Monthly Archives: November 2018

Researchers evaluate efficacy of salivary biomarkers for early detection of oral cancer

Source: www.news-medical.net
Author: staff, reviewed by Kate Anderton, B.Sc.

Over 90% of malign tumors in the head and neck are originated from carcinomas of squamous cells that appear in superficial areas of the oral cavity. Their detection with salivary biomarkers can contribute to their early treatment, before they transform into tumors. Researchers of the Oral Microbiology Research Group of the CEU Cardenal Herrera University (CEU UCH) in Valencia, Spain, have conducted a systematic review and a meta-analysis of the salivary markers that show the highest efficacy for the early detection of oral cancer in different clinical trials. The results have just been published in the Journal of Oral Pathology and Medicine, the official magazine of the International Association of Oral Pathogens in the field of Dentistry, Oral Surgery and Medicine.

According to Verónica Veses, head researcher of the Group and professor at the Biomedical Sciences Department of the CEU UCH, “detection of this type of squamous cell cancer in the surface of the mouth essentially depends of the visual examination on behalf of oral health professionals. This is why it is important to find new diagnostic methods to help with accurate early detection. Specially if we take into account that oral cancer is the most common of the tumors in the head and neck, and which is increasingly prevalent among the young population due to the consumption of tobacco and alcohol”.

Three types of biomarkers
The research team headed by Dr. Veses has conducted a systematic review and a meta-analysis of the clinical trials that have thus far evaluated the efficacy of the three types of salivary biomarkers that are the most promising for the early detection of this type of oral cancer. These salivary markers are two types of cytokines, proteins involved in cellular proliferation and differentiation; two markers that are present in the ribonucleic acid that transfers the genetic code, the messenger RNA or mRNA (DUSP‐1 and S100P); and two more in the micro-RNA (miRNA) of the saliva, but which require further research.

Research team
The results are part of the final degree project of UCH CEU Dentistry student Fariah Gaba, under the guidance of professors Verónica Veses and Chirag Sheth, members of the Oral Microbiology Research Group of this university. Fariah Gaba, who has obtained the Extraordinary Degree Prize for her Dentistry studies, is currently working as a dentist in Holland and began her research efforts working on one of the UCH CEU’s research and teaching projects of the Oral Microbiology Group.

Source:
http://ruvid.org/ri-world/researchers-detect-the-most-efficient-salivary-biomarkers-for-detecting-oral-cancer/

November, 2018|Oral Cancer News|

Early detection, treatment helps conquer oral cancer

Source: www.newsbug.info
Author: Bob Moulesong

According to the Oral Cancer Foundation, almost 50,000 cases of oral cancer will be diagnosed in the U.S. in 2018. The American Cancer Society reports that 10,000 people will die from the disease this year. Half of all people diagnosed with oral cancer will be alive in five years, according to both sources.

While those are disquieting statistics, Region physicians say routine checkups and early diagnosis improve the odds.

Oral cancer
Oral cancer includes cancers of the lips, tongue, cheeks, floor of the mouth, hard and soft palate, sinuses, saliva glands, and throat.

“People we see usually come to us for a lesion or ulcer found in the mouth or throat,” says Dr. Akta Kakodkar, an ear, nose and throat specialist with Community Healthcare System. “Some of them experience no pain but notice a growth or patch of discolored tissue in their mouth, cheek or gum.”

Kakodkar, who with her husband and fellow Community ENT physician, Dr. Kedar Kakodkar, treats oral cancer patients, is quick to point out that not every lesion, ulcer or mouth sore is cancer.

“We see hundreds of nervous patients who have bacterial or fungal infections,” she says. “Treatment with antibiotics or antifungal medications clear up many of these lesions. There are also many white and red patches that clear up on their own.”

The only way to know is a thorough examination.

Types and risk factors
“Most cases of oral cancer are linked to use of tobacco, alcohol and betel nuts, or infection with HPV,” Kakodkar says. “There are major risks associated with tobacco use, whether it’s smoking or chewing.”

There are two main types of oral cancer. Most prevalent is squamous cell carcinoma, accounting for more than 90 percent of cancers that occur in the oral cavity and oropharynx. Slow-growing verrucous carcinoma makes up more than 5 percent of oral cavity tumors.

First steps
Kakodkar says prevention is the best defense. “Your primary care physician may examine your head, neck, mouth and throat for abnormalities,” she says.

Self-exam may uncover a lesion or sore. “Remember, many of these are very treatable and are not cancer,” Kakodkar says. “But don’t wait. Cancer never goes away by itself.”

When Kakodkar discovers a suspicious lesion, she recommends a biopsy: “Depending on several variables, we might do the biopsy in clinic, or we may do it in a hospital setting.”

