Year: 2026
Type: article
Study design: Observational Study
Abstract: PURPOSE: We evaluated the risk of malignancy following herpes zoster ophthalmicus (HZO) and ophthalmic herpes simplex virus (HSV) in a large, diverse United States cohort. DESIGN: Matched, retrospective cohort study. PARTICIPANTS: Adults enrolled in the National Institutes of Health All of Us Research Program. METHODS: 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). MAIN OUTCOME MEASURES: 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. RESULTS: 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. CONCLUSIONS: 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. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Source: Ophthalmology
Institutions: University of Toronto, St. Michael's Hospital
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,990
Awards: Illinois Precision Medicine Consortium , Healthy Americas: All of Us Research Program, Empowerment-focused Outreach, Education and Enrollment of Tennessee Older Adults in the All of Us Research Program through Community Efforts by FiftyForward, Research Matters: Creating Possibilities to Achieve Health and Wellness for All of Us Research Program, Precision Medicine Initiative Cohort Program Biobank, Communications Design and Development for NIH Precision Medicine Initiative Research Projects, New York City Consortium for Precision Medicine, Technology to Empower Changes in Health (TECH) Network Participant Technologies Center, University of Arizona-Banner Health All of Us Research Program , The New England Precision Medicine Consortium of the All of Us Research Program, All of Us Wisconsin , Data and Research Support Center , All of Us Pennsylvania, Trans-America Consortium of the Health Care Systems Research Network for the All of Us Research Program, Southern All of Us Network, SouthEast Enrollment Center (SEEC) , Adaptive Platform for Personalized Engagement, California Precision Medicine Research Program Consortium, Communication Implementation and Coordination for NIH Precision Medicine Initiative Research Projects, PRIDEnet for the All of Us Research Program
OpenAlex ID: W7152698698