Adolescent Thyroid Cancer After the Fukushima Nuclear Power Plant Accident: Mass Screening Effect or a Real Increase?

By Shunichi Yamashita, MD, PhD

Article Highlights

• Out of the 2 million residents in Fukushima, there were approximately 367,000 children and adolescents aged less than 18 years at the time of the Fukushima Daiichi Nuclear Power Plant accident. Because of the urgent requests from parents, the public, and the central and local governments, thyroid ultrasound examination was implemented for neonates, infants, children, and adolescents to address fear and anxiety about thyroid cancer risk.
• Although the risk of radiation-associated health consequences in Fukushima is considerably low based on the estimated radiation doses individuals received during the accident, a high prevalence of childhood and adolescent thyroid cancers detected by a mass screening aggravates radiation fear and anxiety.
• It is critically important for medical professionals to explain the current situation of thyroid diseases to the public correctly. This means understanding the baseline prevalence of thyroid pathology including childhood and adolescent thyroid cancers as a mass screening effect but not as an epidemic.

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Five years have passed since the Great East Japan Earthquake on March 11, 2011, and the subsequent Fukushima Daiichi Nuclear Power Plant (NPP) accident, moving the problems in Fukushima from an acute nuclear disaster to a chronic environmental contamination with complicated psychological, social, economic, and political consequences. Continuous monitoring and characterization of the levels of radioactivity in the environment and foods in Fukushima are now essential for obtaining informed consent to the residents’ decisions on living in radio-contaminated areas and also on returning to the evacuated areas once permitted for re-entrance.¹

There are now accumulating data on radiation dose estimates in Fukushima, including official reports from international organizations such as the World Health Organization,² the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR),³ the International Atomic Energy Agency,⁴ and from many research institutes in Japan.⁵ Overall assumption of initial thyroid dose as a result of exposure to radioactive iodine just after the accident suggests less than 50 to 100 mSv maximum theoretically, and the vast majority of affected individuals received less than 1 mSv. However, although health effects directly related to radiation exposure are highly unlikely in Fukushima, the results of the first round of thyroid ultrasound examination targeting approximately 300,000 children aged 0 to 18 years at the time of the accident in Fukushima are now in the world spotlight because of a high prevalence of thyroid cancer (0.038%) detected over the last 4 years.⁶

Furthermore, the fear of the second coming of the Chernobyl disaster exaggerates misconceptions such as an
increase of radiation-associated childhood thyroid cancer,⁷ which evoked many critical comments in the Journal of Epidemiology.^8-16 In contrast, potential overdiagnosis using sophisticated ultrasound examination in Fukushima is pointed out^17,18 as analogous to a high rate of adult thyroid cancer detection by advanced ultrasound recently observed in other countries.^19-27 Before starting thyroid ultrasound examination in Fukushima, we carefully determined a diagnostic criteria and screening protocol.²⁸ Therefore, clinical oncologists should correctly understand the current situation and problems in Fukushima at the fifth anniversary of the NPP accident.

Fukushima Health Management Survey

Large-scale surveys in Fukushima are a specific response to initial radiation exposure and to mental traumas caused by the accident and evacuation.²⁹ The surveys are designed to assess radiation exposure doses after the accident and to monitor residents’ health conditions, enabling disease prevention, early detection, and early medical treatment.^30,31

One well-known radiation-associated late-onset health consequence is childhood thyroid cancer, as demonstrated by Chernobyl in 1991.³² However, there are many differences between Chernobyl and Fukushima,^33,34 and we now understand that exposure doses on the thyroid, as well as for the whole body, are too low to reveal any radiation-associated thyroid cancer risk in Fukushima.⁵ On the other hand, psychosocial and mental issues in Fukushima, including post-traumatic stress disorder, are similar to those seen after Chernobyl.^35-38

On the basis of our own knowledge and experience accumulated from Hiroshima, Nagasaki, and Chernobyl, the difficult challenge of health survey and management is now ongoing in Fukushima.³⁹ The Fukushima Health Management Survey is the largest health monitoring project to date and includes a basic survey for the estimation of external radiation doses received during the first 4 months after the accident.⁴⁰ The survey targets approximately 2 million people and includes four detailed surveys: a thyroid ultrasound examination, a comprehensive health checkup, mental health and lifestyle, and a survey for pregnant women and nursing mothers.²⁹ The goal is to prospectively take care of the health of all Fukushima Prefecture residents.

Results of Thyroid Ultrasound Examination in Fukushima

In this editorial, the results of thyroid ultrasound examination are introduced in hopes of avoiding confusion and misunderstanding of data obtained after the Fukushima NPP accident. On the basis of ultrasound results and the common understanding of radiation health effects and thyroid cancer risk, it is a timely opportunity to discuss whether we’ve observed a mass screening effect or a real increase of childhood thyroid cancer in Fukushima.

