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Research Leader Discusses FDA-Funded Immunotherapy for Head and Neck Cancer

Tue, Sep 29, 2015


Author: Gina Columbus
Brett Miles, MD, DDS


The investigational immunotherapy axalimogene filolisbac (ADXS11-001) has emerged as a potentially practice-changing agent in the treatment of HPV-related oropharyngeal cancer.

Shown to generate T cells directed against a cancer antigen and neutralize suppressor regulatory T cells and myeloid-derived suppressor cells that protect the tumor microenvironment from an immunologic attack and contribute to tumor growth, ADXS11-001 is the first of its kind—a therapeutic vaccine for the disease.

The agent is being examined in an ongoing phase II trial, which was reported as one of 18 recipients of research grants recently awarded by the FDA’s Office of Orphan Product Development. The grants, given to sites for product development in rare diseases, total more than $19 million. The ADXS11-001 grant provides collaborating researchers from Baylor College of Medicine and the Icahn School of Medicine at Mount Sinai with more than $1.1 million over 3 years.

Eligible patients for the phase II study are newly diagnosed with stage II to IV HPV16-positive oropharynx squamous cell carcinoma who are scheduled to receive ablative transoral robotic surgery.

In an interview with OncLive, the study’s surgical principal investigator, Brett Miles, MD, DDS, associate professor of Otolaryngology Head and Neck Surgery, co-chief, Division of Head and Neck Oncology, Icahn School of Medicine at Mount Sinai, discusses the potential of ADXS11-001 in HPV-associated head and neck cancer and other emerging therapies and treatment strategies.

OncLive: Congratulations on your study being awarded a research grant from the FDA. How does it feel to be selected and how will it help further the phase II research?

  1. Miles: Number one, the beauty of having this award is that it allows us to know that we are in line with what the FDA is interested in and, especially, what the National Institutes of Health (NIH) is interested in, in terms of immunotherapy for head and neck cancer. It gives a little bit of confirmation that our work is headed in the right direction from the standpoint of the major funding agencies.

    Certainly, having that NIH funding is actually going to allow us to propel this study along. We are getting some preliminary results that appear to be encouraging and we really need to confirm those results; this is going to allow us to do that. That is the most exciting part.

Can you provide an overview of ADXS11-001 and how it operates in the immune system?

This is a therapeutic vaccine for HPV-related head and neck cancer and other cancers that are HPV-related. It is contrasting to the preventative vaccines that are widely known, such as Gardasil, for example. Gardasil is a vaccine that if you have not been exposed to the virus, it allows your immune system to fight HPV infection before it happens. The concept behind ADXS11-001 is to allow your immune system to recognize and attack cells that have already been infected with HPV. Therefore, it is a therapeutic vaccine, not a preventative vaccine. It is the only one available for head and neck cancer at this time in a clinical trial.

This is an attenuated virus that is given to the patient in the form of two vaccines, and then it tricks the immune system into thinking that these cells are infected with the bacteria. However, what they are recognizing is the viral proteins. Therefore, they attack the cells that are infected with HPV. That is the theory.

We have administered it to several patients on the trial, and we just got some preliminary data back on the response, and we are seeing some definite changes in the immune system and in the cell surface markers in patients who have had the vaccine. We do not have quite enough data yet to interpret what those changes mean. In other words, we know the vaccine is causing some type of immune response; we are not sure if that vaccine is effectively killing tumor cells yet, and we have not confirmed what those T cells are doing. We are still gathering data for that. Hopefully, with the next batch of patients that we enroll, we will be able to tell if this is actually an effective therapy for this disease. That is kind of where we are right now.

How has the safety profile of ADXS11-001 been thus far?

