DNA

HPV blood test shows promise for tracking head and neck cancer after treatment

Source: www.eurekalert.org
Author: from UNC Lineberger Comprehensive Cancer Center

A new blood test developed by University of North Carolina Lineberger Comprehensive Cancer Center researchers shows promise for tracking HPV-linked head and neck cancer patients to ensure they remain cancer-free after treatment.

Researchers will present preliminary findings at the 60th Annual Meeting of the American Society for Radiation Oncology in San Antonio on Tuesday, Oct. 23. Their study evaluated a blood test for HPV-linked oropharyngeal squamous cell carcinoma, which is a cancer of the back of the throat. The findings demonstrated the test could be an effective and less costly alternative for monitoring for cancer recurrence after radiation treatment.

“The goal of this study was to evaluate whether this test can be used to track patients who are completely asymptomatic, and thought to have no active cancer,” said UNC Lineberger’s Gaorav P. Gupta, MD, PhD, assistant professor in the UNC School of Medicine Department of Radiation Oncology. “We already knew that our test was very sensitive and specific, but we did not know the degree to which it would be useful in early detection of disease recurrence in patients who are otherwise thought to be disease-free.”

HPV, or the human papillomavirus, is the most common cause of sexually transmitted infection in the United States, according to the U.S. Centers for Disease Control and Prevention. Infection with certain strains of HPV can cause cervical cancer in women, genital cancers in both men and women, and cancer of the oropharynx, which is the back of the throat, including the base of the tongue and tonsils. The CDC estimates that approximately 70 percent of oropharyngeal cancer cases diagnosed in the United States are probably caused by HPV, which accounts for nearly 13,000 cases per year.

Gupta and his colleagues developed a blood test that can detect fragments of HPV’s genetic material that have been released into the blood by dying cancer cells.

“We realized it is important to distinguish HPV DNA that’s being released by dying tumor cells from the natural HPV DNA that is present during a viral infection,” Gupta said. “Our method accomplishes this feat, thus making it a more sensitive and specific test for cancer.”

For their study, the researchers followed 89 patients with HPV-associated oropharyngeal squamous cell carcinoma who received chemotherapy and radiation treatment. They administered the blood test before and during treatment, and then during follow-up visits. The patients received scans three months after treatment, and then came back for clinical exams every two to four months during the first two years, and then every six months in years three through five. Patients received X-rays or CT scans every six months, and again if they had positive HPV results.

“We are detecting subclinical disease with this blood test, and the imaging patients received confirmed those findings,” said UNC Lineberger’s Bhishamjit S. Chera, MD, associate professor in the UNC School of Medicine Department of Radiation Oncology and the study’s co-corresponding author. Chera presented the findings from the study at the ASTRO meeting.

Of the 70 patients whose blood tests were negative three months after treatment, none developed recurrence. Nineteen patients had positive blood tests, and eight of those patients developed recurrence. Physicians are continuing to monitor the remaining eleven who had positive blood tests but no evidence of recurrence.

“The most striking finding of our study is that of the patients who did not have any signal using our blood test, none of them developed disease recurrence,” Chera said. “That raises the question: Do we need to be scanning these patients? Scans come with a lot of cost, and because of the cost, we’re not able to do it as frequently. Patients end up having a lot of anxiety from one scan to the next, wondering if their cancer has come back. This blood test could spare patients the need for additional imaging and potentially alleviate some anxiety.”

The researchers say the next steps will involve investigating whether the test can be used prospectively to monitor patients and to make decisions that could avoid unnecessary imaging, thereby reducing costs. They also see additional applications for the blood test, including monitoring for other HPV-linked cancers, including cervical cancer.

“We are confident this blood test will be translatable to other cancers driven by HPV, and as a monitoring tool for cancer diagnosis,” Chera said. “We strongly believe that this test may also have a role in screening, not just for oropharyngeal cancer, but also cervical or anal cancers, possibly in a general population setting, or at least in patients who may be at higher risk of developing these conditions.”

In addition to Chera and Gupta, other authors include Sunil Kumar, PhD; Colette Shen, MD, PhD; Robert Amdur, MD; Roi Dagan, MD; Jared Weiss, MD; Juneko Grilley-Olson, MD; Adam Zanation, MD; Trevor Hackman, MD; Jeff Blumberg, MD; Samip Patel, MD; Brian Thorp, MD; Mark Weissler, MD; Nathan Sheets, MD; and William Mendenhall, MD.

