Draft Research Plan

Thyroid Cancer: Screening

January 08, 2015

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.

Abbreviation: QOL = quality of life.

Text Description.

The figure is an analytic framework that depicts the five key questions described in the research plan. In general, it illustrates the overarching questions of whether screening asymptomatic adults for thyroid cancer leads to improved health outcomes or potential harms. It also illustrates the intermediate steps and key questions about the accuracy of screening tests for early detection of thyroid cancer. Finally, it illustrates whether treatment of thyroid cancer leads to improved health outcomes or potential harms.

  1. Does screening for thyroid cancer (using palpation or ultrasonography) in average-risk adults reduce the risk for thyroid-specific and all-cause mortality and/or improve quality of life?
    1. Does selective screening in high-risk persons (based on a combination of one or more risk factors, such as family history or radiation exposure) reduce the risk for thyroid-specific and all-cause mortality and/or improve quality of life?
  2. What are the test performance characteristics of screening tests (palpation or ultrasonography) for detecting malignant thyroid nodules in adults?
  3. What are the harms of screening for thyroid cancer (either as a single application or in a screening program) in adults, including followup confirmatory testing?
  4. Does treatment of screen-detected thyroid cancer reduce thyroid-specific and all-cause mortality and/or improve quality of life?
  5. What are the harms of treatment of screen-detected thyroid cancer?

Contextual questions will not be systematically reviewed and are not shown in the Analytic Framework.

  1. What is the natural history of thyroid nodules by age, race, and ethnicity?
  2. What is the natural history of and prognosis for each type and stage of thyroid cancer (i.e., papillary, follicular, Hurthle cell, medullary, and anaplastic)?
  3. What are the test performance characteristics of fine needle aspiration for diagnosing thyroid cancer?
  4. What factors are associated with the apparent increase in thyroid cancer incidence observed in the United States over the past 30 years?

The Proposed Research Approach identifies the study characteristics and criteria that the Evidence-based Practice Center will use to search for publications and to determine whether identified studies should be included or excluded from the Evidence Review. Criteria are overarching as well as specific to each of the key questions (KQs).

  Include Exclude
  • Asymptomatic adults age ≥18 years
  • High-risk populations (i.e., history of radiation exposure or family history of thyroid cancer)
  • Persons already under surveillance for thyroid cancer because of previous thyroid cancer
  • Persons who have symptoms that may lead to thyroid evaluation
  • Persons with known inherited genetic syndromes, such as multiple endocrine neoplasia type II, as selection criteria for studies
  • Children and adolescents
Screening tests KQs 1–3: Palpation or ultrasonography (including ultrasound-based technologies such as elastography) of the neck conducted by primary care providers or specialists as part of a routine well care visit
  • Diagnostic procedures (e.g., fine needle aspiration) will be excluded as screening tests but will be reviewed under harms of screening
  • Other imaging tests (e.g., magnetic resonance imaging, positron emission tomography) that incidentally identify thyroid nodules
  • Blood tests (e.g., calcitonin, thyroid-stimulating hormone)
  • Self examination
Treatment interventions KQs 4, 5: Surgery (including lobectomy, near-total thyroidectomy, total thyroidectomy, and lymphadenectomy), radioactive iodine ablation
  • Chemotherapy
  • External-beam radiation therapy
Comparisons KQs 1–3: No screening

KQs 4, 5: No treatment


Outcomes KQs 1, 4: Reduced morbidity associated with any thyroid cancer (including papillary, follicular, Hurthle cell, medullary, anaplastic), including:
  • Improved quality of life
  • Decreased thyroid cancer mortality
  • Decreased all-cause mortality

KQ 2: Sensitivity, specificity, positive predictive value, false-positives, false-negatives, nodule detection rate, cancer detection rate

KQs 3, 5: Any harm from screening or treatment, including overdiagnosis, diagnostic tests, overtreatment, psychosocial harms, secondary malignancies, or procedure-related adverse events
Incidentally identified thyroid nodules
  • U.S. primary care settings
  • Countries categorized as “High” on the Human Development Index (as defined by the World Health Organization)
Countries with environmental disasters that led to very high radiation exposure (e.g., Ukraine, Japan)
Study designs All KQs: Fair- to good-quality studies published since January 1, 1966 to March 31, 2015

KQ 1: RCTs

KQ 2: Diagnostic accuracy studies with a reference standard, systematic evidence reviews

KQs 3, 5: RCTs, CCTs, cohort studies, case-control studies

KQ 4: RCTs, CCTs, cohort studies
All other study designs

Abbreviations: CCT = controlled clinical trial; KQ = key question; RCT = randomized, controlled trial.