High Rate of Papillary Thyroid Cancer Overdiagnosis Shown in Simulation Study

Most papillary thyroid cancer (PTC) cases identified in the United States over the past 3 decades likely represent overdiagnosis, identifying cancer in patients that would likely have remained asymptomatic had no effect on a patient's lifespan, according to a new simulation study published in JAMA Network Open.¹

The findings suggest that scaling back thyroid ultrasonography referrals, particularly for incidentally found nodules, could meaningfully reduce diagnoses without affecting survival.

Investigators from the University of Wisconsin School of Medicine and Public Health built the analysis on the Papillary Thyroid Carcinoma Microsimulation Model (PATCAM), a validated tool reconstructing US PTC incidence, stage, and mortality from Surveillance, Epidemiology, and End Results (SEER) data, applied to the adult US population from 1991 through 2019 to separate cases that would never have caused symptoms or death from those reflecting a true, biology-driven rise in disease.

The model attributed 72% to 94% of PTC diagnoses over the study period to overdiagnosis. The proportion ran only modestly higher in women than men (75%-95% vs 63%-90%), but absolute rates diverged more sharply, at 13 to 17 cases per 100,000 individuals in women versus 3 to 5 in men, translating nationally to an estimated 443,212 to 573,705 overdiagnosed women and 107,804 to 154,504 overdiagnosed men from 1991 to 2019.

The relative proportion held steady across age groups and time, but absolute numbers rose: overdiagnosis rates climbed from 8-10 to 18-23 per 100,000 in women and from 2-3 to 5-7 per 100,000 in men between 1991-2000 and 2011-2019, with the steepest climbs among women aged 35 to 64. Sensitivity analyses modeling a substantial true rise in biological risk still found its contribution negligible next to diagnostic intensity.

“Even when we account for a potential true increase in the underlying rates of thyroid cancer, the majority of thyroid cancers diagnosed and treated over the past 30 years represent overdiagnosis. Overdiagnosis can lead to unnecessary surgery or other interventions, with side effects of needing lifelong thyroid hormone therapy, and avoidable psychological and financial harm,” Louise Davies, MD, MS, professor of otolaryngology at the University of Wisconsin School of Medicine and Public Health and study co-first author, stated in a news release.²

Potential Impact of Reducing Ultrasonography Referrals

Modeled referral reductions showed real leverage: a 33% cut in ultrasonography for nonpalpable nodules would have lowered 2019 PTC incidence by 17% (to 15 from 18 per 100,000 individuals), and a 67% cut would have lowered it by 41% (to 11 per 100,000). Full elimination would have brought 2019 incidence to 4.5 per 100,000, close to the 3.8 per 100,000 SEER reported in 1991, with mortality changing by less than 0.1% in every scenario.¹ The tradeoff was a slow rise in palpable-nodule cancers, projected at 0.6% annually in women and 0.5% in men under complete elimination.¹

“Small changes in referral practices could reduce overdiagnosis by tens of thousands of cases each year, without changing mortality,” David O. Francis, MD, MS, professor of otolaryngology and head and neck surgery at the University of Wisconsin School of Medicine and Public Health and the study's corresponding and co-first author, stated in the news release.² “This is a powerful opportunity to create guidelines that would help align practice with evidence and reduce overtreatment.”

“This is about making sure patients receive care that truly benefits them,” added Francis.² “By being thoughtful about when we use imaging, we can reduce unnecessary diagnoses and treatments while still identifying and treating the cancers more likely to cause harm.”

References

1. Francis DO, Davies L, Zhang Y, et al. Overdiagnosis of papillary thyroid cancer. JAMA Netw Open. 2026;9(2):e2559852. doi:10.1001/jamanetworkopen.2025.59852

2. Overdiagnosis of thyroid cancer remains high. University of Wisconsin School of Medicine and Public Health. Published September 8, 2026. Accessed September 9, 2026. https://tinyurl.com/msk9puh5