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Microbes & Immunity Correlation between VZV and cancer

reported a positive significant RR of 1.27 (95% CI: 1.05 – the time the individual developed HZ. In this context, the
1.53) in colorectal cancer development after HZ diagnosis. occurrence of HZ may serve as a clinical manifestation of
Cotton et al. also reported a significantly positive HR of tumor-associated immunodeficiency, where the immune
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1.87 27 (95% CI: 1.45 – 2.40) in colorectal cancer but no system is weakened by the presence of the tumor, facilitating
association in stomach cancer with an HR of 1.04 27 (95% the reactivation of VZV. Sim et al. provides an
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CI: 0.40 – 2.72). Interestingly, Sim et al. reported a explanation to their findings when noting an inconsistency
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decreased risk of GI cancers in HZ patients without PHN, with previous publications after determining a lower risk
with a hazard ratio (HR) of 0.86 (95% CI: 0.81 – 0.91). of cancers in the oropharynx, GI, and respiratory systems
However, an increased risk of GI cancer diagnosis was in a South Korean population-based matched control
evident in PHN patients, with an HR of 1.33 (95% CI: study. They claimed that their inconsistent results could be
1.20 – 1.47), compared to non-PHN patients. Contrary to attributed to controls matching by age, gender, and health
the positive associations found in the previous studies, a status, or to a trend specific to the Korean population.
large retrospective cohort study by Leyh et al. analyzed Preferential incidence of cancers caused by Herpesviridae
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data from over 200,000 outpatients in Germany and found family viruses would not be unique to VZV as EBV has
no significant association between HZ infection and the also shown significantly higher rates of nasopharyngeal
subsequent development of GI cancer. The study included cancer in Asian and Pacific islander populations. Choi
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103,123 patients with a first diagnosis of HZ and a matched et al. offer another explanation for conflicting results
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cohort of 103,123 patients without HZ. Over a follow-up determined by Liu et al. and Wang et al. in lymphoid
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period of up to 10 years, the incidence of GI cancer did neoplasms, stating that the conflicting data may be due
not differ significantly between the two cohorts (HZ to differences in ethnicity (Han vs. Korean) or variations
cohort: 2.26 cases/1000 patient-years vs. non-HZ cohort: in study methods, such as differing criteria for subject
2.37 cases/1000 patient-years, p=0.548). The hazard ratio inclusion. These studies often point to the complexities
(HR) for developing GI cancer in the HZ cohort was of cancer etiology, where multiple factors – genetic,
0.97 (95% CI: 0.89 – 1.05). Further, population-based environmental, and viral – may influence disease onset.
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studies and meta-analysis publications investigating While VZV’s role in cancer remains a topic of debate,
associations between HZ infection with GI cancer these findings underscore the need for further research to
diagnosis also refute any significant associations. 102,107 clarify whether VZV has any direct or indirect influence
on cancer risk. 9
6. Studies in cancers potentially associated
with VZV 7. Conclusion
While several studies have explored the potential link In recent years, there has been growing evidence linking
between VZV and cancer, not all research has found a VZV infection, particularly in individuals with a history
clear association. Some studies have failed to establish of HZ, to certain types of cancers, such as hematologic,
any significant connection between VZV infection or pulmonary, and GI cancers. Studies have consistently
reactivation and cancer diagnosis, suggesting that the shown higher cancer incidence rates in patients diagnosed
virus may not play a major role in tumor development. with VZV-related conditions and the risk of cancer seems
Meanwhile, studies that determine a clear association of to be highest in the 1 year after HZ infection, with the
st
VZV with some cancers fail to replicate the association risk decreasing in the following months which may be
with cancers as shown in different papers. For example, through its modulation of immune checkpoint proteins,
Chiu et al. offer suggestions for the discrepancy detected cell-surface proteins, chemokines, apoptotic enzymes, and
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in their results to four other studies, stating that the lack cell cycle regulatory enzymes. This raises the question of
of statistically significant associations may suggest either whether VZV infection triggers the manifestation of a
insufficient statistical power or a weak or non-existent pre-existing, subclinical malignancy, or wheher VZV’s
relationship when comparing results to populations of impact on the immune system enables opportunistic
men and women in the other papers. Leyh et al. concurs cancer development. While some even suggest enhancing
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with this hypothesis of insufficient statistical power when post-HZ infection cancer detection efforts, which others
their comparison yielded no association of HZ infection never attempted. 113,117,118 Nonetheless, despite numerous
with subsequent GI cancer as determined in another study studies suggesting a link between certain cancers and VZV
that suggests a statistically significant increase in cancer infection, many others contradict these findings, and the
rates after HZ infection. It is plausible to speculate that a results remain conflicting, with no consensus having been
cancer diagnosis made shortly after the onset of HZ could reached. Further investigation into how VZV interacts with
suggest the existence of an undiagnosed, latent tumor at cellular pathways, particularly those related to apoptosis

Volume 2 Issue 3 (2025) 24 doi: 10.36922/mi.8320