Once the results return, a plan of action can be established. “Usually, the next steps include imaging, such as a CT scan,” she says. “We also order a PET scan, which tells us what stage the cancer is in and whether or not it has spread.”

Treatment
Kakodkar says she prefers to go straight to surgery. “Many oral cancers are still small and local,” she explains. “Removing them completely is the best way to stop the spread of the cancer.”

Depending on the type and stage of the cancer, radiation and/or chemotherapy may be used.

“I want people to know that surgery for oral cancer is frequently a simple procedure,” Kakodkar says. “Oral cancer is frequently found early due to its visibility. Almost 90 percent of cancer patients in stage 1 or 2 recover and survive.”

A dental checkup
“Oral cancer screening is crucial during a dental examination,” says Dr. Ami Pandya, dentist at Family Dental Care in Valparaiso. “Recognizing abnormal tissue in a patient’s mouth could indicate precancerous tissues, and when identified early could save your life.”

A dentist will perform a thorough head and neck exam, which includes an oral cancer screening. “Dentists will complete extraoral examinations by palpating your jaw line to feel for any suspicious lumps that are not routinely present in these areas,” Pandya says.

A dentist will examine the intraoral tissues of your mouth and look for any suspicious lesions. “We examine the patient’s tongue, the floor of their mouth, and their gingival tissue,” Pandya says. Red and/or white patches can become cancerous.

Many doctors including Pandya have begun using VELscope, a light-based technology to detect precancerous tissues. It’s a wireless hand-held device that scans tissue, with abnormalities showing up as a dark black color.

“VELscope can detect abnormalities before they have a clinical presentation,” Pandya says. “It’s an incredible aid with oral cancer screening.”

Pandya recommends an annual VELscope examination for low-risk adults. Higher risk patients should get a VELscope exam each appointment.

Under the VELscope, cancer shows up as black, says Dr. Ami Pandya

If the dentist detects an abnormality, he or she informs the patient, noting the size, color and location of the lesion. A two-week follow-up is standard. “Oftentimes, these lesions resolve,” Pandya says. If it doesn’t resolve after two weeks, the patient is referred for further evaluation.

Note: This article originally ran on nwitimes.com.

November, 2018|Oral Cancer News|

Research Update: Vaccine Plus Checkpoint Inhibitor Combos for HPV-related Cancers

Source: MedPage Today
Author: Mark L. Feurst

Two new studies show the profound impact of a combined vaccine and anti-programmed death-1 (PD-1) antibody approach in the treatment of human papilloma virus (HPV)-related cancers.

HPV causes nearly all cervical cancers, as well as most oropharyngeal, anal, penile, vulvar, and vaginal cancers. HPV16 and HPV18 are the leading viral genotypes that increase cancer risk. Given the viral cause of these cancers, immunotherapy has been considered a strong potential approach.

Many patients with the HPV16 and HPV18 subtypes of head and neck squamous cell carcinoma have good outcomes from treatment that includes surgery or chemotherapy and radiation. Although anti-PD-1 therapy is approved for patients who do not respond to treatment or who develop metastatic disease, it benefits only about 15% of patients. The theory, therefore, is that a vaccine could potentially boost the immune systems of patients with HPV-related head and neck cancer, opening the door for better responses to other existing therapies.

Vaccine + Nivolumab in Phase II Study

In the first study, a phase II trial, a tumor-specific vaccine combined with the immune checkpoint inhibitor nivolumab was found to shrink tumors in patients with incurable HPV-related cancers.

“Ours are the first results with this particular approach,” Bonnie Glisson, MD, of the Department of Thoracic Head and Neck Medical Oncology at the University of Texas MD Anderson Cancer Center in Houston, told the Reading Room. “The rates of response and survival are approximately double what have been observed with nivolumab given alone to similar patients. These results will lead to larger, randomized clinical trials of this combination.”

Vaccines specific to HPV antigens found on tumors had previously sparked a strong immune response, but had not by themselves been active against established cancers, she noted.

“Vaccines are revving up the immune system, but the immunosuppressive tumor microenvironment probably prevents them from working. Our thinking was that inhibition of programmed death-1 (PD-1) would address one mechanism of immunosuppression, empowering the vaccine-activated T lymphocytes to attack the cancer.”

Glisson and colleagues combined the vaccine ISA101, which targets peptides produced by the strongly cancer-promoting HPV16 genotype of the virus, along with nivolumab, a checkpoint inhibitor that blocks activation of PD-1 on T cells.

