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