Draft Recommendation Statement
Thyroid Cancer: Screening
November 22, 2016
Recommendations made by the USPSTF are independent of the U.S. government. They should not be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.
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.
In 2014, the incidence rate of thyroid cancer in the United States was 14.3 cases per 100,000 persons. This is a significant increase from 1975, when the incidence rate was 4.9 cases per 100,000 persons.1 However, according to Surveillance, Epidemiology, and End Results (SEER) data from 2009 to 2013, mortality rates have remained stable at about 0.5 deaths per 100,000 persons each year.2 Most cases of thyroid cancer have a good prognosis.3 Papillary thyroid cancer, which accounts for about 70% to 80% of all thyroid cancer cases, has a 10-year overall survival rate of 93%. Follicular thyroid cancer accounts for another 10% to 15% of all cases and has a 10-year overall survival rate of 85%; both papillary and follicular thyroid cancer are treated similarly.4
The USPSTF found inadequate evidence to estimate the accuracy of 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 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 following factors: the relative rarity of thyroid cancer, the apparent lack of difference in outcomes between patients who are treated and patients who are only monitored (for the most common tumor types), and the observational evidence demonstrating no change in mortality over time after introduction of a population-wide screening program.
Harms of Early Detection and Treatment
The USPSTF found inadequate direct evidence to assess the harms of screening. 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.
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 statement applies to screening in asymptomatic adults. It does not apply to persons who are at increased risk of thyroid cancer due to a history of high radiation exposure (such as an environmental disaster), inherited genetic syndromes associated with thyroid cancer, or a personal history of thyroid cancer.5
Assessment of Risk
Although the USPSTF recommends against screening in the general asymptomatic adult population, a number of 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 disease or thyroid cancer, and genetic conditions that raise the risk of thyroid cancer, such as familial medullary thyroid cancer or multiple endocrine neoplasia syndrome (type 2A or 2B).5
Although screening for thyroid cancer using neck palpation and ultrasound of the thyroid has been studied, the USPSTF recommends against screening in the asymptomatic adult population.
Treatment or Interventions
Surgery (i.e., 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 versus unscreened populations or immediate surgery versus surveillance/observation and reported health outcomes (i.e., morbidity, mortality, quality of life, or harms). Trials or well-designed observational studies that address the benefit of screening in high-risk persons (i.e., those with a personal history of radiation or family history of differentiated thyroid cancer) are important to understanding how to best advise these patients. Trials or well-designed observational studies of early treatment versus observation or surveillance of patients with small, well-differentiated thyroid cancer are also needed to identify patients at greatest risk for clinical deterioration. Last, risk prediction tools and molecular markers are needed to help understand the prognosis of differentiated thyroid cancer.
Burden of Disease
An estimated 637,115 people in the United States were living with thyroid cancer in 2013, based on SEER data.2 In 2016, an estimated 64,300 new cases of thyroid cancer will develop, which represents 3.8% of all new cancer cases in the United States, and 1,980 related deaths will occur (0.3% of all cancer deaths), with the highest percentage of deaths occurring among adults ages 75 to 84 years (27.5%). The incidence of thyroid cancer detection has increased by 4.5% each 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 2013.2 The estimated 5-year survival rate is 98.1% but ranges from 99.9% for localized disease (68% of cancer cases at diagnosis) to 55.3% for metastatic disease (4% of cancer cases at diagnosis).2
Scope of Review
To update its 1996 recommendation, the USPSTF commissioned a systematic evidence review6 to examine the benefits and harms of screening for thyroid cancer in 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 two applicable studies for each method, all of which compared the screening modality with a reference standard in a screening population. Two fair-quality prospective studies from Finland by the same investigator reported low sensitivity of palpation to detect nodules. In a study of randomly selected adults (n=253), 5.1% had an abnormal neck examination (thyroid nodule or diffuse enlargement), and the sensitivity and specificity to detect thyroid nodules was 11.6% (95% CI, 5.1 to 21.6) and 97.3% (95% CI, 93.8 to 99.1), respectively.7 One study of women presenting for mammography (n=101) reported a 27.8% sensitivity of palpation to detect nodules in women with an abnormal ultrasound result (women with a negative palpation examination were not followed, so the false-positive rate could not be estimated).8
Two fair-quality population-based studies, both conducted in South Korea by the same investigator, reported on diagnostic accuracy of screening using ultrasound only.9,10 The prospective study (n=2,079 screened and 113 referred for fine needle aspiration) found that the sensitivity and specificity of having one or more malignant features (i.e., 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 1,009 persons who had fine needle aspiration based on ultrasound findings (i.e., >2 high-risk sonographic characteristics) reported sensitivity and specificity of 94.8% and 86.6%, respectively (calculated for nodules rather than patients; confidence intervals not provided). However, this study did not follow up with patients with negative ultrasounds, and therefore may have overestimated the sensitivity of this method.
