E-CIGS AND CANCER

What should oncologists know about e-cigarettes?

Electronic nicotine delivery systems (ENDS) or e-cigarettes were supposedly designed to be a short-term bridge to smoking cessation.

Now they are increasingly used by youth and non-smokers and may be a gateway to traditional tobacco cigarettes. Evidence on the long-term use of these devices is lacking and the harm of aerosols is still uncertain. More studies are needed to determine the role of ENDS in cancer development or treatment.

Electronic nicotine delivery systems (ENDS) are battery-powered products that create an aerosol by heating a liquid consisting of propylene glycol and vegetable glycerin and flavouring agents. The liquid may or may not (but usually does) contain nicotine, at variable doses. Differently from conventional cigarettes, there is no combustion of tobacco in ENDS, thus making people think they cause less harm. However, the varying voltage that is applied to the liquid creates a mixture of potentially toxic substances in the aerosols that are then inhaled by users.

While the scientific community is still questioning the health risks associated to the use of electronic nicotine delivery systems (ENDS) or e-cigarettes, manufacturers are increasing the attractiveness of these devices. Making them more coloured, with glamourous shapes and smelling deliciously tasty, the result is that vaping is often perceived as less harmful than smoking as no tobacco combustion is involved.


The rapidly growing use of ENDS is emerging as a worrying trend globally, thus giving life to what seems to be an ENDS paradox: supposedly designed to be a short-term bridge to smoking cessation, some evidence now suggest that they may be related to a transition to traditional tobacco cigarettes, especially among youth, raising safety concerns for a long-term use of these electronic devices and dual use with persistent tobacco smoking.


“Although the EU has banned sales of electronic devices containing nicotine to minors, they can buy them on the internet without effective controls”, commented Cinzia De Marco, a researcher of the Tobacco Control Unit of the IRCCSS Istituto nazionale dei tumori in Milan, Italy. “ENDS are expanding the nicotine market by attracting youth who were at low risk of initiating nicotine use with conventional cigarettes, but many of whom are now moving on to conventional cigarettes. Even if they do not progress, promoting nicotine use to youth is bad public health policy and it is also necessary to consider that more and more young people are using these devices”. According to a recent survey of the European Commission, about 15% of the European population had tried ENDS at least once in their life in 2017.


The current landscape around e-cigarettes echoes the 1950s when, while smoking tobacco cigarettes was an increasingly popular social habit, the initial evidence on the carcinogenic effects of the substances released by tobacco combustion emerged from research confirming the involvement of tobacco products in cancer development. After some decades, it is now part of common knowledge that smoking is the one of the main avoidable causes of cancer. But what about ENDS?


At the European Lung Cancer Congress (ELCC) 2019 last April, a discussion on ENDS and cancer prevention aimed to investigate how oncologists engage with this emerging issue in public health. “As a medical oncologist”, commented David Spigel from Sarah Cannon Research Institute-Cancer Center in Nashville, US, “I talk a lot about smoking cessation to my patients and their families, but e-cigarettes do not really come up as a topic”. In his opinion, more evidence is needed to clarify the role of these devices in cancer prevention thus providing guidance to oncologists to deal with their patients’ requests or concerns. “When someone asks me if these devices are harmful, my answer is that we don’t know, but probably they are due to the many substances in the aerosol. Unfortunately, what we have learnt so far comes from popular press, and there is limited evidence in the traditional medical press. A lot of us assume that somebody must be watching, approving, assuring safety and understanding what these devices are, but this does not always seem the case”, he said.


One of the biggest concerns of Carolyn Dresler, a member of the International Association for the Study of Lung Cancer (IASLC), is that people who smoke may become dual users - that is, keeping on smoking both traditional cigarettes and ENDS. “Most people agree that ENDS are less harmful than traditional cigarettes are”, she commented at ELCC 2019. “But although we have not much evidence on their harmful effects at the moment, there is one very important message that healthcare providers should deliver to their patients: to quit any kind of smoking as soon as possible.” Dresler continued: “This is an area of significant controversy even within our oncology colleagues. Some advocate that patients must stop the known most deadly product - cigarettes, and if they cannot stop with the more traditional smoking cessation products, then, they should try e-cigarettes. Then, they should stop using e-cigarettes. Basically, the important point is for patients to get off of deadly cigarettes, and then, stop the other interventions (medicines or e-cigarettes) as soon as possible.”


