Occupational polycyclic aromatic hydrocarbon exposure and risk of larynx cancer: a systematic review and meta-analysis

Polycyclic aromatic hydrocarbons (PAH) are genotoxic substances formed during combustion. Occupational PAH exposure has been shown to increase the risk of lung cancer and may be associated with other respiratory cancers. We conducted a systematic review and meta-analysis to clarify the relationship between occupational PAH exposures and larynx malignancies. We searched EMBASE and MEDLINE (until July 2014) using a series of search strings developed to seek case-control studies or longitudinal studies of workers (Population) exposed to PAHs (Exposure) and their risk for larynx cancer incidence and/or mortality (Outcome). Two independent reviewers screened the titles and abstracts for eligible articles and a third reviewer negotiated consensus. Further assessments of eligibility and sources of bias were conducted in a similar manner. The study results were pooled with random effects meta-analysis. The search resulted in 3377 records. The data of 92 full-text articles representing 63 studies were included and extracted. The majority of studies (n=47) was judged likely to be biased; only 16 studies were judged as methodologically adequate. The pooled effect size was 1.45 (95% CI 1.30 to 1.62; I-2=30.7%; (tau) over cap (2)=0.03) for larynx cancer incidence and 1.34 (95% CI 1.18 to 1.53; I-2=23.8%; (tau) over cap (2)=0.03) for larynx cancer mortality. While few studies allowed an investigation of dose-response, these indicate a positive dose-response effect. Although most studies may underestimate the true effect due to inexact approximations of PAH exposure, the metaanalysis suggests a robust positive association between PAH and larynx cancer.