized definitions for terms describing tobacco use history, such as “current smoking,” “current ENDS use,” “former smoking,” etc. Evidence-based definitions provided by the FDA or National Cancer Institute will be helpful to further advance tobacco research.

Figure 2.

Evidence-based cessation therapies. FDA, U.S. Food and Drug Administration.

Figure 2.

Evidence-based cessation therapies. FDA, U.S. Food and Drug Administration.

Close modal

Little is known about the interaction of smoking and ENDS use and subsequent impact on different anticancer treatments or on cancer prognoses. In the context of cancer treatment, smoking by patients with cancer and survivors increases the risk of overall or cancer related mortality by roughly 50% to 60%, increases risk for a second primary cancer, and has strong associations with increased cancer treatment toxicity (6). Consequently, it is important to consider the biologic and clinical effects of smoking when considering the effects of ENDS use by patients with cancer. Quitting smoking after a cancer diagnosis is associated with a median 45% improvement in survival (2). Therefore, evidence-based smoking cessation is considered a critical component of cancer care by AACR, ASCO, and other major oncology organizations (93). However, large surveys demonstrate that few oncology providers regularly assist patients with quitting (94, 95). Compared with the general adult population, the data are even less clear on whether ENDS aid cessation efforts by patients with cancer, or whether ENDS will have a positive or negative effect on cancer treatment. This is further complicated by frequent transitions between smoking and ENDS. However, smoking cessation confers significant benefits by reducing cancer risk, improving cancer treatment outcomes, and improving several other health outcomes beyond cancer (2). Given the clear and strong evidence for the adverse effects of smoking on cancer treatment outcomes, quitting smoking should remain the top priority for patients with cancer and providers, with emphasis on the importance of quitting smoking to improve cancer treatment outcomes. When considering these important data and findings, it is critical that patients with cancer who are using ENDS currently not return to cigarette smoking.

A significant hurdle to evidence-based cessation therapies is inconsistent insurance coverage. This is most pronounced among uninsured smokers, who are 33% less likely than the general population to use evidence-based therapies (96). After Massachusetts implemented comprehensive Medicaid smoking cessation coverage in 2006, the smoking rate of beneficiaries dropped by 26% in two years (97); every dollar spent on cessation coverage saved $3.12 in U.S. dollars (USD) in spending on tobacco-related illnesses (98). Unfortunately, most state Medicaid plans do not cover all FDA-approved medications, and coverage of behavioral therapy is inconsistent (99). Additional barriers such as extreme shortages of healthcare workers, demanding physician schedules, medical preauthorizations, co-payments, and limits on quit attempts per year also reduce success rates (100–102). Nonphysician certified tobacco cessation specialists are also often not reimbursed by insurance plans. Payment reform for cessation specialists, FDA-approved therapies, and addressing other barriers to cessation could be powerful cost-saving interventions to increase quit rates by making it as easy as possible to receive evidence-based help. An improved coverage and reimbursement environment for tobacco cessation services and medications will benefit population health; this would even apply should an ENDS product ever become an FDA-approved cessation device.

A number of awareness campaigns and free cessation resources (Fig. 2) have emerged over the past decade to prevent initiation and help tobacco users quit, some of which could be used or repurposed in the context of ENDS cessation. The “This is Quitting” campaign by the Truth Initiative increased seven-month quit rates among young adult ENDS users to 24.1% compared with 18.6% among participants who did not participate in the campaign (103). The FDA's “The Real Cost” advertising campaign helped prevent an estimated 380,000–587,000 youth from smoking between 2013 and 2016 (104). The CDC's “Tips from Former Smokers” campaign saved an estimated $11 billion (USD) in tobacco-related healthcare spending over 6 years at a cost of $490 million (USD) (105) and helped more than 1 million smokers permanently quit (106). Among smokers who visited the free cessation services website, SmokeFree.gov (107), as part of a randomized clinical trial, 26% successfully quit one year later (108). Finally, Quitline counseling services increased quit rates by 60% (109). Increasing resources for these excellent evidence-based tobacco treatment services could help significantly to expand their reach and quality of service.

Evidence needed to determine if ENDS can help smokers quit smoking

To our knowledge, to date, there is a lack of sufficient evidence for the use of ENDS as tobacco cessation therapies (2–5). This is because very few randomized clinical trials have directly compared the efficacy of ENDS to standard cessation therapies; the failure of ENDS manufacturers to submit an IND application is the primary reason for a lack of ENDS clinical trials in the United States. However, a 2021 systematic review found that preliminary evidence suggests ENDS could be more effective for smoking cessation than nicotine-replacement therapy alone (82), although the authors caution that the small number of studies and variations in study design limit the strength of their conclusions. The moderate strength conclusion of the review was primarily based on two clinical trials that investigated the efficacy of ENDS to help with smoking cessation. The first trial (N = 886), from the United Kingdom, found ENDS helped smokers quit at statistically significantly higher rates than nicotine patches (110); the trial found 18% of participants who used ENDS plus behavioral therapy had quit smoking by one year, compared with 9.9% of participants who used nicotine patches plus behavioral therapy. The second trial (N = 1,124), from New Zealand, found that 18% of those randomly assigned to patches plus a nicotine e-cigarette quit smoking, compared with 10% randomized to a nicotine-free e-cigarette plus patches and 8% randomized to patches alone (111). It is noteworthy in both trials that a large proportion of participants continued using ENDS at the long-term follow-up visit in these studies. Moreover, all groups in the above studies experienced slightly lower but comparable rates of successful cessation as found for 6-month follow-up when using FDA-approved nicotine patches alone (22%; ref. 112). Therefore, we recommend that ENDS manufacturers apply for IND applications to facilitate randomized clinical trials to definitively assess the cessation efficacy of their products compared with FDA-approved cessation therapies.

During the last 15 years, the FDA has attempted to regulate ENDS products with limited success. In 2009, Congress passed the Family Smoking Prevention and Tobacco Control Act (TCA; ref. 113), which granted the FDA the authority to regulate tobacco products. In May 2016, the FDA “deemed” ENDS as tobacco products under the TCA (114). This ruling required ENDS manufacturers to submit a premarket tobacco product application (PMTA) to prove that the product is “appropriate for the protection of public health” (112). In 2017, the FDA elected to delay the PMTA deadlines for ENDS from 2018 to 2022. During this time, many users believed that ENDS were safe and did not contain nicotine (61, 69, 115). As described in the epidemiology section, perceptions of safety contributed to alarming increases in ENDS use among those who never previously used tobacco.