Out of the 2 million residents in Fukushima, there were approximately 367,000 children and adolescents aged less than 18 years at the time of the NPP accident. Because of the urgent requests from parents, the public, and the central and local governments, thyroid ultrasound examination was implemented for neonates, infants, children, and adolescents to address fear and anxiety about thyroid cancer risk in Fukushima residents, despite the fact that their radiation exposure was deemed much lower than that of comparable populations affected by the Chernobyl accident.²⁸

Overcoming many logistic and coordination difficulties just after the accident, 300,476 children out of 367,685 eventually received thyroid ultrasound examination from October 2011 through June 2015. The results of the first round of screening were recently published^6,4 and are as follows (Fig. 1).

Among 300,476 completed examinations, there were 2,275 (0.8%) nodule(s) larger than or equal to 5.1 mm and 1,715 nodule(s) smaller than or equal to 5.0 mm; 12 cyst(s) measuring larger than or equal to 20.1 mm and 143,901 (47.9%) cysts smaller than or equal to 20.0 mm. The 2,294 cases with nodules larger than or equal to 5.1 mm and/or cysts larger than or equal to 20.1 mm were recommended for secondary examinations. Investigations of 2,108 (91.9%) such cases included 537 (39.6%) patients with cytological assessment, 700 (34.0%) patients with lesions reduced in size to smaller than the threshold criteria, and 1,356 patients (66.0%) recommended for re-evaluation after 6 months to a year in the absence of clear indications for cytology.

Of the 537 patients referred for fine needle aspiration cytology, surgery was not indicated for 424 patients because of the lack of sufficient evidence of malignancy. The remaining 113 patients (38 boys and 75 girls aged 6 to 18 [mean age 14.8] years at the time of accident) were diagnosed with or strongly suspicious for thyroid carcinoma by expert consensus; 99 patients have undergone surgery. Pathological examination revealed 95 cases of papillary thyroid carcinoma, three cases of poorly differentiated thyroid carcinoma, and one histologically benign lesion. Tumor size ranged from 5 to 53 mm (mean 14.5 mm). The detection rate of thyroid cancer by ultrasound screening is almost the same in three different geographical areas of Fukushima Prefecture ranging from 0.035% to 0.040% (Fig. 2).

After the completion of the first round of thyroid ultrasound examination, the second round of full-scale thyroid examinations began in April 2014, targeting the same population under the same survey protocol.⁴¹ This full-scale survey will be repeated every 2 years for each person until the age of 20, and every 5 years thereafter for the remainder of each individual’s life.

Merits and Demerits of Mass Screening Using Thyroid Ultrasound in Fukushima

Our first 4-year results gained much attention because of a high detection rate of childhood and adolescent thyroid cancer (0.038%). Note that Fukushima is a special place where the NPP accident has really happened, and it was unavoidable to start health examination requested by the public and the governmental bodies. Thyroid ultrasound screening is a part of this program, and, in principal, is not exclusively aimed at cancer detection, although the latter is naturally a matter of major concern. Therefore it is a pity that thyroid ultrasound examination results exaggerate the fear and anxiety in Fukushima residents.

Like any screening aimed at disease detection, ultrasound examination in Fukushima has certain advantages and disadvantages. Applicably to thyroid cancer, setting aside the chance of treatment-related complications, an obvious benefit for patients and their families is the early detection of a potentially cancerous nodule, timely preoperative diagnosis, and appropriate disease management. The possibility of overdiagnosis exists and will be addressed during the second and third rounds of screening. However, the targeted population and their parents may be confused by the concept of overdiagnosis. More generally, the Fukushima population will likely benefit from better understanding of the situation and a significant health care program by the prefectural and central authorities, who may direct resources and more purposefully define planning for future medical needs and follow-up programs.

On the other hand, we must remember that newly introduced sensitive and targeted screening inevitably increases disease incidence. Although it has been long known that thyroid cancer affects, on average, 1 to 2 children per 1 million, this estimate is based on cancer registries data and not mass screening. In this relation, it would be pertinent to mention a recent ultrasound screening study in three prefectures of Japan—Aomori, Yamanashi, and Nagasaki—which employed exactly the same protocol as in Fukushima. Among the detected thyroid abnormalities,⁴² one case of cancer was found among 4,365 schoolchildren aged 3 to 18 years who were not exposed to excessive radiation (thus, detection rate 0.023%), which is not meaningfully different from Fukushima.⁴³ By contrast, ultrasound screenings of exposed children in contaminated Chernobyl areas from 1990 to 2000 usually resulted in an order of magnitude higher detection rates.^44-46

