Malignancy Risk after Ophthalmic Herpes Infection within a Diverse United States Cohort

We evaluated the risk of malignancy following herpes zoster ophthalmicus (HZO) and ophthalmic herpes simplex virus (HSV) in a large, diverse United States cohort.

Matched, retrospective cohort study.

Adults enrolled in the National Institutes of Health All of Us Research Program.

Participants with incident diagnoses of HZO or ophthalmic HSV were propensity score-matched (1:3) to controls based on sociodemographic characteristics and preexisting immune dysregulation (i.e., autoimmune disease or immunodeficient states).

Stratified Cox proportional hazards models were applied to estimate relative hazards of incident malignancy within 1-, 2-, and 3-year intervals and over the entire follow-up period. Effect modification was investigated based on age, sex, and baseline immune dysregulation.

The HZO cohort comprised 327 patients matched to 981 control participants (mean follow-up, 7.48 ± 5.33 years), and the ophthalmic HSV cohort included 292 patients matched to 876 control participants (mean follow-up, 8.66 ± 5.89 years). Incident malignancy risk did not differ between patients with HZO and matched control participants within 1 year or less (P = 1.00), 2 years or less (P = 0.36), 3 years or less (P = 0.27), or across the full follow-up period (hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.76-1.36; P = 0.93). However, significant effect modification by immune dysregulation was observed, with HZO associated with an increased risk of malignancy among participants with autoimmune disease (HR, 2.91; 95% CI, 1.48-5.74; P < 0.01) or immunodeficient status (HR, 5.75; 95% CI, 2.16-15.35; P < 0.01). For ophthalmic HSV, no increased malignancy risk was observed within 1 year or less (P = 0.86), 2 years or less (P = 0.18), 3 years or less (P = 0.10), or across the full follow-up period (HR, 0.97; 95% CI, 0.72-1.32; P = 0.87), with no evidence of effect modification.

Ophthalmic herpes infections were not associated with an increased risk of malignancy in the overall cohort. However, HZO was associated with a higher subsequent risk of cancer among individuals with preexisting immune dysregulation, potentially warranting heightened oncologic vigilance in this patient demographic.

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