In 2019, U.S. District Judge Paul W. Grimm ruled that the FDA had acted improperly by delaying ENDS regulations (116). Citing a “clear public health emergency,” Judge Grimm required PMTA applications for ENDS to be submitted by May 2020, but this was delayed to September 2020 due to the COVID-19 pandemic. By September 2020, more than 6 million PMTAs for ENDS products were submitted for FDA review (117). The FDA has denied marketing orders for more than 98% of those products, which requires those products to be removed from the market (118). However, the FDA is still reviewing PMTAs for ENDS products from manufacturers with the largest market shares and permitting those products to remain on the market in the meantime.

Two additional policies have also had a major impact on the use of ENDS products: age restrictions and taxation. In 2015, Hawaii became the first state to raise the minimum legal age to purchase tobacco products to 21 years (119), based on a NASEM report that estimated nearly 250,000 premature deaths could be prevented over 30 years (120). Following Hawaii's lead, 18 additional states and Washington D.C. also raised the minimum age to 21 years between 2016 and 2019. As part of the federal fiscal year 2020 appropriations package, Congress raised the minimum legal age to purchase tobacco products to 21 years in the entire United States (121). Separately, for every 1% increase in the price of tobacco products, consumption decreases by 0.4% on average (122). While the federal government does not yet tax ENDS, 24 states have passed ENDS taxes (123). Due to the powerful disincentivizing effect of taxes on tobacco use, the AACR and ASCO support imposing a federal excise tax on all products that contain natural or synthetic nicotine in a manner that promotes public health benefit (124, 125). Additional policy recommendations are included in Table 2.

Table 2.

AACR and ASCO recommendations.

Legislative Recommendations 
Ban all non-tobacco-flavored products that contain natural or synthetic nicotine; flavors may only be used for research purposes or FDA-approved tobacco cessation therapies. 
Tax all products that contain natural or synthetic nicotine in a manner that reduces tobacco use and promotes public health. 
Increase funding for evidence-based tobacco control programs and campaigns such as the CDC's Office on Smoking and Health, state tobacco control programs, and Quit Lines. 
Prohibit the use of ENDS in places where combustible tobacco use is prohibited by federal, state, or local laws. All tobacco use should be prohibited at medical facilities. 
Limit the sale of tobacco products to stores or areas within stores that require age verification upon entrance. 
Require health insurance plans, including Medicare/Medicaid, to cover all FDA-approved cessation therapies, expand coverage limits, and reimburse healthcare providers, including cessation specialists, for time helping patients quit smoking and vaping. 
Regulatory Recommendations 
Regulate predatory tobacco advertising practices including packaging, product designs, and labeling appealing to youth; misleading statements about cessation efficacy; athletic, musical, social, or cultural event sponsorship; giveaways when buying tobacco products; branded clothing; social media, digital, and print advertising; and tobacco use in movies and television. 
The FDA should enforce removal of ENDS products from the market that have not received a marketing order, publish PMTAs with confidential information redacted, and update PMTA review progress with a publicly available database. 
The FDA should develop product standards for tobacco products to improve public health, including but not limited to minimizing appeal to youth; capping the amount of nicotine delivery to minimize addictiveness; eliminating or substantially reducing human exposure to known carcinogens (e.g., heavy metals) and other toxicants (e.g., additives, contaminants, and manufacturing residues); and regulating the power and operating temperature of ENDS products. 
PMTAs should require information regarding: composition of ENDS and e-liquid components; appeal to people who have never used tobacco products; impacts on health; geotracking or biometric capabilities; and steps taken to protect consumer privacy. 
Require health warning and safety labels on ENDS packaging and advertising; these labels should contain ENDS/e-liquid composition information from PMTAs. 
The FDA and/or NCI should provide evidence-based, non-stigmatizing definitions for categories of tobacco use for human studies, for example no tobacco history; no smoking history; no ENDS history; currently smoking; currently using ENDS; former smoking history. The FDA and/or NCI should provide guidance on best practices for measuring tobacco use data in human studies. The FDA should require all oncology clinical trials to assess tobacco use and report findings. 
The FDA should increase enforcement of the minimum age to legally purchase tobacco products 
Additional Research Needs 
Research is needed to determine effective ENDS cessation therapies for youth, young adults, and adults, as well as cessation therapies for youth combustible tobacco users. 
Large prospective epidemiological studies are needed to investigate the long-term health impacts of ENDS use and disparities in tobacco-related illness. 
Additional research is needed for a comprehensive understanding of the acute and long-term biologic effects of ENDS use, carcinogen exposures, and the use of ENDS in the context of smoke exposure. 
Additional research is needed on how patients diagnosed with cancer use tobacco products, their reasons for use, perceptions of health impacts, impact of cessation on cancer-related outcomes, and interactions with anticancer therapies. 
Randomized clinical trials are needed to investigate the cessation efficacy of ENDS compared to FDA-approved cessation therapies. Investigational New Drug applications are necessary to facilitate such trials. 
Research is needed to monitor the impacts of federal, state, and local tobacco policies on youth and adult use patterns, as well as the use of evidence-based approaches to develop policy. 
Legislative Recommendations 
Ban all non-tobacco-flavored products that contain natural or synthetic nicotine; flavors may only be used for research purposes or FDA-approved tobacco cessation therapies. 
Tax all products that contain natural or synthetic nicotine in a manner that reduces tobacco use and promotes public health. 
Increase funding for evidence-based tobacco control programs and campaigns such as the CDC's Office on Smoking and Health, state tobacco control programs, and Quit Lines. 
Prohibit the use of ENDS in places where combustible tobacco use is prohibited by federal, state, or local laws. All tobacco use should be prohibited at medical facilities. 
Limit the sale of tobacco products to stores or areas within stores that require age verification upon entrance. 
Require health insurance plans, including Medicare/Medicaid, to cover all FDA-approved cessation therapies, expand coverage limits, and reimburse healthcare providers, including cessation specialists, for time helping patients quit smoking and vaping. 
Regulatory Recommendations 
Regulate predatory tobacco advertising practices including packaging, product designs, and labeling appealing to youth; misleading statements about cessation efficacy; athletic, musical, social, or cultural event sponsorship; giveaways when buying tobacco products; branded clothing; social media, digital, and print advertising; and tobacco use in movies and television. 
The FDA should enforce removal of ENDS products from the market that have not received a marketing order, publish PMTAs with confidential information redacted, and update PMTA review progress with a publicly available database. 
The FDA should develop product standards for tobacco products to improve public health, including but not limited to minimizing appeal to youth; capping the amount of nicotine delivery to minimize addictiveness; eliminating or substantially reducing human exposure to known carcinogens (e.g., heavy metals) and other toxicants (e.g., additives, contaminants, and manufacturing residues); and regulating the power and operating temperature of ENDS products. 
PMTAs should require information regarding: composition of ENDS and e-liquid components; appeal to people who have never used tobacco products; impacts on health; geotracking or biometric capabilities; and steps taken to protect consumer privacy. 
Require health warning and safety labels on ENDS packaging and advertising; these labels should contain ENDS/e-liquid composition information from PMTAs. 
The FDA and/or NCI should provide evidence-based, non-stigmatizing definitions for categories of tobacco use for human studies, for example no tobacco history; no smoking history; no ENDS history; currently smoking; currently using ENDS; former smoking history. The FDA and/or NCI should provide guidance on best practices for measuring tobacco use data in human studies. The FDA should require all oncology clinical trials to assess tobacco use and report findings. 
The FDA should increase enforcement of the minimum age to legally purchase tobacco products 
Additional Research Needs 
Research is needed to determine effective ENDS cessation therapies for youth, young adults, and adults, as well as cessation therapies for youth combustible tobacco users. 
Large prospective epidemiological studies are needed to investigate the long-term health impacts of ENDS use and disparities in tobacco-related illness. 
Additional research is needed for a comprehensive understanding of the acute and long-term biologic effects of ENDS use, carcinogen exposures, and the use of ENDS in the context of smoke exposure. 
Additional research is needed on how patients diagnosed with cancer use tobacco products, their reasons for use, perceptions of health impacts, impact of cessation on cancer-related outcomes, and interactions with anticancer therapies. 
Randomized clinical trials are needed to investigate the cessation efficacy of ENDS compared to FDA-approved cessation therapies. Investigational New Drug applications are necessary to facilitate such trials. 
Research is needed to monitor the impacts of federal, state, and local tobacco policies on youth and adult use patterns, as well as the use of evidence-based approaches to develop policy. 

