Association between Formaldehyde Exposure and Laryngeal, Hypopharyngeal, and Nasopharyngeal Cancer: A Systematic Review and Meta-analysis

Assessment of possible association between formaldehyde exposure and risk for the development of laryngeal, hypopharynx, and nasopharynx cancer. The review adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines 2020 and registered in PROSPERO – Not registered in PROSPERO. Electronic databases were searched for studies evaluating the possible association between formaldehyde exposure and the development of laryngeal, hypopharynx, and nasopharynx cancer. Screening and data extraction were done by two independent reviewers. The quality assessment of studies was evaluated through the Newcastle–Ottawa scale tool. The risk ratio (RR) was used as a summary statistic measure with a random effect model and P < 0.05 as statistically significant through Review Manager (RevMan) version 5.3. Eleven studies were included in qualitative synthesis and five studies for meta-analysis, with data evaluated from 329,397 occupational workers exposed to formaldehyde with a mean exposure duration year of ± 10 years with an exposure dosage ranging from 0.02 to 0.50 ppm. Included studies showed moderate-to-low ROB. Meta-analysis revealed that occupational workers exposed to formaldehyde had shown an increased risk for laryngeal (RR: 1.42 [1.01–2.01]), hypopharynx (RR: 1.10 [0.75–1.61]), and nasopharynx cancer (RR: 1.16 [0.99–1.36]). The funnel plot did not show the presence of publication bias in the meta-analysis. Occupational formaldehyde exposure demonstrated a statistically significant association with laryngeal cancer risk. However, the associations with hypopharyngeal and nasopharyngeal cancers were not statistically significant. Further large-scale prospective studies controlling for smoking and alcohol-related confounders are recommended.