Effectiveness of Early Detection and Treatment
No studies directly compared patient health outcomes for screened versus unscreened populations. No randomized trials evaluated if earlier treatment or treatment of screen-detected, well-differentiated thyroid cancer results in better patient outcomes compared with observation (i.e., delayed or no treatment). Two observational studies (reported in five articles11-15) met the inclusion criteria for benefit of early treatment. One fair-quality retrospective observational study using SEER data from 1973 to 2005 compared survival rates of persons treated (n=35,663) versus not treated (n=440) for papillary thyroid cancer.11 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 two groups, and the study did not adjust for potential confounders. Another fair-quality prospective study in Japan reported the recurrence and survival rates for two separate cohorts (1993–2004 and 2005–2013) with papillary microcarcinoma.12-15 In the first cohort, 1,055 persons chose immediate surgery and 340 opted for surveillance. After approximately 6 years of followup, 32% of patients who opted for surveillance ultimately had surgery, and two patients in the immediate surgery group and none in the observation group had died. In the second cohort, 974 persons opted for immediate surgery and 1,179 opted for active surveillance. After approximately 4 years of followup, 8% of patients who opted for observation ultimately had surgery, and no patients in either group developed distant metastases or died from thyroid cancer. Because of major limitations in the design of both studies (e.g., lack of adjustment for confounders), it is uncertain if earlier or immediate treatment versus delayed or no surgical treatment improves patient outcomes for papillary carcinoma or papillary microcarcinoma.
Potential Harms of Screening and Treatment
No studies directly examined the harms of screening for thyroid cancer using palpation or ultrasound. Overall, there is very limited evidence on the harms of screening for thyroid cancer, including harms of diagnostic followup with fine needle aspiration (e.g., hospitalization, postprocedural hematoma, and needle tract implementation).16-17 The USPSTF found 36 fair-quality studies that reported on surgical harms, 32 studies reporting on permanent hypoparathyroidism (hypocalcemia), 28 studies reporting on permanent recurrent laryngeal nerve palsy (vocal cord paralysis), two studies reporting on surgical mortality, and 15 studies reporting on other major surgical harms.6 The majority of studies were retrospective observational studies, although three randomized trials were included. Cohort size ranged from 76 to 13,854 persons. Only seven studies were conducted in the United States.
Considerable evidence documents the harms of surgery and radioactive iodine therapy for the treatment of thyroid cancer. The rate of permanent hypoparathyroidism varied widely (among 15 study arms); best estimates were from 2 to 6 events per 100 total thyroidectomies, and estimates varied more for thyroidectomy with lymph node dissection. The rate of permanent recurrent laryngeal nerve palsy was less variable (among 14 study arms), at an estimated 1 to 2 events per 100 surgeries (with or without lymph node dissection). Evidence for potential harms of radioactive iodine remnant ablation or therapy included 16 fair-quality studies (n=94,823). Estimates of secondary malignancies ranged from approximately 12 to 13 excess cancers per 10,000 person-years18,19 and salivary gland harms (e.g., dry mouth) ranged from 2.3 to 21 events per 100 persons.20-25
Although there are no direct studies of whether screening causes overdiagnosis, ecological and cross-sectional data suggest that thyroid cancer screening leads to an increase in incidence without any resulting change in mortality. Multiple studies in the United States show a rising incidence in thyroid cancer detection over time with no change in the mortality rate.6 The best ecological evidence on the overdiagnosis of thyroid cancer comes from South Korea, which has had an organized cancer screening program since 1999.26 Although the program did not officially include screening for thyroid cancer, providers 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 rate of thyroid cancer mortality remained stable.26
Autopsy studies have provided additional evidence on overdiagnosis of thyroid cancer. A 2014 review by Lee and colleagues27 summarized 15 studies published between 1969 and 2005 on latent thyroid cancer discovered at autopsy. Of the 8,619 thyroid glands incidentally obtained at autopsy, 989 (11.5%) were positive for papillary thyroid carcinoma. The majority of the tumors were tiny (diameter of <1 to 3 mm).
