Oral Cancer Foundation News Team - A

About Oral Cancer Foundation News Team - A

This author has not yet filled in any details.
So far Oral Cancer Foundation News Team - A has created 2040 blog entries.

New blood test capable of detecting multiple types of cancer

Source: www.sciencedaily.com
Author: Materials provided by Dana-Farber Cancer Institute.

A new blood test in development has shown ability to screen for numerous types of cancer with a high degree of accuracy, a trial of the test shows. Dana-Farber Cancer Institute investigators will present the results of the multi-center trial during a session today at the European Society for Medical Oncology (ESMO) 2019 Congress.

The test, developed by GRAIL, Inc., uses next-generation sequencing technology to probe DNA for tiny chemical tags (methylation) that influence whether genes are active or inactive. When applied to nearly 3,600 blood samples — some from patients with cancer, some from people who had not been diagnosed with cancer at the time of the blood draw — the test successfully picked up a cancer signal from the cancer patient samples, and correctly identified the tissue from where the cancer began (the tissue of origin). The test’s specificity — its ability to return a positive result only when cancer is actually present — was high, as was its ability to pinpoint the organ or tissue of origin, researchers found.

The new test looks for DNA, which cancer cells shed into the bloodstream when they die. In contrast to “liquid biopsies,” which detect genetic mutations or other cancer-related alterations in DNA, the technology focuses on modifications to DNA known as methyl groups. Methyl groups are chemical units that can be attached to DNA, in a process called methylation, to control which genes are “on” and which are “off.” Abnormal patterns of methylation turn out to be, in many cases, more indicative of cancer — and cancer type — than mutations are. The new test zeroes in on portions of the genome where abnormal methylation patterns are found in cancer cells.

“Our previous work indicated that methylation-based assays outperform traditional DNA-sequencing approaches to detecting multiple forms of cancer in blood samples,” said the study’s lead author, Geoffrey Oxnard, MD, of Dana-Farber. “The results of the new study demonstrate that such assays are a feasible way of screening people for cancer.”

In the study, investigators analyzed cell-free DNA (DNA that had once been confined to cells but had entered the bloodstream upon the cells’ death) in 3,583 blood samples, including 1,530 from patients diagnosed with cancer and 2,053 from people without cancer. The patient samples comprised more than 20 types of cancer, including hormone receptor-negative breast, colorectal, esophageal, gallbladder, gastric, head and neck, lung, lymphoid leukemia, multiple myeloma, ovarian, and pancreatic cancer.

The overall specificity was 99.4%, meaning only 0.6% of the results incorrectly indicated that cancer was present. The sensitivity of the assay for detecting a pre-specified high mortality cancers (the percent of blood samples from these patients that tested positive for cancer) was 76%. Within this group, the sensitivity was 32% for patients with stage I cancer; 76% for those with stage II; 85% for stage III; and 93% for stage IV. Sensitivity across all cancer types was 55%, with similar increases in detection by stage. For the 97% of samples that returned a tissue of origin result, the test correctly identified the organ or tissue of origin in 89% of cases.

Detecting even a modest percent of common cancers early could translate into many patients who may be able to receive more effective treatment if the test were in wide use, Oxnard remarked.

Note:
Materials provided by Dana-Farber Cancer Institute. Content may be edited for style and length.

September, 2019|Oral Cancer News|

AI can predict the chances of surviving oral cancer

Source: medicalxpress.com
Author: University of Warwick

Whole slide images are multi-gigapixel images and cannot be used directly for image analysis tasks particularly training a deep learning based classifier. Therefore, we divide the WSIs into small regions (patches) for processing. A deep learning based classifier is applied on the patches to identify whether the patch contains tumour, lymphocytes or other histological primitives. However, the regions where the lymphocytes are infiltrating the tumour may not be confined within a patch. Besides, there is considerable variation in the size of TIL regions, making the quantification of TILs a non-trivial task. We address this issue by adopting the widely accepted definition of TILs, i.e., lymphocytes that lie in the neighbourhood of tumour areas. The patch labels predicted as lymphocytes or tumour are then used to compute a statistical measure of co-localization, which is further incorporated into the computation of the TILAb score of lymphocytic infiltration. Credit: University of Warwick

 

The chances of surviving oral cancers can be predicted by state of the art AI algorithms—developed by scientists at the Department of Computer Science at the University of Warwick—that precisely calculate the abundance of immune cells in the midst of tumour cells to help better understand the spread of and resistance to cancer.
In 2014 there were more than 11,000 cases of head and neck cancers in the UK and more than 2,300 deaths resulting from the most common of them; oral cavity cancer.

Oral cancer is most prevalent in South Asia, particularly India, Pakistan and Sri Lanka, mainly due to tobacco chewing, betel quid consumption and viral infections such as HPV (Human papillomavirus).

The chances of surviving such cancers can be predicted thanks to research in a pilot study from the University of Warwick’s Department of Computer Science in the paper “A Novel Digital Score for Abundance of Tumour Infiltrating Lymphocytes Predicts Disease Free Survival in Oral Squamous Cell Carcinoma,” published today, Monday 16 September, in the journal Nature Scientific Reports.

Researchers managed to develop a digital score that could measure Tumour Infiltrating Lymphocytes (TILs). The more TILs present the higher the chance of survival and longer disease free survival of oral cancer.