The study was supported by the University Cancer Research Fund, Burroughs Wellcome Fund, the University of North Carolina School of Medicine Department of Radiation Oncology, UNC Lineberger and the University of Florida School of Medicine Department of Radiation Oncology.

Intellectual property related to the test and held by the University of North Carolina at Chapel Hill has been licensed to Naveris, a company in which Chera and Gupta hold equity stakes.

October, 2018|Oral Cancer News|

E-cigarettes ‘could give you mouth cancer by damaging your DNA’

Source: metro.co.uk
Author: Zoe Drewett

Researchers say vaping could lead to an increased risk of developing mouth cancer. A study carried out by the American Chemical Society found evidence to suggest using e-cigarettes raises the level of DNA-damaging compounds in the mouth. If cells in the body are unable to repair the DNA damage after vaping, the risk of cancer can increase, the study claims.

The long-term effects of e-cigarettes are not yet known but researchers say they should be investigated further (Picture: PA)

The researchers admit the long-term health effects of using electronic cigarettes are still unknown. Researcher Dr Romel Dator said: ‘We want to characterize the chemicals that vapers are exposed to, as well as any DNA damage they may cause.’

Since they were introduced in 2004, e-cigarettes have been marketed as a safer alternative to smoking. But the team carrying out the study claim genetic material in the oral cells of people who vape could be altered by toxic chemicals. E-cigarettes work by heating a liquid – which usually contains nicotine – into an aerosol that the user inhales. It is often flavoured to taste like fruit, chocolate or bubblegum.

‘It’s clear that more carcinogens arise from the combustion of tobacco in regular cigarettes than from the vapor of e-cigarettes,’ Silvia Balbo, the project’s lead investigator said. ‘However, we don’t really know the impact of inhaling the combination of compounds produced by this device. ‘Just because the threats are different doesn’t mean that e-cigarettes are completely safe.’ The latest study, due to be presented at a meeting of the American Chemical Society this week, analysed the saliva and mouth cells of five e-cigarette users before and after a 15-minute vaping session.

Researchers found levels of the toxic chemicals formaldehyde, acrolein and methylglyoxal had increased after vaping. Now they plan to follow up on the preliminary study with a larger one involving more e-cigarette users. They also want to see how the level of toxic chemicals differs between e-cigarette users and regular cigarette smokers.

According to a 2016 report by the US Surgeon General, 13.5% of middle school students, 37.7% of high school students and 35.8% of 18 to 24-year-olds have used e-cigarettes, compared with 16.4% of adults aged 25 and over. Ms Balbo, a professor at the Masonic Cancer Center at the University of Minnesota, said:

‘Comparing e-cigarettes and tobacco cigarettes is really like comparing apples and oranges.  The exposures are completely different. ‘We still don’t know exactly what these e-cigarette devices are doing and what kinds of effects they may have on health, but our findings suggest that a closer look is warranted.’

 

August, 2018|Oral Cancer News|

How oral bacteria could lead to breakthroughs in cancer, weight loss, and overall health

Source: www.mensjournal.com
Author: Marjorie Korn

As if you don’t have enough reasons to feel guilty for avoiding the dentist, it turns out a healthy mouth is linked to a lot more. than the absence of cavities and plaque. Researchers say our mouths are home to an ecosystem of billions of bacteria with influence far beyond our teeth and gums—influence they are just starting to unravel.

“We know that oral bacteria affect almost every aspect of our health—metabolism, cardiovascular system, neurological health, and more,” says Yiping Han, a microbiologist at Columbia University Dental and Medical Schools in New York City.

Scientists like Han are grappling with questions that will change our understanding of how the body works. Not only are they studying the ways bacteria in our mouths interact with one another but they’re also investigating why mouth bacteria show up in other parts of the body, such as the lining of the heart, around tumors, and even in the brain.

The idea that our bodies host a world of bacteria may sound familiar. For the past decade, we’ve seen a surge of scientific research on the gut microbiome, which describes the bacteria that live in the gastrointestinal tract. Gut bacteria seem to have a hand in a surprising number of functions, from the predictable (like digestion and nutrient uptake) to the more surprising (obesity and depression). So it makes sense that the next place for a breakthrough would be upstream—the mouth.

Scientists have identified 700-plus strains of bacteria swiped from cheeks around the world, which makes the mouth the second-largest microbiome in the body (just behind the GI tract). And they’re trying to figure out the roles of these strains. Sussing out what combination of bacteria makes a person healthy or sick would be a major step in staving off diseases.

