Among patients in the United States diagnosed with thyroid cancer from 1974-2013, the overall incidence of thyroid cancer increased 3% annually, with increases in the incidence rate and thyroid cancer mortality rate for advanced-stage papillary thyroid cancer. These findings are consistent with a true increase in the occurrence of thyroid cancer in the United States.
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Question: What have been the trends in US thyroid cancer incidence and mortality, and have they differed by tumor characteristics at diagnosis?
Findings: In this analysis of 77,276 thyroid cancer patients diagnosed during 1974-2013 and of 2,371 thyroid cancer deaths during 1994-2013, average annual increases in incidence and mortality rates, respectively, were 3.6% and 1.1% overall and 2.4% and 2.9% for patients diagnosed with advanced-stage papillary thyroid cancer.
Meaning: Thyroid cancer incidence and mortality rates have increased for patients diagnosed with advanced-stage papillary thyroid cancer in the United States since 1974, suggesting a true increase in the occurrence of thyroid cancer.
Importance: Thyroid cancer incidence has increased substantially in the United States over the last 4 decades, driven largely by increases in papillary thyroid cancer. It is unclear whether the increasing incidence of papillary thyroid cancer has been related to thyroid cancer mortality trends.
Main Outcomes and Measures: Annual percent changes in age-adjusted thyroid cancer incidence and incidence-based mortality rates by histologic type and SEER stage for cases diagnosed during 1974-2013.
Results: Among 77, 276 patients (mean age at diagnosis, 48 years; 75% women) diagnosed with thyroid cancer from 1974-2013, papillary thyroid cancer was the most common histologic type (64,625 cases), and 2371 deaths from thyroid cancer occurred during 1994-2013. Thyroid cancer incidence increased, on average, 3.6% per year during 1974-2013, primarily related to increases in papillary thyroid cancer (annual percent change, 4.4%). Papillary thyroid cancer incidence increased for all SEER stages at diagnosis (4.6% per year for localized, 4.3% per year for regional, 2.4% per year for distant, 1.8% per year for unknown). During 1994-2013, incidence-based mortality increased 1.1% per year overall and 2.9% per year for SEER distant stage papillary thyroid cancer.
Conclusions and Relevance: Among patients in the United States diagnosed with thyroid cancer from 1974-2013, the overall incidence of thyroid cancer increased 3% annually, with increases in the incidence rate and thyroid cancer mortality rate for advanced-stage papillary thyroid cancer. These findings are consistent with a true increase in the occurrence of thyroid cancer in the United States.
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In the United States, thyroid cancer incidence rates have increased by 211% between 1975 and 2013, with papillary thyroid cancer (PTC), the most common and least-aggressive histologic type, accounting for most of the new cases. Some investigators have suggested that overdiagnosis, or the increased ability to detect and diagnose small indolent tumors that would never otherwise cause symptoms or require treatment, explains a substantial proportion of the increase.
However, growing evidence supports a true increase in the occurrence of thyroid cancer. An analysis of Surveillance, Epidemiology, and End Results (SEER) cancer registry data from 1980-2005 revealed substantial increases in the incidence of advanced-stage PTCs and PTCs > 5 cm in diameter; these tumors are generally large enough to be detected via palpation, to cause symptoms, or both. The rates of increase for the largest (>5 cm) and the smallest PTCs (≤1 cm) were nearly equal among white women, a group considered to be particularly susceptible to overdiagnosis. Although thyroid cancer mortality rates are much lower relative to incidence, providing the impression of stability over time, thyroid cancer mortality rates have increased significantly since the late 1980s (0.7% per year). These trends are consistent with temporal changes in the prevalence of some risk factors, including obesity and smoking.
To our knowledge, the current study is the first to describe US trends in thyroid cancer mortality by demographic and tumor characteristics at diagnosis and to systematically compare trends in thyroid cancer incidence and mortality rates by these characteristics. The main finding from this study was the significant increase in thyroid cancer incidence-based mortality from 1994 to 2013 (approximately 1.1% per year) for thyroid cancer patients overall and for those who were diagnosed with advanced-stage PTC (2.9% per year). This finding appears to be associated with the increasing incidence of advanced-stage PTC (3.5% per year since 1981).
