Low-Risk HPV May Contribute to Thyroid Eye Disease in Autoimmune Hyperthyroidism: Study

Thyroid eye disease is a debilitating autoimmune condition that is most commonly seen in the context of autoimmune hyperthyroidism. It is characterized by inflammation of the orbit, which results in exophthalmos, retraction of the eyelids, diplopia, defects in the visual fields, and, in some cases, blindness. While the role of genetic and immunological factors has been suggested, the possible role of infectious causes has remained an area of investigation.

A retrospective case-control study was performed using the TriNetX electronic health record system, which pools data from about 150 million patients in various health systems. From this pool, 246,957 patients with autoimmune hyperthyroidism were selected. Of these, 26,824 patients had TED due to clinical manifestations of exophthalmos, eyelid retraction, visual field defects, or ocular motility disorders. Both groups were matched for demographic variables, and each group consisted of 26,823 patients. The average age of the patients was 51.9 years, and 75.4% were female, which is consistent with the female predominance of autoimmune thyroid disease.

Key findings

• The results showed that patients with TED had more than 1.5 times the risk of previous low-risk HPV infection than controls.

• The risk was more evident in the case of HPV infection diagnosed before the development of autoimmune hyperthyroidism, which was approximately three times more frequent in patients with TED than in those whose infection occurred after the diagnosis of hyperthyroidism.

• Conversely, new infections with HPV that occurred after the diagnosis of autoimmune hyperthyroidism did not show any statistically significant difference between the TED and control groups.

• Moreover, there was no relationship between high-risk HPV and TED, irrespective of the time of infection, indicating a particular association between low-risk HPV and the development of the disease.

• Secondary analysis was also conducted to determine the severity of the disease in 201 patients with TED and proven low-risk HPV infection, compared to patients with TED and no HPV infection.

• Of these patients, those with past HPV infection had a greater rate of orbital decompression surgery, which occurred in 13.4% compared to 5.5% in patients with TED and no HPV infection.

• There were no differences in the use of corticosteroids, vision loss, eyelid retraction, and strabismus between the two groups.

The study shows that patients with thyroid eye disease have a significantly higher prevalence of previous low-risk HPV infection, especially in cases of infection preceding the development of autoimmune hyperthyroidism. These results are in support of the hypothesis that viral molecular mimicry may play a role in the pathogenesis of TED.

Reference:

Weber MI, Karanfilian T, Gupta L, Barmettler A. Thyroid Eye Disease and the Prevalence of Human Papillomavirus. JAMA Ophthalmol. Published online February 12, 2026. doi:10.1001/jamaophthalmol.2025.6244