Abbreviations: AACR, American Association for Cancer Research; ASCO, American Society of Clinical Oncology; ENDS, electronic nicotine delivery systems; FDA, US Food and Drug Administration; NCI, National Cancer Institute; PMTA, premarket tobacco product application.

ENDS emit fewer carcinogens than combustible tobacco primarily due to the absence of combustion products, and for some ENDS, the absence of some tobacco-specific nitrosamines, but it is clear that they still pose health risks. Additionally, e-cigarettes have addicted a new generation of youth and young adults to nicotine and threaten to hinder progress against tobacco-related illnesses. For these reasons, the AACR and ASCO call for urgent action by Congress, state legislatures, and regulatory agencies to implement the various legislative, regulatory, and research recommendations outlined in this report, including calling for an immediate ban on all non-tobacco-flavored ENDS products that contain natural or synthetic nicotine with the goal of reducing ENDS use by youth and adults who never previously used tobacco. The top tobacco control priorities for the AACR and ASCO continue to be preventing initiation of tobacco use, including ENDS, preventing smoking relapse, and promotion of evidence-based tobacco cessation treatment for all groups.

R.S. Herbst reports personal fees from Cybrexa Therapeutics, personal fees from eFFECTOR Therapeutics, Inc., personal fees from Eli Lilly and Company, personal fees from EMD Serono, personal fees from Genentech, personal fees from Gilead, personal fees from Janssen, personal fees from Merck and Company, personal fees from Mirati Therapeutics, personal fees from NextCure, personal fees from Novartis, personal fees from Ocean Biomedical, Inc, personal fees from Oncocyte Corp, personal fees from Oncternal Therapeutics, personal fees from Pfizer, personal fees from Regeneron Pharmaceuticals, personal fees from Revelar Biotherapeutics, Inc, personal fees from Ribbon Therapeutics, Inc, personal fees from Roche, personal fees from Sanofi, personal fees from Xencor, Inc, other support from American Association for cancer Research, other support from International Association for Cancer Research, other support from Society for Immunotherapy of Cancer, other support from Southwest Oncology Group, other support from Merck and Company, and other support from Eli Lilly and Compamy outside the submitted work. M. Giuliani reports other support from AstraZeneca, other support from Bristol Myers Squibb, and other support from International Journal of Radiation Oncology, Biology and Physics outside the submitted work. B.A. Toll reports grants from National Cancer Institute and personal fees from Expert Testimony outside the submitted work. G.W. Warren reports grants and other support from National Cancer Institute, Agency for Healthcare Research and Quality, Canadian Partnership Against Cancer outside the submitted work. No disclosures were reported by the other authors.