The images were produced by scans from patients at Shaukat Khanum Memorial Cancer Hospital Research Centre in Pakistan, who had all already been treated by radiation and a head and neck surgery. The cancer tissue samples were then sent to University Hospital Coventry and Warwickshire in the UK, where using a state of the art imaging machine researchers were able to digitally produce high-resolution images of the samples at a microscopic scale.

The presence of lymphocytes in the vicinity of the tumor cells doesn’t only help determine the stage of the cancer, it can be used to predict the progression of it accurately.

The more TILs present in the scans indicates the patient’s immunity to the cancer and the response to treatment, and the density and spatial arrangement of TILs correlates with the chances of overall survival and disease free survival.

Professor Nasir Rajpoot from the Department of Computer Science at the University of Warwick, who led the study, comments:

“We are only beginning to unravel the remarkable potential of wealth of information present in pathology image data. This pilot study shows that with the help of modern cancer image analytics algorithms, we can precisely calculate the score of abundance of TILs in oral cancers in an objective manner and then use that score for risk stratification in terms of disease free survival.”

Prof Hisham Mehanna, Professor of Head & Neck Oncology at the University of Birmingham, comments:

“This is a very exciting development. Not only is this one of the first artificial intelligence based scores to be validated in oral cancer, this score also seems to have a strong prognostic power, which could eventually lead to stratifying patients for different treatment modalities.”

Dr. Asif Loya, Medical Director at the Shaukat Khanum Memorial Cancer Hospital & Research Centre in Pakistan where the patient samples were sourced from, comments:

“With almost 13,000 new cases every year, oral cancers have the highest incidence rates among cancers in Pakistan, second highest mortality rate, and a very low five-year survival. However, there is little known about the histological signatures corresponding to patient subgroups with differing outcomes in this part of the world. Histologic risk assessment is strongly predictive of local disease-free and overall survival in oral squamous cell carcinoma thus there is need for a validated scoring system to be used as an aid in treatment decision making in these cancers in our patients . Strong pilot data from this collaborative research using the objective assessment method of digital analysis may play a role in establishing such prognostication models so that treatment decisions related to elective neck dissection (END) and adjuvant radiotherapy can be made more appropriately.”

September, 2019|Oral Cancer News|

Researchers: Favorable survival, fewer side effects after reduced therapy for HPV-linked head and neck cancer

Source: medicalxpress.com
Author: University of North Carolina at Chapel Hill School of Medicine

University of North Carolina Lineberger Comprehensive Cancer Center researchers reported that reducing the intensity of radiation treatment for patients with human papillomavirus-associated head and neck cancer produced a promising two-year progression-free survival rate and resulted in fewer side effects.

The findings, published in the Journal of Clinical Oncology, were drawn from a phase II clinical trial that included 114 patients with HPV-linked head and neck cancer and a limited smoking history. The researchers reported that they saw a similar progression free survival rate, and that patients experienced fewer long-term side effects in the study compared with patients who received standard intensity treatment in previous studies.

“A simple de-intensification strategy of reducing radiation and chemotherapy appears to be as effective at cancer control as the standard seven-week regimen,” said UNC Lineberger’s Bhishamjit S. Chera, MD, associate professor in the UNC School of Medicine Department of Radiation Oncology. “Furthermore, there were fewer toxicities.”

For the trial, patients received six weeks of treatment, including a reduced intensity of radiation therapy of 60 Gray with weekly low-dose chemotherapy of cisplatin. The standard of care regimen is seven weeks of treatment 70 Gray and high-dose chemotherapy.

The main outcome that the researchers were studying was two-year progression-free survival. On the reduced regimen, researchers found that the two-year progression free survival was 86 percent, compared to a two-year progression free survival reported from other studies using standard treatment doses of 87 percent.

Chera said the major long-term side effects of radiation treatment are related to swallowing and dry mouth. Previous studies have shown the majority of patients treated with standard intensity chemoradiotherapy require a temporary feeding tube and some have significant long-term swallowing dysfunction.

Notably, in this study, patients reported that their swallowing returned to baseline after de-intensified treatment, and only 34 percent required a temporary feeding tube.

The results need to be validated in larger, randomized clinical trials, Chera said, and studies are ongoing to investigate this.

He added that while this study included patients with a limited smoking history, other current studies include patients with more extensive smoking histories.

Chera said that researchers want to continue to improve two-year progression free response rates while achieving better side effect results. They want to do that by identifying additional biomarkers to drive precision medicine strategies.

Although traditional clinical risk help clinicians predict outcomes and select patients for clinical trials of de-intensified treatments, Chera said that these risk factors are imprecise. He and his colleagues are currently evaluating additional novel biomarkers that they believe could be used to better predict a patient’s prognosis and outline a course of treatment.

Specifically, they have shown in a previous study how levels of circulating HPV DNA in the blood, and how quickly patients clear this from the blood, were linked to outcomes.

September, 2019|Oral Cancer News|

Which feeding tubes do head and neck cancer clinicians prefer to use in patients undergoing radiotherapy?

Source: www.oncologynurseadvisor.com
Author: Susan Moench, PhD, PA-C

A study of the perceptions of health care professionals involved in the care of patients with head and neck cancer undergoing radiation therapy regarding optimal feeding tube practices showed no consensus; however, feeding tube placement was considered important for some patients. This study was published in JPEN Journal of Parenteral Enteral Nutrition.

