A diagnostic bias might be a much simpler explanation for the apparently elevated risk for nasopharyngeal cancer with respect to formaldehyde
© The Author(s). 2016
Received: 22 October 2016
Accepted: 29 November 2016
Published: 5 December 2016
In 2009, a working group of the International Agency for Research on Cancer classified formaldehyde as carcinogenic to humans (Group 1) and concluded that formaldehyde causes cancer of the nasopharynx (NPC) and leukemia. The results of a large cohort study of industrial workers exposed to formaldehyde, conducted by the U.S. National Cancer Institute, mainly contributed to the available body of epidemiologic evidence. In their recent updated re-analysis of these cohort data published in your journal, Dr Marsh and his colleagues concluded that the results of the original analysis of NPC-risk are misleading because they are based on inappropriate regression analyses. In our view the reason for the elevated NPC risk reported in the original analysis might be also another one - a diagnostic bias. Therefore, it would be very helpful if the authors provided results for all other sub-categories (as three-digit categories of the International Classification of Diseases) of the pharynx to verify the hypothesis described and, hence, to clarify the relationship between exposure to formaldehyde and the risk of NPC.
KeywordsFormaldehyde Nasopharyngeal cancer Cohort study Standardized mortality ratio Diagnostic bias
In 2009, a working group of the International Agency for Research on Cancer classified formaldehyde (FA) as carcinogenic to humans (Group 1) and concluded that FA causes cancer of the nasopharynx (NPC) and leukemia . The results of a large cohort study of industrial workers exposed to FA, conducted by the U.S. National Cancer Institute (NCI) [2, 3], mainly contributed to the available body of epidemiologic evidence. In their recent updated re-analysis of these cohort data published in your journal, Dr Marsh and his colleagues concluded that the results of the original analysis of NPC-risk are misleading because they are based on inappropriate regression analyses and that their updated re-analysis did not support NCI’s suggestion of a persistent association between FA exposure and NPC risk .
Incidence and Mortality 2003–2007, Connecticut, Males
Nose, sinuses, etc.
The results of the primary analysis of the first follow-up  support our hypothesis. Only one case was observed for pharynx, unspecified (ICD-8: 149), whereas 4.4 cases were expected, resulting in a SMR of 0.23 (95% CI: 0.01 – 1.27). Hence, the relationship between the number of cases for NPC and PCns in the cohort followed up is quite different from that for the catchment area of the cancer registry.
Mortality from pharyngeal cancer by cumulative exposure to formaldehyde (own calculations, based on data from table 5 )
Cumulative exposure (ppm-years)
SMR (95% CI)
1.82 (0.22 – 6.57)
2.22 (0.96 – 4.38)
0.73 (0.15 – 2.14)
0.77 (0.09 – 2.78)
1.26 (0.67 – 2.16)
No funding. The authors prepared the paper as part of their normal professional work activities.
Availability of data and materials
All data used are taken from published results of the original study. The corresponding references are given in the manuscript.
MM wrote a first draft of the manuscript. AW contributed to the writing and editing of the manuscript. Both authors read and approved the final manuscript.
The authors declare that they have no competing interests.
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Ethics approval and consent to participate
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