1.
Brandon
TH
,
Goniewicz
ML
,
Hanna
NH
,
Hatsukami
DK
,
Herbst
RS
,
Hobin
JA
, et al
.
Electronic nicotine delivery systems: a policy statement from the American Association for Cancer Research and the American Society of Clinical Oncology
.
Clin Cancer Res
2015
;
21
:
514
25
.
2.
U.S. Department of Health and Human Services
.
Smoking cessation: a report of the surgeon general
.
Atlanta, GA
:
U.S. Department of Health and Human Services, Centers for Disease Control and Prevention
;
2020
.
Available from
: https://www.hhs.gov/sites/default/files/2020-cessation-sgr-full-report.pdf.
3.
National Academies of Sciences, Engineering, and Medicine
.
Public health consequences of e-cigarettes
.
Washington, D.C.
:
National Academies Press
;
2018
.
Available from
: https://www.nap.edu/catalog/24952.
4.
U.S. Preventive Services Task Force
,
Krist
AH
,
Davidson
KW
,
Mangione
CM
,
Barry
MJ
,
Cabana
M
, et al
.
Interventions for tobacco smoking cessation in adults, including pregnant persons: U.S. Preventive Services Task Force recommendation statement
.
JAMA
2021
;
325
:
265
.
5.
Shields
PG
,
Bierut
LJ
,
Arenberg
D
,
Balis
D
,
Benowitz
NL
,
Burdalski
C
, et al
.
Smoking cessation
.
National Comprehensive Cancer Network
;
2021
.
Available from
: https://www.nccn.org/professionals/physician_gls/pdf/smoking.pdf.
6.
U.S. Department of Health and Human Services
.
The health consequences of smoking—50 years of progress: a report of the Surgeon General
.
Atlanta, GA
:
U.S. Department of Health and Human Services, Centers for Disease Control and Prevention
;
2014
.
Available from
: http://www.ncbi.nlm.nih.gov/books/NBK179276/.
7.
World Health Organization
.
Tobacco
.
2021
.
Available from
: https://www.who.int/news-room/fact-sheets/detail/tobacco.
8.
Hecht
SS
.
Tobacco smoke carcinogens and lung cancer
.
J Natl Cancer Inst
1999
;
91
:
1194
210
.
9.
Swierupski
R
.,
U.S. Department of Homeland Security
,
U.S. Customs and Border Protection
.
M85579: The tariff classification of a nicotine inhaler and parts from China
.
2006
.
Available from
: https://rulings.cbp.gov/ruling/M85579.
10.
Prochaska
JJ
,
Vogel
EA
,
Benowitz
N
.
Nicotine delivery and cigarette equivalents from vaping a JUULpod
.
Tob Control
2022
;
31
:
e88
93
.
11.
Rao
P
,
Liu
J
,
Springer
ML
.
JUUL and combusted cigarettes comparably impair endothelial function
.
Tob Regul Sci
2020
;
6
:
30
7
.
12.
Benowitz
NL
.
Nicotine addiction
.
N Engl J Med
2010
;
362
:
2295
303
.
13.
Palmer
AM
,
Toll
BA
,
Carpenter
MJ
,
Donny
EC
,
Hatsukami
DK
,
Rojewski
AM
, et al
.
Reappraising choice in addiction: novel conceptualizations and treatments for tobacco use disorder
.
Nicotine Tob Res
2022
;
24
:
3
9
.
14.
Goriounova
NA
,
Mansvelder
HD
.
Short- and long-term consequences of nicotine exposure during adolescence for prefrontal cortex neuronal network function
.
Cold Spring Harb Perspect Med
2012
;
2
:
a012120
.
15.
Benowitz
NL
,
Porchet
H
,
Sheiner
L
,
Jacob
P
.
Nicotine absorption and cardiovascular effects with smokeless tobacco use: comparison with cigarettes and nicotine gum
.
Clin Pharmacol Ther
1988
;
44
:
23
8
.
16.
McAllister-Sistilli
CG
,
Caggiula
AR
,
Knopf
S
,
Rose
CA
,
Miller
AL
,
Donny
EC
.
The effects of nicotine on the immune system
.
Psychoneuroendocrinology
1998
;
23
:
175
87
.
17.
Smith
TT
,
Koopmeiners
JS
,
Tessier
KM
,
Davis
EM
,
Conklin
CA
,
Denlinger-Apte
RL
, et al
.
Randomized trial of low-nicotine cigarettes and transdermal nicotine
.
Am J Prev Med
2019
;
57
:
515
24
.
18.
World Health Organization
.
Advisory note: global nicotine reduction strategy: WHO Study Group on Tobacco Product Regulation
.
Geneva
:
World Health Organization
;
2015
.
Available from
: https://apps.who.int/iris/handle/10665/189651.
19.
Donny
EC
,
Denlinger
RL
,
Tidey
JW
,
Koopmeiners
JS
,
Benowitz
NL
,
Vandrey
RG
, et al
.
Randomized trial of reduced-nicotine standards for cigarettes
.
N Engl J Med
2015
;
373
:
1340
9
.
20.
Cassidy
RN
,
Tidey
JW
,
Cao
Q
,
Colby
SM
,
McClernon
FJ
,
Koopmeiners
JS
, et al
.
Age moderates smokers’ subjective response to very-low nicotine content cigarettes: evidence from a randomized controlled trial
.
Nicotine Tob Res
2018
;
21
:
962
9
.
21.
Cassidy
RN
,
Colby
SM
,
Tidey
JW
,
Jackson
KM
,
Cioe
PA
,
Krishnan-Sarin
S
, et al
.
Adolescent smokers’ response to reducing the nicotine content of cigarettes: Acute effects on withdrawal symptoms and subjective evaluations
.
Drug Alcohol Depend
2018
;
188
:
153
60
.
22.
U.S. Food and Drug Administration
.
Tobacco product standard for nicotine level of combusted cigarettes
.
Fed Regist
2018
. Available from: https://www.federalregister.gov/documents/2018/03/16/2018-05345/tobacco-product-standard-for-nicotine-level-of-combusted-cigarettes
23.
Goniewicz
ML
,
Smith
DM
,
Edwards
KC
,
Blount
BC
,
Caldwell
KL
,
Feng
J
, et al
.
Comparison of nicotine and toxicant exposure in users of electronic cigarettes and combustible cigarettes
.
JAMA Netw Open
2018
;
1
:
e185937
.
24.
Fuller
TW
,
Acharya
AP
,
Meyyappan
T
,
Yu
M
,
Bhaskar
G
,
Little
SR
, et al
.
Comparison of bladder carcinogens in the urine of e-cigarette users versus non e-cigarette using controls
.
Sci Rep
2018
;
8
:
507
.
25.
Rubinstein
ML
,
Delucchi
K
,
Benowitz
NL
,
Ramo
DE
.
Adolescent exposure to toxic volatile organic chemicals from e-cigarettes
.
Pediatrics
2018
;
141
:
e20173557
.
26.
Bustamante
G
,
Ma
B
,
Yakovlev
G
,
Yershova
K
,
Le
C
,
Jensen
J
, et al
.
Presence of the carcinogen N′-nitrosonornicotine in saliva of e-cigarette users
