Herpes Zoster Ophthalmicus Linked to Higher Cancer Risk in Immunocompromised Patients: Study

A new research published in the journal of Ophthalmology found eye herpes infections, including herpes zoster ophthalmicus (HZO) and ophthalmic herpes simplex, not to be associated with an increased overall cancer risk. However, these findings suggest that herpes zoster ophthalmicus show a significantly higher malignancy risk in individuals with underlying immune dysregulation, such as autoimmune disorders or immunodeficiency.

Herpes zoster ophthalmicus occurs when reactivated varicella-zoster virus affects the ophthalmic branch of the trigeminal nerve. This causes severe eye inflammation, pain, and vision complications. Ophthalmic HSV infections can similarly affect the cornea and surrounding ocular tissues, which leads to recurrent disease and visual impairment.

Studies have suggested possible links between shingles and malignancy, particularly in immunocompromised populations, but evidence specifically involving ophthalmic infections has remained limited. Thus, this research identified adults diagnosed with either HZO or ophthalmic HSV and matched them with control participants using propensity scoring to account for demographic factors and baseline immune-related conditions like autoimmune disease or immunodeficiency.

This study analyzed data from the National Institutes of Health’s “All of Us” Research Program, to determine whether eye-related herpes infections might signal underlying immune dysfunction associated with future malignancy risk. The HZO cohort included 327 patients matched to 981 controls, while the ophthalmic HSV cohort included 292 patients matched to 876 controls.

These participants were followed for an average of approximately 7 to 9 years. The primary analysis showed no significant increase in cancer risk among patients with either HZO or ophthalmic HSV during one-year, two-year, three-year, or total follow-up periods. For HZO, the overall hazard ratio for malignancy was 1.01, which indicated essentially no difference when compared to controls. Similarly, ophthalmic HSV showed no statistically significant association with future cancer risk.

However, subgroup analysis revealed that the patients with HZO who also had autoimmune disease experienced nearly a 3-fold increase in malignancy risk when compared to matched controls. The risk was even higher among immunodeficient individuals, who showed more than a 5-fold increase in cancer risk following HZO diagnosis.

HZO in immunocompromised individuals may act as a clinical marker of deeper immune dysfunction rather than directly causing cancer itself. Reactivation of varicella-zoster virus is already known to occur more frequently in patients with impaired cellular immunity, including those with cancer or receiving immunosuppressive therapies. Overall, the findings may have practical implications to manage patients with autoimmune diseases or immunodeficiency disorders who develop HZO. 

Reference:

Mihalache, A., Huang, R. S., Popovic, M. M., & Chan, C. C. (2026). Malignancy risk after ophthalmic herpes infection within a diverse United States cohort. Ophthalmology. https://doi.org/10.1016/j.ophtha.2026.03.029