From Microbiome to Inflammation: The Key Drivers of Cervical Cancer

Abstract

Cervical cancer is the third leading cause of cancer-related death worldwide. Microbes and hosts form a mutually beneficial symbiosis relationship, and various parts of the host body are microbial habitats. Microbes can trigger inflammation in certain parts of the host body, contributing to cervical cancer development. This article reviews the relationship between cervicovaginal microbes, inflammation and cervical cancer, and discusses the effect of some key cervical microbes on cervical cancer. Finally, probiotic therapy and immunotherapy are summarized.

Keywords: cervical cancer; immunotherapy; inflammation; microbiome; probiotic.

FIGURE 1

The distribution of vaginal microorganisms in a healthy or inflammatory state. The vaginal microbial environment of healthy people is usually dominated by lactobacillus with high abundance. Lactobacillus depends on glycogen products for growth. Lactic acid, bacteriocins and H₂O₂ produced by Lactobacillus may inhibit the growth and development of pathogenic bacteria. When female reproductive tract is in disorder or inflammation, the microbial community is dominated by anaerobic bacteria and has the characteristics of high diversity. This could results in pH > 4.5. Simultaneously promote oxidation and nitrification reactions. The associated pro-inflammatory cytokines and ROS are increased, and metabolites in female reproductive tract are converted from lactic acid to biogenic amines. In addition, microbial co-infection can damage epithelial cells and disrupt the mucosal barrier.

FIGURE 2

Mechanisms of lactobacillus maintaining health for female reproductive tract (FRT). When the microbial community of female reproductive tract is in dynamic balance, lactobacillus with high abundance will not only produce lactic acid, H₂O₂ and other products but also compete with anaerobic bacteria for vaginal epithelial cells. In addition, the complement system could be activated by lactobacillus. These features prevent the growth of pathogens and thus ensure the health of the host.

FIGURE 3

Mechanisms of microbial dysregulation and inflammation leading to cervical cancer. When the balance of microbial environment of female reproductive tract is upset, the inflammatory response is activated. H₂O₂, the amount of lactic acid decreases because of the increase in the number of anaerobic bacteria. At the same time, the production of a large number of pro-inflammatory cytokines affects the protective ability of the mucosal epithelial barrier. These phenomena can increase the likelihood of persistent HPV infection, which can lead to cervical cancer. Abnormal expression of cytokines and abnormal activation of signal pathways also lead to the occurrence of cervical cancer. It is important to note that the presence of HPV could also influence microbial homeostasis and the activation of inflammation-related mechanisms.