For instance, certain bacteria are the culprits behind a bunch of maladies that send you to the dentist, like plaque, gum disease, and bad breath. Those kinds of discoveries get dentists excited. That said, what’s really interesting is that oral bacteria pop up all over the body and are linked to a host of other medical issues.

This newfound knowledge is made possible by advancements in DNA and RNA decoding, and microscopic imaging. Scientists upload new information to oral microbiome repositories at the Forsyth Institute in Cambridge, Massachusetts; Ohio State University; and Los Alamos National Laboratory in New Mexico.

This knowledge sharing has helped to unravel some long-standing medical mysteries. For instance, doctors have, for decades, puzzled over why people with cardiovascular issues, like endocarditis (an infection of the lining of the heart) or clogged arteries, also have gum disease. Turns out that the inflamed gums allow oral bacteria to get into the bloodstream, where they can wreak havoc on the heart and vessels.

That’s not the only way that bacteria in the mouth end up elsewhere. Swallowing a teaspoon of saliva disperses 5 million bacteria into your digestive tract, says Colleen Cavanaugh, a biology researcher at Harvard University. (Preliminary findings suggest that oral sex can be a conduit, too, Han says.)

“It’s a mobile microbiome,” Han says. “There are some bacteria that, when they’re in the mouth, they’re mostly harmless, but when they go to other sites in the body, they become pathogens,” Han says.

Take Fusobacterium nucleatum, or Fn for short. In your mouth, it causes dental plaque. But it’s a menace if it encounters a colon cancer tumor. Han’s lab has found that Fn acts as an accelerant, prompting a tumor to grow faster, protecting it from chemotherapy drugs, and encouraging it to metastasize to the liver (which is particularly dangerous). Fn has also been found in the joint fluid in people with rheumatoid arthritis, an inflammatory disease. And it’s even been detected in brain abscesses, meaning it has the ability to jump the blood-brain barrier, which is quite a feat— very few substances that float in the blood can get to the brain and spinal cord.

Does Fn cause colon cancer? No. But down the road, knowing that a patient’s tumor is being bodyguarded by Fn may change the way he’s cared for.

And new research suggests that the oral bacteria can also have a direct impact on how cancer plays out. A study published in Scientific Reports found that people who are diagnosed with oral or throat cancers—which are notoriously difficult to treat and have high rates of mortality—had similar oral microbiome compositions.

There are a couple of explanations for why people with the same disease would share similar bacteria. It could be that bad habits like drinking, smoking, and poor oral hygiene create the perfect conditions for certain bacteria to grow (and others to die off). Genetics probably play a role, in that a person’s mouth is predisposed to having more of some bacteria, less of others. Most likely, it’s a little bit of both. Regardless, knowing how the microbiome changes composition when it’s sick may help doctors prevent and treat disease.

Scientists are interested not only in the bacteria they find but also in what they don’t. A six-year study from the University of Copenhagen finds that not enough of bacteria called Lactobacillus can be a predictor of weight gain. We’re not at the place that simply peppering a person’s mouth with some Lactobacillus would get people to drop pounds. But that could be where things are headed.

Bacteria also interact with one another. It’s an ecosystem, after all. Decoding these relationships could be the beginning of a new way to treat oral issues, says Ted Jin. He’s the founder of Qii, which makes a canned tea drink designed to encourage balanced mouth bacteria. The beverage is more anti-plaque than anti-cancer, but it’s part of a larger effort by Jin and his team of researchers to understand the intricacies of the mouth biome in order to make better oral-care products down the road.

What experts are learning about the state of our maws isn’t entirely rosy. For one, there’s a hypothesis that the mouths of people in the U.S. aren’t as diverse as they should be. Crappy, overly processed diets with too much sugar and not enough fresh produce are not great for a healthy oral ecosystem. Nor is our fascination with all things antibacterial, which is why experts are beginning to discourage patients from using harsh mouthwashes that kill good and bad bacteria indiscriminately. (The Food and Drug Administration banned certain ingredients in antibacterial hand soap in 2016, in part because they were killing off good bacterial strains and promoting “superbugs.”)

These differences may also help explain why there are areas of the world with less-advanced oral hygiene practices, but where people generally have teeth and gums that are just fine. And in addition to geography and diet, there’s certainly a genetic component to all of this, so if your kid’s got a mouthful of cavities, you’re at least partially to blame.

