News, Analysis, Trends, Management Innovations for
Clinical Laboratories and Pathology Groups

Hosted by Robert Michel

News, Analysis, Trends, Management Innovations for
Clinical Laboratories and Pathology Groups

Hosted by Robert Michel
Sign In

British Researchers Discover Common Mouth Bacteria That ‘Melts’ Head and Neck Cancers

Bacteria could become new biomarker for testing patients’ reaction to cancer treatments which would give microbiologists and clinical laboratories a new tool for aiding diagnosis and in the selection of appropriate therapies

In a surprising study conducted at King’s College London and Guy’s and St Thomas’ NHS Foundation Trust, British scientists have discovered that a common bacteria found in the mouth may be able to “melt” certain cancers. The bacteria could also be used as a clinical laboratory biomarker to determine how patients may react to specific cancer treatments.

The researchers found that the presence of Fusobacterium can help neutralize head and neck cancers and provide better outcomes in patients with those diseases, according to a Kings College London news release.

Fusobacterium is a genus of anaerobic gram-negative bacteria that are prevalent colonizers of the mouth microbiome. It can be associated with mouth abscesses, periodontal disease, skin ulcers, and Lemierre’s syndrome. The most common species of the genus, Fusobacterium nucleatum, is a marker for the early prediction, diagnosis, and prognosis of colorectal cancer.

“In essence, we found that when you find these bacteria within head and neck cancers, [patients] have much better outcomes,” said Miguel Reis Ferreira, MD, PhD, clinical oncologist at Guy’s and St Thomas’, adjunct senior clinical lecturer at King’s College London and senior author of the study, in the news release. “The other thing that we found is that in cell cultures this bacterium is capable of killing cancer.”

The researchers published their findings in the journal Cancer Communications titled, “Fusobacterium is Toxic for Head and Neck Squamous Cell Carcinoma, and its Presence May Determine a Better Prognosis.”

“This research reveals that these bacteria play a more complex role than previously known in their relationship with cancer—that they essentially melt head and neck cancer cells,” said Miguel Reis Ferreira, MD, PhD (above), clinical oncologist at Guy’s and St Thomas’, adjunct senior clinical lecturer at King’s College London and senior author of the study, in a news release. “However, this finding should be balanced by their known role in making cancers such as those in the bowel get worse.” Should these findings prove sound, clinical laboratories may soon have a new biomarker for testing patients’ reaction to cancer treatments. (Photo copyright: King’s College London.)

Researchers Surprised by Their Findings

The researchers began their research by using computer modeling to identify the types of bacteria to further scrutinize. They then studied the effect of those bacteria on cancer cells by analyzing data on 155 head and neck cancer patients whose tumor information had been submitted to the Cancer Genome Atlas. Head and neck cancers include cancers of the mouth, throat, voice box, nose, and sinuses.

The scientists placed Fusobacterium in petri dishes and kept the bacteria there for a few days. They observed the effect of that bacteria on head and neck cancers and discovered there was a 70% to 90% reduction in the number of viable cancer cells after being infused with the Fusobacterium.

Due to the known correlation between Fusobacterium and colorectal cancer, the team was astonished to find the cancer cells present in head and neck cancers had almost been eradicated.

In the news release, Ferreira said the researchers initially expected the Fusobacterium to boost the growth of the cancers and render those cancers more resistant to treatments like radiotherapy. However, they found the opposite to be true.

“The research in colorectal cancer indicates that these bacteria are bad, and that was kind of ingrained into our minds, and we were expecting to find the same thing,” said Ferreira in a Press Association (PA) interview, The Independent reported. “When we started finding things the other way around, we were brutally surprised.”

Predicting Better Outcomes, Lower Risk of Death

“You put it in the cancer at very low quantities and it just starts killing it very quickly,” Ferreira said in the King’s College London news release. “What we’re finding is that this little bug is causing a better outcome based on something that it’s doing inside the cancer. So we are looking for that mechanism at present, and it should be the theme for a new paper in the very short-term future.”