Patients have been tolerating it quite well. In terms of toxicity, it is like an immunotherapy. Therefore, you may get rashes and low-grade fevers, kind of feeling like you have the flu, and some other things that are relatively standard with immunotherapies. Remember, anything that activates your immune system to a sufficient level to fight off a tumor infection is also going to cause some level of low-grade side effects. However, we have not seen any severe side effects or any major issues with it. We have seen some changes in blood pressure during the infusions, so we give the vaccine in the cancer center. It is two doses and you are supervised for several hours after administration of the vaccine. We have not seen any major toxicities with the vaccine, but the low-grade ones are relatively common. People know when their immune system has been activated, that’s for sure.

What other immunotherapy agents on the horizon do you see having promise in the treatment of head and neck cancer?

One other study, that we have not yet opened but we are going to do, is combining the ADXS11-001 vaccine with MEDI4736, a PD-L1 inhibitor. That study will be for patients who have metastatic or recurrent disease. This ought to be kind of interesting because then you are attacking the immune system from two different angles. It is going to compare ADXS11-001 monotherapy with the PD-L1 monotherapy with a third arm that has both agents combined. I am not sure when that trial is going to be open, but that is the one coming up on the horizon.

Aside from immunotherapy, what other treatment-related research in head and neck cancer are you interested in seeing the results of?

The other main trial is our robotic surgery trial, which is called a de-escalation trial. As you may be aware, patients with HPV-related head and neck cancer have a good prognosis. One of the problems is, when they get standard concurrent chemoradiotherapy, they have a lot of functional morbidity. We have an ongoing robotics trial that basically treats patients with robotic surgery upfront and then they get standard chemotherapy with a reduced dose of radiation, a reduced dose of radiation, or no radiation based on their pathology.

We are hoping to offer the same cure rate for these earlier-stage HPV-related cancers, but with a more functional long-term outcome by tailoring what the patient gets, based on the pathology report, after the minimally invasive robotic surgery. That is something we are currently accruing for, and we are really excited to see if our survival data is comparable, which we think it will be. Our functional outcomes, based on the data we have, should certainly be improved over standard therapy.

There was research presented at the 2015 ASCO Annual Meeting that showed that reducing radiation and chemotherapy dosage in low-risk HPV-associated oropharyngeal squamous cell carcinoma may prevent disease recurrence while still improving quality of life. Can you comment on this study?

Both of these studies are consistent with the prevailing thoughts on de-escalation of therapy in appropriately selected patients. When properly stratified, many patients can enjoy high rates of oncologic cure, with reduced long-term morbidity. It highlights the difficult balance between administering just enough therapy to cure the cancer, without permanently destroying the quality of life in terms of speech and swallowing.

The investigational immunotherapy axalimogene filolisbac (ADXS11-001) has emerged as a potentially practice-changing agent in the treatment of HPV-related oropharyngeal cancer.

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

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Patient Support in Oral Cancer: From Sydney to New York to London, survivors and patients interact through an important portal to get through difficult times

Tue, Sep 29, 2015


Author: Press Release

NEWPORT BEACH, Calif., Sept. 28, 2015 – The word “cancer” will incite fear in anyone. When that word comes at the end of a sentence that began with your name, the impact can be life changing. “I had a great job, a beautiful house and a happy family life,” recalls oral cancer survivor and Oral Cancer Foundation (OCF) Director of Patient Support Services, Christine Brader. “All that changed once I got sick.” Those affected by oral cancer, like Christine, are saddled not only with the physical challenges of treating and surviving the disease, but they must also live with the emotional uncertainty and anxiety that accompanies a diagnosis. OCF’s Patient Support Forum ( was created specifically to provide patients with the information, guidance, and support they need to face a cancer diagnosis. Now in its 15th year, it has helped tens of thousands navigate a difficult path.

