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.
“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.”
“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.
Study findings could lead to new clinical laboratory diagnostics that give pathologists a more detailed understanding about certain types of cancer
New studies proving artificial intelligence (AI) can be used effectively in clinical laboratory diagnostics and personalized healthcare continue to emerge. Scientists in the UK recently trained an AI model using machine learning and deep learning to enable earlier, more accurate detection of 13 different types of cancer.
DNA stores genetic information in sequences of four nucleotide bases: A (adenine), T (thymine), G (guanine) and C (cytosine). These bases can be modified through DNA methylation. There are millions of DNA methylation markers in every single cell, and they change in the early stages of cancer development.
One common characteristic of many cancers is an epigenetic phenomenon called aberrant DNA methylation. Modifications in DNA can influence gene expression and are observable in cancer cells. A methylation profile can differentiate tumor types and subtypes and changes in the process often come before malignancy appears. This renders methylation very useful in catching cancers while in the early stages.
However, deciphering slight changes in methylation patterns can be extremely difficult. According to the scientists, “identifying the specific DNA methylation signatures indicative of different cancer types is akin to searching for a needle in a haystack.”
Nevertheless, the researchers believe identifying these changes could become a useful biomarker for early detection of cancers, which is why they built their AI models.
“Computational methods such as this model, through better training on more varied data and rigorous testing in the clinic, will eventually provide AI models that can help doctors with early detection and screening of cancers,” said Shamith Samarajiwa, PhD (above), Senior Lecturer and Group Leader, Computational Biology and Genomic Data Science, Imperial College London, in a news release. “This will provide better patient outcomes.” With additional research, clinical laboratories and pathologists may soon have new cancer diagnostics based on these AI models. (Photo copyright: University of Cambridge.)
The researchers then used a combination of machine learning and deep learning techniques to train an AI algorithm to examine DNA methylation patterns of the collected data. The algorithm identified and differentiated specific cancer types, including breast, liver, lung and prostate, from non-cancerous tissue with a 98.2% accuracy rate. The team evaluated their AI model by comparing the results to independent research.
In their Biology Methods and Protocols paper, the authors noted that their model does require further training and testing and stressed that “the important aspect of this study was the use of an explainable and interpretable core AI model.” They also claim their model could help medical professionals understand “the underlying mechanisms that contribute to the development of cancer.”
Using AI to Lower Cancer Rates Worldwide
According to the Centers for Disease Control and Prevention (CDC), cancer ranks as the second leading cause of death in the United States with 608,371 deaths reported in 2022. The leading cause of death in the US is heart disease with 702,880 deaths reported in the same year.
Globally cancer diagnoses and death rates are even more alarming. World Health Organization (WHO) data shows an estimated 20 million new cancer cases worldwide in 2022, with 9.7 million persons perishing from various cancers that year.
The UK researchers are hopeful their new AI model will help lower those numbers. They state in their paper that “most cancers are treatable and curable if detected early enough.”
More research and studies are needed to confirm the results of this study, but it appears to be a very promising line of exploration and development of using AI to detect, identify, and diagnose cancer earlier. This type of probing could provide pathologists with improved tools for determining the presence of cancer and lead to better patient outcomes.
By emphasizing HPV vaccinations while having clinical laboratories continue to perform Pap smears, Australia’s rate of cervical cancer has dropped notably
There is currently a global push to completely eradicate cervical cancer and Australia is leading the way with increased funding. It is also focusing on hard-to-reach and underserved populations. Australia is hoping to be first in the world to accomplish this feat by 2035.
For a number of decades, the Pap smear has been the primary screening tool for cervical cancer, as most pathologists and clinical laboratory managers know. However, today it plays a lesser role due to the effectiveness of HPV (human papillomavirus) diagnostic testing, which was put into cervical cancer screening guidelines in 2004.
Then came the first HPV vaccine in 2006. Australia was one of the first nations to implement HPV vaccination programs. By 2010, Australia was working to vaccinate every child. Now, 14 years later, the pool of adults vaccinated against HPV in that nation is causing the rates of cervical cancer to fall.