In addition, the scientists discovered that patients with Fusobacterium within their cancer showed improved survival rates when compared to those without the bacteria. The presence of the bacteria correlated with a 65% reduction in death risk.

“What it could mean is that we can use these bacteria to better predict which patients are more likely to have good or worse outcomes, and based on that, we could change their treatment to make it kinder in the patients that have better outcomes or make it more intense in patients that are more likely to have their cancers come back,” said Ferreira in the PA interview.

“Our findings are remarkable and very surprising. We had a eureka moment when we found that our international colleagues also found data that validated the discovery,” said Anjali Chander, PhD student, senior clinical research fellow, Comprehensive Cancer Center, King’s College London, and lead author of the study in the news release.

More to Learn about Bacteria as Biomarkers

According to the National Cancer Institute (NCI), more than 71,000 people will be diagnosed with one of the major types of head and neck cancer this year in the US and more than 16,000 patients will die from these diseases.

The Global Cancer Observatory (GLOBOCAN) estimates there are about 900,000 new cases of head and neck cancers diagnosed annually worldwide with approximately 450,000 deaths attributed to those cancers every year. GLOBOCAN also claims head and neck cancers are the seventh most common cancer globally.

More research and studies are needed to confirm the virtue of this latest venture into the human microbiome. However, the preliminary results of this study appear promising.

The study of human microbiota continues to bring unexpected surprises, as scientists gain more insights and identify specific strains of bacteria that may have a positive or negative influence on an individual’s health. These discoveries may give microbiologists and clinical laboratories intriguing new biomarkers that could be incorporated into medical tests that aid diagnosis and the selection of appropriate therapies.

—JP Schlingman

Related Information:

Type of Mouth Bacteria ‘Melts’ Some Cancers, Study Finds

Bacteria ‘Melts’ Head and Neck Cancer in Revolutionary Discovery

Fusobacterium is Toxic for Head and Neck Squamous Cell Carcinoma, and its Presence May Determine a Better Prognosis

Bacteria ‘Melts’ Head and Neck Cancer in Revolutionary Discovery

Common Mouth Bacteria Found to ‘Melt’ Certain Cancers in ‘Surprising’ Discovery

Fusobacterium Nucleatum, a Key Pathogenic Factor and Microbial Biomarker for Colorectal Cancer

Detection of Fusobacterium in Oral and Head and Neck Cancer Samples: A Systematic Review and Meta-analysis

Researchers at University of Michigan Rogel Cancer Center Develop Urine Test That Detects Head and Neck Cancer

Proof-of-concept study may eventually lead to new clinical laboratory urine tests for fast, non-invasive detection of cancer

Here is the latest example of researchers finding useful biomarkers in urine for diagnosing certain cancers. The discovery comes from the University of Michigan Health Rogel Cancer Center, where, in a proof-of-concept study, scientists developed a urine-based test that screens for circulating free DNA (cfDNA) fragments (aka, cell-free DNA) released by tumors in the head and neck. If they confirm these findings, it’s possible the technology could be adapted into a non-invasive clinical laboratory test for selected cancers.

One such cancer is human papillomavirus (HPV) which, though “widely recognized for causing cervical cancer” is “increasingly found to cause cancers in the mouth, throat, and other head and neck regions,” according to a U-M Medical School press release.

The U-M study findings could lead to an early, non-invasive test for the detection of cancer, as compared to traditional urine or blood-based liquid biopsy testing.

The researchers published their findings in the journal JCI Insight titled, “ctDNA Transiting into Urine is Ultrashort and Facilitates Noninvasive Liquid Biopsy of HPV+ Oropharyngeal Cancer.”

“In this study, we provide evidence to support the hypothesis that conventional assays do not detect ultrashort fragments found in urine since they are designed to support longer DNA fragments. Our team used an unconventional approach to develop a urine test for HPV-positive head and neck cancer ctDNA detection,” said Chandan Bhambhani, PhD (above), Research Lab Specialist Intermediate at University of Michigan and co-first author of the study, in a news release. Clinical laboratories may soon have a new urine-based test for detecting cancer. (Photo copyright: LinkedIn.)

