Clinical and Public Health Microbiology

Is There a Link Between Vaginal Microbiome and Gynecological Cancer?

Until recently, researchers studying human microbiomes have primarily concentrated on how microbiomes change to produce, or as a result of, disease; now, the way our indigenous microflora maintains our health is getting increasing attention.  A quintessential example of how finely tuned these relationships can be is the microbiome of the human vagina.

We already know that a well-balanced vaginal microbiome is essential to preventing vaginal infections, especially yeast infections; but there is recent evidence that the vaginal microbiome may play a role in the development of malignant changes in the cervix and other parts of the genital tract as well.

Examining the link between the vaginal microbiome and gynecological malignancies is an ever-evolving and compelling field of research.  The general hypothesis is that vaginal bacteria play a major role in the tumor microenvironment.  For instance, the evidence that there is a link between the vaginal microbiome and cervical cancer caused by the human papillomavirus (HPV) is mounting.  Women with HPV have more bacterial diversity in their vaginal microbiome (most notably higher levels of Gardnerella vaginalis and Lactobacillus gasseri), and lower levels of Lactobacillus.

New studies have also demonstrated that specific vaginal microbiome signatures are characteristic for either the presence or absence of HPV and the severity of the associated cervical neoplasias, while vaginal infections caused by the sexually-transmitted pathogen Chlamydia trachomatis seem to predispose women to develop HPV infections simply by altering the vaginal microbiome.  The ability to fight off HPV is also influenced by vaginal microbiome composition, especially the presence of the bacterium  Atopobium, which was repeatedly linked to low HPV clearance.

Although the vaginal microbiome may influence cervical carcinogenesis, a plethora of other factors have to be taken into account, including the type and pathogenicity of the strain of HPV involved, sexual behavior, and the immunocompetence of the host.

Disruption of the vaginal microbiome may also influence the development of endometrial and ovarian cancer.  Recent research has shown that the ovaries, fallopian tubes, and uterus each have distinctive microbial profiles, and variations in these profiles may be linked to certain malignant states.  Endometrial cancer was linked to the presence of Porphyromonas and Atopobium bacteria, but this type of malignancy may also be influenced by the vaginal microbiome changes associated with pelvic inflammatory disease.

The burgeoning recognition of the crucial role the vaginal microbiome plays in carcinogenesis prompts scientists to think about ways to restore or maintain a healthy ratio of resident microbial species in the vagina.  One of the main tools for maintaining a healthy microbial balance in the gut are probiotics: dietary supplements that contain live, beneficial bacteria.  Would such a formulation be possible for the vagina as well?  Could we improve gynecological cancer outcomes by treating patients with probiotics?

The role of the vaginal microbiome in the etiology of other gynecological cancers is still purely speculative.  An emerging theory is that chronic exposure to the vaginal microbiome affects the delicate balance of local inflammatory and inhibitory mediators, with malignant consequences for susceptible cells (primarily those of the tubal fimbria and ovaries). This is corroborated by the fact that hysterectomy with tubal ligation and conservation of the ovaries reduces the risk of tubal and ovarian carcinogenesis.

The putative role of the vaginal microbiome in endometrial carcinogenesis is based on a single retrospective study that revealed a modest increase of risk in women with prior pelvic inflammatory disease.  Unfortunately, all the potential confounders (such as reproductive history, hysterectomy, obesity, and oral contraceptive usage) were not taken into account.

In conclusion, the idea that the vaginal microbiome holds the secret of gynecological carcinogenesis is tantalizing, but more studies that corroborate this relationship are needed.

For more information, go to BJOG: An International Journal of Obstetrics & Gynaecology