TOPLINE:

Herpes infections of the eye — including herpes zoster ophthalmicus and ophthalmic herpes simplex virus infection — were not linked to a higher risk for cancer generally; however, herpes zoster ophthalmicus was associated with a markedly increased risk for malignancy among people with preexisting immune dysregulation, such as autoimmune disease or immunodeficiency.

METHODOLOGY:

• Researchers conducted a retrospective cohort study using electronic health record data from a large, diverse US cohort to evaluate the risk for malignancy after a diagnosis of herpes zoster ophthalmicus or ophthalmic herpes simplex virus infection.
• They analyzed data of 327 patients with herpes zoster ophthalmicus (mean age at diagnosis, 54.9 years; 65.1% women) matched to 981 control individuals and 292 patients with ophthalmic herpes simplex virus infection (mean age at diagnosis, 51.7 years; 61% women) matched to 876 control individuals; anyone with a diagnosis of cancer before or at the time of the herpes infection was excluded.
• Each participant’s medical history before the diagnosis of herpes infection was recorded, capturing autoimmune disorders, immunodeficiency conditions (such as HIV infection or prior transplant), and any use of systemic immunosuppressants in the preceding 12 months.
• The primary outcome was the first recorded malignancy after the diagnosis of herpes infection, evaluated within 1, 2, and 3 years and across the entire follow-up period (mean follow-up, 7.48 years for the herpes zoster cohort and 8.66 years for the herpes simplex cohort).
• The analysis also tested whether results varied by age less than 60 years vs age 60 or more, sex, or baseline immune dysregulation — defined as the presence of autoimmune disease or immunodeficiency.

TAKEAWAY:

• Among participants with herpes zoster ophthalmicus, no increased risk for malignancy was observed in the overall cohort across the full follow-up period; however, the risk was higher in those with autoimmune disease (hazard ratio [HR], 2.91), immunodeficient status (HR, 5.75), or any immune dysregulation (HR, 3.14; P < .01 for all).
• For ophthalmic herpes simplex virus infection, no increased risk for malignancy was observed across the full follow-up period, and there was no evidence that sex, age, or immune dysregulation modified the association.

IN PRACTICE:

“The development of HZO [herpes zoster ophthalmicus] in patients with preexisting immune dysregulation might warrant special consideration and heightened oncologic vigilance,” the researchers reported.

SOURCE:

The study was led by Andrew Mihalache, MD(C), of the Temerty School of Medicine at the University of Toronto in Toronto, Ontario, Canada. It was published online on April 9, 2026, in Ophthalmology.

LIMITATIONS:

The number of participants with ophthalmic herpes diagnoses was in the hundreds, which limited statistical power for nuanced subgroup analyses. Granular clinical data regarding disease severity among individuals with herpes zoster ophthalmicus or ophthalmic herpes simplex virus were not available. Whether the risk for malignancy differed between patients receiving biologic agents and those receiving conventional immunosuppressive therapies was unknown. 

DISCLOSURES:

The research received no specific grant from any funding agency. Some authors disclosed serving as consultant and/or receiving honoraria, financial support, and lecture fees from various organizations.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.