Surreal image of a mouth with a galaxy inside, symbolizing the oral microbiome and its potential link to oral cancer.

Oral Microbiome: The Unanswered Questions About Its Role in Oral Cancer

Reese Marlowe in Health & Wellness December 2025 • 5 min read.

"Uncover the mysteries of the oral microbiome and its potential link to oral cancer development. What we know, what we don't, and why it matters."

Oral squamous cell carcinoma (OSCC) is a major global health concern, accounting for over 90% of all oral cancers. Despite advancements in treatment, the 5-year survival rate remains around 50%, highlighting the need for better understanding and prevention. While tobacco and alcohol are well-known risk factors, many cases occur in individuals without these exposures, prompting investigation into other potential contributors.

One emerging area of interest is the role of the oral microbiome – the complex community of bacteria, fungi, and viruses residing in our mouths – in the development of OSCC. Initial clues came from epidemiological studies linking poor oral hygiene and tooth loss to increased cancer risk, suggesting that oral bacteria might play a part. This idea is further supported by the connection between infection-driven inflammation and cancers in other parts of the body, such as the association of Helicobacter pylori with gastric cancer.

This article explores the current state of research on the oral microbiome and its relationship to oral cancer. We'll delve into the evidence for microbiome shifts in OSCC, examine whether these changes occur during the early stages of cancer development, and discuss the factors that might be driving these shifts. Ultimately, we aim to highlight the unanswered questions and areas that require further investigation to determine the true role of the oral microbiome in oral cancer.

Microbiome Shifts in Oral Cancer: Cause or Consequence?

Surreal image of a mouth with a galaxy inside, symbolizing the oral microbiome and its potential link to oral cancer.

Over the past few years, numerous studies have characterized the oral microbiome associated with OSCC. These studies, often involving direct examination of malignant tissue, have consistently found an enrichment of Gram-negative Fusobacteria and Bacteroidetes, coupled with a reduction in Streptococcus and Rothia species. Some researchers interpret this enrichment as evidence of the microbiome's involvement in malignant transformation.

However, an alternative perspective suggests that these microbiome changes might be a consequence of the cancer itself. The inflamed tumor microenvironment could selectively favor the growth of certain bacterial species. Therefore, definitive evidence demonstrating the direct involvement of microbiome shifts in OSCC development remains elusive. Key questions remain:

Are specific bacterial species actively promoting cancer development, or are they simply opportunistic colonizers of the tumor microenvironment?
Do microbiome changes precede and contribute to malignant transformation, or do they occur after the cancer has already developed?
What are the specific mechanisms by which the oral microbiome could influence oral cancer development or progression?

Addressing these questions requires further research, including longitudinal studies that track microbiome changes over time in individuals at risk of developing oral cancer. Such studies could help determine whether specific microbiome shifts can serve as early indicators of cancer development or potential targets for prevention.

The Road Ahead: Unlocking the Microbiome's Secrets

While the link between the oral microbiome and oral cancer is intriguing, significant research is still needed to fully understand this relationship. Large cohort studies are crucial to confirm any associations and determine the direction of causality. OSCC is a complex disease involving multiple genetic and environmental factors, and the microbiome is likely just one piece of the puzzle.

Future research should focus on identifying the specific mechanisms by which the oral microbiome might influence cancer development. This includes investigating the role of microbial byproducts, such as acetaldehyde and N-nitrosamine compounds, as well as the potential for the microbiome to modulate inflammation and immune responses in the oral cavity.

Ultimately, a better understanding of the oral microbiome's role in oral cancer could lead to new strategies for prevention, early detection, and treatment. This could involve developing microbiome-based diagnostics, targeted therapies that modulate the oral microbiome, or personalized prevention strategies based on an individual's microbiome profile. As research progresses, we may finally unlock the secrets of the oral microbiome and harness its power to combat oral cancer.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1016/j.oraloncology.2018.12.003, Alternate LINK

Title: The Microbiome And Oral Cancer: More Questions Than Answers

Subject: Cancer Research

Journal: Oral Oncology

Publisher: Elsevier BV

Authors: Claire M. Healy, Gary P. Moran

Published: 2019-02-01

Everything You Need To Know

What is the oral microbiome, and why is it relevant to oral cancer?

The oral microbiome is a complex community of bacteria, fungi, and viruses residing in the mouth. Its significance in the context of oral cancer lies in the potential for these microorganisms to influence the development and progression of Oral squamous cell carcinoma (OSCC). Recent research suggests that shifts in the oral microbiome, such as an enrichment of Gram-negative Fusobacteria and Bacteroidetes, may be associated with OSCC. Understanding the role of the oral microbiome is crucial because it could lead to new strategies for prevention, early detection, and treatment of OSCC, which currently has a low 5-year survival rate.

What is the significance of Oral squamous cell carcinoma (OSCC), and why is research into the oral microbiome important in this context?

Oral squamous cell carcinoma (OSCC) accounts for over 90% of all oral cancers. The 5-year survival rate remains around 50%. Tobacco and alcohol are well-known risk factors, but many cases occur in individuals without these exposures. Research into the oral microbiome's involvement is important because it could help to explain the causes of OSCC in people without these risk factors, which may lead to improved early detection, prevention, and treatment. Addressing the unanswered questions could improve outcomes significantly.

What is the current understanding of the relationship between the oral microbiome and oral cancer?

Current research suggests that changes in the composition of the oral microbiome are associated with the presence of Oral squamous cell carcinoma (OSCC). These studies have observed an enrichment of Gram-negative Fusobacteria and Bacteroidetes, coupled with a reduction in Streptococcus and Rothia species. However, it is not yet clear whether these shifts are a cause or a consequence of the cancer. Further studies are needed to determine whether these changes precede cancer development and contribute to the malignant transformation, or if they occur after the cancer has already developed. Longitudinal studies are crucial for determining the direction of causality.

Does the current research prove that specific bacteria cause oral cancer?

The research does not definitively prove that specific bacteria directly cause oral cancer. While some studies suggest a link, it's unclear if the changes in the oral microbiome are a cause or a result of the cancer. Several unanswered questions remain, including whether specific bacterial species promote cancer development or simply colonize the tumor environment. Additional research, including longitudinal studies, is needed to determine the precise mechanisms by which the oral microbiome may influence the development or progression of OSCC.

What are the implications of further research into the oral microbiome and oral cancer?

The implications of the oral microbiome's role in oral cancer are potentially significant for prevention and treatment. If specific shifts in the oral microbiome are found to contribute to the development of Oral squamous cell carcinoma (OSCC), they could serve as early indicators of cancer risk. This would allow for earlier detection. Also, such findings could lead to interventions that prevent cancer. Further research is needed to understand the specific mechanisms by which the oral microbiome interacts with the development and progression of OSCC, which may reveal new targets for treatment or prevention strategies.