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.