In this scenario, one of the major problems is that the ENDS market and research proceed at different speeds. While the former is growing rapidly and expanding its offer to attract an increasing number of consumers – it is expected to cross 43 billion USD by 2023 with a 15% steady annual growth rate since 2017 – the latter is still at its early times and many more years will be spent waiting for robust evidence from the studies.


Evidence of the impact of e-cigarettes on human health are still sparse. A systematic review in 2017 (CA Cancer J Clin. 2017 Nov;67(6):449-471) reported that short-term use of ENDS does not adversely affect cardiovascular function, apart from the already known effects of nicotine on heart rate. Another review (Cancer Epidemiol Biomarkers Prev. 2017 Aug; 26(8): 1175–1191) showed that ENDS can induce inflammation at the pulmonary level given the toxic and irritating mixture of components in their aerosols, although at a lower rate than tobacco smoking.


Regarding the carcinogenic aspect of using ENDS, results will be acquired from epidemiologic studies that will take years. At present ample research demonstrates significantly lower levels of carcinogens from these devices. A recent report from the National Academies of Sciences, Engineering, and Medicine concluded that there is no available evidence whether or not e-cigarette use is associated with intermediate cancer endpoints in humans. “I think that ENDS have much lower levels of carcinogens”, said Dresler, “but what about the other constituents in the aerosol? They do not seem harmless, and we need more research particularly in cardiovascular and pulmonary impacts to assess if ENDS use plays a role in the development of other diseases too.”


A precautionary approach toward the use of ENDS has been adopted globally. In 2016, the World Health Organisation (WHO) recognised that these devices might be less harmful than conventional cigarettes but called for more regulation to deter their promotion to non-smokers and young people, minimise potential health risks to vapers and non-vapers and prohibit health claims about their use. In Europe, the market is regulated by the recently revised Tobacco Products Directive (TPD) 2014/40/EU, that aims to harmonise the safety and quality specifications for ENDS including but not limited to the volume of the refill container, the nicotine content and the existence of child-resistant refill containers.


While safety and health concerns still need to be assessed, the role of these devices in smoking cessation is also questioned. A recent meta-analysis (Annu Rev Public Health. 2018 Apr 1;39:215-235) has reported that vapers are about one third less likely to quit smoking, compared to smokers who do not use e-cigarettes. “We need more research to understand why devices like that would make more sense than those we have already to help our patients to quit smoking”, continued Spigel, “because we do not know the long-term effects of this strategy. Also, it would be relevant to understand what happens in the long-term. What are the behavioural consequences of moving to e-cigarettes? Does it really open-up to other addictive behaviours? These are the questions we have no answers to and that can have an impact on our role as oncologists”.


In cancer patients, smoking cessation has been associated with improved survival, higher quality of life, and better outcomes of surgery, chemotherapy, radiotherapy, and biological therapies. According to De Marco, ENDS, if used properly, may represent a useful tool to support patients in early phases of smoking cessation. “It will take several years to have reliable data on the consequences of long-term use”, she said. “It is possible that the long-term health benefits associated with their use might outweigh the short-term risks, nevertheless, this aspect would need to be clarified”. De Marco concluded, “The greatest difficulty of research in this area, both short and long term, is the possibility for researchers to receive funds not derived from tobacco multinationals companies so as to be able to conduct independent studies.

Oncologists can play an active role in smoking cessation. For this, according to Cinzia De Marco, researcher from the Tobacco Control Unit of the IRCCS Istituto nazionale dei tumori in Milan, Italy, they should keep up-to-date on the latest findings from research about e-cigarettes and how these devices potentially affect health.