Being a non- or never-smoker appears to provide little protection against the ravages of cancer nowadays, with an increasing proportion of people being diagnosed with lung cancer who have never lit up, and with air pollution being an “important factor”, the World Health Organisation’s cancer agency has said.

Lung cancer in people who have never smoked cigarettes or tobacco is now estimated to be the fifth highest cause of cancer deaths worldwide, according to the International Agency for Research on Cancer (IARC).

In never-smokers, it is also occurring almost exclusively as adenocarcinoma, which has become the most dominant of the four main subtypes of the disease in both men and women globally.

About 200 000 cases of adenocarcinoma were associated with exposure to air pollution in 2022, according to the IARC study published in The Lancet Respiratory Medicine journal.

The largest burden of adenocarcinoma attributable to air pollution was found in east Asia, particularly China.

The study’s lead author and head of the IARC’s cancer surveillance branch, Dr Freddie Bray, toldThe Guardian that the findings underscored the need for urgent monitoring of the changing risk of lung cancer.

Further studies were also required to identify possible causal factors, like air pollution, in populations where smoking was not considered the main cause of lung cancer, he added.

“With declines in smoking prevalence – as seen in the UK and US – the proportion of lung cancers diagnosed among those who have never smoked tends to increase,” Bray said. “Whether the global proportion of adenocarcinomas attributable to ambient air pollution will increase depends on the relative success of future strategies to curtail tobacco use and air pollution worldwide.”

Lung cancer remains the leading cause of cancer incidence and mortality worldwide. In 2022, about 2.5m people were diagnosed with the disease. But the patterns of incidence by subtype have changed dramatically in recent decades.

Of the four main subtypes of lung cancer (adenocarcinoma, squamous cell carcinoma, small-cell carcinoma and large-cell carcinoma), adenocarcinoma has become the dominant subtype among both men and women, the IARC found.

Adenocarcinoma accounted for 45.6% of global lung cancer cases among men and 59.7% of global lung cancer cases among women in 2022. The respective figures were 39.0% and 57.1% in 2020.

Adenocarcinoma accounts for as much as 70% of lung cancer cases among never-smokers, the IARC said.

While lung cancer incidence rates for men have generally decreased in most countries during the past 40 years, rates among women have tended to continue to rise.

Current trends suggest that while men still comprise most lung cancer cases (about 1.6m in 2022), the gap between lung cancer incidences in males and females is narrowing, with about 900 000 women diagnosed with lung cancer in 2022.

In 2023, The Guardian revealed how the number of women diagnosed with lung cancer in the UK was overtaking men for the first time, prompting calls for women to be as vigilant about it as they are about breast cancer.

Cancer experts said the figures reflected historical differences in smoking prevalence, specifically that smoking rates peaked much earlier in men than women. Women should now be as alert to potential lung cancer signs as they were about checking for lumps in their breasts, they said.

Changes in cigarette manufacturing and smoking patterns in recent decades have influenced the trends in lung cancer incidence by subtype, and there is accumulating evidence of a causal link between air pollution and an increased risk of adenocarcinoma, the IARC said.

It is not known what proportion of global lung cancer cases are in never-smokers, only that evidence suggests it is rising. Scientists are racing to learn more about what else is causing lung cancer, beyond smoking.

“Air pollution can be considered an important factor partly explaining the emerging predominance of adenocarcinoma that accounts for 53% to 70% of cases of lung cancer among people who have never smoked worldwide,” the study reported.

Bray said the research provided important insights into how both lung cancer and the underlying risk factors were evolving, “offering clues as to how we can optimally prevent lung cancer worldwide”.

“Changes in smoking patterns and exposure to air pollution are among the main determinants of the changing risk profile of lung cancer incidence by subtype that we see today.

“The diverging trends by sex … offer insights to cancer prevention specialists and policymakers seeking to develop and implement tobacco and air pollution control strategies tailored to high-risk populations.”