Another upshot to all of this will come in the form of precision medicine. In the future, you may be able to send off some spit and receive back a mouthwash tailored specifically for your oral microbiome, Jin says. If you have too much of a certain bacteria strain, you could swish with a formula that contains another, which would act like a microscopic smart bomb to get conditions like halitosis (bad breath) or gum disease under control.

You don’t have to wait for the mouthwash of the future to do right by your mouth. For starters, eat a Mediterranean diet, says Jason Tetro, a visiting scientist at the University of Guelph in Ontario and author of The Germ Code. “Staples of the diet, such as fish and vegetables, have omega fatty acids and phytochemicals,” Tetro says. “And in some cases, things like pomegranates have antimicrobials, which seek out and kill bad bacteria and help maintain a less acidic environment.”

His secret weapon against oral inflammation? The sesame paste tahini. It helps promote an alkaline environment in the mouth, Tetro says. So if your maw feels a little sore from fast food or booze, swish with a spoonful of tahini for some low-tech relief.

And low-tech is kind of the point. While researchers like Han are teasing out microscopic secrets, one petri dish at a time, what we’re learning seems to substantiate what we already know. Brushing and flossing is still a great way to keep your oral microbiome healthy. And no more excuses: time to schedule that dentist appointment.

Changes in cancer staging: what you should know

Source: health.clevelandclinic.org
Author: staff

When you learn you have cancer, you want to know what to expect: How will doctors treat your illness? How effective is treatment likely to be?

Much depends on the way doctors first classify, or “stage,” your cancer, using the official staging manual from the American Joint Committee on Cancer. Staging guidelines continue to evolve as knowledge about individual tumor growth and innovative technologies come into play.

An ever-evolving system
“Historically, we staged cancers according to tumor size, lymph node involvement and the presence of metastases,” says oncologist Dale Shepard, MD, PhD.

“The latest staging manual incorporates new findings on the importance of changes in molecular DNA and tumor genomic profiling. This will affect many patients going forward.”

Among those most impacted by changes in staging are people newly diagnosed with breast cancer; head and neck cancer caused by human papillomavirus (HPV); or sarcoma.

How staging works
“Staging allows us to stratify patients into groups based on anatomic and other criteria. It gives us a framework for understanding the extent of disease,” Dr. Shepard explains.

Cancers are staged clinically and pathologically:

  • The clinical stage is determined during the initial workup for cancer.
  • The pathologic stage is determined by studying a surgically removed tumor sample under the microscope.

Adds Tumor Registry Manager Kate Tullio, MPH, MS, “Staging helps physicians and other researchers to compare patients with the same types of cancer to each other in a consistent way — so that we might learn more about these cancers and how to effectively treat them.”

Staging allows doctors to determine the best course of treatment for different types of cancer and helps families to understand the prognosis, or likely outcome, of that treatment.

It also allows doctors to offer patients a chance to participate in clinical trials of new therapies targeting their form of cancer.

The impact of DNA changes on breast cancer
In the past, most breast cancer patients with lymph node involvement were automatically classified as stage II or higher, and were often given chemotherapy.

“Previously, physicians considered only tumor size, lymph node involvement and spread of the cancer to distant areas of the body when staging breast cancer,” says Ms. Tullio.

Today, staging has improved with the addition of advanced multi-gene panel testing and specific information on the biology of the tumor.

“This incorporates what we have found clinically: that some patients previously identified with stage II breast cancer did better than others,” says Dr. Shepard. “In essence, patients with HER2-positive disease were more like patients with stage I disease.”

HPV’s effect on head and neck cancers
The classification of head and neck tumors has changed because of advances in genomic profiling.

“We now have a separate system for classifying head and neck cancer caused by HPV infection because we realize that, clinically, it is a different disease,” says Dr. Shepard.

Ms. Tullio notes that patients with head and neck cancers caused by HPV have a better prognosis — living longer, on average, than head and neck cancer patients without HPV.

“Patients with HPV-positive mouth or throat cancers usually respond well to treatment and may need less aggressive therapy than those who are HPV-negative,” she says.

Also new, adds Dr. Shepard, are separate classification systems for soft-tissue cancers called sarcomas. Doctors have found that, based on the primary tumor’s location, sarcomas will behave and respond to treatment differently.

How will these changes affect you?
The impact of these staging changes will be far greater for patients with cancers diagnosed on or after Jan. 1, 2018.

“If your cancer is new, then changes in classification may affect early decisions about your initial care and likely prognosis,” says Dr. Shepard.

