The emerging role of oral microbiota in oral cancer initiation, progression and stemness

Abstract

Oral squamous cell carcinoma (OSCC) is the most prevalent malignancy among the Head and Neck cancer. OSCCs are highly inflammatory, immune-suppressive, and aggressive tumors. Recent sequencing based studies demonstrated the involvement of different oral microbiota in oral cavity diseases leading OSCC carcinogenesis, initiation and progression. Researches showed that oral microbiota can activate different inflammatory pathways and cancer stem cells (CSCs) associated stemness pathways for tumor progression. We speculate that CSCs and their niche cells may interact with the microbiotas to promote tumor progression and stemness. Certain oral microbiotas are reported to be involved in dysbiosis, pre-cancerous lesions, and OSCC development. Identification of these specific microbiota including Human papillomavirus (HPV), Porphyromonas gingivalis (PG), and Fusobacterium nucleatum (FN) provides us with a new opportunity to study the bacteria/stem cell, as well as bacteria/OSCC cells interaction that promote OSCC initiation, progression and stemness. Importantly, these evidences enabled us to develop in-vitro and in-vivo models to study microbiota interaction with stem cell niche defense as well as CSC niche defense. Thus in this review, the role of oral microbiota in OSCC has been explored with a special focus on how oral microbiota induces OSCC initiation and stemness by modulating the oral mucosal stem cell and CSC niche defense.

Diversity and compositional differences in the oral microbiome of oral squamous cell carcinoma patients and healthy controls: a scoping review

“…Moreover, it increases inflammation by influencing the AIM2 and POP1 pathway leading to the increased expression of IL-1B ( 18 ). Saikia et al, described the role of specific members of the oral microbiome, such as by influencing the defence mechanisms of oral mucosal stem cells and cancer stem cells ( 45 ). So, F. nucleatum has various ways of contributing to OSCC development.…”

State of the Art in the Diagnosis and Assessment of Oral Malignant and Potentially Malignant Disorders: Present Insights and Future Outlook—An Overview

“…Although there is a large group of mostly rare malignant neoplasms affecting the oromaxilofacial area [ 74 , 75 , 76 ], Oral Squamous Cell Carcinoma (OSCC) represents a malignant neoplasm involving the oral cavity, leading to more than 90% of malignant tumors of the head and neck area, ranking as the 16th most common worldwide cancer [ 77 ], and it stands as the most common malignancy in South-East Asia (India, Sri Lanka, Pakistan, Bangladesh, and Taiwan) and the Pacific regions (Papua New Guinea and Melanesia) due to the betel chewing habit [ 78 ] ( Figure 2 ). Tobacco and alcohol consumption represent two of the major risk factors for the development of oral cancer [ 79 ]; nevertheless, many other elements have been reported to increase the risk of OSCC, such as micronutrient depletion, hormonal, protein and enzyme imbalances [ 80 , 81 , 82 , 83 , 84 ], poor oral hygiene, chronic traumatism, and viruses [ 85 , 86 ]. Poor oral hygiene has been always associated with the risk of the development of periodontal disease, so current investigations are focusing on the possible association between the periodontal status of health and oral cancer risk [ 87 ].…”

The Roles and Interactions of Porphyromonas gingivalis and Fusobacterium nucleatum in Oral and Gastrointestinal Carcinogenesis: A Narrative Review

“…nucleatum and cancer, including OSCC, CRC, and PDAC, and the underlying mechanisms have been extensively reviewed [19,81,84,86,91,92]. Many of these reviews summarized the role of F. nucleatum in the development of OSCC and CRC [81,84,86,91], whereas Saikia et al and Irfan et al discussed the involvement of both P. gingivalis and F. nucleatum in carcinogenesis [19,92]. We noticed that most reviews discussed the role of individual bacterial species in carcinogenesis.…”