Thyroid Cancer Screening (PDQ®): Screening - Health Professional Information [NCI]

Risk Factors

Radiation therapy administered in infancy or childhood for benign conditions of the head and neck (such as enlarged thymus, tonsils, or adenoids; or acne) increases the risk of thyroid cancer, with diagnosis occurring in as few as 5 years after exposure.[11] Radiation exposure as a consequence of nuclear fallout has also been associated with a high risk of thyroid cancer, especially in children.[22,33,44] Other risk factors include family history of thyroid disease (including thyroid cancer), history of enlarged thyroid (goiter), female sex, and Asian race.[55] A hereditary condition, multiple endocrine neoplasia type 2 (MEN2), increases the risk of medullary thyroid cancer caused by mutations in the RET gene.[66,77] For more information, see Genetics of Endocrine and Neuroendocrine NeoplasiasGenetics of Endocrine and Neuroendocrine Neoplasias.

References:

1. Carling T, Udelsman R: Thyroid tumors. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Lippincott Williams & Wilkins, 2011, pp 1457-72.
2. Pacini F, Vorontsova T, Molinaro E, et al.: Prevalence of thyroid autoantibodies in children and adolescents from Belarus exposed to the Chernobyl radioactive fallout. Lancet 352 (9130): 763-6, 1998.
3. Cardis E, Kesminiene A, Ivanov V, et al.: Risk of thyroid cancer after exposure to 131I in childhood. J Natl Cancer Inst 97 (10): 724-32, 2005.
4. Tronko MD, Howe GR, Bogdanova TI, et al.: A cohort study of thyroid cancer and other thyroid diseases after the chornobyl accident: thyroid cancer in Ukraine detected during first screening. J Natl Cancer Inst 98 (13): 897-903, 2006.
5. Iribarren C, Haselkorn T, Tekawa IS, et al.: Cohort study of thyroid cancer in a San Francisco Bay area population. Int J Cancer 93 (5): 745-50, 2001.
6. American Cancer Society: Cancer Facts and Figures 2024. American Cancer Society, 2024. Available onlineAvailable online. Last accessed June 21, 2024.
7. Salvatore G, Giannini R, Faviana P, et al.: Analysis of BRAF point mutation and RET/PTC rearrangement refines the fine-needle aspiration diagnosis of papillary thyroid carcinoma. J Clin Endocrinol Metab 89 (10): 5175-80, 2004.

Evidence of No Benefit Associated With Screening

Screening for thyroid cancer is primarily accomplished by neck palpation or ultrasound imaging. In the absence of formal screening, asymptomatic thyroid cancers are most commonly detected incidentally on cross-sectional imaging performed for other medical conditions or on surgical specimens of benign diseases such as goiter.[11]

The efficacy of thyroid cancer screening has never been evaluated in a randomized controlled trial (RCT).[22] No RCTs of intermediate end points (e.g., changes in stage at diagnosis) have been conducted. No population-based screening programs for thyroid cancer exist in the United States, the United Kingdom, or Europe, although neck palpation screening results in incidental detection of asymptomatic cancers. Over time, U.S. and U.K. thyroid cancer incidence rates have increased, but thyroid cancer mortality has remained constant or decreased slightly.[33,44] That pattern is consistent with the detection of cancers that are not destined to cause symptoms or result in death (overdiagnosis).

In South Korea, thyroid cancer screening increased dramatically in conjunction with the 1999 establishment of a free national cancer screening program. Although not offered as part of the package of free screening exams, thyroid cancer screening with ultrasound was offered simultaneously at low cost in most clinics, and many South Koreans opted for the exams.[55] Thyroid cancer incidence in South Korea increased 15-fold from 1993 to 2011, although no change in thyroid cancer mortality occurred concurrently.[66] In 2011, the number of people diagnosed with thyroid cancer (40,000) was more than 100 times higher than the number who died of thyroid cancer (typically 300–400 each year, with little change in mortality rates since 1999).[66,77] The practice of thyroid cancer screening in South Korea began to wane in 2013 because of concerns about overdiagnosis and overtreatment. In 2015, the Korean Committee for National Cancer Screening Guidelines issued a recommendation against thyroid cancer screening with ultrasonography for healthy individuals.[77]

In 2017, the U.S. Preventive Services Task Force recommended against thyroid cancer screening. The Task Force's conclusion, based on observational evidence, was that "the net benefit of screening for thyroid cancer is negative."[22,88] The American College of Radiology does not recommend screening for thyroid cancer with imaging and, in a white paper, addressed the management of incidental nodules detected on imaging for other medical problems.[99] The American College of Radiology stated that workup was not required for incidental thyroid nodules detected on imaging if nodules were smaller than 1 cm in patients younger than 35 years and smaller than 1.5 cm in patients aged 35 years and older.

