A 20-Year Natural Experiment: What Is the Outcome? Do E-Cigarettes Cause Cancer?

From 2003 to 2026: One product, four generations, no mature data

The modern nicotine e-cigarette was developed in 2003 by Chinese pharmacist Hon Lik; after his father's death from lung cancer, it emerged from his search for "a way to obtain nicotine without combustion." The patent was registered in 2003, the product entered the Chinese market in 2004, and it spread to Europe and the US in 2007. Twenty years later, according to 2024 data, at least 100 million people worldwide use e-cigarettes. By the end of 2025, Turkey's adult smoking prevalence had fallen to around %22; successful tobacco-control policies on the one hand and the spread of e-cigarette/vape use in the illicit market on the other may underlie this decline, but there are no definitive data.

How did epidemiological evidence mature for conventional cigarettes? Given the boom in commercial cigarettes in the early 1900s, the first major case-control studies (Doll-Hill 1950 BMJ, Wynder-Graham 1950 JAMA) were, after the product entered the market, approximately fifty years later published. Our current moment corresponds to the years 1925-1930 for e-cigarettes — meaning that we are still ten to fifteen years away from the emergence of major epidemiological evidence. What Stewart and colleagues did in 2026 was precisely this: during this gap in the evidence, without waiting for classic epidemiological cases, weigh the total evidence within IARC's "Ten Key Characteristics of Carcinogens" (KCC) framework.

IARC's standard for evaluating oncological carcinogens since 2012

Developed by Smith and colleagues in Berkeley in 2012 and formally used by IARC in carcinogen evaluations from 2019 onward, the "ten key characteristics" approach evaluates whether a substance is carcinogenic by considering the totality of mechanistic evidence, rather than epidemiology alone. Stewart's team applied this framework to e-cigarette aerosol and reviewed current laboratory and in vivo evidence for each characteristic.

The "positive for 9 of 10 characteristics" table in this image is an extremely strong mechanistic signature in carcinogen evaluation. Most substances classified as Group 1 carcinogens (human carcinogens), including tobacco smoke, asbestos, formaldehyde, and kuruşal-altı 1,3-butadiene, show a similar profile. The crucial difference is this: the Group 1 classification of these classic substances has, in addition to mechanistic evidence, through human epidemiology , also been confirmed. For e-cigarettes, this epidemiological link has not yet been completed — and completing it takes time.

What are nonsmoking vape users exposed to?

The entirety of the biomarker studies compiled by Stewart and colleagues, in individuals who have never smoked but regularly vape, shows an exposure level below that of cigarette smokers but above that of people who do not vape as a carcinogen-exposure signature. There is thus a three-tier hierarchy: non-vaper < vape user < cigarette smoker. But the jump from "non-vaper" to "vape user" is biologically meaningful.

Mice and young patients: Two fronts of 2026

The Stewart 2026 review contains two groups of evidence that partly fill the gap in epidemiological evidence:

First, the mouse inhalation bioassay. In 2019, Tang and colleagues (NYU) exposed mice to nicotine-containing e-cigarette aerosol by inhalation for 54 weeks, then observed lung adenocarcinoma in %22,5 and bladder hyperplasia in %57,5. This study was partly replicated in different laboratories in subsequent years; despite methodological debates, it constitutes e-cigarette aerosol's first documented in vivo tumor-induction evidence.

Second, case reports. Stewart's team examined a total of twenty-two case reports published between 2017-2025: mostly squamous-cell carcinoma of the floor of the mouth or tongue, with some small-cell lung cancer and verrucous oral-cavity lesions. The common features of the cases are striking: typically aged 35-50, 10+ years of vaping, limited or no smoking history, and heavy alcohol use excluded. These cases are not a classic epidemiological tool for proving a carcinogenic association, but they are serious warning signals. In medical history, the first evidence linking smoking and lung cancer also came from similar case series (particularly Ochsner-DeBakey's series of 79 patients in 1939).

Graphical Abstract:

The graphic above summarizes how, in e-cigarette aerosol, nicotine, volatile organic compounds, flavorings, metals, and polycyclic aromatic hydrocarbons may produce DNA damage, cellular stress, inflammation, and possible harmful effects on lung tissue.