If you received a cancer diagnosis before that date, the stage of your tumor will not change, Ms. Tullio notes. However, new data in the manual may allow your doctors to better assess and treat you.

Adds Dr. Shepard, “Talk to your doctor if you have any questions about the new staging systems. It’s important to be sure all the right tests are ordered to accurately assess your cancer.”

DNA shed from head and neck tumors detected in blood and saliva

Source: www.medicalexpress.com
Author: Wang et al., Science Translational Medicine (2015)
 
558ae7a9b6d9b-2
Schematic showing the shedding of tumor DNA from head and neck cancers into the saliva or plasma. Tumors from various anatomic locations shed DNA fragments containing tumor-specific mutations and human papillomavirus DNA into the saliva or the circulation. The detectability of tumor DNA in the saliva varied with anatomic location of the tumor, with the highest sensitivity for oral cavity cancers. The detectability in plasma varied much less in regard to the tumor’s anatomic location. Credit: Wang et al., Science Translational Medicine (2015)

 

On the hunt for better cancer screening tests, Johns Hopkins scientists led a proof of principle study that successfully identified tumor DNA shed into the blood and saliva of 93 patients with head and neck cancer. A report on the findings is published in the June 24 issue of Science Translational Medicine.

“We have shown that tumor DNA in the blood or saliva can successfully be measured for these cancers,” says Nishant Agrawal, M.D., associate professor of otolaryngology—head and neck surgery—and of oncology at the Johns Hopkins University School of Medicine. “In our study, testing saliva seemed to be the best way to detect cancers in the oral cavity, and blood tests appeared to find more cancers in the larynx, hypopharynx and oropharynx. However, combining blood and saliva tests may offer the best chance of finding cancer in any of those regions.”

Agrawal explains that inborn genetic predispositions for most head and neck cancers are rare, but other mutations that don’t generally occur in normal cells have long been considered good targets for screening tests.

In the case of head and neck cancers associated with HPV—tumors on the rise among Americans—Agrawal and his colleagues searched patients’ blood and saliva samples for certain tumor-promoting, HPV-related DNA. For non-HPV-related cancers, which account for the worldwide majority of head and neck tumors, they looked for mutations in cancer-related genes that included TP53, PIK3CA, CDKN2A, FBXW7, HRAS and NRAS.

The major risk factors for head and neck cancers are alcohol, tobacco—including chewing tobacco—and HPV infection.

For the study, 93 patients with newly diagnosed and recurrent head and neck cancer gave saliva samples, and 47 of them also donated blood samples before their treatment at The Johns Hopkins Hospital and MD Anderson Cancer Center in Texas. The scientists detected tumor DNA in the saliva of 71 of the 93 patients (76 percent) and in the blood of 41 of the 47 (87 percent). In the 47 who gave blood and saliva samples, scientists were able to detect tumor DNA in at least one of the body fluids in 45 of them (96 percent).

When the scientists analyzed how well their tumor DNA tests found cancers in certain regions of the head and neck, they found that saliva tests fared better than blood tests for oral cavity cancers. All 46 oral cavity cancers were correctly identified through saliva tests, compared with 16 of 34 oropharynx cancers (47 percent), seven of 10 larynx cancers (70 percent) and two of three hypopharynx cancers (67 percent).

The oral cavity refers to areas within the mouth, including the lips, front of the tongue, cheeks and gums. The oropharynx and hypopharynx are located in the back of the throat. The larynx, also in the throat, is typically known as the voice box.

“One reason that saliva tests may not have been as effective for cancer sites in the back of the throat is because we didn’t ask patients to gargle; we only asked them to rinse their mouths to provide the samples,” says Agrawal, a member of Johns Hopkins’ Kimmel Cancer Center and Ludwig Center.

Blood tests correctly identified tumor DNA more often in 20 of 22 oropharynx cancers (91 percent), six of seven larynx cancers (86 percent) and all three hypopharynx cancers. Taken together, blood and saliva tests correctly identified all oral cavity, larynx and hypopharynx cancers and 20 of 22 oropharynx cancers (91 percent).

Agrawal says the sensitivity of the tests overall depended on the cancer site, stage and HPV status, ranging between 86 to 100 percent. He also reports that saliva tests performed better for early-stage cancers, finding all 20 cancers, compared with blood tests that correctly identified seven of 10. He and his team found the opposite was true for late-stage cancers: Blood tests found more late-stage cancers (34 of 37), compared with saliva tests (51 of 73). Blood tests also correctly identified HPV-related tumors, occurring in 30 of the 93 patients, more often than saliva tests, probably because HPV-related tumors tend to occur in the back of the throat, which may not have been reached with the saliva rinse.