Much of what is known about the impact of thyroid cancer screening comes from South Korea's experience. Investigators examined thyroid cancer trends in South Korea using the following three data sources:[55]

• The 2010 Korea Community Health Survey.
• The Korea Cancer Registry.
• Mortality data from Statistics Korea.

The Korea Community Health Survey asked more than 200,000 people whether they had been screened for thyroid cancer in the past 2 years. Thyroid cancer incidence from 2008 to 2010, mortality from 2007 to 2010, and the percent of people who reported thyroid cancer screening were calculated for each of the 16 administrative units of Korea, and correlations were calculated. The authors identified a strong positive correlation between rates of reported thyroid cancer screening and thyroid cancer incidence in the 16 areas (correlation coefficient [r], 0.77; 95% confidence interval [CI], 0.70–0.82). The correlation was stronger in women (r, 0.88; 95% CI, 0.83–0.92) than in men (r, 0.76; 95% CI, 0.67–0.84). However, there was no correlation between thyroid cancer incidence and mortality (r, -0.08; 95% CI, -0.59 to -0.63). Thyroid cancer screening was correlated with increased detection of papillary thyroid cancer (r, 0.74; 95% CI, 0.59–0.88) and no other histological subtypes.[55]

The South Korean data are limited because they are not experimental; however, they present a compelling argument against thyroid cancer screening in community settings. Similar trends of increased incidence without decreased mortality in other developed nations support the interpretation of the South Korean findings.[1010]

References:

1. Bahl M, Sosa JA, Nelson RC, et al.: Trends in incidentally identified thyroid cancers over a decade: a retrospective analysis of 2,090 surgical patients. World J Surg 38 (6): 1312-7, 2014.
2. Lin JS, Bowles EJA, Williams SB, et al.: Screening for Thyroid Cancer: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA 317 (18): 1888-1903, 2017.
3. Cancer Research UK: Thyroid Cancer Incidence Statistics. London, UK: Cancer Research UK. Available onlineAvailable online. Last accessed December 19, 2024.
4. Lim H, Devesa SS, Sosa JA, et al.: Trends in Thyroid Cancer Incidence and Mortality in the United States, 1974-2013. JAMA 317 (13): 1338-1348, 2017.
5. Ahn HS, Kim HJ, Kim KH, et al.: Thyroid Cancer Screening in South Korea Increases Detection of Papillary Cancers with No Impact on Other Subtypes or Thyroid Cancer Mortality. Thyroid 26 (11): 1535-1540, 2016.
6. Ahn HS, Kim HJ, Welch HG: Korea's thyroid-cancer "epidemic"--screening and overdiagnosis. N Engl J Med 371 (19): 1765-7, 2014.
7. Park S, Oh CM, Cho H, et al.: Association between screening and the thyroid cancer "epidemic" in South Korea: evidence from a nationwide study. BMJ 355: i5745, 2016.
8. Bibbins-Domingo K, Grossman DC, Curry SJ, et al.: Screening for Thyroid Cancer: US Preventive Services Task Force Recommendation Statement. JAMA 317 (18): 1882-1887, 2017.
9. Hoang JK, Langer JE, Middleton WD, et al.: Managing incidental thyroid nodules detected on imaging: white paper of the ACR Incidental Thyroid Findings Committee. J Am Coll Radiol 12 (2): 143-50, 2015.
10. Vaccarella S, Franceschi S, Bray F, et al.: Worldwide Thyroid-Cancer Epidemic? The Increasing Impact of Overdiagnosis. N Engl J Med 375 (7): 614-7, 2016.

