Vaginal Microbiome and Its Role in HPV Induced Cervical Carcinogenesis

HPVs representing the most common sexually transmitted disease are a group of carcinogenic viruses with diferent oncogenic potential. Vaginal microbiome represent the modifiable and important risk factor in HPV-induced carcinogenesis. HPV infection significantly increases vaginal microbiome diversity and induces local inflammation, leading to gradual increases in the abundance of anaerobic bacteria and consequently the severity of cervical dysplasia. Anaerobic bacteria produce pro-inflammatory mediators and induce oxidative stress with subsequent epigenetic alterations resulting in formation of tumor microenvironment. Delineation of the exact composition of the vaginal microbiome, epigenetic state of cervical epithelium and immune environment before HPV acquisition, during persistent/progressive infections and after clearance, provides insights into the complex mechanisms of cervical carcinogenesis. It gives hints regarding the prediction of malignant potential. Relative high HPV prevalence in the general population is a challenge for modern and personalized diagnostics and therapeutic guidelines. Identifying the dominant microbial as well as epigenetic and immune response biomarkers of high-grade and low-grade dysplasia could help us to triage the patients with marked chances of lesion regression or progression. Any unnecessary surgical treatment of cervical dysplasia could negatively affect obstetrical outcomes and sexual life. Therefore, understanding the effect and role of microbiome-based therapies is a breaking point in the conservative management of HPV-associated precancerous lesions. Sequentially, the immune response and epigenetic rearrangement of cervical epithelium could help to control the therapy outcome. Qualitative and quantitative assessment of local microbial environment and associated risk factors constitutes the critical background for preventive, predictive, and personalized medicine that is essential for improving state-of-the-art medical care in patients with cervical precancerous lesions and cervical cancer. This chapter focuses on the influence and potential diagnostic and therapeutic applications of the microbial markers in HPV-related cancers in the context of 3P medicine.