Patients with head and neck cancer frequently undergo intensive treatment that may include a long course of radiation therapy in addition to surgery and chemotherapy. Treatment-related toxicity can involve severe dysphagia and mucositis, as well as reduced food intake and unintentional weight loss; these clinical sequelae can also lead to treatment delays and an increased risk of hospitalization.

Clinical practice guidelines include recommendations for early enteral feeding in patients with stage IV disease or hypopharyngeal tumors who are receiving chemoradiotherapy, as well as other patients with head and neck cancer, “depending on factors including their treatment, nutrition status, dysphagia, social support, and food intake.” However, there is no conclusive evidence as to which of the most commonly used feeding tubes — a nasogastric tube (NGT) placed when additional nutritional support is needed or a prophylactic gastrostomy tube (PGT) placed before radiation therapy — is preferable.

In this qualitative study, in-depth interviews were conducted with interdisciplinary health care professionals from 4 radiation therapy departments (2 in the United States and 2 in Australia) to evaluate their perspectives and experiences regarding feeding tube practices in patients with head and neck cancer.

Of the 46 health care professionals participating in the study, 26% were nurses, 37% were radiation oncologists, 24% dieticians, and 13% were speech pathologists.

One of the interesting findings from this study was the lack of a feeding tube protocol in place at all 4 radiation oncology departments, with decisions regarding feeding tube placement typically made by staff specialists on a case-by-case basis.

When use of a feeding tube was deemed appropriate, healthcare professionals at 3 of the radiation oncology departments favored the use of PGT, whereas NGT was preferred at the remaining department.

Patient-related factors considered to be important in decision making regarding feeding tube placement included planned treatment, tumor characteristics, nutrition and swallow status, risk of tube dependence, psychosocial status, and patient preferences. Other factors cited as potentially bearing on decisions related to feeding tubes were access to a dietician and a speech pathologist, as well as interdisciplinary collaboration, and the infrastructure to support timely feeding tube placements and intravenous fluids.

“Further research is needed to explore patient preferences, tube dependence, interdisciplinary collaboration, and department infrastructure to promote consistent evidence-based and patient-centered feeding tube practices,” the investigators concluded.

Reference
Hazzard E, Walton K, McMahon AT, et al. Healthcare professionals’ perceptions of feeding tube practices for patients with head and neck cancer across 4 international radiation oncology departments [published online September 2, 2019]. JPEN J Parenter Enteral Nutr. doi: 10.1002/jpen.1699

September, 2019|Oral Cancer News|

OU researcher creating novel device for early detection of oral cancer

Source: www.eurekalert.org
Author: press release

Because two-thirds of oral cancer diagnoses are made when the cancer is advanced, treating it usually requires complex surgeries, followed by reconstructive procedures that are necessary because tissue has been removed from the patient’s face.

A University of Oklahoma researcher is developing computer technology and a new medical device that he hopes can detect oral cancer at an early stage, when the survival rate is much higher. Javier Jo, Ph.D., is a professor with the School of Electrical and Computer Engineering on OU’s Norman campus, and a member of Stephenson Cancer Center at OU Medicine. His expertise in applying engineering concepts to solve a medical problem earned him a $2.5 million grant from the National Cancer Institute.

Jo’s research involves creating a hand-held endoscope to look for precancerous and cancerous lesions of the mouth, and “training” it to recognize patterns and signatures of those lesions with more accuracy and at an earlier stage.

“When oral cancer is diagnosed early, treating the patient is much more effective and a lot less invasive,” he said. “The survival rate and quality of life of the patient is fairly high if the cancer is detected early.”

Jo’s technology aims to address two problems in oral cancer detection. A person’s general dentist is usually the first health provider to examine the tissue inside the mouth and search for lesions based on look and feel. However, it’s difficult to distinguish a benign lesion from a cancerous or precancerous lesion, Jo said. In addition, dentists have varying degrees of experience in oral cancer screening.

If a dentist discovers a suspicious lesion, the patient will usually be referred to an oral pathologist, who may decide to do a tissue biopsy. However, because some lesions are quite large, the pathologist has to decide from which area to take the biopsy sample. Unfortunately, the pathologist may take a sample from a non-cancerous portion of the lesion, yet another area is cancerous, Jo said.

“Those are two main barriers to detecting oral cancer early,” Jo said. “What’s missing is an objective and quantitative tool to provide more precise information about the presence of malignant vs. benign lesions.”

Jo is developing fluorescence imaging endoscopes and combining them with artificial intelligence technologies. When he shines light of a specific color into the tissues of a person’s mouth, the molecules in those tissues respond by emitting light of their own, known as fluorescence. Because cancer cells divide very quickly, Jo is looking for changes in the fluorescence characteristics of specific molecules associated with increased cell activity – a hallmark of cancer cells.

At the current stage of his research, Jo’s team is engineering the endoscopes, which will be sent to several clinical centers where patients with suspicious lesions will be imaged before having a biopsy to confirm whether oral cancer is present. This multicenter study will provide data to develop artificial intelligence algorithms that aim to distinguish between benign, precancerous and cancerous oral lesions.

“Once we have a computer algorithm that can discern different types of lesions, we can put that algorithm into the endoscope and test it on a larger group of patients to see if it works with enough accuracy to be clinically useful,” Jo said.

Jo’s aim is that the technology will first be used in the dentist’s office for a more accurate determination of whether a patient needs to be referred to an oral pathologist. He also envisions an oral pathologist using the tool to determine which area of the lesion needs to biopsied.