Evidence of Harm Associated With Screening

Although neck palpation and thyroid ultrasound carry very low risk, a suspicious screening result can set off a chain of events that may lead to opportunities for harms.[11,22] The next step after detection of a suspicious nodule is diagnostic evaluation with fine-needle aspiration of the lesion. The risks of thyroid fine-needle aspiration are hospitalization, postprocedural hematoma, and needle tract tumor implantation, although two observational studies suggest that the rate of each of the three outcomes is lower than 1%.[11] More importantly, the results of cytology can lead to additional tests and surgery. In a meta-analysis of 23,445 nodules that were biopsied, 60% of the nodules were benign, and 5% of the nodules were malignant. However, the remaining 35% of the nodules required repeat biopsy or surgery.[33] In patients who had a diagnostic lobectomy or excision, 64% of the nodules were benign on final histological evaluation.[33]

Thyroid surgery for benign disease has the same risks as it does for malignancy. In 2013, about 80% of surgeries for small localized papillary thyroid cancers were total thyroidectomies and 20% were lobectomies. However, the 25-year cumulative risk of death caused by thyroid cancer does not differ by type of surgery.[44] Surgical risks are lower for a lobectomy than for total thyroidectomy. In addition to the general risks of surgery, specific risks of thyroid surgery include recurrent laryngeal nerve injury and hypoparathyroidism. Recurrent laryngeal nerve injury causes vocal cord paresis, which can result in difficulty speaking, difficulty swallowing, and hoarseness. Breathing difficulties are possible if both laryngeal nerves are affected.[55,66] Hypoparathyroidism leads to hypocalcemia. A cross-sectional population-based survey included 2,632 thyroid cancer patients, 2 to 4 years after diagnosis, from two U.S. SEER registries. The study reported that 25.8% of patients had voice changes more than 3 months after surgery, and 4.7% of patients had vocal fold paralysis or paresis.[77]

A meta-analysis of hypoparathyroidism lasting more than 6 months after thyroidectomy produced a summary event measure of 3.57 per 100 procedures (95% confidence interval [CI], 2.12–5.93). Summary event measures were 1.86 per 100 procedures (95% CI, 0.84–4.04) with unilateral lymph node dissection and 3.46 per 100 procedures (95% CI, 1.20–9.56) with bilateral lymph node dissection. In Korea, the trend in the incidence rate of postoperative hypoparathyroidism paralleled that of the incidence rate of thyroid cancer, increasing from 2.6 per 100,000 in 2007 to 7.3 per 100,000 in 2012.[88] Event measures from individual studies were quite variable and, in most instances, were based on very small numbers of events; however, summary measures did not vary much by extent of thyroid or lymph node resection.[11]

A meta-analysis of laryngeal nerve palsy (a cause of unilateral vocal cord paralysis and hoarseness) lasting more than 6 months produced a summary event measure of 1.46 per 100 procedures. Although the individual study measures were less variable than those for hypoparathyroidism, the measures were based on very small numbers of events. Patients who have total thyroidectomy also require lifelong thyroid-replacement therapy and corresponding blood level monitoring.[55,66] In patients who undergo total thyroidectomy, the process of optimizing hormone replacement therapy and the resultant changes in other medications, weight, or estrogen status may cause iatrogenic hypothyroidism or hyperthyroidism.

Patients with malignant nodules have additional risks if they receive radioactive iodine therapy. Studies of harms of radioactive iodine treatment addressed the risk of second primary malignancy and permanent harms on the salivary glands. The authors concluded, from the available eight studies, that there is a small increase in primary second malignancies, of 12 to 13 excess cancers per 10,000 patients.[11] The authors expressed some concern with that estimate, though, given differences in study designs, reporting of administered doses, and the fact that changes in indication and dose had occurred over time.[11] The most-common permanent salivary adverse effect was xerostomia (dry mouth), which is a risk factor for dental caries; the percentage of affected individuals ranged from 2.3% to 35%.[11] Xerostomia increases the chance of dental decay, demineralization of teeth, tooth sensitivity, and oral infections.[99]

The harms of surgery and radioactive iodine treatments raise concerns because many of these treated cancers may not progress to cause morbidity and mortality. There are no randomized controlled trials of thyroid cancer screening that could be used to estimate overdiagnosis, but it is clear from ecological data that thyroid cancer screening results in detection of thyroid cancers that would not have been diagnosed otherwise.[1010] Increases in incidence without changes in mortality in South Korea and other countries in which opportunistic thyroid cancer screening occurs cannot be explained by changes in treatment or risk factor prevalence over the years. Investigators measured thyroid cancer overdiagnosis by studying cancer registry data from high-income countries, estimating age-specific trends in thyroid cancer incidence in the 1960s before ultrasound was introduced, then comparing the shape of the age-specific curves since the 1980s.[1010] The investigators reported the rate of overdiagnosis in the United States to be increasing and estimated that it accounted for 77% of thyroid cancer cases. The estimation for overdiagnosis in South Korea was 90% of thyroid cancers cases.

