Global trends in thyroid cancer incidence and the impact of overdiagnosis

In recent decades, the incidence of thyroid cancer in several affluent countries has markedly increased,1Vaccarella S Franceschi S Bray F Wild CP Plummer M Dal Maso L Worldwide thyroid cancer epidemic? The increasing impact of overdiagnosis.N Engl J Med. 2016; 375: 614-617Crossref PubMed Scopus (634) Google Scholar, 2Dal Maso L Panato C Franceschi S et al.The impact of overdiagnosis on thyroid cancer epidemic in Italy, 1998–2012.Eur J Cancer. 2018; 94: 6-15Summary Full Text Full Text PDF PubMed Scopus (51) Google Scholar although mortality from thyroid cancer has remained relatively low and stable or has steadily declined in these and other countries.3Li M Brito JP Vaccarella S Long term declines of thyroid cancer mortality: an international age-period-cohort analysis.Thyroid. 2020; (published online March 2.)DOI:10.1089/thy.2019.0684Crossref Scopus (29) Google Scholar This increase in incidence has predominantly been a reflection of the growing scrutiny of the thyroid gland with ultrasonography and other diagnostic techniques.4Davies L Welch HG Increasing incidence of thyroid cancer in the United States, 1973–2002.JAMA. 2006; 295: 2164-2167Crossref PubMed Scopus (2651) Google Scholar Overdiagnosis is the detection and histological confirmation of a disease that would have otherwise not been diagnosed in a person's lifetime had testing not been done. We previously estimated that over half a million individuals might have been overdiagnosed with thyroid cancer between 1988 and 2007 in 12 high-income countries, with trends continuing to increase rapidly at the end of the study period.1Vaccarella S Franceschi S Bray F Wild CP Plummer M Dal Maso L Worldwide thyroid cancer epidemic? The increasing impact of overdiagnosis.N Engl J Med. 2016; 375: 614-617Crossref PubMed Scopus (634) Google Scholar No studies published thus far have quantified the degree of thyroid cancer overdiagnosis in less affluent settings. The aim of this report was to assess how thyroid cancer overdiagnosis has progressed in high-income countries, and the extent to which it has affected middle-income countries undergoing a rapid socioeconomic transition. We analysed the most up-to-date, high-quality data from population-based cancer registries in 26 countries spanning four continents (appendix p 6). All cases of thyroid cancer reported between 1998 and 2012 among men and women aged 15–84 years were included in our analysis. We found that the incidence of thyroid cancer continued to increase steadily from 1998–02 to 2008–12 in all high-income countries, and that the same trend was observed in less affluent populations, notably in China, Colombia, Lithuania, and Belarus. The increase in incidence differed across countries, but was always more marked among middle-aged women (ie, those aged 35–64 years), leading to a progressive transformation of the age-specific curves towards an inverted U-shape (figure). The most striking distortion of the age-specific curve was observed in South Korea, where the incidence of thyroid cancer in women aged 50–59 years more than doubled from around 120 cases per 100 000 women in this age-group in 2003–07 to over 260 cases per 100 000 women in 2008–2012; a figure that was approximately eight times higher than that in 1998–2002 (35 cases per 100 000 women). A similar pattern, though less pronounced, was seen in the USA, Canada, Australia, France, Italy, Lithuania, Belarus, Colombia, and China, where increases in incidence in men and women accelerated in the most recent period, peaking among individuals aged 45–54 years in 2008–12 (47 cases per 100 000 women and 14 cases per 100 000 men). The most recent estimates of thyroid cancer incidence in middle-aged women was also high in Lithuania (42 cases per 100 000 women aged 55–64 years), Colombia (39 cases per 100 000 women aged 55–64 years), Croatia (35 cases per 100 000 women aged 55–64 years), and in Belarus (35 cases per 100 000 women aged 50–59 years). To estimate the effects of overdiagnosis, we identified a so-called historical age-specific curve of symptomatic thyroid cancer incidence before the introduction of ultrasonography, and attributed the progressive departure from the historical pattern (ie, towards an inverted U-shape curve) to the intense search for thyroid nodules in middle-aged individuals that seldom lead to death (appendix pp 2–5). The estimated proportion of thyroid cancer cases in women attributable to overdiagnosis between 2008 and 2012 was approximately 93% in South Korea, 91% in Belarus, 87% in China, 84% in Italy and Croatia, and 83% in Slovakia and France. According to our estimations, over 830 000 women might have been overdiagnosed between 2008 and 2012 in the 26 countries analysed, including approximately 390 000 women in China, 140 000 women in South Korea, 120 000 women in the USA, 31 000 women in Italy, and 25 000 women in France. Compared with these countries, the estimated proportions and absolute numbers of thyroid cancer cases in women attributable to overdiagnosis were lower in Denmark (66%; 500 women), Norway (65%; 600 women), Ireland (63%; 500 women), the UK (58%; 5000 women), Japan (55%; 24 000 women), and Thailand (44%; 4000 women). Similar patterns to women, although of a lower magnitude (ie, the proportion of cases attributable to overdiagnosis was approximately 10% lower in men than in women in each country), were observed in men. Overall, more than 220 000 men might have been overdiagnosed with thyroid cancer between 2008 and 2012 in the 26 study countries (appendix p 9). According to our analysis, the contribution of overdiagnosis to the increasing incidence of thyroid cancer was substantial. The peak in incidence among middle-aged individuals across all countries, the rapid temporal increases in incidence, and the high variability between countries probably reflect local medical practices. In South Korea, thyroid cancer overdiagnosis was a consequence of the opportunistic examination of the thyroid offered as an extra service within the context of national screening programmes,1Vaccarella S Franceschi S Bray F Wild CP Plummer M Dal Maso L Worldwide thyroid cancer epidemic? The increasing impact of overdiagnosis.N Engl J Med. 2016; 375: 614-617Crossref PubMed Scopus (634) Google Scholar whereas in other countries, overdiagnosis probably depended on the intensity of surveillance and the extent to which ultrasound and other diagnostic techniques were used.5Udelsman R Zhang YW The epidemic of thyroid cancer in the United States: the role of endocrinologists and ultrasounds.Thyroid. 