Thyroid Cancer: Screening

The US Preventive Services Task Force (USPSTF) makes recommendations about the effectiveness of specific preventive care services for patients without obvious related signs or symptoms.

It bases its recommendations on the evidence of both the benefits and harms of the service and an assessment of the balance. The USPSTF does not consider the costs of providing a service in this assessment.

The USPSTF recognizes that clinical decisions involve more considerations than evidence alone. Clinicians should understand the evidence but individualize decision making to the specific patient or situation. Similarly, the USPSTF notes that policy and coverage decisions involve considerations in addition to the evidence of clinical benefits and harms.

Importance

In 2013, the incidence rate of thyroid cancer in the United States was 15.3 cases per 100,000 persons, which is a significant increase from 1975, when the incidence rate was 4.9 cases per 100,000 persons.¹ The increase was 6.7% per year from 1997 to 2009, but the rate of increase has slowed to 2.1% per year in recent years (2009–2013).¹ Meanwhile, the change in mortality rate has increased by only about 0.7 deaths per 100,000 persons each year.¹ Most cases of thyroid cancer have a good prognosis.² The 5-year survival rate for thyroid cancer overall is 98.1% and varies from 99.9% for localized disease to 55.3% for distant disease.³

Detection

The USPSTF found inadequate evidence to estimate the accuracy of neck palpation or ultrasound as a screening test for thyroid cancer in asymptomatic persons.

Benefits of Early Detection and Treatment

The USPSTF found inadequate direct evidence to determine whether screening for thyroid cancer in asymptomatic persons using neck palpation or ultrasound improves health outcomes. However, the USPSTF determined that the magnitude of benefit can be bounded as no greater than small, based on the relative rarity of thyroid cancer, the apparent lack of difference in outcomes between patients who are treated vs only monitored (ie, for the most common tumor types), and the observational evidence demonstrating no change in mortality over time after introduction of a population-based screening program.

Harms of Early Detection and Treatment

The USPSTF found inadequate direct evidence to assess the harms of screening for thyroid cancer in asymptomatic persons. The USPSTF found adequate evidence to bound the magnitude of the overall harms of screening and treatment as at least moderate, based on adequate evidence of serious harms of treatment of thyroid cancer and evidence that overdiagnosis and overtreatment are likely consequences of screening.

USPSTF Assessment

The USPSTF concludes with moderate certainty that screening for thyroid cancer in asymptomatic persons results in harms that outweigh the benefits.

Patient Population Under Consideration

This recommendation applies to screening in asymptomatic adults. It does not apply to persons who experience hoarseness, pain, difficulty swallowing, or other throat symptoms or persons who have lumps, swelling, asymmetry of the neck, or other reasons for a neck examination. It also does not apply to persons at increased risk of thyroid cancer because of a history of exposure to ionizing radiation (eg, medical treatment or radiation fallout), particularly persons with a diet low in iodine, an inherited genetic syndrome associated with thyroid cancer (eg, familial adenomatous polyposis), or a first-degree relative with a history of thyroid cancer.^4,5

Assessment of Risk

Although the USPSTF recommends against screening in the general asymptomatic adult population, several factors substantially increase the risk for thyroid cancer, including a history of radiation exposure to the head and neck as a child, exposure to radioactive fallout, family history of thyroid cancer in a first-degree relative, and certain genetic conditions, such as familial medullary thyroid cancer or multiple endocrine neoplasia syndrome (type 2A or 2B).⁴

Screening Tests

Although screening for thyroid cancer using neck palpation and ultrasound of the thyroid has been studied, the USPSTF recommends against screening in the general asymptomatic adult population.

Treatment and Interventions

Surgery (ie, total or partial thyroidectomy, with or without lymphadenectomy) is the main treatment of thyroid cancer. Additional treatment, including radioactive iodine therapy, may be indicated, depending on postoperative disease status, tumor stage, and type of thyroid cancer. External-beam radiation therapy and chemotherapy are not generally used to treat early-stage, differentiated thyroid cancer.

Research Needs and Gaps

The USPSTF found no direct studies that compared screened vs unscreened populations or immediate surgery vs surveillance or observation and reported health outcomes (ie, morbidity, mortality, quality of life, or harms). Trials or well-designed observational studies that address the benefit of screening in high-risk persons (ie, persons with a history of radiation or family history of differentiated thyroid cancer) are important for understanding how to best advise these patients. Trials or well-designed observational studies of early treatment vs surveillance or observation of patients with small, well-differentiated thyroid cancer are also needed to identify patients at greatest risk for clinical deterioration. Finally, risk prediction tools and molecular markers are needed to help understand the prognosis of differentiated thyroid cancer.

