Human Papillomavirus May Trigger onset and progression of thyroid eye disease, reports research
A recent study from Bascom Palmer Eye Institute uncovered potential molecular evidence linking human papillomavirus (HPV) to thyroid eye disease (TED). These findings published in the Journal of American Medical Ophthalmology suggest that viral infections, particularly HPV18, may play a previously unrecognized role in the onset and progression of TED through a process called molecular mimicry.
TED is characterized by inflammation and tissue remodeling around the eyes, often leading to bulging eyes, double vision, and in severe cases, vision loss. While the condition is already associated with autoimmune responses against thyroid-stimulating hormone receptor (TSHR) and insulin-like growth factor-1 receptor (IGF-1R), its exact cause has remained elusive.
This study utilized the National Center for Biotechnology Information's BLAST tool to compare protein sequences from TSHR and IGF-1R with those of various viruses. The analysis revealed significant amino acid sequence homologies between these receptors and the L1 capsid protein of HPV18, a high-risk strain of the virus known primarily for its role in cervical cancer.
Also, conserved motifs labeled FGXV and IXEXT+NP were consistently found across HPV serotypes and within both TSHR and IGF-1R proteins. These matching sequences suggest that an immune response originally targeting HPV may cross-react with human proteins involved in TED, inadvertently triggering autoimmunity.
To test this theory in living tissue, the researchers collected orbital fat samples from 11 patients undergoing surgery for TED and compared them with samples from 11 control patients undergoing cosmetic eyelid procedures. Enzyme-linked immunosorbent assays (ELISAs) were used to quantify antibodies against the HPV18 L1 protein.
The data revealed striking differences. Mean optical density (a measure of antibody concentration) in controls was 0.94. In patients with chronic TED, levels were significantly higher, with a mean increase of 1.37 (95% CI: −2.64 to −0.09; P = .03). Even more notably, patients with acute active TED showed a dramatic increase, with a mean difference of 3.15 when compared to controls (95% CI: −4.69 to −1.61; P < .001). Comparing chronic and acute TED cases also showed a significant differential of 1.78 (P = .03).
Most participants were female (86.4%) with a mean age of 58.6 years, reflecting TED’s typical demographic pattern. Overall, this study is the first to demonstrate a potential viral mimicry mechanism involving HPV and TED, and this opens new research directions in both disease prevention and therapeutic targeting.
Source:
Garg, I., Meyer, B. I., Gallo, R. A., Wester, S. T., & Pelaez, D. (2025). Human Papillomavirus and thyroid eye disease. JAMA Ophthalmology. https://doi.org/10.1001/jamaophthalmol.2025.0847