Robert Mannel, M.D., Stephenson Cancer Center director and Rainbolt Family Chair in Cancer, said Jo’s research has the potential to dramatically increase the number of oral cancer patients who are diagnosed at an earlier stage.

“We are excited by the prospects of Dr. Jo’s innovative research,” Mannel said. “Not only does it point to a promising avenue of improving patient outcomes through earlier cancer detection, it also underscores the close collaboration between Stephenson Cancer Center researchers at the OU Health Sciences Center and OU Norman campuses.”

September, 2019|Oral Cancer News|

Treatment delay in HNSCC tied to worse outcomes

Source: www.medpagetoday.com
Author: Leah Lawrence, Contributing Writer

Treatment delayed longer than 2 months from the time of diagnosis negatively affected survival and increased recurrence among patients with head and neck squamous cell carcinoma (HNSCC), a retrospective study found.

Looking at a group of 956 patients treated at a single urban academic center, those with a time to treatment initiation (TTI) longer than 60 days were significantly more likely to die from their disease (odds ratio [OR] 1.69, 95% CI 1.32-2.18) and have disease recurrence (OR 1.77, 95% CI 1.07-2.93) compared to those treated within this timeframe, reported Vikas Mehta, MD, MPH, of Montefiore Medical Center in New York City, and colleagues.

As described in JAMA Otolaryngology–Head & Neck Surgery, the 5-year overall survival for patients dropped from 64.5% to 47.0% when the TTI stretched beyond 60 days.

“If I invented a drug that could give a 20% improved survival in head and neck cancer patients, a disease where survival has not changed for many years, I would probably be getting handed a large amount of funding,” Mehta told MedPage Today.

“This study is just as important,” he continued. “Getting patients to treatment in a timely manner can independently improve survival.”

Initial diagnoses at the treatment institution decreased the odds of TTI delay by almost 50% (OR 0.53, 95% CI 0.37-0.76). However, patients with Medicaid as compared with commercial insurance were significantly more likely to have treatment delays (OR 2.17, 95% CI 1.28-3.66). As were African-American patients and those with a body mass index (BMI) of 18.5.

“Unlike studies that look at things from a national perspective, this study shows that not all populations are created equal,” Mehta said. “For some populations the issue with delays is that the population covers a large geographical area where it is hard for people to travel. In our population, the big issue is socioeconomic and comorbidities.”

In an editorial that accompanied the article, Evan Graboyes, MD, and Chanita Hughes-Halbert, PhD, of the Medical University of South Carolina, wrote that these new data add to an existing body of evidence about delays in HNSCC and the call to “recognize the devastating oncologic consequences of treatment delays.”

Specifically, Graboyes and Hughes-Halbert pointed out that identification of missed appointments (21.2%), extensive pretreatment evaluation (21.2%), and treatment refusal (13.6%) as the three most common reasons for delay are “key to advancing our understanding of HNSCC care delivery.”

However, they cautioned that these results should be seen only as hypothesis generating.

“It is imperative that the science move beyond continuing to characterize the frequency and oncologic consequences of treatment delays and instead focus on identifying and understanding the barriers to timely care at the patient, healthcare provider, and system levels so that we may develop and test novel interventions specifically targeted at these barriers,” Graboyes and Hughes-Halbert wrote.

Mehta agreed with this conclusion, telling MedPage Today that he and colleagues at his cancer center are now beginning work to measure these outcomes in real time.

“We want to have the ability to measure month to month and patient by patient how we are performing in terms of when we diagnose and when we first treat,” Mehta said. “By looking at that benchmark we can begin planning interventions in an organized, quality-improvement-based fashion. Collaborating with other institutions will be key.”

Study Details
All 956 participants in the retrospective study had primary HNSCC diagnosed from February 2005 to July 2017 and were identified using the Montefiore Medical Center Cancer Registry.

The median TTI among all patients was 40 days. About one-fifth of patients were identified as having a TTI of longer than 60 days and considered to have delayed treatment.

September, 2019|Oral Cancer News|

Machine learning improves the diagnosis of patients with head and neck cancers

Source: www.sciencedaily.com
Author: materials from Charité – Universitätsmedizin Berlin

Researchers from Charité — Universitätsmedizin Berlin and the German Cancer Consortium (DKTK) have successfully solved a longstanding problem in the diagnosis of head and neck cancers. Working alongside colleagues from Technische Universität (TU) Berlin, the researchers used artificial intelligence to develop a new classification method which identifies the primary origins of cancerous tissue based on chemical DNA changes. The potential for introduction into routine medical practice is currently being tested. Results from this research have been published in Science Translational Medicine.

Every year, more than 17,000 people in Germany are diagnosed with head and neck cancers. These include cancers of the oral cavity, larynx and nose, but can also affect other areas of the head and neck. Some head and neck cancer patients will also develop lung cancer. “In the large majority of cases, it is impossible to determine whether these represent pulmonary metastases of the patient’s head and neck cancer or a second primary cancer, i.e. primary lung cancer,” explains Prof. Dr. Frederick Klauschen of Charité’s Institute of Pathology, who co-led the study alongside Prof. Dr. David Capper of Charité’s Department of Neuropathology. “This distinction is hugely important in the treatment of people affected by these cancers,” emphasizes Prof. Klauschen, adding: “While surgery may provide a cure in patients with localized lung cancers, patients with metastatic head and neck cancers fare significantly worse in terms of survival and will require treatments such as chemoradiotherapy.”