The single-arm, single-center clinical trial included 24 patients with incurable HPV-16–positive cancer who were followed for 12.2 months. The vaccine was given subcutaneously on days 1, 22, and 50. A nivolumab dose of 3 mg/kg was given intravenously every 2 weeks beginning on day 8 for up to 1 year. Of the 24 patients with recurrent HPV16-related cancers, 22 had oropharyngeal cancer, one had cervical cancer, and one had anal cancer. The overall response rate was 33% (eight patients), and the median duration of response was 10.3 months. Five of eight patients remain in response, the team reported.

The overall median survival was 17.5 months, progression-free survival was 2.7 months, and 70% of patients survived to 12 months.

Grades 3 to 4 toxicity occurred in two patients (asymptomatic grade 3 transaminase level elevation in one patient and grade 4 lipase elevation in one patient), requiring discontinuation of nivolumab therapy. The researchers observed side effects expected from the two treatments separately, but said they were encouraged to see no sign of synergistic side effects caused by the combination.

“The combination was very well tolerated as opposed to other immunotherapy combinations such as combined blockade of PD-1 and CTLA-4,” Glisson said. “The vaccine did stimulate a strong HPV-specific immune response in peripheral blood T cells, although this was not correlated with response or survival. This suggests that other immune-suppressive factors in the tumor environment are contributing to immune evasion.”

Randomized clinical trials of the vaccine and anti-PD1 combinations for cervical and oropharyngeal cancer are ongoing, she added. “These are promising data that will be confirmed in a randomized trial. Positive results could lead to marketing of the first therapeutic HPV vaccine.”

Vaccine Helps T cells Infiltrate HPV-related Head and Neck Cancer

In the second study, another vaccine was shown to boost antibodies and T cells to help them infiltrate tumors and fight off HPV-related head and neck cancer. This approach might complement PD-1 or programmed death-ligand 1 inhibition in HPV-associated head and neck cancers to improve therapeutic outcomes, explained the study’s lead author, Charu Aggarwal, MD, MPH, of the Perelman School of Medicine at the University of Pennsylvania.

“We wanted to know if this vaccine can boost the immune systems of patients with HPV-related head and neck cancer, potentially opening the door for better response rates to other existing therapies. Our findings show that we can.”

Aggarwal and colleagues conducted a Phase Ib/II safety, tolerability, and immunogenicity study of immunotherapy with MEDI0457, a DNA immunotherapy targeting HPV16/18 E6/E7 with interleukin-12 encoding plasmids. The vaccine was delivered via electroporation to 21 patients. One group of patients received one dose before surgery, followed by three doses after surgery. The second group received four doses following chemotherapy and radiation.

Eighteen of the 21 patients (86%) showed elevated T cell activity that lasted at least 3 months after the final vaccine dose, the team reported. Five tumors were biopsied both before and after one dose of the vaccine, and there was evidence of T cells reacting with antigens contained in the vaccine in all five of these samples. One patient who developed metastatic disease and was treated with anti-PD-1 therapy developed a rapid and durable complete response that has lasted more than 2 years.

“We have not seen that kind of infiltration with just one dose of a vaccine before. These findings open the door for utilizing targeted immunotherapy approaches against specific cancer-causing targets like HPV,” said Aggarwal, adding that the vaccine was well tolerated, with no serious side effects reported.

“This response suggests that the vaccine may, in some manner, prime the immune system, potentially boosting the effects of subsequent anti-PD-1 therapy,” she explained, noting that a multi-site clinical trial is now open to patients with metastatic HPV-associated head and neck cancer, who will receive a combination of the vaccine with anti-PD-1 therapy.

Previously, the CheckMate-141 trial tested nivolumab in 361 patients with recurrent or metastatic, chemotherapy-refractory squamous cell head and neck cancer, and the results led to FDA approval in that setting. Sixty three of these patients were HPV16-positive, and the overall response rate among this group was 15.9%, with a median overall survival of 9.1 months.

 

November, 2018|Oral Cancer News|

Cultural barriers still stand in the way of HPV vaccine uptake

Source: arstechnica.com
Author: Cathleen O’Grady

Every year, nearly 34,000 cases of cancer in the US can be attributed to HPV, the human papillomavirus . The CDC estimates that vaccination could prevent around 93 percent of those cancers. Yet HPV vaccination rates are abysmal: only half of the teenagers in the US were fully vaccinated in 2017.

Cultural barriers play a role in that low rate. Vaccinating pre-teens against a sexually transmitted infection has had parents concerned that that this would encourage their kids to have sex sooner, with more partners, or without protection or birth control. And vaccine rates vary across different social and cultural groups: for instance, rural teenagers are less likely to be vaccinated than urban ones.

