Gynecological Cancers and Microbiota Dynamics: Insights into Pathogenesis and Therapy

Abstract

In recent years, the relationship between the microbiota and various aspects of health has become a focal point of scientific investigation. Although the most studied microbiota concern the gastrointestinal tract, recently, the interest has also been extended to other body districts. Female genital tract dysbiosis and its possible impact on pathologies such as endometriosis, polycystic ovary syndrome (PCOS), pelvic inflammatory disease (PID), and gynecological cancers have been unveiled. The incursion of pathogenic microbes alters the ecological equilibrium of the vagina, triggering inflammation and compromising immune defense, potentially fostering an environment conducive to cancer development. The most common types of gynecological cancer include cervical, endometrial, and ovarian cancer, which occur in women of any age but especially in postmenopausal women. Several studies highlighted that a low presence of lactobacilli at the vaginal level, and consequently, in related areas (such as the endometrium and ovary), correlates with a higher risk of gynecological pathology and likely contributes to increased incidence and worse prognosis of gynecological cancers. The complex interplay between microbial communities and the development, progression, and treatment of gynecologic malignancies is a burgeoning field not yet fully understood. The intricate crosstalk between the gut microbiota and systemic inflammation introduces a new dimension to our understanding of gynecologic cancers. The objective of this review is to focus attention on the association between vaginal microbiota and gynecological malignancies and provide detailed knowledge for future diagnostic and therapeutic strategies.

Keywords: cervical cancer; endometrial cancer; estrobolome; gynecological cancer; microbiota; ovarian cancer.

Figure 1

CST I, CST II, and CST V, respectively dominated by L.crispatus, L. gasseri, and L. jensenii, are associated with a rapid clearance of an acute HPV infection. Conversely, in bacterial vaginosis, it assists the depletion of Lactobacillus spp., and CST IV and CST III dominance promoting proinflammatory environment, uncontrolled transcription of E6 and E7, genomic instability, viral integration, and telomerase activation, which are crucial for carcinogenesis processes.

Figure 2

Enteric bacterial genes (estrobolome) produce beta-glucuronidase, an enzyme that deconjugates estrogens in their active form, making them available and free to bind to estrogen receptors and, therefore, able to influence estrogen-dependent processes. An alteration in the estrobolome (dysbiosis) and its regulatory functions leads to an imbalance of various biological processes and an estrogen increase, contributing to the early stages of endometrial cancer.

Figure 3

Women with BRCA1 or BRCA2 genes mutation carriers express increased concentrations of progesterone compared to women with BRCA gene wild type, which reduces vaginal glycogen concentrations, resulting in an environment that is less favorable to the growth of Lactobacilli. High estrogen levels in BRCA wild type release glycogen from vaginal epithelial cells that is cleaved by the vaginal α-amylase enzyme into maltose, maltotriose, and α-dextrins, producing lactic acid through fermentation. Lactic acid keeps the vaginal pH around 4.5, inhibiting pathogen invasion and growth.