Study: HZO Only Associated with High Risk of Malignancy in Those with Autoimmune Disease

HZO was associated with a nearly threefold higher risk of cancer among individuals with preexisting immune dysregulation in this study. Photo: Alan Kabat, OD. Click image to enlarge. There has been a longstanding debate as to whether herpes zoster ophthalmicus (HZO) serves as a clinical marker of cancer risk, with differing findings observed across epidemiologic studies worldwide. In contrast, the relationship between ophthalmic herpes simplex virus (HSV) infection and malignancy remains unknown. In a recent study, researchers evaluated the malignancy risk following HZO and ophthalmic HSV and found that those with a preexisting condition or autoimmune disease were associated with a higher risk of malignancy. The findings were published last week in Ophthalmology.The HZO cohort comprised 327 cases matched to 981 controls and the ophthalmic HSV cohort included 292 cases matched to 876 controls. There was no increased risk of malignancy associated with either HZO or ophthalmic HSV. However, among participants with pre-existing immune dysregulation (autoimmune disease or immunodeficient status), HZO was associated with a higher subsequent risk of malignancy. Participants with autoimmune disease showed a hazard ratio (HR) of 2.91, while those with immunodeficient status showed an HR of 5.75.“These findings suggest that ophthalmic herpes infections—particularly those related to HSV—may not be reliable clinical indicators of elevated cancer risk in the general population, whereas the development of HZO in patients with pre-existing immune dysregulation might warrant special consideration and heightened oncologic vigilance,” the authors wrote in their paper. “Given that disruptions in host immunity can contribute both to herpes zoster reactivation and to carcinogenesis, the occurrence of HZO in the setting of immune dysregulation may reflect a clinical milieu in which subsequent malignancy is more likely than when HZO arises in immunocompetent individuals.”Even though HZO or ophthalmic HSV infection—in isolation—should not be construed as justification for an extensive work-up for occult malignancy beyond evidence-based, age-appropriate cancer screening recommendations, a comprehensive medical history and physical examination remain imperative in all cases, the researchers stressed in their paper. The authors explained that special consideration should be given to the possibility of an increased risk of cancer among individuals with significant immune dysregulation in the context of HZO, compared with other individuals with immune dysregulation but without HZO.“From a public health perspective, at-risk patients should be counseled on the well-established value of zoster vaccination, given its potential to mitigate shingles-related morbidity, such as postherpetic neuralgia and vision loss,” the team concluded in their paper. “Fostering multidisciplinary collaboration in the management of patients found to have occult malignancies in the setting of ophthalmic herpes infection is also crucial to ensure coordinated care and optimize outcomes.”Click here for the journal source. Mihalache A, Huang RS, Popovic MM, Chan CC. Malignancy risk following ophthalmic herpes infection within a diverse U.S. cohort. Ophthalmology. March 31, 2026. [Epub ahead of print]. This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.