Two recent studies explore different facets of the cultural barriers standing in the way of better HPV vaccine uptake. The first, a paper published last month in the Canadian Medical Association Journal, looks at the data on whether the vaccine encourages riskier sexual behavior and finds no evidence that it does. And the second, an early draft of a paper presented at an American Association for Cancer Research meeting this week, reports the results of a culturally-targeted intervention aiming to increase vaccine uptake among low-income Chinese Americans.

The kids are alright
Although the vaccine is now recommended for both boys and girls, the initial drive was to get teenage girls vaccinated, given the link between HPV and cervical cancer. That’s why girls are the focus of the recent study on risky sexual behavior: the researchers used data from high school girls in Canada, where a huge survey on adolescent health is administered every few years.

A team of researchers was able to use this data to compare results from the survey before and after a large-scale HPV vaccine program was implemented across high schools in Canada in 2008. The researchers compared data from 2003, before the program began, to data from 2008 and 2013. Altogether, nearly 300,000 girls’ survey responses were analyzed.

The researchers found that, on every measure they looked at, risky sexual behaviors either decreased or stayed the same. The number of girls who had ever had sex decreased from 21.3 percent in 2003 to 18.3 percent in 2013. The girls who’d had sex before age 14 decreased from 14.3 percent to 10.2 percent, and girls who’d ever been pregnant went from 5.9 percent to 3.4 percent. The use of condoms increased, as did the use of birth control pills.

The researchers are careful to point out that they don’t think the HPV vaccine caused the increase in safe sex among the teenagers. That shift was already underway, they write, pointing to data showing “a downward trend in risky sexual behaviors since before 2003.” But it does suggest that the introduction of the vaccine in 2008 wasn’t associated with an increase in risky sexual behaviors.

Survey data like this has its problems, especially when the questions involve sex. It’s likely that the girls aren’t telling all, even when the survey is anonymous. But because all three years of the survey are likely to suffer from the same problem, the comparison is still apples with apples. And it’s possible that in a parallel universe without the vaccine, the risky behaviors could have plummeted even further; there’s simply no way to tell.

The researchers plan to explore whether risky behavior looks different in girls who had been vaccinated compared to those who hadn’t. To do this, they will introduce a new question in the survey, which asks girls about their HPV vaccination status. But in the meantime, these results fit in well with a growing body of literature: a study in the US that compared girls who were and weren’t vaccinated found no differences in pregnancy or STD rates between the two groups, while a different Canadian study found similar results.

Some research has even found that girls who’ve had the vaccine have safer sex than those who haven’t. That could be because HPV vaccine programs often go hand-in-hand with sex education, and teasing apart those influences is extremely difficult. But it seems unlikely that a significant change in risky behavior is lurking hidden in the data.

Different tactics for different groups
The obvious benefits of the vaccine make it important for us to understand why its uptake isn’t higher. The rate is even lower among certain groups, says Grace X. Ma, director of the Center for Asian Health in Philadelphia. While Asian American teenagers have rates similar to the average, “there are certain subgroups, such as Chinese Americans whose parents are low-income and have limited English proficiency, for whom uptake is much lower.” According to Ma, different sources placed the rate at between 10 and 30 percent at the time she started her research.

Ma designed a program to reach these parents through doctors, using materials written in their own languages and delivered through a source they were inclined to trust. In a small pilot study, Ma engaged pediatricians working in low-income Asian communities in Philadelphia and New York. By the end of the study, 110 parents had been reached by the materials, while a control group of 70 hadn’t. More than 70 percent of the teenagers of those 110 parents “had at least one dose of the HPV vaccine, compared with 10 percent of adolescents whose parents did not receive the intervention,” Ma reports.

Without a lot more information, it’s difficult to know what was driving this difference: it could be the cultural specificity of the materials, it could simply be access to the information in a language the parents understand, or a longer and more focused conversation with the doctor might drive the change.

But research in this vein, exploring the effects of different kinds of interventions, could give important clues to how vaccine uptake could be improved in a wider range of population groups. The potential barriers could range from cultural attitudes about sex to language issues to financial access to medical care. But clearly, simple access to the vaccine isn’t enough to encourage widespread adoption.

Source: Canadian Medical Association Journal, 2018. DOI: 10.1503/cmaj.180628 (About DOIs).

November, 2018|Oral Cancer News|

Scientists untangle the evolutionary history of the world’s most common STI

Source: www.iflscience.com
Author: Rosie McCall

Scientists have analyzed the genomes of viruses to reveal the surprisingly complex evolutionary past of the human papillomavirus (HPV), exposing the salacious details of our ancestors’ sexual history in the process.

HPV comes in several flavors but HPV16 is the most common subtype worldwide – and it is the one most frequently identified in cervical cancer. Together HPV16 and HPV18 are responsible for 70 percent of all cases, accord to stats from the World Health Organization (WHO).