When trying to distinguish between metastases and a second primary tumor, pathologists will usually use established techniques such as analyzing the cancer’s microstructure and detecting characteristic proteins in the tissue. However, due to the marked similarities between head and neck cancers and lung cancers in this regard, these tests are usually inconclusive. “In order to solve this problem, we tested tissue samples for a specific chemical alteration known as DNA methylation,” explains Prof. Capper who, like Prof. Klauschen, is a Scientific Member of the DKTK in Berlin. He adds: “We know from earlier studies that DNA methylation patterns in cancer cells are highly dependent on the organ in which the cancer originated.”

Working with Prof. Dr. Klaus-Robert Müller, Professor for Machine Learning at TU Berlin, the research group employed artificial intelligence-based methods to render this information useful in practice. The researchers used DNA methylation data from several hundred head and neck and lung cancers in order to train a deep neural network to distinguish between the two types of cancer. “Our neural network is now able to distinguish between lung cancers and head and neck cancer metastases in the majority of cases, achieving an accuracy of over 99 percent,” emphasizes Prof. Klauschen. He continues: “To ensure that patients with head and neck cancers and additional lung cancers will benefit from the results of our study as quickly as possible, we are currently in the process of testing the implementation of this diagnostic method in routine practice. This will include a prospective validation study to ensure that the new method can be made available to all affected patients.”

Having worked alongside the researchers from Charité, the Director of the Berlin Center for Machine Learning (BZML), Prof. Müller, is similarly delighted at their results: “Artificial intelligence is playing an increasingly important role, not only in our daily lives and in industry, but also in natural sciences and medical research. The use of artificial intelligence is, however, particularly complex within the medical field; this is why, until now, research findings have only rarely delivered direct benefits for patients. This could now be about to change.”

September, 2019|Oral Cancer News|

HPV ‘Herd Immunity’ Is on the Rise Among Adults

Source: www.webmd.com
Author: Dennis Thompson, HealthDay Reporter

The United States could be approaching a state of herd immunity against human papillomavirus (HPV), a virus linked to several cancers.

Oral HPV infections declined by 37% among unvaccinated 18- to 59-year-old men between 2009 and 2016, according to a Sept. 10 report in the Journal of the American Medical Association.

That included a decline in infections of HPV16, the strain found in more than 9 out of 10 cases of head and neck cancer related to the virus, said senior researcher Dr. Maura Gillison, a professor of medicine at MD Anderson Cancer Center in Houston.

Researchers say men are benefitting from increased HPV vaccination rates among American women, who receive the vaccine to prevent virus-caused cervical cancer.

“In contrast to cervical cancers, we have no means by which to screen for HPV-positive head and neck cancers,” Gillison said. “The vaccine is our best hope for prevention.”

HPV vaccination has been recommended for girls since 2006 and for boys since 2011. The virus has been linked to cancers of the cervix, penis, anus, mouth and throat.

Vaccination rates among boys and girls are steadily rising, according to the U.S. Centers for Disease Control and Prevention.

About half of teens were up to date on the HPV vaccine in 2017, and two-thirds of 13- to 17-year-olds had received the first dose to start the series. On average, the percentage of teens who started the HPV vaccine series rose by 5 percentage points each year between 2013 and 2017, the CDC says.

“At least 75% vaccine coverage of boys and girls would be necessary to eradicate HPV16, the HPV type that is most likely to lead to cancer development,” Gillison said.

But vaccination rates have lagged among males.

To see if males are receiving some protection from greater HVP vaccination among females, Gillison and her colleagues reviewed U.S. federal health survey data gathered between 2009 and 2016.

They found that by 2016, about 15% of women and 6% of men had received the vaccine.

Despite lower vaccination rates among males, oral HPV infections declined from 2.7% to 1.6% in men between 2009 and 2016.

Interestingly, prevention of oral HPV infections and the head and neck cancers they cause is not listed as a reason to get the vaccine, Gillison said. No clinical trials have been undertaken to show that the HPV vaccine could prevent such cancers.

The decrease in HPV infections among the unvaccinated men is consistent with a decline in genital HPV infections among unvaccinated women between 2004 and 2014, the researchers noted.

“This study demonstrates that even with suboptimal uptake of the HPV vaccine, important gains are being made in herd immunity against oral HPV types included in the vaccine,” said Dr. Amesh Adalja, a senior scholar at the Johns Hopkins Center for Health Security in Baltimore. He was not involved with the study.

“Oral HPV infection is a major factor in the development of head and neck cancer, and this vaccine has the potential to be game-changing as more individuals are vaccinated,” Adalja said.

HPV-positive head and neck cancers are the most rapidly rising cancers in the United States among men under age 60, Gillison said.

She called on doctors to use the data from this and other studies to promote HPV vaccination.

“I can guarantee that all of my patients diagnosed with HPV-positive head and neck cancer would exchange two or three shots for three months of toxic cancer therapy in a heartbeat,” she said.

“The HPV vaccine, together with the hepatitis B vaccine, are the two most important advances in the history of cancer prevention, period,” Gillison concluded.

September, 2019|Oral Cancer News|

Say No to Glow: Reducing the Carcinogenic Effects of ALDH2 Deficiency

Source: blogs.plos.org
Author: Catherine Chang et al.

