domingo, 27 de agosto de 2017

Vaginal Microbiome and Gynecological Cancer

Download PDF Copy

By Dr Tomislav Meštrović, MD, PhD

The vaginal microbiome is comprised of a plethora of bacterial species (ranging from 20 to 140), with the most abundant representation by Lactobacillus species. Next generation sequencing and other modern methods have been used to characterize healthy vaginal microbiome and discern between different “healthy” profiles that keep vaginal homeostasis in check.

It is already known that a well-balanced microbiome in the vaginal region is pivotal in preventing infections of the genital tract; however, recent evidence shows it may even influence the development of malignant changes in the cervix and other constituents of the genital tract.

Exploring the Influence on Carcinogenesis

Exploring the link between the vaginal microbiome and gynecological malignancies is a developing and exciting field of research, as several studies that were published recently suggested that such relationship may exist. The overall hypothesis is that vaginal bacteria play an important role in the tumor microenvironment.

The evidence on how the vaginal microbiome influences cervical cancer induced by human papillomavirus (HPV) is mounting. One study has shown that microbiome in women with HPV showed greater diversity of bacteria, especially Gardnerella vaginalis and Lactobacillus gasseri species, which was corroborated by another study that found higher HPV rates in women with generally lower levels of Lactobacillus species and higher microbiome diversity.

Furthermore, HPV clearance rates (and consequently the risk of malignant transformation) are also influenced by the vaginal microbiome composition, and one bacterial genus that was repeatedly linked to stagnant HPV clearance was Atopobium. In addition, vaginal infection with Chlamydia trachomatis seems to predispose women to HPV infection simply by altering the vaginal microbiome.

Some studies have tried to elucidate certain putative species that may act alone. For example, Lactobacillus crispatus has been associated with healthy women, whereas Lactobacillus iners has been found in those with cervical cancer – either alone or together with HPV (especially in those patients with high grades of cervical intraepithelial neoplasia).

Disruption of the vaginal microbiome may also be an indirect risk factor for the development of endometrial and ovarian cancer. Recent studies have shown that the ovaries, fallopian tubes and uterus are characterized by unique microbial profiles, and that differences in their composition can be linked to certain malignant states.

Clinical Implications

Such growing recognition of the important role the vaginal microbiome may play in cancer encourages potential interventions in order to restore or maintain a healthy ratio of resident microbial species. One of the main tools used in achieving such a healthy balance is the use of probiotics – dietary supplements that contain live (but beneficial) bacteria.

In line with the previous studies, vaginal use of probiotics may reduce the rate of HPV infection, increase the rate of clearance and, consequently, diminish the risk of cancer development. Depending on the type of probiotic used, there might also be promotion of immune surveillance and regulatory T cells to reduce chronic inflammatory processes that are also associated with cervical neoplasia.

Furthermore, the vaginal microbiome may be a key player in the treatment via modulation of the tumor microenvironment. Immunotherapy with CpG oligonucleotides (which are single-stranded DNA molecules with a cytosine triphosphate deoxynucleotide) or platinum chemotherapy are approaches that may be highly influenced by the composition of vaginal flora.

In conclusion, the notion that the vaginal microbiome may hold a secret of cervical carcinogenesis is intriguing, and may represent a completely different outlook on the optimal prevention and treatment of this frequent malignant process. However, more studies that prove this relationship are needed, and thus far there is simply not enough proof for the link between the vaginal microbiome and other gynecological cancers.

Reviewed by Afsaneh Khetrapal BSc (Hons)