The problem is, it isn’t exactly clear how HPV strains contribute to cervical cancer (and other types, including cancer of the anus, the throat, the base of the tongue, and the tonsils). Or why the virus naturally clears in some people but not others. Researchers hope that studying the evolution of the virus will expose biological insights and point at mechanisms that might explain how cervical cancer develops.

To try to untangle HPV16’s thorny evolutionary past, scientists led by the Chinese University of Hong Kong isolated and examined oral, perianal, and genital samples in 10 adult female squirrel monkeys (Saimiri sciureus) and eight adult rhesus monkeys (Macaca mulatta), half of whom were male and half of whom were female.

They found that the virus strains with most in common came from the same part of the body – meaning the oral samples from the squirrel monkeys and rhesus monkeys had more in common than oral and genital samples from the same species, for example. This, the authors say, implies the viruses adapted to a specific body part (or niche) where they co-evolved with their host for millions of years before passing to humans.

For the next part of the study, published in the journal PLOS Pathogens, the researchers compared 212 complete HPV16 virus genomes and 3,582 partial sequences to find out when exactly the HPV16 variants A, B, C, and D diverged from one another.

Schematic illustration of HPV16 codivergence with archaic hominins. Chen et al./PLOS Pathogens

Previous studies have shown that one (the HPV16 A variant) was a lover’s gift from our hominid relatives, the Neanderthals, transmitted to modern humans after a few too many nights of interspecies shagging. Now, it looks like this particular variant split from the virus’ “family tree”, setting off its own trajectory, just as modern humans and archaic hominins (Neanderthals and Denisovans) parted ways, evolutionarily speaking, 618,000 or so years ago.

While the HPV16 A variant co-evolved with its Neanderthal and Denisovan hosts, HPV16 B and HPV16 C variants co-evolved with modern humans. The different strains remained in their respective hosts for hundreds of thousands of years, the study authors say. Then, 100,000 years ago or thereabouts, a small band of Homo sapiens ventured outside of Africa and into Eurasia where they met – and intermingled – with other hominin species, contracting certain HPV16 A variants in the process.

The consequences of this can still be seen today and can help explain why certain variants are more commonly seen in certain groups, the HPV16 A variant in Europeans and Asians, for instance. Hopefully, the authors say, this new information will improve our understanding of why some variants of HPV16 may be inherently more carcinogenic than others.

November, 2018|Oral Cancer News|

A Look at Therapy Toxicities & Biology in Head & Neck Cancers

Source: journals.lww.com
Author: Valerie Neff Newitt

A measure of intrigue and discovery pertaining to head and neck cancer, spiked with compassion for patients struggling against treatment toxicities, helps quench the intellectual thirst of Yvonne Mowery, MD, PhD, Butler Harris Assistant Professor of Radiation Oncology at Duke University Medical Center, Durham, N.C.

Splitting time between the clinic and laboratory, Mowery is actively engaged in patient care as well as preclinical, translational, and clinical research. “I hope to get a better understanding of the biology of head and neck cancer and determine pathways that we can target to reduce metastatic spread of the disease and improve responsiveness to available treatments,” she told Oncology Times.

Long before reaching her current status as an award-winning investigator, Mowery grew up in Richmond, Va., in the midst of a “completely non-scientific” family. “I was an oddball,” she joked, while recalling her parents’ patience with her backyard composting experiments that became so foul-smelling that the health department was contacted. As a kid, her idea of a great present was an encyclopedia of science, and the thing that caught her eye at the toy store was a junior chemistry set.

Science was clearly her path when she headed to the University of Virginia. In her sophomore year, Mowery began working in a genetics lab. That’s where the lure of fruit flies took hold. “I looked at the development of their reproductive system and found that very interesting,” she recalled.

Nearing the completion of her undergraduate education, Mowery debated between attending medical school or graduate school. The eventual winner? Both. “I investigated physician-scientist training programs and arrived at Duke in 2004 to do a combined MD/PhD.” Today, Mowery spends 1 day a week in clinic where she sees patients, then moves to the lab for the remainder of the week to find strategies to improve patient care and develop therapies to deliver better outcomes for patients, both present and future.

Clinical Challenges
“I treat cancers primarily of the head and neck—such as oral cavity, larynx, tonsils, base of tongue, sinuses—with radiation therapy. I think of head and neck cancers as being in a ‘very high-stakes real estate’ area,” she said, “because they are often close to saliva glands, vocal cords, etc. This requires intricate planning for radiation treatment. Visualization of the tumor through fiberoptic laryngoscopy allows me to see a tumor responding to radiation and chemotherapy during the weeks of treatment; it is gratifying to watch it happen with your own eyes.”

