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.
Abstract Persistent infection with oncogenic Human Papillomavirus (HPV) is necessary for cervical carcinogenesis. Although evidence suggests that the vaginal microbiome plays a functional role in the persistence or regression of HPV infections, this has yet to be described in women with cervical intra-epithelial neoplasia (CIN). We hypothesised that increasing microbiome diversity is associated with increasing CIN severity. llumina MiSeq sequencing of 16S rRNA gene amplicons was used to characterise the vaginal microbiota of women with low-grade squamous intra-epithelial lesions (LSIL; n = 52), high-grade (HSIL; n = 92), invasive cervical cancer (ICC; n = 5) and healthy controls (n = 20). Hierarchical clustering analysis revealed an increased prevalence of microbiomes characterised by high-diversity and low levels of Lactobacillus spp. (community state type-CST IV) with increasing disease severity, irrespective of HPV status (Normal = 2/20,10%; LSIL = 11/52,21%; HSIL = 25/92,27%; ICC = 2/5,40%). Increasing disease severity was associated with decreasing relative abundance of Lactobacillus spp. The vaginal microbiome in HSIL was characterised by higher levels of Sneathia sanguinegens (P < 0.01), Anaerococcus tetradius (P < 0.05) and Peptostreptococcus anaerobius (P < 0.05) and lower levels of Lactobacillus jensenii (P < 0.01) compared to LSIL. Our results suggest advancing CIN disease severity is associated with increasing vaginal microbiota diversity and may be involved in regulating viral persistence and disease progression.
The role of the vaginal microbiome in gynaecological cancer
Abstract Human microbiome research has shown commensal bacteria to be a major factor in both wellness and disease pathogenesis. Interest in the microbiome has recently expanded beyond the gut to include a multitude of other organ systems for which the microbiome may have health implications. Here, we review the role of the vaginal microbiome in health and disease, with a particular focus on gynaecologic malignancies. Further, we suggest that it may be possible to expand the use of probiotics in the treatment of gynaecological cancers.
A review of the research to date on the relation between the vaginal microbiome and gynaecological cancers.
Persistent infection with oncogenic human papillomavirus (HPV) is necessary but not sufficient for the development of cervical cancer. The factors promoting persistence as well those triggering carcinogenetic pathways are incompletely understood. Rapidly evolving evidence indicates that the vaginal microbiome (VM) may play a functional role (both protective and harmful) in the acquisition and persistence of HPV, and subsequent development of cervical cancer. The first studies examining the VM and the presence of an HPV infection using next-generation sequencing techniques identified higher microbial diversity in HPV-positive as opposed to HPV-negative women. Furthermore, there appears to be a temporal relationship between the VM and HPV infection in that specific community state types may be correlated with a higher chance of progression or regression of the infection. Studies describing the VM in women with preinvasive disease (squamous intraepithelial neoplasia [SIL]) consistently demonstrate a dysbiosis in women with the more severe disease. Although it is plausible that the composition of the VM may influence the host’s innate immune response, susceptibility to infection, and the development of cervical disease, the studies to date do not prove causality. Future studies should explore the causal link between the VM and the clinical outcome in longitudinal samples from existing biobanks.
The vaginal microbiota, human papillomavirus infection and cervical intraepithelial neoplasia: what do we know and where are we going next?
The vaginal microbiota plays a significant role in health and disease of the female reproductive tract. Next-generation sequencing techniques based upon the analysis of bacterial 16S rRNA genes permit in-depth study of vaginal microbial community structure to a level of detail not possible with standard culture-based microbiological techniques. The human papillomavirus (HPV) causes both cervical intraepithelial neoplasia (CIN) and cervical cancer. Although the virus is highly prevalent, only a small number of women have a persistent HPV infection and subsequently develop clinically significant disease. There is emerging evidence which leads us to conclude that increased diversity of vaginal microbiota combined with reduced relative abundance of Lactobacillus spp. is involved in HPV acquisition and persistence and the development of cervical precancer and cancer. In this review, we summarise the current literature and discuss potential mechanisms for the involvement of vaginal microbiota in the evolution of CIN and cervical cancer. The concept of manipulation of vaginal bacterial communities using pre- and probiotics is also discussed as an exciting prospect for the field of cervical pathology.
The vaginal and gastrointestinal microbiomes in gynecologic cancers: A review of applications in etiology, symptoms and treatment
The human microbiome is the collection of microorganisms in the body that exist in a mutualistic relationship with the host. Recent studies indicate that perturbations in the microbiome may be implicated in a number of diseases, including cancer. More specifically, changes in the gut and vaginal microbiomes may be associated with a variety of gynecologic cancers, including cervical cancer, uterine cancer, and ovarian cancer. Current research and gaps in knowledge regarding the association between the gut and vaginal microbiomes and the development, progression, and treatment of gynecologic cancers are reviewed here. In addition, the potential use of probiotics to manage symptoms of these gynecologic cancers is discussed. A better understanding of how the microbiome composition is altered at these sites and its interaction with the host may aid in prevention, optimization of current therapies, development of new therapeutic agents and/or dosing regimens, and possibly limit the side effects associated with cancer treatment.