This analysis of SEER database county incidence data of HNCs demonstrates an association with exposure to PM2.5 at various time intervals. This association was seen in all HNCs combined and pertinent subsites including non-oropharyngeal sites, oral cavity, and laryngeal cancer. This study contributes to the current body of literature that identifies air pollution as an important modifiable risk factor for the development of HNCs and supports improving air quality standards given the potential impact of air pollution on oncologic disease development.
The strength of this current research includes the high number of incidence cases that were included from the SEER registry, as well as the heterogeneity of the location and geography of the counties within the data set. Currently, the SEER registries capture a large representative sample of the US population, making it a favorable choice for epidemiological studies in the US. Furthermore, defined lag time models were utilized to highlight the carcinogenic effects of air pollution exposure over time. This data includes total head and neck aerodigestive cancer incidence relating to air pollution, and this is further delineated by subsites compared to previously more broad studies of cancer incidence.
In previous studies, there is a heterogeneity of latency from pollution exposure to cancer incidence, with latency ranges of virtually no lag time with up to 15 years of lag time. Latency is important due to the variable nature of the rate of carcinogenesis after exposure from various risk factors, and faulty lag models are prone to exposure misclassification and bias21. Additionally, it is important to model exposure latency given the changes in air quality over time. Air quality as measured by air pollutant concentration has improved nationally over 40 years. However, studies have shown that even low levels of air pollutants can have deleterious effects on health. Small changes in PM2.5 and ozone concentrations even below the levels set by the EPA’s National Ambient Air Quality Standards (NAAQS) can have significant effects on mortality22,23. Choosing the correct lag models including longer latency periods can help account for these variations and improve accuracy in predicting HNC incidence and defining at-risk patient populations.
Air pollution exposure is an under recognized social determinant of health. Studies have shown that historically marginalized communities, specifically communities of color and those of lower socioeconomic status, are disproportionately exposed to adverse environmental conditions, including air pollution and heat24. The effects of disproportionate air pollution exposure on disease development and health outcomes in marginalized populations have been described in a range of conditions, including COVID-19 mortality25. Given this and the known disparities in stage at presentation and outcomes in HNC patients, the role of air pollution in pathogenesis should be considered.
The deleterious health effects of air pollution have been well established in the literature, with robust evidence linking air pollution exposure to increased cancer incidence and mortality, particularly in lung cancer7,8,9,10,23,26. These studies mostly focus on PM2.5 but other pollutants include nitrous oxide (NO2) and coarse particulate matter have been associated with lung cancer as well. For lung cancer studies, mortality was often used as an endpoint variable of interest. It is important to note that lung cancer mortality and incidence are able to be grouped together in these previous studies due to the fact that lung cancer has a high rate of mortality26. In this study, incidence is used as opposed to mortality given that survival rates are relatively high for most HNCs compared to those seen in lung cancer.
Current data on outdoor air pollution and HNC incidence is limited, but there is some evidence linking pharyngeal and laryngeal cancer incidence and indoor air pollution exposure, particularly from the burning of solid fuels for cooking and heating27. Current studies on HNC incidence and outdoor pollution exposure are in areas of high levels of pollution and areas where oral and nasopharyngeal cancer are more common and endemic, such as China and Taiwan. Two recent studies from Taiwan have linked high levels of PM2.5 to oral cancer diagnosed by Taiwan’s biennial screening program for oral cancer. These studies are limited in that they utilized very short lag times, and their classification of oral cancer also included hypopharyngeal and oropharyngeal cancer28,29. Three other studies, two from Taiwan30,31 and the other from China32, have linked outdoor air pollution including NO2, PM2.5 and coarse particulate matter to nasopharyngeal cancer incidence. Other international studies linking air pollution to HNC mortality were conducted in Brazil, with relatively specific cancer subsite definitions33,34. In this study, cancer specific mortality was measured instead of incidence and the study only included a lag time of up to 2 years. Interestingly, PM2.5 from wildfires was separated from other sources of PM2.5 and found to have a greater effect on cancer mortality. Further research is needed to understand the difference in carcinogenic effects seen with wildfire smoke.
In the US, studies assessing the link between pollution and non-lung cancer incidence are limited. Coleman et al.’s previous study on the association between PM2.5 and cancer incident rates derived from more than 8 million cases recorded in the SEER registry. Regarding HNC, only nasal and middle ear were well delineated from other head and neck aerodigestive subsites. In this study, “oral cancer” included ICD-10 codes C00-C14, which included major salivary glands, the oropharynx, nasopharynx, and hypopharynx12. While our study delineated head and neck subsites more specifically, a limitation to our analysis is that the definitions of tongue cancer could not be easily parsed, and as a result some base of tongue cancers were likely classified as oral cancer in our study. The “oropharyngeal” definition used in this study contained only cancers from the oropharyngeal subsite. Subsites were also grouped differently in another recent study of US pollution and head and neck cancer, which included SEER derived HNC incidence data with the addition of salivary gland and esophageal subsites from 2011 to 2019. Of note, this study did not account for a lag period13. Additional studies are needed to better understand the association between air pollution and pathogenesis in specific head and neck subsites, especially given the role of viral-mediated carcinogenesis in the oropharynx and nasopharynx.
There are important limitations to this study that must be acknowledged. This study is limited to the effects of PM2.5, whereas other air pollution components including NO2, PM10, ozone have been shown to impact the incidence of other malignancies, specifically lung cancer35. Another major limitation of this study is that the effects of viral-induced carcinogenesis, specifically human papilloma virus (HPV) in the oropharynx and Epstein-Barr virus (EBV) in the nasopharynx, were not considered because of limited availability of county level data. The availability of smoking and alcohol data was also limited at the county level before 1996, and other important covariate data regarding occupational exposures and racial and ethnic disparities at the county level were not available for the studied period. In general, ecological studies are limited because it is almost impossible to control for all confounding variables, as well as the innate inability to make predictions on the individual level. However, the large representative sample size of the SEER database makes these results more reliable despite population variability.
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