Mowery said toxicity associated with treatment of this area of the body can be severe, partially due to the fact that it is typically “…one of the longer courses of radiation that we do—about 7 weeks, 5 days a week,” she explained. “Patients typically require pain medicine to eat and drink a soft diet, lose their sense of taste, and experience very dry mouth, sometimes requiring a feeding tube for nutrition. In addition, the skin on their neck often falls off.” Comparing it to severe sunburn, Mowery said skin typically blisters and peels off, leaving behind a neck that is “red, angry, and very uncomfortable. It just comes with the territory.”

In addition to these side effects, Mowery said there is also an unusual biological aspect to head and neck cancers which figures largely in her work. “Something very interesting scientifically drew me to these cancers,” she informed. “There are two main causes of cancer in this area: tobacco use and human papillomavirus (HPV). Outcomes for patients with HPV-positive oropharynx cancers are excellent; even when the cancer is locally advanced about 80-90 percent of patients are cured. But the tobacco-induced cancers, by contrast, do much worse (about 60% or less survival rate for locally advanced disease). Even if the tumor size is the same and the number of involved lymph nodes are the same, the biology is completely different for the HPV-related and the HPV-unrelated disease.”

In fact, the staging system was changed at the beginning of this year so that HPV-related cancers and HPV-negative cancers are staged differently. “HPV-positive cancers that used to be staged at IVA may now be staged at I or II, but they remain at stage IVA if the cancer is HPV-negative,” Mowery detailed.

Asked why tobacco-related cancer behaves so badly, Mowery answered, “We do not have a good understanding of that; it is something I am studying. We do know, however, that HPV-negative tumors exhibit a loss of function of the p53 gene, [which] is really the king of all tumor suppressors. In HPV-related tumors, p53 is usually genetically still intact but its activity is affected by HPV.”

She also commented that people still actively smoking during treatment tend to do much worse, likely due in part to having lower oxygen levels in the tumor, which in turn causes the radiation to work less effectively. “If we can figure out ways to make HPV-negative tumors behave more like HPV-positive tumors, outcomes would improve.”

From Clinic to Research
These realities on the clinical side have informed and inspired some of Mowery’s research efforts. One of her projects aims at reducing the toxicity of treatment while maintaining good outcomes in patients.

“A clinical trial that I am about to start will use PET/CT, a type of metabolic imaging, as an early litmus test to evaluate how patients are responding during treatment. If we find they are responding well, we will de-intensify and back off on the chemotherapy and radiation dose while still trying to achieve good outcomes,” Mowery explained.

She noted that because HPV-positive and HPV-negative cancers are still treated exactly the same way when not on a clinical trial, investigators also hope to find out if treatment can be de-intensified for the HPV-positive patients who tend to have more successful outcomes by virtue of their cancer type, thus allowing them to avoid some of the severe side effects.

“Of course, even in HPV-positive cancers, not every patient is cured,” cautioned Mowery, “so we want to see if we can identify, early on, who is going to do well and who, in contrast, still needs that full 7-week intensive course of radiation therapy and chemotherapy.”

Another clinical trial ongoing at Duke in which Mowery is involved is testing a drug called BMX-001 given to patients through a subcutaneous injection during radiation. “We hope the drug will reduce the—the inflammation and irritation of the lining of the mouth and throat during radiation—and dry mouth,” she said.

Mowery is also busy in lab with intensive work in developing new mouse models of both HPV-related and HPV-unrelated squamous cell carcinoma of the head and neck. “My objective is to develop a platform in which I can develop radiation with immunotherapy, as well as with chemotherapy and various novel systemic agents, to try to improve outcomes particularly for HPV-negative disease,” noted Mowery, also the winner of a 2017 Conquer Cancer Young Investigator Award. “I want to discover if there are ways that we can make our bodies and our immune system realize that these cells are not ‘self’ and activate the immune system to attack and eliminate them.”

Tobacco-related cancer is induced in mice by giving them a carcinogen present in tobacco, “… causing them to become like a tobacco chewer or smoker,” Mowery explained. “Having that exposure causes mutations in cells in the lining of their mouth.”

Mowery further said her research is taking advantage of large sequencing projects in which various head and neck tumors have been sequenced. These data are publicly available and published primarily by The Cancer Genome Atlas organization. “I have been able to see which genes are most commonly mutated and then can genetically engineer mice to have those mutations. In other words, I can specifically knock out certain genes in the head and neck to model the cancer in mice.”