Study details

Estimated worldwide variation and trends in incidence of lung cancer by histological subtype in 2022 and over time: a population-based study

Ganfeng Luo, Yanting Zhang, Jerome Vignat et al.

Published in The Lancet Respiratory Journal on 3 February 2025

Summary

Background
Lung cancer is the most common cancer worldwide, yet the current epidemiological profile of lung-cancer incidence by histological subtype is only partly understood. We aimed to assess geographical variation in incidence of lung cancer by subtype worldwide in 2022, geographical variation in adenocarcinoma incidence attributable to ambient particulate matter (PM) pollution worldwide in 2022, temporal trends in lung-cancer incidence by subtype from 1988 to 2017 in 19 countries, and generational changes.

Methods
For this population-based study, we used data from the Global Cancer Observatory (GLOBOCAN) 2022, Cancer Incidence in Five Continents Volumes VII–XII, and members of the African Cancer Registry Network. To obtain national estimates of lung cancer in 2022 for the four main histological subtypes (ie, adenocarcinoma, squamous cell carcinoma [SCC], small-cell carcinoma, and large-cell carcinoma) by year, sex, and age group, we combined national estimates with representative, subsite-specific incidence proportions of lung cancer on the basis of recorded incidence data compiled in Cancer Incidence in Five Continents Volume XII and from members of the African Cancer Registry Network. We calculated country-specific, sex-specific, and age-specific proportions of and sex-specific and age-specific incidence rates per 100 000 people for all four histological subtypes. To account for differences in age composition between populations by country, we calculated age-standardised incidence rates (ASRs) per 100 000 people for lung cancer by subtype and sex at national and regional levels. We also quantified the burden of adenocarcinoma incidence attributable to ambient PM pollution for 179 countries in 2022. We conducted joinpoint regression and age-period-cohort analysis to assess temporal trends in ASRs in 19 countries by sex.

Findings
In 2022, we estimated that there were 1 572 045 new cases of lung cancer worldwide among male individuals, of which 717 211 (45·6%) were adenocarcinoma, 461 171 (29·4%) were SCC, 180 063 (11·5%) were small-cell carcinoma, and 101 861 (6·5%) were large-cell carcinoma. In 2022, we estimated that there were 908 630 new cases of lung cancer worldwide among female individuals, of which 541 971 (59·7%) were adenocarcinoma, 155 598 (17·1%) were SCC, 87 902 (9·7%) were small-cell carcinoma, and 59 271 (6·5%) were large-cell carcinoma. Among male individuals, the highest ASRs were in east Asia for adenocarcinoma (27·12 [95% CI 27·04–27·21] per 100 000 people), east Europe for SCC (21·70 [21·51–21·89] per 100 000 people) and small-cell carcinoma (9·85 [9·72–9·98] per 100 000 people), and north Africa for large-cell carcinoma (4·33 [4·20–4·45] per 100 000 people). Among female individuals, the highest ASRs were in east Asia for adenocarcinoma (19·04 [18·97–19·11] per 100 000 people), north America for SCC (5·28 [5·21–5·35] per 100 000 people) and small-cell carcinoma (4·28 [4·21–4·35] per 100 000 people), and north Europe for large-cell carcinoma (2·87 [2·78–2·96] per 100 000 people). We estimated that 114 486 adenocarcinoma cases among male individuals and 80 378 adenocarcinoma cases among female individuals were attributable to ambient PM pollution worldwide in 2022, with ASRs of 2·35 (95% CI 2·33–2·36) per 100 000 male individuals and 1·46 (1·45–1·47) per 100 000 female individuals. Temporal trends in lung-cancer incidence by subtype and sex during 1988–2017 varied considerably across the 19 countries.

Interpretation
Estimated geographical and temporal distribution of lung-cancer incidence varied across the four main subtypes worldwide. Our study highlights the need for future studies that identify possible causal factors that contribute to the changing risk patterns of lung cancer.