Catching the unsuspecting culprits behind oral cancer

Rupsy Khurana writes about a study that explored reasons behind the compromised immune systems in oral cancer patients

Our mouth is a complex ecosystem, teeming with over 700 bacterial species, making it the second-largest microbial community in the human body after the gut. A balanced microbiome is essential for maintaining both oral and overall health. Growing research suggests that poor oral hygiene may have far-reaching consequences like oral cancer.

A recent study published in the International Journal of Oral Science in January highlighted the role of Fusobacterium nucleatum, a member of the oral microbiome, in the development and progression of oral cancer. 

“Since oral cancers are often diagnosed at very late stages, we wanted to understand immune regulation in oral squamous cell carcinoma,” says Estefanía Nova-Lamperti, Senior Author and Faculty of Pharma at the University of Concepción, South America. “Our focus was on why the immune system in these patients was so exhausted—we did not start by looking at bacteria.”

Since many studies have linked oral cancer to periodontitis, where an imbalance in the microbiome can lead to severe gum inflammation, Nova-Lamperti and the team then decided to take this route of investigation.

Unexplainable causes

According to the Global Cancer Observatory, oral cancer cases are expected to rise by 40% by 2040. While tobacco and alcohol use, oral lesions, and UV exposure are well-known risk factors, clinicians are noticing a surge in aggressive oral cancers worldwide that these causes can’t fully explain. In India, oral cancer remains a major public health challenge, accounting for nearly 40% of all cancer cases, with most diagnoses occurring at advanced stages. 

“We are seeing a notably high number of oral cancers among individuals with no history of alcohol or tobacco use. About 50% of our patients are non-addicts,” says Dr Shawn T Joseph, Senior Consultant, Head and Neck Surgical Oncology, VPS Lakeshore Hospital, Kerala. “This alarming trend points to risk factors beyond the traditional ones and needs to be addressed urgently.”

Certain bacteria can turn harmful when the oral microbiome is disrupted due to untreated plaque or chronic gum inflammation. They start to grow beneath the gum line. In this anaerobic environment, they can become pathogenic and proliferate, secreting toxins that break down tissue. “If the levels remain low, it is not harmful, but in long-standing infections, it can go rogue”, says Sameep Shetty, Associate professor, Consultant oral and maxillofacial surgeon, Manipal College of Dental Sciences, Mangalore.

“This provokes immune defences. The immune cells, such as neutrophils and macrophages, attack these pathogenic bacteria to offset inflammation. However, since pathogens are difficult to eliminate, the immune system becomes exhausted over the years. Over time, this damage may lead to genetic mutations or disrupt cellular pathways, paving the way for cancer”, says Shetty.

To investigate the potential role of bacteria in oral cancer progression, Nova-Lamperti’s team analysed biopsy samples from oral cancer patients and healthy individuals to identify and compare protein levels. The team matched the protein profiles with those found in bacteria commonly linked to gum inflammation or periodontitis: Fusobacterium nucleatum and Porphyromonas gingivalis. Most of the proteins belonged to Fusobacterium nucleatum, also known to cause digestive tract cancers.

“Cancer is a multifactorial disease, so it is unlikely that bacteria alone could cause it. However, they promote tumour growth once the cancer is already underway. The bacterium is very well known to cause metastasis”, says Nova-Lamperti.

The team examined the function of each protein and found that they were involved in a molecular pathway that broke down an amino acid, which served as an energy source for the bacteria. These bacterial pathogens are drawn to this energy resource. They colonise cancer cells, grow voraciously and support the growth of cancer cells as well. 

“Bacteria and cancer cells are talking to each other and promoting each other’s growth,” says Nova-Lamperti.

Challenge of diagnosing

One of the biggest challenges in tackling oral cancer is the lack of awareness about early warning signs. When identified early, gum inflammation can be treated with deep cleaning and prevented with consistent home care. Persistent mouth ulcers and red or white patches often go unnoticed or are dismissed as minor issues. This delays diagnosis and significantly reduces survival rates. “If patients have lesions that do not heal within two weeks, dentists should refer them to oncologists,” says Shetty. 

Another growing concern is the role of diet and environmental pollutants in altering the oral microbiome. Processed foods high in sugar and preservatives can fuel harmful bacteria, causing inflammation. Although the mechanisms are still not understood, research suggests that people exposed to high levels of PM2.5 are at high risk of developing oral cancer.

Heavy metals, such as arsenic and lead, may contribute to chronic inflammation. Human papillomavirus (HPV) is among the important factors contributing to head and neck cancers, including oral cancers, especially among younger individuals. A few genetic studies on Indian populations have uncovered regional differences in HPV prevalence in these cancers, with the highest rates observed in the north, followed by west, east, central and southern regions.

“There is an urgent need to promote genomic and proteomic research to understand the rising incidence of oral cancers,” says Joseph. “Currently, there is a disconnect among dentists, oncologists, and researchers. Fostering more collaboration is essential for advancing these studies to address rising cases, especially in non-addicts.”

(The author is a science communicator)