Burden of Disease

An estimated 637,115 persons in the United States were living with thyroid cancer in 2013, according to data from the Surveillance, Epidemiology, and End Results Program.³ In 2017, an estimated 56,870 new cases of thyroid cancer will develop, representing 3.4% of all new cancer cases in the United States, and 2010 thyroid cancer–related deaths will occur (0.3% of all cancer deaths); the highest percentage of deaths will occur among adults aged 75 to 84 years (27.5%). The incidence of thyroid cancer detection has increased by 4.5% per year over the last 10 years, faster than for any other cancer, but without a corresponding change in the mortality rate, which remained at 0.5 deaths per 100,000 persons in 2013.⁶ The estimated 5-year survival rate is 98% but ranges from 99% for localized disease (68% of cancer cases at diagnosis) to 55% for distant disease (4% of cancer cases at diagnosis).^3,6

Scope of Review

To update its 1996 recommendation, the USPSTF commissioned a systematic evidence review⁷ to examine the benefits and harms of screening for thyroid cancer in asymptomatic adults. The review also assessed the diagnostic accuracy of screening (including neck palpation and ultrasound) and the benefits and harms of treatment of screen-detected thyroid cancer, which were not part of the previous evidence review.

Accuracy of Screening Tests

Evidence on the accuracy of screening for thyroid cancer using neck palpation or ultrasound is very limited, with only 2 applicable studies for each screening method, all of which compared the screening method with a reference standard in a screening population. Two fair-quality prospective studies from Finland by the same investigator reported low sensitivity for neck palpation to detect thyroid nodules.^8,9 In a study of randomly selected adults (n=253), 5.1% had abnormal findings on neck examination (thyroid nodule or diffuse enlargement), and sensitivity and specificity to detect thyroid nodules were 11.6% (95% CI, 5.1% to 21.6%) and 97.3% (95% CI, 93.8% to 99.1%), respectively.^7,8 One study of women presenting for mammography (n=101) reported sensitivity of 27.8% for neck palpation to detect thyroid nodules in women with an abnormal ultrasound finding (women with negative neck palpation findings were not followed up, so the false-positive rate could not be estimated).^7,9

Two fair-quality population-based studies, both conducted in South Korea by the same investigator, reported on diagnostic accuracy of screening using ultrasound only.^10,11 The prospective study (n=2079 screened; 113 referred for biopsy with fine needle aspiration) found that the sensitivity and specificity of having 1 or more malignant features (ie, microcalcification or irregular shape) detected on screening ultrasound were 94.3% (95% CI, 84.3% to 98.8%) and 55.0% (95% CI, 41.6% to 67.9%), respectively. A retrospective analysis of 130 asymptomatic persons selected from 1009 persons who had biopsy with fine-needle aspiration, based on ultrasound findings (ie, having ≥2 high-risk sonographic characteristics), reported sensitivity and specificity of 94.8% and 86.6%, respectively (calculated per thyroid nodule rather than per patient; CIs not provided). However, this study did not follow up patients with negative ultrasound findings, and therefore may have overestimated the sensitivity of this screening method.

Effectiveness of Early Detection and Treatment

No studies directly compared patient health outcomes for screened vs unscreened populations. No randomized trials evaluated whether earlier treatment or treatment of screen-detected, well-differentiated thyroid cancer results in better patient outcomes compared with observation (ie, delayed or no treatment).⁵ Two observational studies (reported in 5 articles)^12-16 met the inclusion criteria for benefit of early treatment. One fair-quality, retrospective, observational study using Surveillance, Epidemiology, and End Results data from 1973 to 2005 compared survival rates of persons treated (n=35,663) vs not treated (n=440) for papillary thyroid cancer.¹² Overall, untreated persons had a slightly worse 20-year survival rate compared with treated persons (97% vs 99%; P <0.001). However, there were statistically significant baseline differences between the 2 groups, and the study did not adjust for potential confounding.

Another fair-quality prospective study conducted in Japan reported the recurrence and survival rates for 2 separate cohorts (1993–2004 and 2005–2013) with papillary microcarcinoma.^13-16 In the first cohort, 1055 persons chose treatment with immediate surgery and 340 opted for surveillance. After approximately 6 years of follow-up, 32.1% of patients who opted for surveillance had surgery, and 2 patients in the immediate surgery group and none in the observation group had died. In the second cohort, 974 persons opted for treatment with immediate surgery, and 1179 opted for active surveillance. After approximately 4 years of follow-up, 8% of patients who opted for active surveillance had surgery, and no patients in either group developed distant metastases or died of thyroid cancer. Because of major limitations in the design of both studies (eg, lack of adjustment for confounding), it is uncertain whether earlier or immediate treatment vs delayed or no surgical treatment improves patient outcomes for papillary carcinoma or microcarcinoma.