Turning red after consuming alcohol may seem like a mere social inconvenience. Yet, behind this red complexion lies a far more serious problem. ALDH2 deficiency, more commonly known as Alcohol Flushing Syndrome or Asian Glow, is a genetic condition that interferes with the metabolism of alcohol. As a result, people with ALDH2 deficiency have increased risks of developing esophageal and head and neck cancers . Globally, this deficiency affects 540 million people — 8% of the world population. In East Asia (which includes Japan, China, and Korea), this is a much bigger problem, where 36% of the population is affected [1]. In our home, Taiwan, approximately 47% of the population carries this genetic mutation — the highest percentage in the world [2]!

Normally, ethanol is first converted to acetaldehyde (a toxic intermediate) by the enzyme alcohol dehydrogenase (ADH). A second enzyme, aldehyde dehydrogenase 2 (ALDH2), then converts toxic acetaldehyde into acetate, a compound which can be safely metabolized in the body. For people who carry wild type ALDH2*1, acetaldehyde can be broken down quickly. People with ALDH2 deficiency, however, have a point mutation which leads to the less efficient mutant ALDH2*2 [3], [4]. Enzymatic activity in ALDH2-deficient individuals can be as low as 4% compared to wild type [4], [5], [6], [7]. As a result, acetaldehyde accumulates and induces an inflammatory response that causes the skin to flush after drinking alcohol [8]. Turning red is the most obvious result of ALDH2 deficiency, but symptoms also include headaches, dizziness, hypotension, and heart palpitations [5], [9].

Acetaldehyde accumulates in ALDH2-deficient individuals. Ethanol is first converted to a toxic intermediate, acetaldehyde, by ADH, then converted to acetate by wild type ALDH2*1. The mutant form, ALDH2*2, cannot fully convert acetaldehyde into acetate, and toxic acetaldehyde accumulates as a result.

For people who are ALDH2-deficient and drink, acetaldehyde can accumulate to toxic levels. The International Agency for Research on Cancer classifies acetaldehyde associated with alcohol consumption as a Group 1 carcinogen [10]. Acetaldehyde levels over 50 μM are considered toxic and cause mutations in DNA, and studies show that the strongest effects are seen in the mouth [11], [12]. After consuming roughly 2 to 3 servings of alcohol (0.5-0.6 g alcohol/kg body weight), salivary acetaldehyde levels in ALDH2-deficient individuals reached over 100 μM, compared to normal levels of <20 μM without drinking [13], [14], [15], [16]. Because of the increased salivary acetaldehyde, people with ALDH2 deficiency are 2 to 8 times more likely to develop head and neck cancers (including oral cancer, pharyngeal cancer, laryngeal cancer, etc.), and 2 to 12 times more likely to develop esophageal cancer compared to people with normal ALDH2*1 [17-25].

Our ALDH2*1 probiotic candy significantly reduces acetaldehyde levels in simulated oral conditions. (A) The conversion of acetaldehyde to acetate by ALDH2 uses NAD+ and produces NADH. (B) Experimental setup. The candies were dissolved, the probiotic (Nissle) was lysed to release ALDH2 enzymes, and the supernatant was placed into artificial saliva. NADH concentration was measured by taking absorbance readings at 340 nm. (C) Enzymatic activity of ALDH2*1 and ALDH2*2 from the probiotic candies. A negative control of candy without Nissle was also included (gray). Under these conditions, the ALDH2*1 candies metabolized significantly more acetaldehyde compared to both the ALDH2*2 candies and the negative control. Error bars represent standard error.

To directly address the increased esophageal and head and neck cancer risks, we developed a probiotic (E. coli Nissle 1917) candy carrying recombinant human ALDH2*1 to maintain normal acetaldehyde levels in the mouths of ALDH2-deficient individuals. We tested the candy’s ability to break down acetaldehyde by measuring NADH, a byproduct of acetaldehyde metabolism. In simulated oral conditions, we observed a significant decrease in acetaldehyde levels when we added the contents of our ALDH2*1 candy (compared to the mutant ALDH2*2 or control candy). Through mathematical modeling, we also determined the exact amount of recombinant ALDH2*1 needed in each piece of candy. Our modeling shows that if a consumer eats our candy while drinking, the released ALDH2*1 will be able to combat the high salivary acetaldehyde levels and match the normally low levels found in wild type individuals.

 

Our final product, an ALDH2*1 probiotic candy!

Nearly half of Taiwan’s population is ALDH2 deficient. To combat the increased cancer risks associated with this deficiency, we developed and tested a method to regulate acetaldehyde levels in ALDH2-deficient individuals.

The TAS_Taipei iGEM Team have produced a full research article detailing their project. You can access that article here.

Note:Please note that the team’s full research article has not been peer-reviewed.

Authors: Catherine Chang, Tim Ho, Iris Huang, Justin Wu

References:
1. Brooks PJ, Enoch MA, Goldman D, Li TK, Yokoyama A. (2009). The alcohol flushing response: an unrecognized risk factor for esophageal cancer from alcohol consumption. PLoS Med. 24;6(3):e50.

2. Chang JS, Hsiao JR, Chen CH. (2017). ALDH2 polymorphism and alcohol-related cancers in Asians: a public health perspective. J Biomed Sci. 24(1):19.

3. Larson HN, Weiner H, Hurley TD. (2005). Disruption of the Coenzyme Binding Site and Dimer Interface Revealed in the Crystal Structure of Mitochondrial Aldehyde Dehydrogenase “Asian” Variant. J Biol Chem. 280(34):30550-6.