One of the lessons learned from Chernobyl is that the increase in thyroid cancer incidence in children was documented 4 years after the accident. Time between radiation exposure and detection of a radiation-related disease is called the period of latency, during which cancerous nodules grow to the size detectable by ultrasound or (rarely) manifest clinically. That is why the first round of screening occurred within the first 3 to 4 years after the Fukushima accident. This is exactly the establishment of baseline prevalence of thyroid abnormalities without radiation excess because of too short latency for biological cancer induction by radiation. The findings obtained during the second and third rounds of screening will be compared to this baseline, providing more evidence to be used in the dialog with patients and residents. The natural history of childhood and adolescent thyroid cancer is another important issue needing clarification, despite the difficulty of a “watch and wait” therapeutic strategy. Then, the current diagnostic criteria and management of thyroid cancer should be re-evaluated, referring to the recent two guidelines from the American Thyroid Association.^47,48

The reality demonstrates that not only the public but also the mass media could not properly interpret the baseline prevalence of thyroid diseases in Fukushima. Our task is to carefully, diligently, and ethically convey to the stakeholders in Fukushima and countrywide that we cannot compare thyroid screening results with any other data such as from cancer registries and other screenings under different protocols, and that the staggering finding is not related to radiation exposure.

Radiation Exposure and Thyroid Cancer Risk

To clarify the difficulty of proving any positive relationship between low-dose radiation exposure and the increased risk of thyroid cancer, we should bear in mind that the accumulated knowledge from the data on atomic bomb survivors has, for a long time, been a basis of our understanding of the dose–response relationship for the risk of late health effects, including various malignancies, such as leukemia and solid cancers,^49,50 and coined the fundamental principle of the linear non-threshold (LNT) model.^51.52 The LNT hypothesis assumes that cancer risk will increase linearly depending on the dose at the standpoint of radiation protection. However, the LNT model for assessing risk of cancers induced by radiation brings about radiophobia, which is a serious public health and mental health issue, suggesting the necessity of careful consideration and research on low-dose and low-dose rate health effects.^53,54

The recent epidemiological report from the Life Span Study by the Radiation Research Effects Foundation has indicated a relative increase in cancer risk in the study population because of the external radiation at a given dose, but it also noted that in the dose range of 0 to 150 mSv, the excess risk of solid cancer is not statistically significant, especially below 100 mSv.⁵⁵ It is well known that external and internal exposure to radioactive iodine can increase the risk of thyroid cancer.^56-58 The most important modifier of radiation-induced thyroid cancer risk is age at exposure, and elevated risk is reduced among survivors exposed after the age of 30. Although the LNT model has been used for many years, there is still uncertainty about the linear relationship of low-dose exposure, such as to doses less than 100 mSv, from the standpoint of real health risk. One of the reasons for this uncertainty is insufficient mechanistic evidence available from the studies.^59,60

Another important point is that risk estimates have been discussed mainly from the epidemiological data obtained from the atomic bomb survivors, who received moderate-to-high doses at a high-dose rate. Therefore, these estimates may not be appropriate when applied to populations exposed to radiation at a lower dose and low-dose rates as cautioned by the UNSCEAR 2000 report.⁶¹ Recently, even around Chernobyl, the presence of an environmental risk modifier on childhood thyroid cancer, such as nitrates, has been proposed besides radiation exposure,⁶² suggesting a necessity of integrative studies by epidemiology, biology, pathology, genetic, and molecular biology. Fortunately in Fukushima, there is no contamination of nitrates in drinking water.⁶³

There is also an urgent need to reconcile the recent observations of stem cell radiation biology, which challenge the persistence of stochastic oncogenic events in tissues and organs at the standpoint of radiation protection.⁶⁴

Differences of genetic background in radiation-associated thyroid cancer have been reported,^65,66 but no clear radiation signature genes have been established. Furthermore, a molecular study showed that the genetic profile of thyroid cancers from Fukushima was completely different from that of radiation-associated thyroid cancers in young patients from Chernobyl areas.⁶⁷ This strongly suggests non-radiogenic etiology of cases in Fukushima. Therefore, the current situation in Fukushima, as tentatively concluded by the UNSCEAR 2015 report,⁶⁸ has indicated no concrete evidence of an increased risk of childhood and adolescent thyroid cancer at present.

Conclusions

Although the risk of radiation-associated health consequences in Fukushima residents is quite different from that of Chernobyl and is considerably lower based on the estimated radiation doses individuals received during the accident, a high prevalence of childhood and adolescent thyroid cancers detected by a mass screening aggravates radiation fear and anxiety, and keeps local residents in the indeterminate and uncertain situation of having been evacuated but not relocated.

It is, therefore, critically important for medical professionals, including clinical oncologists, to explain the current situation of thyroid diseases to the public correctly, on the basis of understanding the baseline prevalence of thyroid pathology including childhood and adolescent thyroid cancers as a mass screening effect but not as an epidemic, and that best activities and practices related to recovery are encouraged, supported, and implemented at local and regional levels. The accurate interpretation of the high rate of thyroid diseases in Fukushima is now a key element of psychosocial well-being of individuals and communities, and also of their resilience. Medical and health professionals together with clinical oncologists are uniquely positioned to identify and provide insight into what would be the best actions to meet Fukushima residents’ specific needs.