This is extremely important because it allows Mowery and team to interrogate the biology of the mutations, and determine which genetic changes and pathways lead to the cancer spreading from its site of origin to the lymph nodes or the lungs. “It helps us to develop therapies to block the cancer and keep it at bay, and to determine if there are better ways to sensitize the cancer to radiation and chemotherapy,” she detailed. “And we have an opportunity to test drugs that we hope will help with side effects of radiation. We must make sure that drugs protecting normal tissue are not also protecting the tumor. Having great animal models of human cancer is really important to making progress.”

As if her work in head and neck cancer were not enough, Mowery is continuing an earlier effort begun in the lab of her research mentor David G. Kirsch, MD, PhD, by acting as radiation oncology principal investigator for a multi-site, international prospective randomized clinical trial investigating the combination of the immune checkpoint inhibitor pembrolizumab (anti-PD-1 antibody) and radiation therapy for patients with high-risk soft tissue sarcoma of the extremities. The researchers are also examining the biology behind the effects of radiation combined with pembrolizumab in a co-clinical trial using primary mouse models of sarcoma.

“We saw promising results combining them in this model. Our hope is by using this combination during the early stage of disease we may be able to eliminate those cells that have escaped the primary tumor before they cause a problem.”

Who Has Time for Hobbies?
Asked about her life outside of the clinic and lab, Mowery admitted that little time is left for hobbies. “I used to play tennis, but now I just enjoy watching it,” she said through a chuckle. “I splurged on a Labor Day vacation to the U.S. Open in New York. In my off time, I mostly read and spend time with my family. I am married; my wife is a nurse at Duke working in bone marrow transplant. We have no children.”

But the couple does have the patter of little feet in their midst. “We have two small dogs, Heidi and Cassie, a Maltese and a Maltese Shih Tzu mix—both less than 10 lbs.,” Mowery offered. “We live in downtown Durham, N.C., which is a burgeoning area. It’s kind of cool, and a little bit grungy—but in a good way. I love going for walks and checking out new restaurants. And I love food,” she added brightly.

After a brief pause, Mowery turned her thoughts again to patients. “There is one other clinical trial we’ve recently opened in the head and neck space. We are looking at financial toxicity of patients,” she said. “We are very concerned about the bills patients incur for cancer care and how that affects their quality of life.

“Unfortunately, some people just can’t afford to fill their whole prescription. Some take their drugs every other day because they are worried about cost. Some patients just do not follow through on therapy. We need to get a better sense of how much of that is going on and if there are early warning signs we can detect allowing us to intervene.”

Mowery added that better communications between health care providers and patients are needed to help patients better understand costs they face and identify resources that can help them.

“We just opened this survey-based pilot trial in June. We hope to have data next year and be able to develop a follow-up plan to employ the strategies that we find,” said Mowery. “There are a lot of ways we can try to help our patients.”

November, 2018|Oral Cancer News|

Forms of tobacco that give you cancer

Source: www.medicalnewstoday.com
Author: Zawn Villines, reviewed by Philip Gregory, PharmD, MS

Nicotine is the primary substance in cigarettes that causes addiction, but most experts agree that it does not directly cause cancer.

Most research points to cigarette smoke, not nicotine, as being the primary contributor to cancer among smokers. However, although most experts agree that nicotine does not directly cause cancer, some research suggests that nicotine may lead to a type of DNA damage that increases the risk of cancer.

Research from 2015 reported in the Indian Journal of Medical and Paediatric Oncology suggests that nicotine may increase the risk of cancer because it might damage DNA, initiate cancer and cause it to progress faster, and interact with cancer-causing chemicals.

Research into the role of nicotine in cancer is ongoing. Many studies, however, do not differentiate between nicotine, tobacco, or smoking when they discuss cancer risk. This makes it difficult to determine which of them causes cancer.

Even if nicotine does cause or lead to cancer, the risks of developing cancer through the use of nicotine-only products are much lower than the risks from smoking.

Methods of consuming nicotine and their safety

Nicotine is addictive and is the primary reason most people smoke. However, almost every other nicotine-based product is safer than smoking. No nicotine replacement product is completely safe for all people, but some of the less harmful alternatives include:

Nicotine replacement therapy
A person with a heart condition should speak to a doctor before undergoing NRT.
Nicotine replacement therapy (NRT) refers to a group of treatments designed to help smokers quit. NRT is available in several forms, each of which delivers nicotine without smoke, tobacco, or other carcinogenic (cancer-causing) chemicals:

The following types of NRT are available over the counter:

  • a patch, which delivers nicotine through the skin
  • chewing gum, which allows a user to chew and swallow nicotine
  • a lozenge, which slowly dissolves and releases nicotine into the mouth

Two additional forms of NRT are available with a prescription:

  • an inhaler, which allows users to take in nicotine in a similar way to inhaling it from a cigarette
  • a nasal spray, which delivers nicotine through the nose

NRT poses some risks. In addition to nicotine’s potential link to cancer, it is also a stimulant. This may make it unsuitable for some people with heart disease or certain heart disease risk factors to use.

