AACR and ASCO Call for a Prohibition on Flavored E-Cigarettes

By Nicholas Warren, PhD

Today, the American Association for Cancer Research (AACR) and the American Society of Clinical Oncology (ASCO) issued an updated joint policy statement with recommendations to protect public health from electronic nicotine delivery systems (ENDS), including e-cigarettes. Among the top recommendations was a call to prohibit all non-tobacco-flavored products that contain nicotine, except U.S. Food and Drug Administration (FDA)-approved cessation therapies. The statement also recommended a tax on all nicotine-containing products and increased support for evidence-based smoking cessation initiatives.

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AACR and ASCO previously issued a joint statement in 2015 following a dramatic 400 percent rise in ENDS use between 2012 and 2014 among middle and high school students, as estimated by the National Youth Tobacco Survey (NYTS). Concerningly, youth use rose an additional 46 percent by 2020, reaching up to 3.6 million middle and high school students who reported vaping within the past 30 days. Due to increased public awareness, decreased in-person interactions during the COVID-19 pandemic, and recent laws raising the legal age to buy tobacco products to 21 years, youth ENDS use declined in 2021. Unfortunately, the 2022 NYTS showed a 24 percent increase compared to 2021, highlighting the challenges of addressing youth ENDS after decades of consistent declines in the use of tobacco products by American youth and young adults. These concerning trends and continued lack of regulatory clarity from the FDA prompted AACR and ASCO to issue an updated policy statement to support urgent actions needed to protect public health. In particular, AACR and ASCO are concerned about ENDS as a gateway to nicotine addiction that increases the likelihood of transitions to smoking, which is the leading preventable cause of cancer.

Many ENDS products contain flavored additives, such as fruit, dessert, or mint or menthol flavors to mask the harsh taste of tobacco and solvents. The scientific evidence is clear that the widespread availability of flavored products is a key driver of youth and young adult initiation of ENDS. In 2022, 85 percent of middle and high school students who used ENDS vaped flavored products, and fruit flavors were the most popular. Another study found that teens 13 to 17 years old are six times more likely to try fruit-flavored ENDS compared to tobacco-flavored ENDS. Therefore, to reduce the appeal of these tobacco products on youth and adults who do not smoke, comprehensive prohibition of all non-tobacco-flavored products is a priority recommendation of the new policy statement.

New Evidence of Impacts to Health

Recent reports have advanced the understanding of how ENDS impact human biology. While traditional cigarettes emit greater amounts of carcinogens than ENDS, growing evidence links ENDS use to known cancer development processes—namely, DNA damage and inflammation that promotes cell replication. ENDS aerosols and extracts have been shown to directly and indirectly alter the chemical structure of DNA, which leads to broken DNA strands. Separate studies have shown in mice and humans that ENDS aerosols induce the inflammation signaling molecules IL-6 and CXCL8, which are well documented to transform precancerous cells into cancerous cells. However, high quality long-term studies are needed to characterize the relationship between cancer and ENDS use, as cancer can take decades to develop following exposure to carcinogens. In comparison, an enormous amount of evidence demonstrates smoking traditional cigarettes causes at least 18 types of cancer, including increasing the risk of lung cancer by 25-fold. This is because the process of burning creates a number of carcinogens, such as benzo[a]pyrene.

Additionally, nicotine alone harms health by increasing blood pressure, decreasing immune function, and impairing memory and learning abilities of youth and young adults. ENDS products can rapidly expose individuals to similar levels of nicotine as traditional cigarettes, which contributes to their highly addictive properties.

Evidence-based Smoking Cessation Remains a Top Priority

Quitting smoking is the number one thing a person who smokes can do to improve their health and reduce the risk of cancer. Several FDA-approved tobacco cessation therapies such as behavioral counseling, varenicline, and nicotine replacement therapies including gums, patches, and lozenges have been demonstrated in clinical trials to improve the chances of successfully quitting tobacco. Evidence-based awareness campaigns from the Centers for Disease Control and Prevention and the FDA, as well as National Cancer Institute’s cessation resource website SmokeFree.gov, have helped millions of Americans quit tobacco.

While ENDS have been billed as a new method to help adults quit smoking, several leading health authorities have determined there is insufficient evidence to support the use of ENDS for cessation, including the U.S. Surgeon General, the National Academies of Science, Engineering, and Medicine, the U.S. Preventive Services Task Force, and the National Comprehensive Cancer Network, a coalition of 31 leading cancer centers. The primary reason for a lack of evidence is that no ENDS manufacturer has applied to FDA to develop an ENDS product as a cessation therapy, which is required to conduct clinical trials in the United States.

Evolving Regulatory Landscape

FDA has taken some promising first steps to regulate ENDS and reduce the availability of flavored combustible tobacco products. Starting in 2020, FDA required all ENDS products to submit a “premarket tobacco product application” (PMTA) with sufficient scientific evidence to demonstrate the product is “appropriate for the protection of public health.” More than 8 million ENDS PMTAs have been submitted to FDA thus far. A small number of PMTAs have received a Marketing Order which authorizes them for sale, and the vast majority were found to include insufficient evidence to meet the protection of public health standard. However, dozens of pending PMTAs for very common products are still under review by FDA and those products can remain on the market in the meantime. Additionally, many of the ENDS products that were denied a Marketing Order can still be purchased online or in stores, highlighting the need for stronger FDA enforcement actions to stop the sale of illegally marketed products. Last week, FDA and the Department of Justice filed injunctions against six ENDS manufacturers for selling ENDS without submitting PMTAs. This historic development marks the first time FDA utilized its authority to enforce the PMTA requirement. 

AACR and ASCO Recommendations

The joint ENDS statement update presents evidence to support the need for additional legislation and regulations to protect public health from ENDS and other tobacco products, as well as identify gaps in scientific understanding that require more research. Most importantly, the statement calls for comprehensive prohibition of all non-tobacco-flavored products that contain nicotine due to the key role of flavors in youth initiation. The statement also calls for legislation to tax all tobacco products in a manner that reduces overall tobacco use, increase funding for evidence-based awareness campaigns and cessation resources, limit the sale of tobacco products to stores or areas within stores that require age verification, and improve insurance coverage of evidence-based cessation therapies. In addition to improved enforcement, the regulatory recommendations called on FDA to address predatory advertising practices, develop product standards to reduce the addictiveness and appeal of tobacco products, and increase transparency of the PMTA process. Several research needs were also identified, such as effective strategies for ENDS cessation, studies to understand the long-term health impacts of ENDS, how ENDS and other tobacco products interact with anticancer therapies and impact cancer outcomes, and randomized clinical trials comparing ENDS to FDA-approved smoking cessation therapies.