4. Farrés J, Wang X, Takahashi K, Cunningham SJ, Wang TT, Weiner H. (1994). Effects of changing glutamate 487 to lysine in rat and human liver mitochondrial aldehyde dehydrogenase. A model to study human (Oriental type) class 2 aldehyde dehydrogenase. J Biol Chem. 13;269(19):13854-60.

5. Chen CH, Ferreira JCB, Gross ER, Mochly-Rosen D. (2014). Targeting Aldehyde Dehydrogenase 2: New Therapeutic Opportunities. Physiol Rev. 94(1):1-34.

6. Zhou J, Weiner H. (2000). Basis for half-of-the-site reactivity and the dominance of the K487 oriental subunit over the E487 subunit in heterotetrameric human liver mitochondrial aldehyde dehydrogenase. Biochemistry. 39(39):12019-24.

7. Gross ER, Zambelli VO, Small BA, Ferreira JCB, Chen CH, Mochly-Rosen D. (2015). A personalized medicine approach for Asian Americans with the aldehyde dehydrogenase 2*2 variant. Annu Rev Pharmacol Toxicol. 55:107-27.

8. Ijiri I. (1999). [Biological actions of acetaldehyde]. Nihon Hoigaku Zasshi. 53(3):285-95.

9. Lai CL, Yao CT, Chau GY, Yang LF, Kuo TY, Chiang CP, Yin SJ. (2014) Dominance of the inactive Asian variant over activity and protein contents of mitochondrial aldehyde dehydrogenase 2 in human liver. Alcohol Clin Exp Res. 2014 Jan;38(1):44-50.

10. International Agency for Research on Cancer. (n.d.). List of Classifications, Volumes 1-122. Retrieved from https://monographs.iarc.fr/list-of-classifications-volumes/ .

11. Yamaguchi H, Hosoya M, Shimoyama T, Takahashi S, Zhang JF, Tsutsumi E, Suzuki Y, Suwa Y, Nakayama T. (2012). Catalytic removal of acetaldehyde in saliva by a Gluconobacter strain. J Biosci Bioeng. 114(3):268-74.

12. Kocaelli H, Apaydin A, Aydil B, Ayhan M, Karadeniz A, Ozel S, Yilmaz E, Akgün B, Eren B. (2014) Evaluation of potential salivary acetaldehyde production from ethanol in oral cancer patients and healthy subjects. Hippokratia. 18(3): 269–274.

13. Homann N, Jousimies-Somer H, Jokelainen K, Heine R, Salaspuro M. (1997a). High acetaldehyde levels in saliva after ethanol consumption: methodological aspects and pathogenetic implications. Carcinogenesis. 18(9):1739-43.

14. Yokoyama A, Tsutsumi E, Imazeki H, Suwa Y, Nakamura C, Mizukami T, Yokoyama
(2008). Salivary acetaldehyde concentration according to alcoholic beverage consumed and aldehyde dehydrogenase-2 genotype. Alcohol Clin Exp Res. 32(9):1607-14.

15. Lachenmeier DW, Monakhova YB. (2011). Short-term salivary acetaldehyde increase due to direct exposure to alcoholic beverages as an additional cancer risk factor beyond ethanol metabolism. J Exp Clin Cancer Res. 30 (3).

16. Stornetta A, Guidolin V, Balbo S. (2018). Alcohol-Derived Acetaldehyde Exposure in the Oral Cavity. Cancers (Basel). 10(1). pii: E20.

17. Chao YC, Wang LS, Hsieh TY, Chu CW, Chang FY, Chu HC. (2000). Chinese Alcoholic Patients with Esophageal Cancer are Genetically Different from Alcoholics with Acute Pancreatitis and Liver Cirrhosis. Am J Gastroenterol. 95(10):2958-2964.

18. Yang SJ, Wang HY, Li XQ, Du HZ, Zheng CJ, Chen HG, Mu XY, Yang CX. (2007). Genetic Polymorphisms of ADH2 and ALDH2 Associated with Esophageal Cancer Risk in Southwest China. World J Gastroenterol. 13(43):5760-5764.

19. Yokoyama A, Muramatsu T, Omori T, Yokoyama T, Matsushita S, Higuchi S, Maruyama K, Ishii H. (2001). Alcohol and Aldehyde Dehydrogenase Gene Polymorphisms and Oropharyngolaryngeal, Esophageal and Stomach Cancers in Japanese Alcoholics. Carcinogenesis. 22(3): 433-439.

20. Matsuo K, Hamajima N, Shinoda M, Hatooka S, Inoue M, Takezaki T, Tajima K. (2001). Gene-Environment Interaction between an Aldehyde Dehydrogenase-2 (ALDH2) Polymorphism and Alcohol Consumption for the Risk of Esophageal cancer. Carcinogenesis. 22(6): 913-916.

21. Cui R, Kamatani Y, Takahashi A, Usami M, Hosono N, Kawaguchi T, Tsunoda T, Kamatani N, Kubo M, Nakamura Y, Matsuda K. (2009). Functional variants in ADH1B and ALDH2 coupled with alcohol and smoking synergistically enhance esophageal cancer risk. Gastroenterology. 2009 Nov;137(5):1768-75.

22. Lee CH, Lee JM, Wu DC, Goan YG, Chou SH, Wu IC, Kao EL, Chan TF, Huang MC, Chen PS, Lee CY, Huang CT, Huang HL, Hu CY, Hung YH, Wu MT. (2007). Carcinogenetic impact of ADH1B and ALDH2 genes on squamous cell carcinoma risk of the esophagus with regard to the consumption of alcohol, tobacco and betel quid. Int J Cancer. 122(6):1347-56.