“Our ultimate goal is to develop better screening tests to find head and neck cancers among the general population and improve how we monitor patients with cancer for recurrence of their disease,” says Bert Vogelstein, M.D., the Clayton Professor of Oncology at the Johns Hopkins Kimmel Cancer Center, co-director of the Ludwig Center at Johns Hopkins and a co-author of the study.

The scientists caution that further study of their tumor DNA detection method in larger groups of patients and healthy people is needed before clinical effectiveness can be determined, and that refinements also may be needed in methods of collecting saliva and the range of cancer-specific genes in the gene test panel.

In addition, Agrawal says: “We don’t yet have definitive data on false positive rates, and won’t until there are more studies of the tests in healthy people.” However, he notes, the formulas used to analyze their blood and saliva tests are designed to weed out questionable results.

False results in gene tests arise when DNA are copied many times, sequenced and analyzed. The scientists used a method they developed and tested previously in cervical fluid to find ovarian and cervical cancers. Specifically, they attach a kind of genetic bar code—a random set of 14 DNA base pairs—to trace each copied DNA fragment to its original one. DNA copies lacking the bar code are suspected to be an artifact of the process, and any mutation found in it is disregarded.

Agrawal says that tests like the one his team used, if used commercially, likely would cost several hundred dollars, and “our long-term goal is to create a test that costs less than $50 so it can be administered by physicians or dentists.”

To screen for head and neck cancers, which occur in more than 50,000 people in the U.S. each year, doctors conduct physical examinations. Biopsies are taken of suspicious-looking lesions, but “this method is not ideal, as evidenced by the fact that most head and neck cancers are rarely found at very early stages, when they are most curable,” says Agrawal.

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

Genetic markings could spot cancer before it develops

Source: www.thealmagest.com
Author: press release

Unique DNA markings on certain genes may “predict” the risk of developing head and neck cancer, according to new research led by Queen Mary University of London.

The findings, published in the journal Cancer, raise the potential for the development of non-invasive tests which could pick up these tell-tale signs of early cancer initiation.

Head and neck cancers are cancers that develop anywhere in the head and neck, including mouth cancer and throat cancer. About 16,000 people in the UK are diagnosed with head and neck cancer every year*.

In this study scientists analysed clinical specimens of malignant tissue from 93 cancer patients from Norway and the UK. These were compared with either tissue donated by healthy individuals undergoing wisdom tooth extractions, or with non-cancerous tissue from the same patients.

They were trying to identify whether there were any epigenetic changes in the cancerous cells which were not seen in the healthy cells. Epigenetics is the study of changes in gene expression caused by mechanisms other than changes in the underlying DNA sequence.

Not all genes are active all the time and there are many ways that gene expression is controlled. DNA methylation marks act as ‘switches’, either turning genes on or off. Abnormal DNA methylation is known to precede cancer initiation.

Lead researcher Dr Muy Teck-Teh, from the Institute of Dentistry at Queen Mary, said: “In this study we have identified four genes which were either over or under-expressed in head and neck cancer. The expression of these genes was inversely correlated with particular DNA methylation marks, suggesting the genes are epigenetically modified in these cancers.

“These epigenetic markers could be clinically exploited as biomarkers for early pre-cancer screening of head and neck cancer. However, further work is needed, as we are purely at the discovery stage at the moment and have not used this as a diagnostic test as yet.

“The eventual aim would be to test asymptomatic patients and/or people with unknown mouth lesions. An advantage of epigenetic DNA markers is that it may be possible to measure them using non-invasive specimens. So it could enable the use of saliva, buccal scrapes or blood serum for early cancer screening, diagnosis and prognosis.”

Consultant oral and maxillofacial surgeon Professor Iain Hutchison, co-author on the study, said he was excited by the possibility of diagnostic tests as a result of the research.

“All of us mouth cancer surgeons want to catch the cancer early when the chances of cure are high and the effects of surgery on the patient are minimal. A simple test using the patient’s blood or saliva could mean many patients with pre-cancer changes in the mouth or throat will be treated early and the cancer will never progress.”

The study was partly funded by the research charity Saving Faces – The Facial Surgery Research Foundation. Professor Hutchison founded the charity, which aims to reduce facial injuries and diseases through medical research.