Estimate of Magnitude of Net Benefit
The USPSTF found inadequate direct evidence on the benefits of screening but bounded the overall benefits of screening and treatment 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 type, and ecologic 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 bounded the overall magnitude of the harms of screening and treatment as at least moderate, given adequate evidence of harms of treatment of thyroid cancer 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 thyroid cancer screening is negative.
This is an update of the 1996 USPSTF recommendation. In 1996, the USPSTF also 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 irradiation of the external upper body (primarily 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 American Cancer Society does not recommend screening for thyroid cancer using palpation.28 In 1996, the American Academy of Family Physicians recommended against screening for thyroid cancer using ultrasound in asymptomatic persons.29 The Canadian Task Force on the Periodic Health Examination does not include thyroid examination in its updated Preventive Care Checklist Form.30 The American Association of Clinical Endocrinologists, American College of Endocrinology, and Associazione Medici Endocrinologi issued guidelines for the diagnosis and management of thyroid nodules in 2016, which had no recommendation for screening for thyroid cancer in asymptomatic persons.31
- Davies L, Welch HG. Current thyroid cancer trends in the United States. JAMA Otolaryngol Head Neck Surg. 2014;140(4):317-22.
- National Cancer Institute. SEER Stat Fact Sheets: Thyroid Cancer. 2016. http://seer.cancer.gov/statfacts/html/thyro.html. Accessed November 10, 2016.
- Cooper DS, Doherty GM, Haugen BR, et al; American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2009;19(11):1167-214.
- National Cancer Institute. Thyroid Cancer Treatment (PDQ®)–Health Professional Version. 2016. https://www.cancer.gov/types/thyroid/hp/thyroid-treatment-pdq. Accessed November 14, 2016.
- Pellegriti G, Frasca F, Regalbuto C, Squatrito S, Vigneri R. Worldwide increasing incidence of thyroid cancer: update on epidemiology and risk factors. J Cancer Epidemiol. 2013;2013:965212.
- Lin JS, Bowles EJ, Williams SB, Morrison CC. Screening for Thyroid Cancer: A Systematic Review for the U.S. Preventive Services Task Force. Evidence Synthesis No. 151. AHRQ Publication No. 15-05221-EF-1. Rockville, MD: Agency for Healthcare Research and Quality; 2016.
- Brander A, Viikinkoski P, Nickels J, Kivisaari L. Thyroid gland: US screening in a random adult population. Radiology. 1991;181(3):683-7.
- Brander A, Viikinkoski P, Nickels J, Kivisaari L. Thyroid gland: US screening in middle-aged women with no previous thyroid disease. Radiology. 1989;173(2):507-10.
- Kim SJ, Moon WK, Cho N. Sonographic criteria for fine-needle aspiration cytology in a Korean female population undergoing thyroid ultrasound screening. Acta Radiol. 2010;51(5):475-81.
- Kim JY, Lee CH, Kim SY, et al. Radiologic and pathologic findings of nonpalpable thyroid carcinomas detected by ultrasonography in a medical screening center. J Ultrasound Med. 2008;27(2):215-23.
- Davies L, Welch HG. Thyroid cancer survival in the United States: observational data from 1973 to 2005. Arch Otolaryngol Head Neck Surg. 2010;136(5):440-4.
- Ito Y, Miyauchi A, Inoue H, et al. An observational trial for papillary thyroid microcarcinoma in Japanese patients. World J Surg. 2010;34(1):28-35.