Advantages, Challenges of Urine Testing

Key to their discovery was use of whole genome sequencing to find what conventional assays tend to miss: predominantly ultrashort (under 50 base pairs) of circulating urine transrenal cell-free tumor DNA (TR-ctDNA) fragments, according to the JCI Insight paper.

According to the researchers, benefits of urine testing include:

  • Testing with urine is convenient for people who may be unable to access healthcare and phlebotomy services.
  • Urine has low biohazard risk and may be easily collected in large amounts, compared with blood.
  • Ongoing collection of urine could make way for TR-ctDNA “kinetics to be used as a high time-resolution biomarker” to monitor patients’ response to treatment.

However, urine, the researchers cautioned, must be analyzed in a different manner if it is to be comparable in efficiency to blood-based ctDNA testing.

“There have been mixed reports on the efficiency of TR-ctDNA detection compared with that of blood ctDNA. A potentially crucial factor for the analysis of TR-ctDNA is knowing the length of TR-ctDNA fragments present in urine, because this affects assay design for optimal sensitivity in TR-ctDNA detection,” the researchers explained.

New Assay Detects Ultrashort DNA Fragments

To complete their study, the U-M researchers developed an ultrashort HPV droplet digital PCR (polymerase chain reaction) assay that enabled detection of TR-ctDNA from HPV-associated oropharyngeal squamous cell carcinoma (HPV OPSCC), BioTechniques reported.

The assay was made to target the HPV16 E6 (Human papillomavirus 16) gene and to measure TR-ctDNA in patients with HPV OPSCC, the JCI Insight paper noted.

“The HPV16 E6 gene represents a highly recurrent ctDNA target in the population of patients with HPV OPSCC,” the researchers wrote in JCI Insight, adding:

  • Targeting ultrashort fragments was essential “for robust TR-ctDNA detection.”
  • Results in urine with patients with HPV OPSCC was consistent with results from plasma ctDNA.

The test, still in the discovery phase, was mailed to patients who were being treated for the disease and who reside within 100 miles of Ann Arbor, Mich. They returned urine samples for testing at the U-M lab and to get insights into possible post-treatment needs.

“Using longitudinal urine samples from a small case series, we showed proof of concept for early detection of cancer recurrence. Thus, our results indicate that by targeting ultrashort DNA fragments, TR-ctDNA becomes a viable approach for HPV OPSCC detection and potentially for cancer recurrence monitoring after treatment,” the authors wrote.

Further Studies, Possible Test Expansion

HPV infection—and especially HPV type 16—is a growing risk factor for oropharyngeal cancers, according to the National Cancer Institute.

The U-M Rogel Cancer Center scientists plan more studies to leverage the information urine may carry about an individual’s health. The researchers intend to expand the scope of their new test to other cancers including breast cancer and acute myeloid leukemia.

“The test that has been developed has detected cancer far earlier than would typically happen based on clinical imaging. As such, these promising results have given us the confidence to broaden the scope of this study, seeking to expanding distribution even further,” said J. Chad Brenner, PhD, Associate Professor of Otolaryngology-Head and Neck Surgery, U-M Medicine, and co-senior author of the study, in the news release.

The University of Michigan Health study exemplifies scientists’ commitment to new categories of biomarkers that can be used for medical laboratory tests and prescription drugs. And by focusing on urine, the researchers made it possible for patients to collect specimens themselves and send them to the medical laboratory for analysis and reporting.  

—Donna Marie Pocius

Related Information:

University of Michigan Health Lab Researchers Discover Urine-based Test to Detect Head and Neck Cancer

ctDNA Transiting into Urine is Ultrashort and Facilitates Noninvasive Liquid Biopsy of HPV+ Oropharyngeal Cancer

Urine-based Test Detects Head and Neck Cancer

National Cancer Institute: Head and Neck Fact Cancers

;