Examining Why Thyroid Cancer Incidence Is High in Women

In the last three decades, the incidence of thyroid cancer has increased drastically, largely due to increased detection of small and indolent papillary thyroid cancers. Women have been affected disproportionally by this trend. While most thyroid cancers do not carry high mortality rates, increased diagnosis and treatment of subclinical thyroid cancer contributes to greater morbidity as well as cancer-related worry.

In this important study investigating the reason for the sex difference in thyroid cancer incidence, Fernandes-Taylor et al. retrospectively evaluated 33,589 patients who underwent thyroid ultrasound between 1997 and 2019, were part of the Kaiser Permanente of Washington network, and lived in 1 of the 13 counties covered by the Seattle-Puget Sound Surveillance Epidemiology and End Results cancer registry. ¹ The authors found that females represented 78% of the individuals who received a thyroid ultrasound with females three times more likely to undergo thyroid ultrasound and three times more likely to have an fine needle aspiration (FNA). Related to this disproportionate use of ultrasound, females had 2.4 times higher thyroid cancer incidence than males. Ultrasound rates increased 4- to 5-fold between 1997 and 2019, but FNA rates per ultrasound changed very little over time. Most of the sex difference in thyroid cancer incidence was driven by diagnosis of small papillary thyroid cancers.

LeClair et al. observed similar trends as they found that the female-to-male incidence ratio for small papillary thyroid cancers <2 cm was 4.39:1 between 2013 and 2017. ² This finding raised the question on whether females are at higher risk of developing thyroid cancer. However, when looking at prevalence data of papillary thyroid cancers from autopsies worldwide, they discovered that subclinical PTC was present in 14% of women and 11% of men, a difference that was not statistically significant. Furthermore, the incidence ratio approached 1 with larger papillary thyroid cancers and other subtypes. This prior study by LeClair et al. similarly suggests that the primary reason for the sex difference in thyroid cancer incidence is that women are more likely to be diagnosed with subclinical thyroid cancer.

Complementary to the work by Fernandes-Taylor et al., prior studies have also suggested that imaging drives the greater detection of thyroid cancers in women. Haymart et al. ³ evaluated longitudinal imaging patterns in Medicare patients aged ≥65 years and discovered that thyroid ultrasound as initial imaging increased at a rate of 21% per year from 2002 to 2013, with female patients more likely to have thyroid ultrasound as initial imaging. Prior studies have suggested that some thyroid ultrasounds are ordered for inappropriate indications. When investigating the reason for thyroid ultrasound orders at Mayo Clinic between 2015 and 2017, Soto Jacome et al. found thyroid ultrasound use was triggered by incidental findings on unrelated imaging (32%), thyroid symptoms (20%), abnormal thyroid findings on physical exam (17%), and thyroid dysfunction workup (12%). ⁴ Out of all ultrasound orders, 11% were ordered inappropriately. One study from Portugal found women were more likely to have ultrasounds ordered for reasons unrelated to the thyroid gland, including weight gain or a neighbor diagnosed with thyroid nodule. ⁵ Similarly, Chen et al. surveyed providers who had treated patients with thyroid cancer in the past and found that while most physicians ordered ultrasounds when clinically indicated (e.g., palpable nodule, goiter, nodule on other imaging), a substantial number (22–33%) reported obtaining ultrasound for reasons that are not clinically supported including patient request, abnormal thyroid function tests, or positive thyroid antibodies. ⁶

The study by Fernandes-Taylor et al. supports a growing body of evidence suggesting that the increased incidence of thyroid cancer in women may be due to current clinical practices. Women are receiving disproportionally more thyroid ultrasounds than men, which may be related to greater engagement with the health care system, physician practice patterns, as well as low cost and perceived harmlessness of thyroid ultrasound. Although overdiagnosis of indolent thyroid cancers has not changed mortality, it does lead to risks for treatment complications and cancer-related worry. This overuse of thyroid ultrasound, and its downstream ramifications, especially for women, calls for heightened awareness and more guidance on clinical indications.