- Ito Y, Uruno T, Nakano K, et al. An observation trial without surgical treatment in patients with papillary microcarcinoma of the thyroid. Thyroid. 2003;13(4):381-7.
- Ito Y, Miyauchi A, Kihara M, Higashiyama T, Kobayashi K, Miya A. Patient age is significantly related to the progression of papillary microcarcinoma of the thyroid under observation. Thyroid. 2014;24(1):27-34.
- 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. 2016;26(1):150-5.
- Ito Y, Tomoda C, Uruno T, et al. Needle tract implantation of papillary thyroid carcinoma after fine-needle aspiration biopsy. World J Surg. 2005;29(12):1544-9.
- Abu-Yousef MM, Larson JH, Kuehn DM, Wu AS, Laroia AT. Safety of ultrasound-guided fine needle aspiration biopsy of neck lesions in patients taking antithrombotic/anticoagulant medications. Ultrasound Q. 2011;27(3):157-9.
- Brown AP, Chen J, Hitchcock YJ, Szabo A, Shrieve DC, Tward JD. The risk of second primary malignancies up to three decades after the treatment of differentiated thyroid cancer. J Clin Endocrinol Metab. 2008;93(2):504-15.
- Iyer NG, Morris LG, Tuttle RM, Shaha AR, Ganly I. Rising incidence of second cancers in patients with low-risk (T1N0) thyroid cancer who receive radioactive iodine therapy. Cancer. 2011;117(19):4439-46.
- Hyer S, Kong A, Pratt B, Harmer C. Salivary gland toxicity after radioiodine therapy for thyroid cancer. Clin Oncol (R Coll Radiol). 2007;19(1):83-6.
- Ish-Shalom S, Durleshter L, Segal E, Nagler RM. Sialochemical and oxidative analyses in radioactive I131-treated patients with thyroid carcinoma. Eur J Endocrinol. 2008;158(5):677-81.
- Jeong SY, Kim HW, Lee SW, Ahn BC, Lee J. Salivary gland function 5 years after radioactive iodine ablation in patients with differentiated thyroid cancer: direct comparison of pre- and postablation scintigraphies and their relation to xerostomia symptoms. Thyroid. 2013;23(5):609-16.
- Solans R, Bosch JA, Galofré P, et al. Salivary and lacrimal gland dysfunction (sicca syndrome) after radioiodine therapy. J Nucl Med. 2001;42(5):738-43.
- Grewal RK, Larson SM, Pentlow CE, et al. Salivary gland side effects commonly develop several weeks after initial radioactive iodine ablation. J Nucl Med. 2009;50(10):1605-10.
- Ryu CH, Ryu J, Ryu YM, et al. Administration of radioactive iodine therapy within 1 year after total thyroidectomy does not affect vocal function. J Nucl Med. 2015;56(10):1480-6.
- Ahn HS, Kim HJ, Welch HG. Korea’s thyroid-cancer "epidemic"—screening and overdiagnosis. N Engl J Med. 2014;371(19):1765-7.
- Lee YS, Nam KH, Chung WY, Chang HS, Park CS. Postoperative complications of thyroid cancer in a single center experience. J Korean Med Sci. 2010;25(4):541-5.
- American Cancer Society. Thyroid Cancer. 2016. http://www.cancer.org/cancer/thyroidcancer/detailedguide/thyroid-cancer-detection. Accessed November 10, 2016.
- American Academy of Family Physicians. Clinical Preventive Service Recommendation: Thyroid. 1996. http://www.aafp.org/patient-care/clinical-recommendations/all/thyroid.html. Accessed November 10, 2016.
- Ridley J, Ischayek A, Dubey V, Iglar K. Adult health checkup: update on the Preventive Care Checklist Form. Can Fam Physician. 2016;62(4):307-13.
- Gharib H, Papini E, Garber JR, et al; AACE/ACE/AME Task Force on Thyroid Nodules. American Association of Clinical Endocrinologists, American College of Endocrinology, and Associazione Medici Endocrinologi medical guidelines for clinical practice for the diagnosis and management of thyroid nodules—2016 update. Endocr Pract. 2016;22(5):622-39.