In human studies, among e-cigarette users, cotinine levels indicating nicotine exposure, 100 times higher than in non-users, are highlighted, and in the literature, 3 oral-cancer cases have been reported, as emphasized.

In animal studies, among mice exposed to e-cigarette aerosol, lung adenocarcinoma in %22,5 developed, while in the control group a tumor in only 1/40 mice was observed.

Mechanistic data, meanwhile, show that, rather than a single substance, a complex biological process in which DNA damage, oxidative stress, and inflammation are triggered together may underlie the possible carcinogenic effect of e-cigarettes.

In clinical oncology practice, at Memorial, Acıbadem, Anadolu Sağlık, and other major Turkish centers, alongside smoking history in initial examinations for oral and lung cancer, "vaping history"now needs to be added as a standard item in the medical history as of 2026. In eligibility decisions for low-dose CT lung screening (the 2021 update of the NLST criteria), alongside the threshold of "20 pack-years of smoking," a long-term vaping history should be assessed as an independent risk factor — particularly for young patients who have never smoked but have vaped for 10+ years. This patient profile will move to the forefront of the clinical landscape as we approach the 2030s.

This review has no direct effect on treatment practice; it is an exposure assessment, not a clinically approved drug. But it has three important practical implications over the medium term:

First, bringing oral-cancer screening back onto the agenda. The case reports in the Stewart 2026 review are particularly centered on squamous-cell carcinoma of the floor of the mouth and tongue . The scope of the Ministry of Health's oral-cancer screening program in Turkey expanded after 2020, but it still targets individuals with a tobacco history. Young vape users fall outside this scope. This gap can be filled at the level of dentists and family physicians by making "Do you vape?" a standard question, particularly during oral examinations.

Second, nuance in patient-physician communication. The claim "vaping is less harmful than smoking" is popular and partly true — but it must not turn into the misconception "therefore it is harmless." Clinicians, especially when speaking with young people, need to use the three-way framework of "less harmful than smoking, but more harmful than not vaping."

Third, updating lung-cancer screening criteria over the long term. Current LDCT screening criteria (NCCN, USPSTF) rely only on smoking pack-year history. As we approach the 2030s, cumulative vape exposure is very likely to come onto the agenda as a risk variable for inclusion in the criteria.

• Qualitative assessment — no numbers. The Stewart review does not answer "how much." Quantitative questions such as "how much additional risk, after how long, and with which device type" remain unanswered.
• The dual-user problem. The great majority of studies include people who use cigarettes + vapes together; data on "exclusive vape users" are very limited, particularly almost nonexistent for those aged 35+.
• Product heterogeneity. Refillable mods, closed pods, disposables, high nicotine salts vs free-base, different flavors, different power settings — all produce different aerosol chemistry. "E-cigarettes" are not a single category.
• Literature before 2017 excluded. Stewart's team made this decision to prevent selection bias, but it means that some classic studies from 2014-2016 are excluded.
• Marijuana vaping excluded. Only nicotine-based e-cigarettes were assessed; the carcinogenicity of cannabis vaping is a much less studied area.
• Latency uncertainty. There is an average latency of 20-30 years between smoking and cancer. For e-cigarettes, we do not know whether this period is shorter, longer, or the same.

This article is intended for medical news/information and does not provide individual treatment guidance. On e-cigarette carcinogenicity, the 30 March 2026 Carcinogenesis review is a qualitative assessment; it contains no quantitative risk estimate. Vape products cannot legally be imported or sold in Turkey since February 2020; metal-contamination and quality-control problems in illicit-market products are an additional concern for users. Individuals trying to quit smoking, regarding approved nicotine-replacement therapies (patches, gum, lozenges, sprays) and varenicline , are advised to consult their family physician. Editor's note: This article is based on the Stewart et al. Carcinogenesis review of 30 March 2026, the FDA ENDS marketing authorization announcement of 5 May 2026, and current regulatory documents from the Republic of Türkiye Ministry of Health / Ministry of Trade.