Potential Harms of Screening and Treatment

No studies directly examined the harms of screening for thyroid cancer using neck palpation or ultrasound. Overall, evidence on the harms of screening for thyroid cancer is very limited, including harms of diagnostic biopsy with fine-needle aspiration (eg, hospitalization, postprocedural hematoma, and needle tract implementation).^5,17,18 The USPSTF found 36 fair-quality studies reporting on surgical harms, 32 studies on permanent hypoparathyroidism (hypocalcemia), 28 studies on permanent recurrent laryngeal nerve palsy (vocal cord paralysis), 2 studies on surgical mortality, and 15 studies on other major surgical harms.⁷ The majority of studies were retrospective observational studies, although 3 randomized trials were included. Cohort size ranged from 76 to 13,854 persons. Only 7 studies were conducted in the United States.

Considerable evidence documents the harms of treatment with surgery and radioactive iodine therapy. The rate of permanent hypoparathyroidism varied widely (15 study arms); best estimates were 2 to 6 events per 100 total thyroidectomies, and estimates varied more with lymph node dissection. The rate of permanent recurrent laryngeal nerve palsy varied less (14 study arms), at an estimated 1 to 2 events per 100 operations (with or without lymph node dissection). Sixteen fair-quality studies (n=94,823) provided evidence for potential harms of radioactive iodine remnant ablation or therapy.⁷ Estimates of a secondary malignancy ranged from approximately 12 to 13 excess cancers per 10,000 person-years,^7,19,20 and salivary gland harms (eg, dry mouth) ranged from 2.3 to 21 events per 100 persons.^7,21-26

Although no direct studies of whether screening causes overdiagnosis exist, ecological and cross-sectional data suggest that screening for thyroid cancer leads to an increase in incidence without any resulting change in mortality.⁵ Multiple studies in the United States show a rising incidence in thyroid cancer detection over time, with no corresponding change in the mortality rate.⁷ The best ecological evidence on the overdiagnosis of thyroid cancer comes from South Korea, which has had an organized cancer screening program since 1999.²⁷ Although the program did not officially include screening for thyroid cancer, clinicians frequently offered thyroid screening using ultrasound for a small additional cost. In 2011, the rate of thyroid cancer diagnosis was 15 times the rate in 1993, while the thyroid cancer–specific mortality rate remained stable.²⁷

Autopsy studies provide additional evidence on overdiagnosis of thyroid cancer. A 2014 review by Lee et al²⁸ summarizes 15 studies published between 1969 and 2005 on latent thyroid cancer discovered at autopsy. Of the 8619 thyroid glands incidentally obtained at autopsy, 989 (11.5%) tested positive for papillary thyroid carcinoma. The majority of the tumors were tiny (diameter <1 to 3 mm).

Estimate of Magnitude of Net Benefit

The USPSTF found inadequate direct evidence on the benefits of screening but determined that the magnitude of the overall benefits of screening and treatment can be bounded as no greater than small, given the relative rarity of thyroid cancer, the apparent lack of difference in outcomes between treatment and surveillance (for the most common tumor types), and observational evidence showing no change in mortality over time after introduction of a mass screening program. Similarly, the USPSTF found inadequate direct evidence on the harms of screening but determined that the magnitude of the overall harms of screening and treatment can be bounded as at least moderate, given adequate evidence of harms of treatment and indirect evidence that overdiagnosis and overtreatment are likely to be substantial with population-based screening. Therefore, the USPSTF determined with moderate certainty that the net benefit of screening for thyroid cancer is negative.

Response to Public Comment

A draft version of this recommendation statement was posted for public comment on the USPSTF website from November 22 to December 26, 2016. Many respondents shared personal stories of how their clinician noticed a lump during physical examination, often prompted by symptoms such as hoarseness or throat pain, and expressed concern that the recommendation would prevent diagnosis of such cancer cases. Clinicians who interpreted the recommendation as discouraging them from performing neck examination also expressed concern. In response, the USPSTF expanded the Clinical Considerations section to clarify that this recommendation does not apply to persons who experience hoarseness, pain, difficulty swallowing, or other throat symptoms or persons who have lumps, swelling, asymmetry of the neck, or to other reasons for a neck examination.

