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Microbes & Immunity Correlation between VZV and cancer

burden but also underscore the systemic impact of VZV 2. Epidemiology of VZV
beyond its primary manifestations.
VZV is highly contagious, primarily spreading through
Following primary infection, viral latency occurs respiratory droplets and direct contact with vesicular fluid
in neurons, where it resides until reactivation, either from skin lesions. The contagious period for varicella
13
spontaneously or due to an immunocompromised state starts 1 – 2 days before the rash appears and continues until
in the host. Although there are not typically any clinical all lesions have crusted over, usually 5 days after rash onset
3
symptoms that occur during the latency period, VZV may in immunocompetent individuals. VZV infection has
14
reactivate from ganglia in the entire neuraxis, causing been noted to follow a seasonal pattern, peaking during
a multitude of clinical pathology. The most common the winter and spring months, with many environmental
4
clinical manifestation of VZV reactivation is a pruritic factors influencing its transmission. These factors include
dermatomal rash; however, there are other infrequent and elements such as ultraviolet radiation, which can reduce
more serious complications that can occur if it is reactivated the rupture of vesicles. In addition, population density
15
in the cranial nerves or if cerebral vasculature is affected. increases contact rates, allowing for more infectivity. Both
5
At the molecular and cellular level, it is the interaction of of these factors taken together may explain why there is a
VZV’s genome with the host’s immune cells, which are of higher chance of VZV infection in temperate regions than
particular importance in the link between VZV infection in urban regions. 16
and cancer development. 6 The Centers for Disease Control and Prevention (CDC)

The link between chickenpox and VZV was first estimated that from 1980 to 1990, there were 4 million
described in 1888; however, conclusive evidence proving annual cases of varicella, with 77% of cases in children
this connection was not established until the 1950s. under 9 and over 90% in those under 15. Seroprevalence
7
Although chickenpox and HZ have been clinically data from 1988 to 1994 showed that the majority of adults
characterized from the 16 and 17 centuries, respectively, (95.5% of those aged 20 – 29, 98.9% of those aged 30 –
th
th
the pathophysiology involving viral latency, reactivation 39, and 99.6% of those 40 and older) were immune to
17
triggers, and the role of the immune response in controlling varicella. The varicella vaccination program, introduced
VZV remains poorly understood. This is partly because in the United States in 1996, has had a profound impact on
VZV is a human-specific virus, limiting the use of most the incidence and complications of varicella infections over
animal and animal-derived neuron models. 8 the past 25 years by significantly decreasing the number of
VZV infections per year and reducing complications due
Interestingly, emerging evidence suggests that VZV to infection. Varicella-related hospitalizations and deaths
18
may have oncogenic potential. Previous studies have have been reduced by 94% and 97%, respectively, among
investigated potential links between VZV infection and the those aged <50 years. Moreover, more than 91 million
development of certain neoplasms, such as glioblastomas cases of varicella, 238,000 hospitalizations, and close to
and other malignancies, though the mechanisms 2,000 deaths were prevented during the period between
underlying this association remain unclear. It is 1996 and 2020. 19
9
hypothesized that chronic inflammation, immune evasion
strategies, or viral genome integration may play a role in During primary infection, VZV enters sensory nerve
promoting tumorigenesis associated with VZV infection. endings and establishes latency in the dorsal root ganglion.
10
Others have suggested that cancer diagnosis could result This latency period can last from 5 to 40 years or even longer.
from immune system insufficiency, hypothesizing that a During this time, the virus resides in a non-replicative
weakened immune system may allow HZ to occur, which state within the neurons of the dorsal root ganglia, cranial
20
could serve as an early sign of hidden cancer. The virus nerve ganglia, and autonomic ganglia. Although VZV
may also reduce immune surveillance, enabling tumors to latency is highly prevalent, only approximately 10 – 30%
escape detection. However, other studies have strongly of individuals experience symptomatic reactivation.
11
This reactivation is known as HZ and presents as a
suggested that VZV infection is not associated with occult vesiculopapular rash along a single dermatome, which
malignancy. 12
classically does not cross the midline. Like primary VZV
21
This review evaluates the existing literature on the infection, HZ is typically a self-limiting condition and
association between VZV and various cancer types, usually resolves within 2 – 4 weeks. However, HZ is most
examining potential correlations with oncogenesis, associated with the development of PHN, which is defined
addressing discrepancies and inconsistencies in the as pain that persists for at least 90 days after the resolution
findings, and discussing the suggested mechanisms of the acute rash and can be debilitating, occurring in
responsible for VZV’s potential oncogenic effects. approximately 10 – 20% of HZ cases. 22,23 There are several

Volume 2 Issue 3 (2025) 16 doi: 10.36922/mi.8320