Herpes Zoster as a Marker of Occult Malignancy in Older Adults: A Real‐World Cohort Study

ABSTRACT

This study aimed to evaluate whether herpes zoster (HZ) is associated with an increased short‐term probability of newly diagnosed cancer in older adults, and to determine whether HZ may serve as an early clinical marker of occult cancer. We conducted a retrospective cohort study using de‐identified electronic health record data from the TriNetX Research Network (2006–2024). Adults aged 65–84 years with newly diagnosed HZ were compared with matched controls without HZ. Propensity score matching (1:1) was performed based on demographics and comorbidities. A 1‐month lag period was applied to minimize detection bias. The primary outcome was any newly diagnosed cancer. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models within the TriNetX platform. After propensity score matching and applying a 1‐month lag period, 182,104 adults in the HZ group and 182,463 controls were included. During the 1‐year follow‐up, 4527 adults with HZ and 667 controls developed cancer, corresponding to cumulative incidences of 2.49% and 0.37%, respectively. HZ was associated with a higher probability of cancer diagnosis (HR 5.81; 95% CI, 5.35–6.30). In adults aged 65–84 years, HZ is associated with a higher likelihood of a new diagnosis of cancer within 1 year. These findings suggest that HZ may serve as a clinical marker of occult cancer. Further research is warranted to clarify underlying mechanisms and to evaluate whether targeted cancer surveillance following HZ could improve early cancer detection.