.
Chem Res Toxicol
2018
;
31
:
731
8
.
27.
Olmedo
P
,
Goessler
W
,
Tanda
S
,
Grau-Perez
M
,
Jarmul
S
,
Aherrera
A
, et al
.
Metal concentrations in e-cigarette liquid and aerosol samples: the contribution of metallic coils
.
Environ Health Perspect
2018
;
126
:
027010
.
28.
Zhao
D
,
Navas-Acien
A
,
Ilievski
V
,
Slavkovich
V
,
Olmedo
P
,
Adria-Mora
B
, et al
.
Metal concentrations in electronic cigarette aerosol: effect of open-system and closed-system devices and power settings
.
Environ Res
2019
;
174
:
125
34
.
29.
Aherrera
A
,
Olmedo
P
,
Grau-Perez
M
,
Tanda
S
,
Goessler
W
,
Jarmul
S
, et al
.
The association of e-cigarette use with exposure to nickel and chromium: a preliminary study of non-invasive biomarkers
.
Environ Res
2017
;
159
:
313
20
.
30.
Li
Y
,
Burns
AE
,
Tran
LN
,
Abellar
KA
,
Poindexter
M
,
Li
X
, et al
.
Impact of e-liquid composition, coil temperature, and puff topography on the aerosol chemistry of electronic cigarettes
.
Chem Res Toxicol
2021
;
34
:
1640
54
.
31.
International Agency for Research on Cancer
.
List of classifications – IARC monographs on the identification of carcinogenic hazards to humans
.
IARC: Lyon France
;
2021
.
Available from
: https://monographs.iarc.who.int/list-of-classifications/.
32.
Anderson
C
,
Majeste
A
,
Hanus
J
,
Wang
S
.
E-cigarette aerosol exposure induces reactive oxygen species, DNA damage, and cell death in vascular endothelial cells
.
Toxicol Sci
2016
;
154
:
332
40
.
33.
Ganapathy
V
,
Manyanga
J
,
Brame
L
,
McGuire
D
,
Sadhasivam
B
,
Floyd
E
, et al
.
Electronic cigarette aerosols suppress cellular antioxidant defenses and induce significant oxidative DNA damage
.
PLoS One
2017
;
12
:
e0177780
.
34.
Lee
H-W
,
Park
S-H
,
Weng
M
,
Wang
H-T
,
Huang
WC
,
Lepor
H
, et al
.
E-cigarette smoke damages DNA and reduces repair activity in mouse lung, heart, and bladder as well as in human lung and bladder cells
.
Proc Natl Acad Sci U S A
2018
;
115
:
E1560
9
.
35.
Muthumalage
T
,
Lamb
T
,
Friedman
MR
,
Rahman
I
.
E-cigarette flavored pods induce inflammation, epithelial barrier dysfunction, and DNA damage in lung epithelial cells and monocytes
.
Sci Rep
2019
;
9
:
19035
.
36.
Rankin
GD
,
Wingfors
H
,
Uski
O
,
Hedman
L
,
Ekstrand-Hammarström
B
,
Bosson
J
, et al
.
The toxic potential of a fourth-generation E-cigarette on human lung cell lines and tissue explants
.
J Appl Toxicol
2019
;
39
:
1143
54
.
37.
Yu
V
,
Rahimy
M
,
Korrapati
A
,
Xuan
Y
,
Zou
AE
,
Krishnan
AR
, et al
.
Electronic cigarettes induce DNA strand breaks and cell death independently of nicotine in cell lines
.
Oral Oncol
2016
;
52
:
58
65
.
38.
Mao
Z
,
Bozzella
M
,
Seluanov
A
,
Gorbunova
V
.
DNA repair by nonhomologous end joining and homologous recombination during cell cycle in human cells
.
Cell Cycle Georget Tex
2008
;
7
:
2902
6
.
39.
Nishioka
T
,
Yamamoto
D
,
Zhu
T
,
Guo
J
,
Kim
S-H
,
Chen
CY
.
Nicotine overrides DNA damage-induced G1/S restriction in lung cells
.
PLoS One
2011
;
6
:
e18619
.
40.
Hanahan
D
,
Weinberg
RA
.
Hallmarks of cancer: the next generation
.
Cell
2011
;
144
:
646
74
.
41.
Shen
Y
,
Wolkowicz
MJ
,
Kotova
T
,
Fan
L
,
Timko
MP
.
Transcriptome sequencing reveals e-cigarette vapor and mainstream-smoke from tobacco cigarettes activate different gene expression profiles in human bronchial epithelial cells
.
Sci Rep
2016
;
6
:
23984
.
42.
Scott
A
,
Lugg
ST
,
Aldridge
K
,
Lewis
KE
,
Bowden
A
,
Mahida
RY
, et al
.
Pro-inflammatory effects of e-cigarette vapour condensate on human alveolar macrophages
.
Thorax
2018
;
73
:
1161
9
.
43.
Song
M-A
,
Reisinger
SA
,
Freudenheim
JL
,
Brasky
TM
,
Mathé
EA
,
McElroy
JP
, et al
.
Effects of electronic cigarette constituents on the human lung: a pilot clinical trial
.
Cancer Prev Res
2020
;
13
:
145
52
.
44.
Wang
Q
,
Sundar
IK
,
Li
D
,
Lucas
JH
,
Muthumalage
T
,
McDonough
SR
, et al
.
E-cigarette-induced pulmonary inflammation and dysregulated repair are mediated by nAChR α7 receptor: role of nAChR α7 in SARS-CoV-2 Covid-19 ACE2 receptor regulation
.
Respir Res
2020
;
21
:
154
.
45.
Singh
KP
,
Lawyer
G
,
Muthumalage
T
,
Maremanda
KP
,
Khan
NA
,
McDonough
SR
, et al
.
Systemic biomarkers in electronic cigarette users: implications for noninvasive assessment of vaping-associated pulmonary injuries
.
ERJ Open Res
2019
;
5
:
00182
2019
.
46.
Crotty Alexander
LE
,
Drummond
CA
,
Hepokoski
M
,
Mathew
D
,
Moshensky
A
,
Willeford
A
, et al
.
Chronic inhalation of e-cigarette vapor containing nicotine disrupts airway barrier function and induces systemic inflammation and multiorgan fibrosis in mice
.
Am J Physiol-Regul Integr Comp Physiol
2018
;
314
:
R834
47
.
47.
Zhang
G
,
Tsang
CM
,
Deng
W
,
Yip
YL
,
Lui
VW-Y
,
Wong
SCC
, et al
.
Enhanced IL-6/IL-6R signaling promotes growth and malignant properties in EBV-infected premalignant and cancerous nasopharyngeal epithelial cells
.
PLoS One
2013
;
8
:
e62284
.
48.
Horiguchi
A
,
Oya
M
,
Marumo
K
,
Murai
M
.
STAT3, but not ERKs, mediates the IL-6–induced proliferation of renal cancer cells, ACHN and 769P
.
Kidney Int
2002
;
61
:
926
38
.
49.
Fisher
DT
,
Appenheimer
MM
,
Evans
SS
.
The two faces of IL-6 in the tumor microenvironment
.
Semin Immunol
2014
;
26
:
38
47
.
50.
Toll
BA
,
Brandon
TH
,
Gritz
ER
,
Warren
GW
,
Herbst
RS
.
Assessing tobacco use by cancer patients and facilitating cessation: an American Association for Cancer Research policy statement
.
Clin Cancer Res
2013
;
19
:
1941
8
.
51.
Arrazola
RA
,
Singh
T
,
