Page 45 - JCTR-11-5

Journal of Clinical and
Translational Research Vaginal microbiota in menopause pathologies

offer the potential to enhance therapeutic efficacy and contributes to HPV persistence. This microbial imbalance
improve patients’ quality of life by restoring microbial fosters an inflammatory milieu that supports viral
equilibrium. Research in this field is crucial as it could transformation, including the upregulation of oncogenic
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open new opportunities for the prevention and treatment proteins like E6 and E7, promotion of genomic instability,
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of these cancers, improving clinical outcomes and the and activation of telomerase—processes central to
quality of life for affected patients. 56 cervical carcinogenesis. In addition, women whose VM is
predominantly composed of L. iners have demonstrated
10.1. VM and cervical cancer: Role of HPV increased concentrations of inflammatory cytokines such

Cervical cancer remains one of the leading malignant as TNF-α, IL-1α, interferon gamma, and IL-8, further
tumors affecting women and ranks fourth in global illustrating the link between dysbiosis and heightened
incidence, with around 342,000 deaths recorded in 2020. susceptibility to cervical abnormalities. 69
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More than 95% of cases are attributed to persistent infection C. trachomatis infection has also been implicated
with HPV. Although cervical cancer affects women in enhancing HPV persistence and its progression to
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worldwide, disparities exist between racial and ethnic precancerous changes by disrupting epithelial integrity,
groups. For instance, Hispanic women in the United States increasing basal cell exposure to HPV, and triggering
face a 60% higher likelihood of being diagnosed and a 30% anti-apoptotic pathways that support ongoing infection. 70
greater mortality rate than non-Hispanic white women. Supporting this evidence, recent studies underscore the
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Oncogenic strains such as HPV-16 and HPV-18 are the role of VM in cervical pathology. BV, characterized by
primary contributors to cervical cancer development. 26,56 a depletion of Lactobacillus species and an overgrowth
The cervical transformation zone, where squamous and of anaerobic bacteria, has been linked to increased
columnar cells meet, is particularly vulnerable to HPV susceptibility to HPV infection and reduced viral
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and is the origin site for most cervical malignancies. clearance. A greater diversity of non-Lactobacillus bacteria
While many infections are cleared by the immune system, has been associated with persistent HPV infection and
approximately 10–15% persist and may evolve into cervical progression toward high-grade cervical intraepithelial
intraepithelial neoplasia or invasive cervical cancer. neoplasia. Cross-sectional analyses indicate that HPV-
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Several cofactors, including multiple births, tobacco use, positive women without dysplasia tend to exhibit a more
hormonal contraceptive use, and coinfections with other heterogeneous VM, with higher prevalence of BV-related
sexually transmitted pathogens, increase the risk of disease bacteria such as Gardnerella, Sneathia, Megasphaera,
progression. 56 Dialister, and Atopobium compared to HPV-negative
Recent investigations have emphasized the significant women. 72,73 Furthermore, longitudinal data suggest that
role of the VM in influencing the persistence of HPV L. gasseri may facilitate viral clearance, whereas Atopobium
infections and the development of cervical cancer. This species are more frequently associated with sustained HPV
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association appears especially relevant among Hispanic infection. A decrease in Lactobacillus abundance and
women, who often present with reduced Lactobacillus increased microbial diversity have also been associated
dominance and increased vaginal pH—factors that with elevated vaginal pH, a condition linked to more
may partly explain the higher incidence and mortality severe cervical lesions. 73
from cervical cancer observed in this population. A Taken together, these findings highlight the key role
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meta-analysis based on longitudinal data supports the of the VM in HPV persistence and cervical oncogenesis.
hypothesis that a vaginal microbial environment with high An imbalanced microbiota, particularly when dominated
diversity and lacking Lactobacillus predominance favors by L. iners and BV-associated anaerobes, promotes a
the acquisition and persistence of HPV, as well as the proinflammatory state that supports viral persistence and
development of precancerous cervical lesions. Specifically, transformation. Understanding these microbial dynamics
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women whose microbiota is primarily composed of L. iners is essential for advancing both prevention and therapeutic
show a greater tendency toward persistent infection by strategies targeting cervical cancer.
high-risk HPV types and progression to malignancy
compared to those dominated by L. crispatus. This may 10.2. VM and endometrial cancer
be due to the diminished protective function of L. iners, Endometrial cancer predominantly affects women after
including its weaker ability to suppress harmful microbes menopause, especially those in their 60s and 70s. It ranks
and lower lactic acid production, which contributes to as the leading gynecological malignancy in developed
a microenvironment conducive to HPV survival and nations and is particularly common among women in the
cervical neoplastic changes. Disruption of the vaginal United States. Although genetic and hereditary mutations
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microbial balance, known as vaginal dysbiosis, significantly account for only 10–20% of cases, sociodemographic

Volume 11 Issue 5 (2025) 39 doi: 10.36922/JCTR025150016