**1. Introduction**

The vaginal microenvironment plays an important role in reproductive health. 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 gynecologic malignancies, specifically cervical cancer. Further research is

Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons

required to understand the molecular mechanisms involved in the complex role that bacterial communities can play in the development of cancer.

and regulates the immunity of epithelial barrier. Therefore, the vaginal microbiome plays an essential role not only in health and dysbiosis, but also in modulation of immune response and, possible, in the carcinogenic process. Additionally, the persistence of risk factors, namely,

Microenvironment in Vagina as a Key-Player on Cervical Cancer: Interaction of Polymorphic…

http://dx.doi.org/10.5772/intechopen.73108

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The carcinogenic process in cervical cancer results in systemic and persistent damages, with important changes in immune checkpoints of the involved microenvironment [6]. From the key-players involved in this process, the microbiota influences, locally, physiological functions from the maintenance of barrier homeostasis to the regulation of metabolism, hematopoiesis, inflammation, immunity and other functions systematically [4, 7]. This barrier is supported by immune cells, for example, B cells, which produces IgA that helps to neutralize pathogenic bacteria (**Figure 1**) [8]. When this barrier locally fails it is created a favourable environment for carcinogenesis, the dysregulation of the integrity of vaginal epithelial cells will lead to more susceptibility for infections, causing low-grade chronic inflammation that leads to disease.

HPV and other co-infections, may be associated to the disruption of these barriers [5].

**Figure 1.** The presence of certain types of lactobacillus lowers pH and induces H2

*Lactobacillus iners*; CSTs IV, *Lactobacillus, Sneathia amnii* and *Fusobacterium*; CSTs V, *Lactobacillus jensenii*.

formation of HOCL by myeloperoxidase. CSTs IV are associated to bacterial vaginosis and the other microorganisms, to pre-cancerous lesions and cervical cancer. The types of groups of bacillus may be preponderant for maintaining the vaginal balance. Four species are most important for the balance of the vagina ecosystem: *L. gasseri* (II) *L. crispatus* (I), *L. jensenii* (V) and *L. iners* (III). The inter-individual genetic polymorphic variations should be integrated in a complex model, since a compromise vaginal microflora and inefficient genetic profile may contribute to the development of cervical cancer; CSTs, community state types; CSTs I, *Lactobacillus crispatus*; CSTs II, *Lactobacillus gasseri*; CSTs III,

O2

, which may contribute to the

Cervical cancer is one of the most preventable cancers. However, its progression and above all, the progress towards prevention is often frustrating. Moreover, and despite the continuously growing body of knowledge, the role of factors that affect the human papillomavirus (HPV) persistence are not yet fully understood.

Indeed, the oncogenic HPVs are a necessary cause of cervical cancer; however, they are not a sufficient cause, being other cofactors implicated in the increase of risk. We have also to consider external factors to the host, such as smoking habits, nutritional and behavioural factors (number of partners and their characteristics, age at onset of sexual activity), hormonal therapies-sexual steroids (oral contraceptives and post-menopausal substitution therapy), herpes simplex infections, *Chlamydia trachomatis* or other sexually transmitted infectious diseases and also nonspecific inflammatory diseases. Genetic and immunological factors and other endogenous co-factors may induce initiation and progression associated with genotoxicity, mutagenicity and irreversible cell proliferation [1, 2].

Dysbiosis results from the disruption of equilibrium of the microbiome. Given that the vaginal microbiome composition has been shown to play a role in the HPV infection and the rate of HPV clearance, the vaginal microbiome structure may be associated with the development of cervical cancer secondary to a persistent HPV infection.

Nevertheless, recent and concise data show that composition of the early-life microbiota is critical in the development of the immune system, and how deviations from homeostasis can induce disease later in life [3].

Our group has been presenting data that reflects mainly the influence of genetic, epigenetic and environmental including the vaginal microbiota-derived factors in the natural history of HPV associated lesions leading to cervical cancer as a multifactorial disease process.

In this scenario, the microbiota and its genome (microbiome) fulfils part of the natural history of cervical cancer. In the last years, it has been characterized HPV-genotypes profile, and bacterial vaginosis (BV) leading to its association with the prevalence of HSIL and progression to invasive cervical cancer (ICC) in adult women.

Despite the risk factors status knowledge, we may consider the need of a more proactive behaviour, namely, a strategy for improving the local fora with topic therapy. In this chapter, we will focus in the role of genetic susceptibility associated to the development of cervical cancer. Furthermore, we will discuss opportunities for interventions that modify the microbiome for therapeutic purpose.