December, 2013|Oral Cancer News|

HPV Can Damage Genes and Chromosomes Directly, Whole-Genome Sequencing Study Shows

Press release from the James Cancer Center 

 

COLUMBUS, Ohio – The virus that causes cervical, head and neck, anal and other cancers can damage chromosomes and genes where it inserts its DNA into human DNA, according to a new study led by researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James).

It’s long been known that cancer-causing types of human papillomavirus (HPV)  produce two viral proteins, called E6 and E7, which are essential for the development of cancer. However, they are not sufficient to cause cancer. Additional alterations in host-cell genes are necessary for cancer to develop. Here, scientists identified a new mechanism by which HPV may damage host DNA directly and contribute to cancer development.

Published in the journal Genome Research, this laboratory study used whole-genome sequencing to investigate the relationship between the HPV and host genomes in human cancers.

“Our sequencing data showed in vivid detail that  HPV can damage host-cell genes and chromosomes at sites of viral insertion,” says co-senior author David Symer, MD, PhD, assistant professor of molecular virology, immunology and medical genetics at the OSUCCC – James.

“HPV can act like a tornado hitting the genome, disrupting and rearranging nearby host-cell genes,” Symer explains. “This can lead to overexpression of cancer-causing genes in some cases, or it can disrupt protective tumor-suppressor genes in others. Both kinds of damage likely promote the development of cancer.”

“We observed fragments of the host-cell genome to be removed, rearranged or increased in number at sites of HPV insertion into the genome,” says co-senior author Maura Gillison, MD, PhD, professor of medicine, epidemiology and otolaryngology and the Jeg Coughlin Chair of Cancer Research at the OSUCCC – James. “These remarkable changes in host genes were accompanied by increases in the number of HPV copies in the host cell, thereby also increasing the expression of viral E6 and E7, the cancer-promoting genes.”

HPV causes about 610,000 cancers annually worldwide, including virtually all cervical cancers, and many anogenital and head and neck cancers. How it causes cancer isn’t completely understood.

The two cancer-causing proteins, E6 and E7, silence two key tumor-suppressor genes in host cells, contributing to cancer development. “E6 and E7 are critically important for the virus to cause cancer. Our findings shed light on how HPV, and perhaps other viruses, can disrupt the structure of host chromosomes and genes and thereby contribute to cancer development,” Gillison explains.

For this study, Symer, Gillison and their colleagues examined 10 cancer-cell lines and two head and neck tumor samples from patients. Along with whole-genome sequencing, the scientists used several molecular assays, including RNA sequencing, spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH).

Key technical findings included:

• The genome-wide analysis, at single nucleotide resolution, identified a striking and recurrent association between HPV integrants and adjacent genomic amplifications, deletions and translocations;

• The HPV integrants mapped broadly across the human genome, with no evidence of recurrent integration into particular chromosomal hotspots;

• The researchers proposed a “looping” model by which abnormal viral replication results in the extraordinary damage that occurs to host chromosomes at the sites of viral DNA insertion.

“Our study reveals new and interesting information about what happens to HPV in the ‘end game’ in cancers,” Symer says. “Overall, our results shed new light on the potentially critical, catastrophic steps in the progression from initial viral infection to development of an HPV-associated cancer.”

Funding from the Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James), the Ohio Supercomputer Center, an Ohio Cancer Research Associate grant, the Oral Cancer Foundation and the Intramural Research Program of the National Institutes of Health, National Cancer Institute Center for Cancer Research, supported this research.

 

Black raspberries reduce DNA damage in oral cancer survivors

Source: www.prweb.com
Author: press release

New research presented Wednesday, April 10, at the American Association for Cancer Research Annual Meeting 2013 in Washington, DC, suggests that a food-based cancer prevention study aimed at oral cancer survivors was effective at attenuating highly reactive oxygen molecules that can damage DNA and trigger cancer. In the study, a phase 1b clinical trial conducted at The Ohio State University, participants consumed 4 – 8 grams of black raspberries daily for six months. The berries were well tolerated by the participants and adherence to the regimen was good.

This study provides compelling data that indicate biochemical markers of cancer-causing DNA damage were reduced in participants who adhered to the food-based regimen and supports other evidence from a phase 2 human trial linking application of black raspberry gel to precancerous lesions to a reduced risk of developing oral cancer.

Black raspberries, not to be confused with blackberries, are almost exclusively grown in Oregon, on the west coast of the United States. They have been studied extensively because of their high concentration of certain phytonutrients and antioxidants. BerriProducts, an Oregon-based company, has been supplying black raspberry products to research universities across the country for the last four years.

