Bacterial-Viral Interactions in Human Orodigestive and Female Genital Tract Cancers: A Summary of Epidemiologic and Laboratory Evidence

Abstract

Infectious agents, including viruses, bacteria, fungi, and parasites, have been linked to pathogenesis of human cancers, whereas viruses and bacteria account for more than 99% of infection associated cancers. The human microbiome consists of not only bacteria, but also viruses and fungi. The microbiome co-residing in specific anatomic niches may modulate oncologic potentials of infectious agents in carcinogenesis. In this review, we focused on interactions between viruses and bacteria for cancers arising from the orodigestive tract and the female genital tract. We examined the interactions of these two different biological entities in the context of human carcinogenesis in the following three fashions: (1) direct interactions, (2) indirect interactions, and (3) no interaction between the two groups, but both acting on the same host carcinogenic pathways, yielding synergistic or additive effects in human cancers, e.g., head and neck cancer, liver cancer, colon cancer, gastric cancer, and cervical cancer. We discuss the progress in the current literature and summarize the mechanisms of host-viral-bacterial interactions in various human cancers. Our goal was to evaluate existing evidence and identify gaps in the knowledge for future directions in infection and cancer.

HPV co‐infections with other pathogens in cancer development: A comprehensive review

“…97 According to some reports, NG also increases the risk of cell transformation independently, or in conjunction with HPV. 97 NG may interact with HPV by dysregulation of multiple cellular signaling pathways and inducing DNA double-strand breaks (DSBs). It enhances the expression of proinflammatory cytokines and cyclin-dependent kinase inhibitors p21 and p27, and decreases p53 expression.…”

“…As mentioned above, in the context of HPV‐related cancers, viral infection serves as a necessary agent but inadequate cause of cancer development 37 . Co‐factors such as the immune response to viral infection, the host microbiome health, or other acquired infectious agents play additional roles in carcinogenesis 97 . The microbiome is an important contributor to chronic mucosal inflammation, thus changes in its composition by overgrowth or undergrowth of different bacterial populations in multiple organ sites have been associated with progression to HPV‐associated dysplasia 79 .…”

“…The microbiome is an important contributor to chronic mucosal inflammation, thus changes in its composition by overgrowth or undergrowth of different bacterial populations in multiple organ sites have been associated with progression to HPV‐associated dysplasia 79 . It was proven that bacterial shifts in the microbiome or co‐infection with other bacterial pathogens in the organ affected by HPV can modulate viral proliferation and infection 97 . Co‐infection/co‐presence of some bacteria (either as part of the normal microbiome or as causative agents of infections) with HPV can be assessed by DNA‐based or serology tests.…”

“…The carcinogenic process induced by HPV has been extensively studied in cervical cancer, but the findings have been extrapolated to other HPV‐related cancers like HNSCC, based on similarities in the epithelial cells 188 . The underlying conditions such as poor dental status, especially in heavy alcohol consumers and/or smokers are correlated with shifts in the oral microbiome 97 . Expression of NO and pro‐inflammatory cytokines such as TNF‐α, IL‐1β, and IL‐6 in oral dysbiosis induce chronic inflammation and modulation of immune response.…”

Exosomal miRNA-21 from Toxoplasma gondii-infected microglial cells induces the growth of U87 glioma cells by inhibiting tumor suppressor genes

“…However, the exact causes of these malignancies are yet unclear. Approximately 20% of various malignancies worldwide are due to infectious agents, including viruses, bacteria, and parasites 3 , 4 . Infectious agents can interfere with the host cell’s genetic types of machinery, such as DNA repair and cell cycle, and can lead to chronic inflammations and immune system impairments 5 .…”