23. Wu M, Chang SC, Kampman E, Yang J, Wang XS, Gu XP, Han RQ, Liu AM, Wallar G, Zhou JY, Kok FJ, Zhao JK, Zhang ZF. (2013). Single nucleotide polymorphisms of ADH1B, ADH1C and ALDH2 genes and esophageal cancer: a population-based case-control study in China. Int J Cancer. 132(8):1868-77.

24. Huang CC, Hsiao JR, Lee WT, Lee YC, Ou CY, Chang CC, Lu YC, Huang JS, Wong TY, Chen KC, Tsai ST, Fang SY, Wu JL, Wu YH, Hsueh WT, Yen CJ, Wu SY, Chang JY, Lin CL, Wang YH, Weng YL, Yang HC, Chen YS, Chang JS. (2017). Investigating the Association between Alcohol and Risk of Head and Neck Cancer in Taiwan. Sci Rep. 7(1):9701.

25. Hiraki A, Matsuo K, Wakai K, Suzuki T, Hasegawa Y, Tajima K. (2007). Gene–gene and gene–environment interactions between alcohol drinking habit and polymorphisms in alcohol-metabolizing enzyme genes and the risk of head and neck cancer in Japan. Cancer Science. 98: 1087-1091.

September, 2019|Oral Cancer News|

Light therapy could prevent cancer treatment-related oral mucositis

Source: www.healio.com
Author: Jennifer Southall

Light therapy appeared to be an effective intervention for the prevention of painful oral mucositis associated with cancer treatment, according to results of a systematic review and meta-analysis.

“Many patients [with cancer] can now benefit from this treatment,” Praveen R. Arany, DDS, PhD, assistant professor of oral biology and biomedical engineering at University at Buffalo School of Dental Medicine, said in a press release. “The staggering breadth of clinical application for photobiomodulation therapy, or light therapy, has been both a boon and a bane for the field. Several anecdotal clinical reports have been plagued with questionable rationales and inconsistent outcomes, often relegating this treatment to a pseudoscience.”

Arany and colleagues systematically reviewed published literature in an effort to update the evidence-based clinical practice guidelines on the use of photobiomodulation — including laser and other light therapies — for the prevention and treatment of oral mucositis among patients with cancer. Patients underwent treatment with hematopoietic stem cell transplantation, head and neck radiotherapy, or head and neck radiotherapy plus chemotherapy.

Study findings supported the use of photobiomodulation therapy for the prevention of oral mucositis among certain patients with cancer.

HemOnc Today spoke with Arany about the research and the clinical implications of the findings.

Question: What prompted this research?
Answer: The current forms of cancer treatment are all essential to reduce cancer burden. Unfortunately, complications from these treatments include oral mucositis pain. This not only has a significant impact on quality of life, but also often requires treatment with opioids. The pain and discomfort can be so severe it may even interrupt treatment, which can be lethal. There are no targeted treatments for this condition. We commonly use a mouthwash, which provides relief from symptoms. In contrast to this, there is increasing evidence for the use of light therapy based on precise biological mechanisms.

Q: Can you explain the rationale for this therapy?
A: This treatment has been shown to modulate various biological signaling pathways in cells that results in a positive response, such as alleviation of pain or inflammation. In addition, our lab uncovered a mechanism involving direct activation of a growth factor capable of stimulating wound healing and tissue regeneration. A combination of these responses is responsible for therapeutic benefit in oral mucositis pain.

Q: How did you conduct the study?
A: For the systematic review and meta-analysis, we looked at previously published human clinical studies that focused on how light therapy was used for the prevention of oral mucositis pain. We used the evidence from all studies to establish guidelines, re-analyzing data from each study to develop the final recommendations.

Q: What did you find?
A: There is significant evidence to use photobiomodulation therapy, or light therapy, for the prevention and treatment of oral mucositis pain when patients undergo radiation plus chemotherapy, as well as radiation alone and HSCT. In some instances, photobiomodulation therapy also was used as a preventive measure before and during cancer treatments to reduce the risk for oral mucositis pain.

Q: What will subsequent research entail?
A: The major finding was this treatment is effective. However, most of the studies that we reviewed were performed outside of the United States — including in Brazil, Europe and Asia. It is necessary to conduct studies in the U.S. in a more controlled manner with new devices available. This will be the primary focus of future human clinical research. Preliminary research studies have addressed potential effects of this treatment on tumors and the data are very promising, noting few — if any — deleterious side effects.

Q: Is there anything else that you would like to mention?
A: This is a noninvasive and nonpharmacological approach. This is especially important in the context of opioids in cancer care. Clearly, opioids are effective drugs that have an essential role in pain management. Unfortunately, they have a high threshold for abuse. The use of photobiomodulation therapy can reduce this incidence because patients will not be exposed to opioids. Besides mucositis, photobiomodulation therapy also has been noted to reduce hair loss, depression and fatigue — all key concerns for patients undergoing cancer treatment. Hopefully, we soon will see other published reports that will lead to improved cancer care using this simple but potent new technology. – by Jennifer Southall

Reference:
Zadik Y, et al. “Systematic review of photobiomodulation for the management of oral mucositis in cancer patients and clinical practice guidelines” Support Care Cancer. 2019;doi:10.1007/s00520-019-04890-2.

September, 2019|Oral Cancer News|