The results of this study challenge the prevailing notion that all of the increase in PTC incidence in the United States is related to overdiagnosis, resulting from the introduction and increasing widespread use of diagnostic ultrasound and other imaging modalities and fine-needle aspiration biopsies that have allowed for incidental detection and diagnosis of mostly indolent localized cancers, small (<2 cm) cancers, or both. Such changes could account for the rapid increases in the incidence rates for localized and small PTCs that have been previously observed. Likewise, the deceleration in rates for localized but not advanced PTC incidence rates since 2009, as observed previously, may be explained by less-aggressive diagnostic workup of small thyroid tumors in recent years due to rising awareness of problems associated with overtreatment of low-risk thyroid cancers. However, the significant, albeit less-rapid increase in advanced-stage and larger PTC incidence rates and increasing thyroid cancer mortality rates among patients diagnosed with advanced-stage PTC is not consistent with the notion that overdiagnosis is solely responsible for the changing trends in PTC incidence. Thus, trends in PTC incidence may be explained by 2 underlying processes: the dominant one is overdiagnosis, and the other is a small but actual increase in PTC incidence, possibly resulting from changes in exposure to environmental risk factors.
Additional epidemiological research is needed to identify the specific environmental factors that have contributed to increasing rates of PTC, namely, those with greater aggressive potential. Ionizing radiation exposure in childhood is the most established risk factor for PTC, and exposure has increased in the US general population in recent decades primarily because of more widespread use of diagnostic medical examinations. However, studies of changes in radiation-related somatic mutations have shown declines in the proportion of PTCs with radiation signatures, such as RET/PTC rearrangements over time; whereas point mutations, such as BRAF or RAS, which are more likely to have a nonradiation etiology, have increased.
There is growing evidence suggesting that changes in obesity and smoking prevalence have contributed to increasing thyroid cancer rates. Paralleling trends in thyroid cancer incidence, obesity prevalence has increased 3-fold among US adults between 1960 and 2012, with the fastest rate of increase between 1980 and 2010. In contrast, the prevalence of daily cigarette smoking has significantly decreased in the United States since 1980. Epidemiological studies have consistently found positive associations between excess adiposity in childhood and adulthood and subsequent risk of thyroid cancer, including PTC, whereas current smoking consistently has been associated with a 30% to 40% reduction in thyroid cancer risk, independent of obesity and other risk factors. Obesity and smoking could influence thyroid cancer development via insulin resistance, thyroid hormone, and estrogen-related pathways. Together, these factors have been estimated to be related to more than 40% of all new cases of thyroid cancer annually in the United States.
Endocrine-disrupting chemicals (eg, pesticides, bisphenol A) also have been suspected to contribute to thyroid cancer incidence trends through their effects on thyroid hormone metabolism. However, evidence in support of a causal association between environmental chemicals and thyroid cancer risk is currently lacking, largely due to the challenges in studying exposures that are ubiquitous and for which long-term exposure is extremely difficult to measure accurately.
This study has several important limitations. Due to the descriptive nature of this study, it is only possible to speculate about potential explanations for the observed thyroid cancer trends. Individual-level environmental exposures and lifestyle-related factors were not captured by registries, nor were methods of thyroid cancer detection. Although changes in mortality and incidence-based mortality rates capture secular trends in detection, diagnosis, case ascertainment, and treatment and associated survival, the current study did not evaluate the influence of treatment on these trends.
Analyses relying on tumor size and AJCC/TNM stage data were restricted to the years in which the information was reported to the registries. APC estimates for incidence-based mortality by tumor size and AJCC/TNM stage may be artificially inflated because this information was only available for cases diagnosed during 1983-2013 and 2004-2013, leaving a shorter latency period between diagnosis and death; however, the results generally agree with estimates by SEER stage.
Among patients in the United States diagnosed with thyroid cancer from 1974-2013, the overall incidence of thyroid cancer increased 3% annually, with increases in the incidence rate and thyroid cancer mortality rate for advanced-stage PTC. These findings are consistent with a TRUE INCREASE in the occurrence of thyroid cancer in the United States.