Corey
CG
,
Husten
CG
,
Neff
LJ
,
Apelberg
BJ
, et al
.
Tobacco use among middle and high school students — United States, 2011–2014
.
Morb Mortal Wkly Rep
2015
;
64
:
381
5
.
52.
Wang
TW
,
Neff
L
,
Park-Lee
E
,
Ren
C
,
Cullen
K
,
King
B
.
E-cigarette use among middle and high school students — United States, 2020
.
Morb Mortal Wkly Rep
2020
;
69
:
1310
2
.
53.
Johnston
L
,
Miech
R
,
O'Malley
P
,
Bachman
J
,
Schulenberg
J
,
Patrick
M
.
Monitoring the Future study: national survey results on drug use 1975–2020
.
Institute for Social Research, The University of Michigan
;
2021
;
Available from
: https://monitoringthefuture.org/wp-content/uploads/2022/08/mtf-overview2020.pdf
54.
Arrazola
RA
,
Dube
SR
,
King
BA
.
Tobacco product use among middle and high school students — United States, 2011 and 2012
.
Morb Mortal Wkly Rep
2013
;
62
:
893
7
.
55.
Arrazola
RA
,
Neff
LJ
,
Kennedy
SM
,
Holder-Hayes
E
,
Jones
CD
.
Tobacco use among middle and high school students — United States, 2013
.
Morb Mortal Wkly Rep
2014
;
63
:
1021
6
.
56.
Jamal
A
,
Gentzke
A
,
Hu
S
,
Cullen
K
,
Apelberg
B
,
Homa
D
, et al
.
Tobacco use among middle and high school students — United States, 2011–2016
.
Morb Mortal Wkly Rep
2017
;
66
:
597
603
.
57.
Wang
TW
,
Gentzke
A
,
Sharapova
S
,
Cullen
K
,
Ambrose
B
,
Jamal
A
.
Tobacco product use among middle and high school students — United States, 2011–2017
.
Morb Mortal Wkly Rep
2018
;
67
:
629
33
.
58.
Gentzke
AS
,
Creamer
M
,
Cullen
KA
,
Ambrose
BK
,
Willis
G
,
Jamal
A
, et al
.
Vital signs: tobacco product use among middle and high school students — United States, 2011–2018
.
Morb Mortal Wkly Rep
2019
;
68
:
157
64
.
59.
Wang
TW
,
Gentzke
A
,
Creamer
M
,
Cullen
K
,
Holder-Hayes
E
,
Sawdey
M
, et al
.
Tobacco product use and associated factors among middle and high school students — United States, 2019
.
MMWR Surveill Summ
2019
;
68
:
1
22
.
60.
Singh
T
,
Arrazola
RA
,
Corey
CG
,
Husten
CG
,
Neff
LJ
,
Homa
DM
, et al
.
Tobacco use among middle and high school students –United States, 2011–2015
.
Morb Mortal Wkly Rep
2016
;
65
:
361
7
.
61.
Pepper
JK
,
Ribisl
KM
,
Brewer
NT
.
Adolescents’ interest in trying flavored e-cigarettes
.
Tob Control
2016
;
25
:
ii62
6
.
62.
Leventhal
AM
,
Goldenson
NI
,
Barrington-Trimis
JL
,
Pang
RD
,
Kirkpatrick
MG
.
Effects of non-tobacco flavors and nicotine on e-cigarette product appeal among young adult never, former, and current smokers
.
Drug Alcohol Depend
2019
;
203
:
99
106
.
63.
Schneller
LM
,
Bansal-Travers
M
,
Goniewicz
ML
,
McIntosh
S
,
Ossip
D
,
O'Connor
RJ
.
Use of flavored e-cigarettes and the type of e-cigarette devices used among adults and youth in the US—results from Wave 3 of the Population Assessment of Tobacco and Health Study (2015–2016)
.
Int J Environ Res Public Health
2019
;
16
:
2991
.
64.
Ambrose
BK
,
Day
HR
,
Rostron
B
,
Conway
KP
,
Borek
N
,
Hyland
A
, et al
.
Flavored tobacco product use among US youth aged 12–17 years, 2013–2014
.
JAMA
2015
;
314
:
1871
3
.
65.
Morean
ME
,
Butler
ER
,
Bold
KW
,
Kong
G
,
Camenga
DR
,
Cavallo
DA
, et al
.
Preferring more e-cigarette flavors is associated with e-cigarette use frequency among adolescents but not adults
.
PLoS One
2018
;
13
:
e0189015
.
66.
Bold
KW
,
Kong
G
,
Camenga
DR
,
Simon
P
,
Cavallo
DA
,
Morean
ME
, et al
.
Trajectories of e-cigarette and conventional cigarette use among youth
.
Pediatrics
2018
;
141
:
e20171832
.
67.
Garrison
KA
,
O'Malley
SS
,
Gueorguieva
R
,
Krishnan-Sarin
S
.
A fMRI study on the impact of advertising for flavored e-cigarettes on susceptible young adults
.
Drug Alcohol Depend
2018
;
186
:
233
41
.
68.
Rostron
BL
,
Cheng
Y-C
,
Gardner
LD
,
Ambrose
BK
.
Prevalence and reasons for use of flavored cigars and ENDS among US youth and adults: estimates from wave 4 of the PATH study, 2016–2017
.
Am J Health Behav
2020
;
44
:
76
81
.
69.
Miech
R
,
Leventhal
A
,
Johnston
L
,
O'Malley
PM
,
Patrick
ME
,
Barrington-Trimis
J
.
Trends in use and perceptions of nicotine vaping among US youth from 2017 to 2020
.
JAMA Pediatr
2020
;
175
:
185
90
.
70.
U.S. Department of Health and Human Services
.
Enforcement priorities for electronic nicotine delivery systems (ENDS) and other deemed products on the market without premarket authorization (Revised): guidance for industry
.
U.S. Department of Health and Human Services, Food and Drug Administration Center for Tobacco Products
;
2020
.
Available from
: https://www.fda.gov/media/133880/download
71.
Maloney
J
.
Juul debates pushing back on e-cigarette ban
.
Wall Street Journal
;
2019
.
Available from
: https://www.wsj.com/articles/juul-debates-pushing-back-on-e-cigarette-ban-11568327978.
72.
Obisesan
OH
,
Osei
AD
,
Uddin
SMI
,
Dzaye
O
,
Mirbolouk
M
,
Stokes
A
, et al
.
Trends in e-cigarette use in adults in the United States, 2016–2018
.
JAMA Intern Med
2020
;
180
:
1394
8
.
73.
Palmer
AM
,
Smith
TT
,
Nahhas
GJ
,
Rojewski
AM
,
Sanford
BT
,
Carpenter
MJ
, et al
.
Interest in quitting e-cigarettes among adult e-cigarette users with and without cigarette smoking history
.
JAMA Netw Open
2021
;
4
:
e214146
.
74.
Owusu
D
,
Huang
J
,
Weaver
SR
,
Pechacek
TF
,
Ashley
DL
,
Nayak
P
, et al
.
Patterns and trends of dual use of e-cigarettes and cigarettes among U.S. adults, 2015–2018
.
Prev Med Rep
2019
;
16
:
101009
.
75.
Akinboro
O
,
Nwabudike
S
,
Elias
R
,
Balasire
O
,
Ola
O
,
Ostroff
JS
.
Electronic cigarette use among survivors of smoking-related cancers in the United States
.