Autopsy studies also lend credence to overdiagnosis resulting from thyroid cancer screening.[11] A 2014 review of 15 autopsy studies reported a 12% yield of papillary thyroid cancers, although the range across studies was wide (1%–36%). Natural history studies have demonstrated the slow-growing nature of thyroid tumors, tumor stability, and low potential for recurrence.[11,1111]

References:

1. Lin JS, Bowles EJA, Williams SB, et al.: Screening for Thyroid Cancer: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA 317 (18): 1888-1903, 2017.
2. Bibbins-Domingo K, Grossman DC, Curry SJ, et al.: Screening for Thyroid Cancer: US Preventive Services Task Force Recommendation Statement. JAMA 317 (18): 1882-1887, 2017.
3. Bongiovanni M, Spitale A, Faquin WC, et al.: The Bethesda System for Reporting Thyroid Cytopathology: a meta-analysis. Acta Cytol 56 (4): 333-9, 2012.
4. Welch HG, Doherty GM: Saving Thyroids - Overtreatment of Small Papillary Cancers. N Engl J Med 379 (4): 310-312, 2018.
5. Sandhu GS, Nouraei SAR: Laryngeal and esophageal trauma. In: Flint PW, Haughey BH, Lund V, et al., eds.: Cummings Otolaryngology—Head and Neck Surgery. 6th ed. Saunders, 2015, pp 970-81.
6. Smith PW, Hanks JB: Evaluation of the isolated neck mass. In: Cameron JL, Cameron AM, eds.: Current Surgical Therapy. 11th ed. Saunders, 2014, pp 718-23.
7. Kovatch KJ, Reyes-Gastelum D, Hughes DT, et al.: Assessment of Voice Outcomes Following Surgery for Thyroid Cancer. JAMA Otolaryngol Head Neck Surg 145 (9): 823-829, 2019.
8. Ahn SV, Lee JH, Bove-Fenderson EA, et al.: Incidence of Hypoparathyroidism After Thyroid Cancer Surgery in South Korea, 2007-2016. JAMA 322 (24): 2441-2443, 2019.
9. Plemons JM, Al-Hashimi I, Marek CL, et al.: Managing xerostomia and salivary gland hypofunction: executive summary of a report from the American Dental Association Council on Scientific Affairs. J Am Dent Assoc 145 (8): 867-73, 2014.
10. Hoang JK, Langer JE, Middleton WD, et al.: Managing incidental thyroid nodules detected on imaging: white paper of the ACR Incidental Thyroid Findings Committee. J Am Coll Radiol 12 (2): 143-50, 2015.
11. Oda H, Miyauchi A, Ito Y, et al.: Incidences of Unfavorable Events in the Management of Low-Risk Papillary Microcarcinoma of the Thyroid by Active Surveillance Versus Immediate Surgery. Thyroid 26 (1): 150-5, 2016.

Latest Updates to This Summary (12 / 19 / 2024)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

Incidence and MortalityIncidence and Mortality

Revised texttext to state that thyroid cancer represents about 2% of all new cancer diagnoses in the United States and 0.4% of all cancer deaths. It was estimated that 979,295 people were living with thyroid cancer in the United States in 2021.

This summary is written and maintained by the PDQ Screening and Prevention Editorial BoardPDQ Screening and Prevention Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ SummaryAbout This PDQ Summary and PDQ® Cancer Information for Health ProfessionalsPDQ® Cancer Information for Health Professionals pages.

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Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about thyroid cancer screening. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.

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This summary is reviewed regularly and updated as necessary by the PDQ Screening and Prevention Editorial BoardPDQ Screening and Prevention Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

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PDQ® Screening and Prevention Editorial Board. PDQ Thyroid Cancer Screening. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/thyroid/hp/thryoid-screening-pdqhttps://www.cancer.gov/types/thyroid/hp/thryoid-screening-pdq. Accessed <MM/DD/YYYY>. [PMID: 28876831]

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Last Revised: 2024-12-19