That means much less cervical cancer test volume for cytotechnologists and cytopathologists, freeing them up to devote their skills to other diagnostic tests.
As the country continues to funnel resources into hitting a zero cancer status, the additional drive will “connect Australia’s world-leading cervical cancer expertise with governments across the region to get HPV vaccine programs up and running, expand screening and treatment, and build health workforce capacity,” said Australia’s Minister for Foreign Affairs office in a press release.
“Australia has always punched above its weight when it comes to cervical cancer, and now Australia is on track to be the first country in the world to eliminate this deadly disease,” said Hon Ged Kearney, MP, RN (above), Assistant Minister for Health and Aged Care and a member of the government’s House of Representatives, in a press release. “By supporting the Pacific and Southeast Asia region [to] eliminate cervical cancer, we are another step closer to ridding the world of this disease.” Clinical laboratories and cytopathologists may soon see less reliance on Pap smears for screening and a shift toward HPV vaccinations to lower the rate of cervical cancer in the US as well. (Photo copyright: Australian Labor Party.)
90% of eligible people will be vaccinated against HPV (including girls and boys).
70% of eligible people will be screened every five years.
95% of eligible people will receive the best possible treatment for precancer and cancer.
In addition to $48.2 million in funding over four years, the program provides:
On the spot testing of samples in First Nations [aka, First Peoples] communities, allowing immediate follow up.
Support for nurses, First Nations health practitioners, and midwives to request pathology for cervical screening.
Increasing support for GPs to undertake colposcopies.
Helping the Underserved
Reaching a wider audience is a large part of Australia’s focus.
“One of my priorities is to address inequities in our health system. I want to make sure that everyone can get access to screening—and all healthcare—no matter where [they] live,” Kearney added. Among the populations sought are First Nations, LGBTIQA+, disabled individuals, and those living away from large cities.
“$8.3 million has been allocated to implement innovate screening models to support such communities,” the Minister for Foreign Affairs office noted in the press release.
Meeting people where they are, and reaching underserved populations, can make a huge difference, especially considering how cervical cancer affects these people. “First Nations women are almost twice as likely to be diagnosed with cervical cancer and face significant barriers to participating in cervical screening compared to non-indigenous women,” the press release notes.
“These tests allow privacy and help to break down barriers for thousands of people who have never screened—including women who have experienced sexual violence, LGBTIQA+ people, and culturally and linguistically diverse and First Nations communities,” the Minister for Foreign Affairs office stated.
There is hope that the push will cause a great shift to other underserved communities as well.
“A quarter of global cervical cancer cases occur in our region, the Indo-Pacific. Tragically, in the Pacific, women are dying at up to 13 times the rate of women in Australia,” said Penny Wong, Australian Minister for Foreign Affairs, in the press release.
How the US Fares in Cervical Cancer Vaccinations
Australia’s vaccination rates far exceed those in the United States. The US government currently recommends HPV vaccination between the ages of 11-12 years old, though it could be administered starting at age nine.
“HPV vaccination is recommended for all persons through age 26 years who were not adequately vaccinated earlier,” the NIH’s National Cancer Institute (NCI) reports.
For years the standard focus for cervical cancer screening has been on the Pap smear. Data show the US lags behind many countries on the rate of HPV vaccination. NCI data show that, as of 2021, in the US just 58.5% of 13-15 year-olds “had received two or three doses of HPV vaccine as recommended,” NCI reported.
With the US’s standard of care still focused on the Pap smear, patients are beginning their cervical cancer prevention journey at a later age. This is because the preliminary age to get a Pap smear in the US is 21 years old, with follow-up exams every three years, the NCI reported.
Even those in this country who are sexually active are not recommended to get screening earlier than 21.
The NCI recommends HPV testing every five years starting at age 30 until 65, with Pap tests every three years.
Clinical laboratories may soon find that, while the US has been slower to get on board with HPV vaccinations, trends in other nations indicate that this may soon change. The reliance that was once placed on the Pap smears prior to 2000 will likely give way to HPV vaccinations at ages and vaccination rates that mirror programs in countries like Australia—where marked reductions in the rate of cervical cancer demonstrate the effectiveness of a successful HPV vaccination program.
