Cancer and Herpes Zoster Risk: New Data

Common recognized risk factors for herpes zoster (HZ)¾the reactivation of latent varicella zoster virus (VZV)¾are increased age, immunosuppression, or elements that affect VZV-specific or general cell-mediated immunity. Studies have shown that cancer is associated with increased risk for HZ, with hematological cancers having the strongest relationship. This bond between cancer and HZ may result from immune system dysfunction caused by either the cancer itself and/or by chemotherapy and other cancer treatments. Unfortunately, few studies have examined this question in greater detail.¹

Typically, clinical guidelines recommend antiviral treatment to prevent HZ reactivation in patients with cancer who receive chemotherapy. Recent positive reports on the efficacy and safety of a new non-live VZV vaccine in immunocompromised patients has increased the need to further mine the factors that contribute to the formation of HZ infection in cancer patients, to identify strategies for targeted prevention. To this end, Qian and colleagues prospectively examined data from a large cohort of 241,497 Australian adults (mean age, 62 y; 54.5% female) from the 45 and Up Study, which has accumulated a wealth of sociodemographic, lifestyle, and health-related information.¹ 

Cancer indicates a higher risk of herpes zoster

Participants in the analysis had a record of antiviral medication for HZ or an in-hospital diagnosis of HZ. Diagnosis of cancer was determined by hospital records; all cancers were included except nonmelanoma skin cancer. Cancer treatments included in the analysis were chemotherapy (including cytotoxic chemotherapy and anti-neoplastic agents) and radiotherapy.

Participants were excluded if they were younger than 45 at baseline or had a record of a zoster or cancer diagnosis prior to being recruited for the study. Overall, participants had more than 8 years of follow-up (for a total of more than 1.7 million person-years).

Qian and colleagues determined that participants with a cancer diagnosis had roughly a 40% higher risk for HZ than those without a cancer diagnosis. Those with hematological or solid tumor cancers had a significantly higher risk of zoster (adjusted hazard ratio [aHR] 3.74, 95% confidence interval [CI] 3.11 to 4.51) than those without a cancer diagnosis (aHR 1.30, 95% CI 1.21 to 1.40). Zoster relative risk was also significantly greater for hematological cancers versus solid organ cancers, a risk that was higher during the first year after diagnosis for both types of cancer. The risk of HZ at 3 years post-diagnosis in participants with solid tumor cancers was similar to the risk in those without cancer; conversely, those with hematological cancers maintained a high risk for up to 3 years post-diagnosis.

When compared against participants without cancer, patients with solid tumor cancers who received chemotherapy had a higher risk of HZ than their counterparts who didn’t receive chemotherapy. And, participants with solid organ cancers who received chemotherapy alone showed a relative risk of zoster similar to that for their counterparts who received both radiotherapy and chemotherapy (aHR 1.84 versus 1.81, respectively). The risk of zoster was statistically significant for solid organ cancer patients treated with radiotherapy alone (aHR 1.38, 95% CI 1.17 to 1.63), but not significant for those with no record of having received chemotherapy or radiotherapy (aHR 1.10, 95% CI .99 to 1.21).

Incidence of herpes zoster by cancer diagnosis and treatment*

*Adjusted for age, sex, and other factors.

PY, person years

A strong study, but with limitations

The authors stated that their findings were consistent with other reports of increased risk of HZ related to cancer diagnosis and treatment. They cited a large U.K. study (N >190,000), which reported that, for most cancers, the risk of HZ decreased as time after diagnosis increased. Unfortunately, this study didn’t include information on cancer treatment. Additionally, previous studies of HZ risk focused on cancer patients who had received hematopoietic stem cell transplant (HSCT) or specific chemotherapy agents. The HZ events that did occur in these studies were reported for patients with hematological cancer only, leaving no room for comparisons with solid organ cancer or with the general cancer-free population.

The current study’s lead author, Jiahui Qian, MPH, of the School of Public Health and Community Medicine, University of New South Wales, in Sydney, Australia, summarized for MedPage Today the primary findings of this analysis: “The main finding of our study is that risk of zoster for those with hematological cancer is likely to be attributable to the hematological cancer itself, while that for those with solid organ cancer is likely to be associated with cancer treatment. In the year after a cancer diagnosis, we estimated the incidence of zoster associated with chemotherapy to be 3.4% [34/1000 PY] in participants with hematological cancer and 1.7% [17/1000 PY] in those with solid organ cancer. Therefore, zoster prevention strategies should be considered for cancer patients, especially for those expected to receive chemotherapy.”

The main limitations of the study included a lack of information regarding the stage of cancer, but the authors stated that an earlier study had shown no significant difference in HZ risk among patients with local, regional, or distal cancer spread. There was also the possibility that some people who had no record of chemotherapy or radiotherapy may have actually received these treatments, as evidenced by the low proportion of participants with hematological cancer who had a record of chemotherapy. However, the inclusion of people without cancer makes it unlikely that patients with solid organ cancer receiving chemotherapy would be affected by this misclassification. The authors admitted, too, that they may not have captured all HZ cases, especially milder ones.

The new data have key implications

In an editorial commentary on the Qian study, clinical researchers Kosuke Kawai, ScD, and Barbara P. Yawn, MD, MSc, stated that the study corroborates previous database analyses from the U.S. and U.K., and has “important implications” because of advances in zoster vaccines that report positive efficacy and safety results in various patient groups (HSCT, HZ, and postherpetic neuralgia, to name a few).²

According to the commentary, the safety and efficacy of inactivated VZV in hematologic and solid tumor cancers is being investigated, and the U.S. Food and Drug Administration has recently approved a HZ subunit adjuvanted vaccine (HZ/su) that shows great promise in treating severely immunocompromised individuals. HZ/su vaccine reportedly reduced the risk of HZ in patients who underwent HSCT and in those with hematological cancers by 68% and 87%, respectively. Qian reaffirmed that the Australian team’s findings provide support for prevention strategies that “could include the use of prophylactic antivirals or include new zoster vaccines suitable for immunocompromised people. However, further research assessing the relative benefit of such prevention strategies is needed.”

Published: January 28, 2019