April, 2013|Oral Cancer News|

Researchers document molecular tumor subtypes of head and neck cancer

Source: www.oncologynurseadvisor.com
Author: Kathy Boltz, PhD

Head and neck squamous cell carcinoma (HNSCC) is the seventh most common form of cancer in the United States. However, other than an association with the human papillomavirus (HPV), no validated molecular profile of the disease has been established. By analyzing data from DNA microarrays, a study has confirmed the presence of four molecular classes of the disease. Also, previous results have been extended by suggesting an underlying connection between the molecular classes and observed genomic events, some of which affect cancer genes. This study also demonstrated the clinical relevance of the classes and certain genomic events, paving the way for further studies and possible targeted therapies.

“Cancer is a disease caused by alteration in the DNA and RNA molecules of tumors. A cancer results when broken molecules initiate a cascade of abnormal signals that ultimately results in abnormal growth and spread of tissues that should be under tight control within the body,” said Neil Hayes, MD, MPH, of the University of North Carolina Lineberger Comprehensive Cancer Center and of The Cancer Genome Atlas.

“However, most common tumors, including head and neck cancer, have relatively little information in the public record as to how these signals coordinate to create different patterns of abnormalities. This study is among the largest ever published to document reproducible molecular tumor subtypes. Subtypes, such as those we describe, represent attractive models to understand and attack cancers for treatment and prognosis.”

The team analyzed a set of nearly 140 HNSCC samples. By searching for recurrent patterns known as gene expression signatures, they detected four gene expression subtypes. These subtypes are termed basal, mesenchymal, atypical, and classical, based on similarities to established gene expression subtypes in other tumor types and expression patterns of specific genes. For potential clinical use, these subtypes are complementary to classification by HPV status and the putative high-risk marker CCND1 copy number gain.

In spite of being the seventh most common form of cancer in the United States, HNSCC is relatively understudied in comparison to other tumor types (eg, breast and lung). By leveraging the similarities found in the gene expression subtypes, the results of this study provide a connection to a range of well-established findings and additional insight into the disease.

Source: This study was published in PLOS ONE (2013; doi:10.1371/journal.pone.0056823).

March, 2013|Oral Cancer News|

DNA adducts linked to oral cancer in smokers

Source: www.news-medical.net
Author: Sarah Guy, medwireNews Reporter

Having a high susceptibility to certain types of DNA damage caused by tobacco smoking could significantly increase the risk for oral cancer, show results of a Taiwanese study.

Levels of BaP 7,8-diol 9,10-epoxide (BPDE) – a metabolite of Benzo[a]pyrene, an important carcinogen found in cigarette smoke – correlated positively with smoking status in a cohort of individuals with oral cancer, report the researchers.

The findings also indicate a significantly increased risk for oral cancer among individuals with high DNA adduct levels compared with their peers with low levels.

“Based on our finding, we suggest that detected BPDE-like DNA adducts could be used as a biomarker for oral cancer risk,” write Huei Lee (Taipei Medical University) and colleagues in the Archives of Oral Biology.

The team analyzed BPDE-DNA adduct levels in oral tissue samples from 158 oral cancer patients and 64 individuals without cancer (controls), using immunohistochemistry and enzyme-linked immunosorbent assay (ELISA).

The results of these assays significantly and positively correlated , so that immunohistochemistry-negative patients did not have detectable DNA adduct levels using ELISA and vice versa.

DNA adduct levels also positively correlated with smoking status among the cancer patients, note the researchers, with significantly higher adduct levels among smokers than nonsmokers, at 93.18 versus 0.04 adducts per 108 nucleotides.

Lee and co-workers also observed that cancer patients had significantly higher DNA adduct levels than controls, at a range of 0-358.00 versus 0-39.50 adducts per 108 nucleotides.

Indeed, DNA adduct level was an independent risk biomarker for oral cancer in multivariate analysis, which indicated a 9.94-fold increased risk for the disease among individuals with high levels, defined as more than two standard deviations above the mean adduct level in the low group – which equates to 34.03 adducts per 108 nucleotides.

“These results strongly suggest that a high susceptibility to DNA damage derived from exposure to cigarette carcinogens is associated with the high risk of oral cancer in Taiwanese oral cancer patients,” conclude Lee et al.

Source: medwireNews

January, 2013|Oral Cancer News|