Cancer Epidemiol Biomarkers Prev
2019
;
28
:
2087
94
.
76.
Bjurlin
MA
,
Basak
R
,
Zambrano
I
,
Schatz
D
,
El Shahawy
O
,
Sherman
S
, et al
.
Patterns and associations of smoking and electronic cigarette use among survivors of tobacco related and non-tobacco related cancers: a nationally representative cross-sectional analysis
.
Cancer Epidemiol
2022
;
78
:
101913
.
77.
Hackshaw
A
,
Morris
JK
,
Boniface
S
,
Tang
J-L
,
Milenković
D
.
Low cigarette consumption and risk of coronary heart disease and stroke: meta-analysis of 141 cohort studies in 55 study reports
.
BMJ
2018
;
360
:
j5855
.
78.
O'Brien
D
,
Long
J
,
Quigley
J
,
Lee
C
,
McCarthy
A
,
Kavanagh
P
.
Association between electronic cigarette use and tobacco cigarette smoking initiation in adolescents: a systematic review and meta-analysis
.
BMC Public Health
2021
;
21
:
954
.
79.
Khouja
JN
,
Suddell
SF
,
Peters
SE
,
Taylor
AE
,
Munafò
MR
.
Is e-cigarette use in non-smoking young adults associated with later smoking? A systematic review and meta-analysis
.
Tob Control
2021
;
30
:
8
15
.
80.
Meza
R
,
Jimenez-Mendoza
E
,
Levy
DT
.
Trends in tobacco use among adolescents by grade, sex, and race, 1991–2019
.
JAMA Netw Open
2020
;
3
:
e2027465
.
81.
Balfour
DJK
,
Benowitz
NL
,
Colby
SM
,
Hatsukami
DK
,
Lando
HA
,
Leischow
SJ
, et al
.
Balancing consideration of the risks and benefits of e-cigarettes
.
Am J Public Health
2021
;
111
:
1661
72
.
82.
Hartmann-Boyce
J
,
McRobbie
H
,
Butler
AR
,
Lindson
N
,
Bullen
C
,
Begh
R
, et al
.
Electronic cigarettes for smoking cessation
.
Cochrane Database Syst Rev
2021
;
9
:
CD010216
.
83.
Farrelly
MC
,
Duke
JC
,
Crankshaw
EC
,
Eggers
ME
,
Lee
YO
,
Nonnemaker
JM
, et al
.
A randomized trial of the effect of e-cigarette TV advertisements on intentions to use e-cigarettes
.
Am J Prev Med
2015
;
49
:
686
93
.
84.
Villanti
AC
,
Rath
JM
,
Williams
VF
,
Pearson
JL
,
Richardson
A
,
Abrams
DB
, et al
.
Impact of exposure to electronic cigarette advertising on susceptibility and trial of electronic cigarettes and cigarettes in US young adults: a randomized controlled trial
.
Nicotine Tob Res
2016
;
18
:
1331
9
.
85.
Loukas
A
,
Paddock
EM
,
Li
X
,
Harrell
MB
,
Pasch
KE
,
Perry
CL
.
Electronic nicotine delivery systems marketing and initiation among youth and young adults
.
Pediatrics
2019
;
144
:
e20183601
.
86.
Vogel
EA
,
Ramo
DE
,
Rubinstein
ML
,
Delucchi
KL
,
Darrow
SM
,
Costello
C
, et al
.
Effects of social media on adolescents’ willingness and intention to use e-cigarettes: an experimental investigation
.
Nicotine Tob Res
2021
;
23
:
694
701
.
87.
Camenga
D
,
Gutierrez
KM
,
Kong
G
,
Cavallo
D
,
Simon
P
,
Krishnan-Sarin
S
.
E-cigarette advertising exposure in e-cigarette naïve adolescents and subsequent e-cigarette use: a longitudinal cohort study
.
Addict Behav
2018
;
81
:
78
83
.
88.
Zheng
X
,
Li
W
,
Wong
S-W
,
Lin
H-C
.
Social media and e-cigarette use among US youth: longitudinal evidence on the role of online advertisement exposure and risk perception
.
Addict Behav
2021
;
119
:
106916
.
89.
Marynak
K
,
Gentzke
A
,
Wang
TW
,
Neff
L
,
King
BA
.
Exposure to electronic cigarette advertising among middle and high school students — United States, 2014–2016
.
Morb Mortal Wkly Rep
2018
;
67
:
294
9
.
90.
Pierce
JP
,
Sargent
JD
,
Portnoy
DB
,
White
M
,
Noble
M
,
Kealey
S
, et al
.
Association between receptivity to tobacco advertising and progression to tobacco use in youth and young adults in the PATH study
.
JAMA Pediatr
2018
;
172
:
444
.
91.
Bennett
M
,
Hair
EC
,
Liu
M
,
Pitzer
L
,
Rath
JM
,
Vallone
DM
.
Exposure to tobacco content in episodic programs and tobacco and E-cigarette initiation
.
Prev Med
2020
;
139
:
106169
.
92.
Khangura
SD
,
McGill
SC
.
Pharmacological interventions for vaping cessation
.
Can J Health Technol
2021
;
1
:
1
14
.
93.
Warren
GW
,
Sobus
S
,
Gritz
ER
.
The biological and clinical effects of smoking by patients with cancer and strategies to implement evidence-based tobacco cessation support
.
Lancet Oncol
2014
;
15
:
e568
80
.
94.
Warren
GW
,
Marshall
JR
,
Cummings
KM
,
Toll
BA
,
Gritz
ER
,
Hutson
A
, et al
.
Addressing tobacco use in patients with cancer: a survey of American Society of Clinical Oncology members
.
J Oncol Pract
2013
;
9
:
258
62
.
95.
Warren
GW
,
Marshall
JR
,
Cummings
KM
,
Toll
B
,
Gritz
ER
,
Hutson
A
, et al
.
Practice patterns and perceptions of thoracic oncology providers on tobacco use and cessation in cancer patients
.
J Thorac Oncol
2013
;
8
:
543
8
.
96.
Babb
S
,
Malarcher
A
,
Schauer
G
,
Asman
K
,
Jamal
A
.
Quitting smoking among adults — United States, 2000–2015
.
Morb Mortal Wkly Rep
2017
;
65
:
1457
64
.
97.
Land
T
,
Warner
D
,
Paskowsky
M
,
Cammaerts
A
,
Wetherell
L
,
Kaufmann
R
, et al
.
Medicaid coverage for tobacco dependence treatments in Massachusetts and associated decreases in smoking prevalence
.
PLoS One
2010
;
5
:
e9770
.
98.
Richard
P
,
West
K
,
Ku
L
.
The return on investment of a Medicaid tobacco cessation program in Massachusetts
.
PLoS One
2012
;
7
:
e29665
.
99.
U.S. Centers for Disease Control and Prevention
.
STATE system Medicaid coverage of tobacco cessation treatments fact sheet
;
2020
.
Available from
: https://www.cdc.gov/statesystem/factsheets/medicaid/Cessation.html.
100.
Ramsey
AT
,
Prentice
D
,
Ballard
E
,
Chen
L-S
,
Bierut
LJ
.
Leverage points to improve smoking cessation treatment in a large tertiary care hospital: a systems-based mixed methods study
.
BMJ Open
2019
;
9
:
e030066
.
101.
Singleterry
J
,
Jump