The American Cancer Society does not specifically recommend screening for thyroid cancer using neck palpation or any other method.³⁰ In 1996, the American Academy of Family Physicians recommended against screening for thyroid cancer using neck palpation or ultrasound in asymptomatic persons.³¹ The Canadian Task Force on the Periodic Health Examination does not include examination of the thyroid in its 2015 Preventive Care Checklist Form.³² The American Thyroid Association³³ and the American Association of Clinical Endocrinologists, American College of Endocrinology, and Associazione Medici Endocrinologi³⁴ issued guidelines for the diagnosis and management of thyroid nodules in 2016; these guidelines included no recommendation on screening for thyroid cancer in asymptomatic persons.

This is an update of the 1996 USPSTF recommendation.²⁹ In 1996, the USPSTF recommended against screening for thyroid cancer in asymptomatic adults using either neck palpation or ultrasound (D recommendation). In addition, using older methodology, the USPSTF issued a C recommendation for screening in asymptomatic adults with a history of radiation of the external upper body (primarily the head and neck) in infancy or childhood; in 1996, a C recommendation was defined as "insufficient evidence to recommend for or against." The USPSTF focused its current recommendation on the general asymptomatic adult population.

The US Preventive Services Task Force (USPSTF) members include the following individuals: Kirsten Bibbins-Domingo, PhD, MD, MAS (University of California, San Francisco); David C. Grossman, MD, MPH (Kaiser Permanente Washington Health Research Institute, Seattle, Washington); Susan J. Curry, PhD (University of Iowa, Iowa City); Michael J. Barry, MD (Harvard Medical School, Boston, Massachusetts); Karina W. Davidson, PhD, MASc (Columbia University, New York, New York); Chyke A. Doubeni, MD, MPH (University of Pennsylvania, Philadelphia); John W. Epling Jr, MD, MSEd (Virginia Tech Carilion School of Medicine, Roanoke); Alex R. Kemper, MD, MPH, MS (Duke University, Durham, North Carolina); Alex H. Krist, MD, MPH (Fairfax Family Practice Residency, Fairfax, Virginia, and Virginia Commonwealth University, Richmond); Ann E. Kurth, PhD, RN, MSN, MPH (Yale University, New Haven, Connecticut); C. Seth Landefeld, MD (University of Alabama at Birmingham); Carol M. Mangione, MD, MSPH (University of California, Los Angeles); Maureen G. Phipps, MD, MPH (Brown University, Providence, Rhode Island); Michael Silverstein, MD, MPH (Boston University, Boston, Massachusetts); Melissa A. Simon, MD, MPH (Northwestern University, Evanston, Illinois); Albert L. Siu, MD, MSPH (Mount Sinai Hospital, New York, New York, and James J. Peters Veterans Affairs Medical Center, Bronx, New York); Chien-Wen Tseng, MD, MPH, MSEE (University of Hawaii, Honolulu, and Pacific Health Research and Education Institute, Honolulu, Hawaii).

Source: This article first appeared in JAMA on May 9, 2017.

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Authors followed the policy regarding conflicts of interest described at https://www.uspreventiveservicestaskforce.org/Page/Name/conflict-of-interest-disclosures. All members of the USPSTF receive travel reimbursement and an honorarium for participating in USPSTF meetings.

Funding/Support: The USPSTF is an independent, voluntary body. The US Congress mandates that the Agency for Healthcare Research and Quality (AHRQ) support the operations of the USPSTF.

Disclaimer: Recommendations made by the USPSTF are independent of the US government. They should not be construed as an official position of AHRQ or the US Department of Health and Human Services.

Copyright Notice: USPSTF recommendations are based on a rigorous review of existing peer-reviewed evidence and are intended to help primary care clinicians and patients decide together whether a preventive service is right for a patient's needs. To encourage widespread discussion, consideration, adoption, and implementation of USPSTF recommendations, AHRQ permits members of the public to reproduce, redistribute, publicly display, and incorporate USPSTF work into other materials provided that it is reproduced without any changes tothe work of portions thereof, except as permitted as fair use under the US Copyright Act.

AHRQ and the US Department of Health and Human Services cannot endorse, or appear to endorse, derivative or excerpted materials, and they cannot be held liable for the content or use of adapted products that are incorporated on other Web sites. Any adaptations of these electronic documents and resources must include a disclaimer to this effect. Advertising or implied endorsement for any commercial products or services is strictly prohibited.

This work may not be reproduced, reprinted, or redistributed for a fee, nor may the work be sold for profit or incorporated into a profit-making venture without the express written permission of AHRQ. This work is subject to the restrictions of Section 1140 of the Social Security Act, 42 U.S.C. § 1320b-10. When parts of a recommendation statement are used or quoted, the USPSTF Web page should be cited as the source.