Topic:We evaluated the malignancy risk following herpes zoster ophthalmicus (HZO) and ophthalmic herpes simplex virus (HSV) in a large, diverse U.S. cohort.Clinical Relevance: There has been a longstanding contention as to whether HZO serves as a clinical marker of cancer risk, with discordant findings observed across epidemiologic studies worldwide.In contrast, the relationship between ophthalmic HSV infection and malignancy remains unknown.Methods: This matched, retrospective cohort study analyzed electronic health record data from 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 pre-existing 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. Results:The HZO cohort comprised 327 cases matched to 981 controls (mean follow-up=7.48 5.33 years), and the ophthalmic HSV cohort included 292 cases matched to 876 controls (mean follow-up=8.66 5.89 years).For HZO, incident malignancy risk did not differ from controls within 1 year (p=1.00),2 years (p=0.36),3 years (p=0.27),or across the full follow-up period (HR=1.01,95% 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 J o u r n a l P r e -p r o o f increased malignancy risk was observed within 1 year (p=0.86),2 years (p=0.18),3 years (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:In this large, diverse U.S. cohort, 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, thus refining the interpretation of a longstanding epidemiologic debate.
Mihalache et al. (Wed,) studied this question.