Z
,
DiGiulio
A
,
Babb
S
,
Sneegas
K
,
MacNeil
A
, et al
.
State Medicaid coverage for tobacco cessation treatments and barriers to coverage — United States, 2014–2015
.
Morb Mortal Wkly Rep
2015
;
64
:
1194
9
.
102.
Zhang
X
,
Lin
D
,
Pforsich
H
,
Lin
VW
.
Physician workforce in the United States of America: forecasting nationwide shortages
.
Hum Resour Health
2020
;
18
:
8
.
103.
Graham
AL
,
Amato
MS
,
Cha
S
,
Jacobs
MA
,
Bottcher
MM
,
Papandonatos
GD
.
Effectiveness of a vaping cessation text message program among young adult e-cigarette users: a randomized clinical trial
.
JAMA Intern Med
2021
;
181
:
923
30
.
104.
Duke
JC
,
MacMonegle
AJ
,
Nonnemaker
JM
,
Farrelly
MC
,
Delahanty
JC
,
Zhao
X
, et al
.
Impact of The Real Cost media campaign on youth smoking initiation
.
Am J Prev Med
2019
;
57
:
645
51
.
105.
Shrestha
SS
,
Davis
K
,
Mann
N
,
Taylor
N
,
Nonnemaker
J
,
Murphy-Hoefer
R
, et al
.
Cost effectiveness of the Tips From Former Smokers campaign—U.S., 2012–2018
.
Am J Prev Med
2021
;
60
:
406
10
.
106.
Murphy-Hoefer
R
.
Association between the Tips From Former Smokers campaign and smoking cessation among adults, United States, 2012–2018
.
Prev Chronic Dis
2020
;
17
:
E97
.
107.
National Cancer Institute. SmokeFree.gov [Internet]
.
[cited 2022 Jun 22]. Available from:
https://smokefree.gov/.
108.
Bricker
JB
,
Mull
KE
,
McClure
JB
,
Watson
NL
,
Heffner
JL
.
Improving quit rates of web-delivered interventions for smoking cessation: full-scale randomized trial of WebQuit.org versus Smokefree.gov
.
Addiction
2018
;
113
:
914
23
.
109.
Fiore
M
,
Jaen
CR
,
Bailey
W
,
Benowitz
NL
,
Curry
S
,
Dorfman
SF
, et al
.
Treating tobacco use and dependence: 2008 update
.
Rockville, MD
:
US Department of Health and Human Services. Public Health Service
;
2008
.
Available from
: https://www.ncbi.nlm.nih.gov/books/NBK63952/.
110.
Hajek
P
,
Phillips-Waller
A
,
Przulj
D
,
Pesola
F
,
Smith
KM
,
Bisal
N
, et al
.
A randomized trial of e-cigarettes versus nicotine-replacement therapy
.
N Engl J Med
2019
;
380
:
629
37
.
111.
Walker
N
,
Parag
V
,
Verbiest
M
,
Laking
G
,
Laugesen
M
,
Bullen
C
.
Nicotine patches used in combination with e-cigarettes (with and without nicotine) for smoking cessation: a pragmatic, randomised trial
.
Lancet Respir Med
2020
;
8
:
54
64
.
112.
Fiore
MC
,
Smith
SS
,
Jorenby
DE
,
Baker
TB
.
The effectiveness of the nicotine patch for smoking cessation. A meta-analysis
.
JAMA
1994
;
271
:
1940
7
.
113.
Waxman
HA
.
Family Smoking Prevention and Tobacco Control Act of 2009
.
111–31 Jun 22, 2009. Available from
: https://www.congress.gov/bill/111th-congress/house-bill/1256
114.
U.S. Department of Health and Human Services
.
Deeming tobacco products to be subject to the Federal Food, Drug, and Cosmetic Act, as amended by the Family Smoking Prevention and Tobacco Control Act; restrictions on the sale and distribution of tobacco products and required warning statements for tobacco products
.
U.S. Department of Health and Human Services, Food and Drug Administration Center for Tobacco Products
;
2016
.
Available from
: https://www.govinfo.gov/content/pkg/FR-2016-05-10/pdf/2016-10685.pdf.
115.
Willett
JG
,
Bennett
M
,
Hair
EC
,
Xiao
H
,
Greenberg
MS
,
Harvey
E
, et al
.
Recognition, use and perceptions of JUUL among youth and young adults
.
Tob Control
2019
;
28
:
115
6
.
116.
U.S. District Court for the District of Maryland
,
Grimm
P
.
American Academy of Pediatrics, et al. v. Food and Drug Administration, et al. 2019
.
Available from
: https://www.tobaccofreekids.org/assets/content/press_office/2019/2019_07_12_fda_memo.pdf.
117.
Zeller
M
.
Perspective: FDA's progress on tobacco product application review and related enforcement
.
FDA Center for Tobacco Products
;
2021
.
Available from
: https://www.fda.gov/tobacco-products/ctp-newsroom/perspective-fdas-progress-tobacco-product-application-review-and-related-enforcement.
118.
U.S. Food and Drug Administration Center for Tobacco Products
.
FDA permits marketing of e-cigarette products, marking first authorization of its kind by the agency
.
FDA
;
2021
.
Available from
: https://www.fda.gov/news-events/press-announcements/fda-permits-marketing-e-cigarette-products-marking-first-authorization-its-kind-agency.
119.
Reuters
.
Hawaii becomes first U.S. state to raise smoking age to 21
.
Reuters
;
2015
.
Available from
: https://www.reuters.com/article/us-usa-hawaii-tobacco-idUSKBN0P006V20150620.
120.
Institute of Medicine
.
Public health implications of raising the minimum age of legal access to tobacco products
.
Washington D.C.
:
National Academies Press
;
2015
.
Available from
: http://www.ncbi.nlm.nih.gov/books/NBK310412/.
121.
Pascrell
B
.
Further Consolidated Appropriations Act, 2020
.
116–94
2019
.
Available from
: https://www.govtrack.us/congress/bills/116/hr1865
122.
Chaloupka
FJ
,
Yurekli
A
,
Fong
GT
.
Tobacco taxes as a tobacco control strategy
.
Tob Control
2012
;
21
:
172
80
.
123.
National Conference of State Legislatures
.
E-cigarette & vaping product taxes
.
Natl Conf State Legis
;
2020
.
Available from
: https://www.ncsl.org/research/fiscal-policy/electronic-cigarette-taxation.aspx
124.
Chaloupka
FJ
,
Sweanor
D
,
Warner
KE
.
Differential taxes for differential risks — toward reduced harm from nicotine-yielding products
.
N Engl J Med
2015
;
373
:
594
7
.
125.
Saffer
H
,
Dench
D
,
Grossman
M
,
Dave
D
.
E-cigarettes and adult smoking: evidence from Minnesota
.
J Risk Uncertain
2020
;
60
:
207
28
.