Elsevier

Journal of Infection

Volume 74, Issue 3, March 2017, Pages 215-235
Journal of Infection

Review
Herpes zoster as a marker of occult cancer: A systematic review and meta-analysis

https://doi.org/10.1016/j.jinf.2016.11.005Get rights and content

Highlights

  • This systematic review shows that herpes zoster may be a marker of occult cancer.

  • The highest relative risk was found for hematological cancer.

  • The clinical implications are, however, limited by the low absolute risk of cancer.

  • There are no studies on the effectiveness of cancer work-up in persons with zoster.

Summary

Objectives

Researchers have advocated for an increased awareness of occult cancer among herpes zoster patients, but there are no systematic reviews to support these claims. We therefore conducted a systematic review and meta-analysis of evidence on zoster and risk of occult cancer.

Methods

Through February 18, 2016, we searched PubMed, EMBASE and references of relevant papers for studies on zoster and risk of any cancer. One author screened retrieved papers by title and abstract; included papers were reviewed by two authors for eligibility, data extraction, and potential biases. Despite statistical heterogeneity, associations were consistently in the same direction and we therefore computed pooled relative risks using random-effects models.

Results

We identified 46 eligible studies, 10 of which considered all cancer types combined. The pooled relative risk for any cancer was 1.42 (95% confidence interval: 1.18, 1.71) overall and 1.83 (95% confidence interval: 1.17, 2.87) at one year after zoster. Considering cancer subtypes, the highest estimates were generally reported for occult hematological cancer. The absolute risk of any cancer at one year after presentation with zoster was 0.7–1.8%.

Conclusion

This study supports an association between zoster and occult cancer, but the low absolute risk of cancer limits the clinical implications.

Introduction

Herpes zoster is characterized by a unilateral vesicular rash that is accompanied by severe neuralgia.1, 2 It is caused by reactivation of the varicella-zoster virus, which lies dormant in the sensory ganglia following the primary infection, chickenpox.1, 2 The risk of reactivation increases with age and it is estimated that up to 50% of people who live up to 85 years will develop herpes zoster.1

Several large population-based studies have suggested that patients with herpes zoster have an increased risk of occult cancer.3, 4, 5, 6, 7 These findings have instigated discussion of whether patients with herpes zoster should be examined for cancer in order to expedite diagnosis and ultimately improve prognosis.3, 4, 7, 8, 9 Although such discussions should rely on a sound evidence base, no systematic review exists of studies on the topic. In particular, the types of cancers that are most likely to be associated with reactivation of latent varicella-zoster virus are yet to be uncovered systematically.

The aim of this systematic review was to collate evidence on the association between herpes zoster and the risk of subsequent cancer diagnosis. Because the primary interest was occult cancer, the main focus was on cancer diagnosed in the first year following herpes zoster compared with persons without herpes zoster. As a secondary aim, we specifically examined which cancer types are most strongly associated with herpes zoster.

Section snippets

Search strategy and eligibility criteria

We conducted the study according to The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)10 and Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines11 (Web Methods 1 and 2). We formulated the study protocol (available from study authors upon request) in accordance with PRISMA for protocols,12, 13 with slight modifications to increase applicability to the non-interventional subject under consideration.

In collaboration with a trained librarian, we

Systematic literature search

The search identified 987 unique papers in PubMed and EMBASE (Fig. 1). We excluded 938 papers after scrutinizing titles and abstract, leaving 49 papers for full-text assessment. We additionally identified 17 papers from reference lists and 4 papers when updating the search. We excluded six ineligible studies,20, 21, 22, 23, 24, 25 two non-English studies that could not be retrieved in full-text,9, 26 and 16 studies with duplicate data.27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41,

Discussion

This systematic review shows that herpes zoster may be a marker of occult cancer. Evidence pertaining to subtypes of cancer suggests that a particularly strong association exists between herpes zoster and occult hematological cancer.

One narrative review published in 1995 has previously examined the association between herpes zoster and diagnosis of subsequent malignancy.25 Based on only two small primary publications from the present review,43, 46 authors of the review concluded that there was

Funding

This work was supported by a PhD fellowship from the Graduate School of Health, Aarhus University (awarded to SAJS).

Contributors' statement

SAJS conceived the study idea. All authors contributed to study concept and design. SAJS performed the literature search and initial screening. SAJS and AM performed eligibility screening and data extraction. SAJS carried out the data analysis. All authors participated in the discussion and interpretation of the results. SAJS wrote the initial manuscript draft. All authors critically revised the manuscript for intellectual content and approved the final version. SAJS is the guarantor.

Conflict of interest

The authors declare no conflict of interest. Department of Clinical Epidemiology is, however, involved in studies with funding from various companies as research grants to (and administered by) Aarhus University. None of these studies have relation to the present study. The study funder had no control over the planning, interpretation, writing, or publication of this work.

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