2014; 24: 472-479Crossref PubMed Scopus (145) Google Scholar Scrutiny of the thyroid gland is sometimes commonly done and not regulated, particularly in settings where health-care services are predominantly private and market-based, such as in many middle-income countries undergoing an economic transition. Thyroid cancer can also be identified incidentally when imaging techniques are used for other medical reasons.6Francis DO Davies L Thyroid cancer: the challenge of overdiagnosis.in: Wild CP Weiderpass E Stewart BW World Cancer Report: cancer research for cancer prevention. International Agency for Research on Cancer, Lyon, France2020: 461-467Google Scholar We found that overdiagnosis was more common in women than in men, reflecting the systematic differences in incidence between sexes (a female-to-male ratio of approximately 3:1) found in all countries analysed. Mortality was similarly low in both women and men (<1 death per 100 000 individuals; appendix pp 8–9), and the prevalence of thyroid cancer identified from autopsies is also similar between men and women. It is possible that the interaction of the thyroid gland with a women's reproductive hormones, which are released from around the age of puberty, could induce thyroid diseases and the development of thyroid nodules. Women are, however, generally more exposed to health care than men are (eg, because of reproductive and perimenopausal factors), which could result in additional opportunities for scrutiny of the thyroid gland. Risk factors, such as radiation exposure (particularly during childhood) or having overweight or obesity,6Francis DO Davies L Thyroid cancer: the challenge of overdiagnosis.in: Wild CP Weiderpass E Stewart BW World Cancer Report: cancer research for cancer prevention. International Agency for Research on Cancer, Lyon, France2020: 461-467Google Scholar might also have contributed to the increase in thyroid cancer incidence. However, the aforementioned epidemiological features suggest that the effect of known or unknown risk factors on the rapid increase in thyroid cancer incidence is unlikely to be major. In settings where most thyroid cancer cases are attributable to surveillance, only large and well designed analytical studies can provide non-speculative evidence for the possible effects of spatial and temporal variations in risk factors. The impact of overdiagnosis on the increasing incidence of thyroid cancer highlighted in our report is thus a warning sign for countries with growing economies, where diagnostic technologies are increasingly and routinely offered, usually in exchange for payment, despite evidence that the harms far outweigh benefits. Overdiagnosis could turn healthy people into patients, and expose them to unnecessary harms and lifelong treatments. Most individuals diagnosed with thyroid cancer undergo a total thyroidectomy and other treatments (eg, radiotherapy and neck lymph node dissection), and a non-negligible proportion of these individuals also have post-surgery complications. Besides the physical and psychological consequences, overdiagnosis leads to substantial financial costs for health-care systems, diverting resources that could otherwise be devolved to provide effective, affordable, and equitable medical services for all citizens.7Vaccarella S Davies L The inverse care law: overutilization of health services and overdiagnosis.in: Vaccarella S Lortet-Tieulent J Saracci R Conway D Straif K Wild C Reducing social inequalities in cancer: evidence and priorities for research (IARC Scientific Publication No. 168). International Agency for Research on Cancer, Lyon, France2019: 390-396Google Scholar In summary, our study suggests that overdiagnosis of thyroid cancer is increasing rapidly worldwide and has now become a major global public health challenge. A growing awareness of the substantial impacts of overdiagnosis has led to substantial modifications of national and international guidelines, which now explicitly recommend against screening for thyroid cancer in asymptomatic individuals and advocate active surveillance for microcarcinoma.8Haugen BR Alexander EK Bible KC et al.2015 American Thyroid Association Management Guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: The American Thyroid Association Guidelines Task Force on thyroid nodules and differentiated thyroid cancer.Thyroid. 2016; 26: 1-133Crossref PubMed Scopus (7533) Google Scholar, 9Togawa K Ahn HS Auvinen A et al.Long-term strategies for thyroid health monitoring after nuclear accidents: recommendations from an Expert Group convened by IARC.Lancet Oncol. 2018; 19: 1280-1283Summary Full Text Full Text PDF PubMed Scopus (17) Google Scholar There is evidence that the number of thyroidectomies in South Korea has been decreasing since 2014,10Ahn HS Welch HG South Korea's thyroid-cancer “epidemic” – turning the tide.N Engl J Med. 2015; 373: 2389-2390Crossref PubMed Scopus (157) Google Scholar probably as a consequence of an increased awareness about overdiagnosis among physicians and the general public, and suggests that the trends in overdiagnosis can be reverted. Although, besides South Korea, the global picture of thyroid cancer overdiagnosis after 2012 remains yet largely unknown, the extent of overdiagnosis indicates an urgent need to closely monitor its evolution worldwide and the impact of recent guidelines. We declare no competing interests. Download .pdf (.57 MB) Help with pdf files Supplementary appendix Mapping overdiagnosis of thyroid cancer in ChinaGlobally, the incidence of thyroid cancer has increased substantially in the past three decades,1 particularly among young adults and even in adolescents,2 whereas mortality due to thyroid cancer has remained relatively stable at low levels, or decreased, almost everywhere.3 The intense scrutiny of the thyroid gland and widespread use of ultrasonography and other modern diagnostic techniques have allowed the discovery of a large reservoir of previously undetectable, small, and predominantly papillary thyroid tumours. Full-Text PDF