The effect of occupational exposure to solar ultraviolet radiation on malignant skin melanoma and non-melanoma skin cancer: a systematic review and meta-analysis from the WHO/ILO joint estimates of the work-related burden of disease and injury
A systematic review and meta-analysis of studies were conducted reporting on the association between occupational exposure to solar ultraviolet radiation (UVR) and both malignant skin melanoma (melanoma) and non-melanoma skin cancer (NMSC), with the aim of enabling the estimation of the numbers of deaths and disability-adjusted life years from melanoma and NMSC attributable to occupational exposure to solar UVR, for the development of the World Health Organization (WHO)/International Labour Organization (ILO) Joint Estimates of the Work-related Burden of Disease and Injury (WHO/ILO Joint Estimates). A protocol was developed and published, applying the Navigation Guide as an organizing systematic review framework where feasible. Electronic bibliographic databases were searched for potentially relevant records; electronic grey literature databases and organizational websites were also searched, reference lists of previous systematic reviews and included study records were hand-searched, and additional experts were consulted. Randomized controlled trials and cohort, case–control and other non-randomized studies were included that estimated the effect of any occupational exposure to solar UVR, compared with no occupational exposure to solar UVR, on melanoma (excluding melanoma of the lip or eye) or NMSC prevalence, inci- dence or mortality. At least two reviewers independently screened titles and abstracts against the eligibility criteria at a first stage and full texts of potentially eligible records at a second stage. Adjusted relative risks were combined using random-effects meta-analysis. Two or more reviewers assessed the risk of bias, quality of evidence and strength of evidence. Fifty-three (48 case–control, three case–case and two cohort) eligible studies were found, published in 62 study records, including over 457 000 participants in 26 countries of three WHO regions (Region of the Americas, European Region and Western Pacific Region), reporting on the effect on melanoma or NMSC incidence or mortality. No studies on the prevalence of melanoma or NMSC were found. In most studies, exposure was self-reported in questionnaires during interviews and the health outcome was assessed via physician diagnosis based on biopsy and histopathological confirmation. The risk of bias of the body of evidence was judged to be generally “probably low”, although there were some concerns regarding risks of exposure misclassification bias, detection bias and confounding. The main meta-analyses of relevant case–control studies revealed a relative risk (RR) of melanoma and NMSC incidence of 1.45 (95% confidence interval (CI): 1.08–1.94; I2 = 81%) and 1.60 (95% CI: 1.21–2.11; I 2 = 91%), respectively. No statistically significant differences in risk of melanoma and NMSC incidence were found when conducting subgroup analyses by WHO region, and no differences in risk of NMSC incidence in a subgroup analysis by sex. However, in a subgroup analysis by NMSC subtype, the increased risk of basal cell carcinoma (RR: 1.50; 95% CI: 1.10–2.04; 15 studies) was probably lower ( P = 0.05 for subgroup differences) than the increased risk for squamous cell carcinoma (RR: 2.42; 95% CI: 1.66–3.53; 6 studies). The sensitivity analyses found that effect estimates of NMSC incidence were significantly higher in studies with any risk of bias domain rated as “high” or “probably high” compared with studies with only a “low” or “probably low” risk of bias, and in studies not reporting the health outcome by International Statistical Classification of Diseases and Related Health Problems (ICD) code compared with the two studies reporting ICD codes. The quality of available evidence of the effect of any occupational exposure to solar UVR on melanoma incidence and mortality and on NMSC mortality was rated as “low”, and the quality of evidence for NMSC incidence was rated as “moderate”. The strength of the existing bodies of evidence reporting on occupational exposure to solar UVR was judged as “inadequate evidence for harmfulness” for melanoma mortality and NMSC mortality. For the health outcome of melanoma incidence, the strength of evidence was judged as “limited evidence for harmfulness”, that is, a positive relationship was observed between exposure and outcome where chance, bias and confounding cannot be ruled out with reasona- ble confidence. For the health outcome of NMSC incidence, the strength of evidence was judged as “sufficient evidence of harmfulness”, that is, a positive relationship is observed between exposure and outcome where chance, bias and confounding can be ruled out with reasonable confidence. The 2009 International Agency for Research on Cancer classification of solar UVR as a Group 1 carcinogen that causes cutaneous melanoma and NMSC is a compelling attribute for the strength of evidence on occupational exposure to solar UVR and skin cancer incidence. Producing estimates for the burden of NMSC attributable to occupational exposure to solar UVR appears evidence-based (while acknowledging the limitations of the bodies of evidence), and the pooled effect estimates can be used as input data for the WHO/ILO Joint Estimates.