However, most people who have a heart condition can use NRT. However, there is a small group of people who should not use NRT, such as those with severe arrhythmia, severe angina, or people who have recently had a heart attack. People should talk to their doctor for individual advice if they are in any doubt about using NRT.

Some people also use NRT as a means of consuming nicotine regularly, instead of for cutting down or quitting, and the long-term effects of NRT are not clear.

A 2010 study in the American Journal of Public Health concludes that the benefits of NRT far outweigh the risks. Researchers specifically state that increasing NRT use could save 40,000 lives per year by preventing heart disease and lung cancer.

Electronic cigarettes
Electronic cigarettes, or e-cigarettes, sometimes called vaporizers or vapes, all work by vaporizing nicotine. The amount of nicotine in each electronic cigarette varies; some even allow users to decide the amount of nicotine they use.

E-cigarettes have been the subject of dozens of safety studies in recent years, often producing conflicting results. A 2013 study found that amounts of nicotine vary with these products and that some may provide dangerously high, or even fatal, levels of nicotine.

Other research, including another 2013 study comparing several e-cigarette brands, found that they may contain toxic chemicals. When e-cigarettes do contain these chemicals, they are generally fewer in number and quantity than in traditional cigarettes.

Despite these risks, most studies agree that e-cigarettes are significantly safer than tobacco or smoking. A 2014 systematic review in the journal Therapeutic Advances in Drug Safety argues that smokers who switch to vaping can expect significant health benefits.

Smokeless tobacco
Researchers have linked chewing tobacco with an increased risk of cancer.
Smokeless tobaccos are chewed or put in the nose. They contain nicotine, as well as a range of other carcinogenic chemicals. According to the American Cancer Society, smokeless tobaccos are safer than cigarettes, but still have links to cancer.

Some types of smokeless tobacco include:

Snus or Swedish tobacco
Snus, sometimes called Swedish tobacco, is a moist powder form of tobacco. The user can suck on or chew the tobacco. Unlike chewing tobacco, people swallow it instead of spitting it out. According to the American Cancer Society, Snus may contain less nicotine than other types of moist tobacco types. However, because it is tobacco, it contains a variety of chemicals that may be carcinogenic.

A World Health Organization (WHO) analysis of previous research argues that snus is unlikely to cause oral or gastric cancer. As a result of this research, the WHO suggest that snus may be an important method of harm reduction.

However, not all research supports this claim. A 2013 case study reported on snus users in Iran who presented with oral cancer. The authors of that study argue that snus and other forms of smokeless tobacco significantly increase the risk of oral cancer. However, this risk appears to vary by region.

Overall the potential risks of snus are unclear.

Chewing tobacco
Chewing tobacco, sometimes called dip, allows a user to chew on or suck tobacco. Some people hold it between their cheeks and gum while tissues in the mouth absorb the nicotine. People then spit it out.

However, the American Cancer Society note that while users consume roughly the same amount of nicotine as people who smoke cigarettes, they also take in lots of dangerous chemicals.

The Society state that there are strong correlations between chewing tobacco and the development of oral cancer, pancreatic cancer, and esophageal cancer, as well as gum disease and other mouth health problems.


Quitting or cutting down on nicotine

Smokeless nicotine products that do not contain tobacco may offer a useful harm reduction strategy for many smokers, and also a way of reducing the side effects of quitting nicotine.

Smokeless nicotine products, such as NRT, provide the most significant benefit. Users should steadily reduce the amount of nicotine they use, or increase the time between each use until they are no longer regularly consuming nicotine and are not experiencing withdrawal or side effect symptoms.

Smokers who are unable or do not want to quit should still consider alternative forms of consuming nicotine. Though not wholly safe, e-cigarettes and vaping offer an experience similar to smoking, but with less exposure to harmful chemicals and an overall reduction in the risk of cancer.

Takeaway

Nicotine is a drug, and no drug can be completely safe — particularly at higher levels of consumption. People with heart disease or heart disease risk factors may be more vulnerable to the adverse effects of nicotine.

It is smoking and the many chemicals it exposes a person to, not nicotine itself, which presents the highest risk. Switching to a nicotine-only product does not remove all likelihood, but it greatly reduces the risk of cancer. People interested in trying these products can consider NRT or vaping, but not smokeless tobacco, as safer alternatives.

November, 2018|Oral Cancer News|