Scientists in South Africa are exploring a surprising new way to detect one of the world’s deadliest cancers: saliva.
Researchers at the Sydney Brenner Institute for Molecular Bioscience at Wits University believe that bacteria living in the mouth may provide important clues about esophageal squamous cell carcinoma, a dangerous form of cancer that affects the esophagus, the tube carrying food from the mouth to the stomach.
Their findings were published in the journal Communications Medicine.
Esophageal cancer is already known as one of the most difficult cancers to diagnose and treat. In many patients, the disease is only discovered after swallowing becomes very difficult.
By the time symptoms become severe enough to seek medical help, the cancer is often already advanced. At that stage, treatment options may be limited, and doctors may only be able to offer care that reduces pain and discomfort rather than cures the disease.
Globally, more than 600,000 people developed esophageal cancer in 2020, and more than 540,000 people died from it. Large numbers of cases occur in parts of Africa and Asia.
The type of cancer studied by the researchers, esophageal squamous cell carcinoma, is especially common in certain regions of South Africa, including the Eastern Cape and KwaZulu-Natal.
What makes this disease particularly puzzling is that many patients develop it at relatively young ages. According to Professor Christopher Mathew from Wits University, the average age of patients is around 50 years old, and nearly one in five patients develops the disease before the age of 40.
Scientists have struggled for decades to fully understand why this cancer occurs so frequently in some regions but not others.
Researchers know that smoking and heavy alcohol use increase risk. Other factors linked to the disease include living in rural areas, lower levels of education, and the use of biomass fuels or household smoke from cooking and heating.
However, these known risk factors still do not fully explain why the disease clusters in certain geographic regions or why some people develop cancer without obvious exposures.
This led researchers to investigate whether bacteria in saliva might provide additional clues.
The human mouth contains billions of bacteria, collectively known as the oral microbiome. Some bacteria are helpful and support normal health, while others may contribute to disease under certain conditions.
In the new study, researchers compared saliva samples from people with esophageal squamous cell carcinoma to samples from healthy individuals.
Using genetic sequencing technology and machine-learning analysis, the scientists discovered clear differences in the bacterial patterns found in the saliva of cancer patients.
One bacterium, called Fusobacterium nucleatum, was found at higher levels in people with cancer. This bacterium has already been linked to several other cancers in earlier research.
The scientists created a microbiome-based model that used saliva bacteria patterns to identify possible cancer cases. Interestingly, this model performed better than models based only on clinical information and demographic factors.
However, the researchers stress that the findings do not prove the bacteria are causing the cancer.
Dr. Wenlong Carl Chen explained that the bacterial changes may instead happen because the disease is already developing inside the esophagus.
He compared it to a blocked kitchen sink. When the esophagus gradually becomes narrowed by cancer, bacteria and other materials may begin to accumulate differently in the mouth and throat.
Even if the bacteria are only reacting to the disease rather than causing it, the discovery could still be medically useful.
Researchers believe saliva bacteria patterns may someday help doctors identify people who need further testing much earlier.
At the moment, the main method used to diagnose esophageal cancer is endoscopy. During this procedure, doctors insert a flexible tube with a camera into the esophagus to look for tumors or abnormal tissue.
Although effective, endoscopy is expensive, invasive, and not always easily available in low-resource communities.
A simple saliva or cheek-swab test could potentially provide a much cheaper and easier first step for identifying high-risk patients.
The scientists say such a test would not replace endoscopy, but it could help doctors decide who should receive urgent specialist care sooner.
This may be especially important in rural or underserved communities where healthcare access is limited.
The research team is now expanding its work to better understand the disease.
Scientists are studying whether some people may inherit genetic differences that increase their vulnerability to this cancer. They are also examining tumors for mutation signatures, which are special DNA patterns that may act like fingerprints left behind by environmental exposures such as smoke, chemicals, pollutants, or contaminated water.
However, the researchers caution that the saliva model is still in the early stages of development.
The study has only been internally validated so far, meaning it still needs to be tested in larger groups of people from different regions and backgrounds.
This is important because oral bacteria patterns can vary widely depending on geography, diet, environment, and lifestyle.
Future studies will include cancer patients, healthy volunteers, and people with non-cancerous esophageal conditions that may also cause swallowing problems.
The researchers hope this will help determine whether the saliva signal specifically identifies cancer or simply reflects other abnormalities in the esophagus.
This study is important because it explores a low-cost and non-invasive way to identify a cancer that is often detected too late. Using saliva samples instead of invasive procedures could be especially valuable in low-resource areas where access to specialist care is limited.
One strength of the research is the use of genetic sequencing and machine-learning analysis, which allowed scientists to identify complex bacterial patterns that may not be visible through traditional methods.
However, the study does not yet prove that saliva bacteria can reliably diagnose cancer. The findings are still preliminary, and bacterial patterns may differ greatly between populations and environments.
The researchers also acknowledge that the bacterial changes may simply be a consequence of the disease rather than a direct cause.
Even so, the work provides an exciting new direction for esophageal cancer research. If future studies confirm the findings, saliva-based screening tools could eventually help doctors identify high-risk patients earlier and improve survival rates for this deadly disease.
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Source: Wits University.
