Exposure to per- and poly-fluoroalkyl substances and lung, head and neck, and thyroid cancer: A systematic review and meta-analysis

Recent evidence suggests that exposure to per- and polyfluoroalkyl substances (PFAS) may increase the risk of different cancer types, such as kidney and testicular cancers. Instead, evidence for lung, head and neck, and thyroid cancer is sparse. Hence, we aimed to summarize available literature on the topic. We searched Pubmed and Scopus in January 2024 to retrieve relevant studies and estimated pooled relative risks (RRs) and 95% confidence intervals (CIs) for lung, head and neck, and thyroid cancers according to PFAS exposure using restricted maximum likelihood method. Pooled RRs for occupational or environmental PFAS exposure were 1.20 (95% CI: 1.12-1.28; I² = 0.0%, p_het = 0.9; n. studies = 9), 1.15 (95% CI: 0.96-1.37; I² = 0.0%, p_het = 0.7; n. studies = 3), and 1.54 (95% CI: 0.86-2.78; I² = 69.0%, p_het = 0.02; n. studies = 4) for lung, head and neck, and thyroid cancer, respectively. We did not find compelling evidence of publication bias for lung cancer (p = 0.3). Studies on statistically modelled serum PFAS levels did not support associations with these cancers. We found no positive associations between measured serum levels of 6 different types of PFAS and thyroid cancer. However, the pooled RR of two case-control studies nested within cohorts on the association between natural log-unit increase of perfluorooctanesulfonic acid (PFOS) and thyroid cancer was 1.51 (95% CI: 1.11-2.05; I² = 21.1%, p_het = 0.3). PFAS exposure may be associated with lung and thyroid cancer. Due to the limited number of studies and their limitations, further prospective studies with appropriate account of co-exposure with other carcinogens and detailed exposure assessment are needed to establish causality of observed associations.