It was nearly 16 years ago that oral cancer survivor and OCF founder Brian Hill began his search for answers. “When I was first diagnosed,” Hill recalls, “I was scrambling for the right information. Once inside the treatment world I was faced with decisions about which treatment path was right for me, uncertainties of what would lay ahead, the arrival of complications unexpected, pain, and ultimately a sense of the loss of control and a resulting fear.” While hospital support groups and some online chat rooms existed at the time, they fell short of providing the insights, guidance and accessibility necessary to have real benefit to a newly diagnosed cancer patient undergoing treatment. “My problems were complex and changing daily. Every day it seemed that something new was occurring that complicated matters, and I needed to talk with someone who could help me digest everything from the new medical terminology, to dealing with side effects of what I was undergoing.” It was through building relationships with other survivors and exchanging stories and information that Hill was able regain hope and envision life after cancer.

In 2001, seeing a need for patients to connect with one another, Hill worked to develop an interactive online forum where patients and survivors could share their knowledge and tell their stories. Christine Brader joined the forum after her first oral cancer diagnosis in 2007. “When I was diagnosed I didn’t know which way to turn, and by finding others who had gone through it, I gained significant peace of mind,” she recalls. “After my third cancer recurrence, I lost 65 pounds, was hospitalized twice for dehydration and malnutrition and was ready to quit. The doctors don’t always prepare patients for the realities of the difficult treatments.” It was the advice from other survivors, words of encouragement and support from the OCF forum community that convinced Christine to continue her treatments and gave her hope. “There’s a whole world of people who have gotten through it and survived, they are living in a world after cancer and are thriving” she says. “Given the extensive disfiguring surgeries, and compromises that I would be forced to live with, I was uncertain if there was even a place for me in the world after fighting to survive. Single, unable to work in my previous vocation, I could not wrap my mind around how I would fit back into a world where everything from esthetics, to the ability to speak clearly carry so much weight. But through this online vehicle, I built friendships, and through one person in particular I was repeatedly told that there can be a rich vibrant life after this terrible cancer, which can leave its visible damage even after survival, no matter how different I was after it all. The transition was not easy, but they were right. Life after my battle is rich in relationships, and meaningful work.” Now, as the patient support administrator for OCF, Christine offers her experience-based insights and emotional support to others just beginning their own battles.

Unlike public chat rooms and social media based groups, OCF’s Patient Support Forum was designed with the users’ privacy and safety in mind. OCF’s forum users’ personal information will never be marketed to by outside companies, and they will never be exposed to advertising; both considerations associated with social media platforms. Anonymous screen names protect privacy and facilitate an open dialogue for difficult topics such as intimacy and depression. “It was important to develop rules to ensure that the information on the forum is reputable, and accurate. Misinformation can facilitate poor decision making, and harm people,” says Hill. To that end, the forum is heavily monitored by volunteer staff with diverse medical backgrounds including dentistry, oncology, research, and nursing and of course long term survivors themselves. Both Hill and Brader agree that the survivors are often the most adept at answering questions correctly and sensitively. “Survivors direct experience many times trumps clinical experience of professionals, though we would never suggest that they have the same level of knowledge. But living on the receiving end of the treatment process definitely provides you with a much different perspective. We don’t let inaccurate information live on our boards,” says Hill, “and we will correct or eliminate the information/comments that are incorrect or scientifically unsupported.”

It is this kind of monitoring and oversight that earned OCF’s websites, and, Health on the Net’s HONcode certification. The HONcode is a designation reserved for online publishers of trustworthy and reliable medical and health information who have volunteered to adhere to hundreds of strict guidelines and Health on the Net’s code of ethics. This certification is an oversight process that is ongoing, to ensure the consumer that information presented is trustworthy and scientifically accurate; and that protocols for proper informed interaction are in place. With the understanding that poor information can lead to poor choices, OCF has gone to great lengths to protect its members from misleading information.

Today, the Oral Cancer Foundation is working hard to make patients and their families aware that support and answers are available online, for free, 24 hours a day by visiting the web based forum. In keeping with OCF’s missions to reduce suffering and save lives through prevention, education, research, advocacy, and patient support, the forum has been designed to fulfill the need for reliable medical information and emotional support. With over 10,000 active members, thousands more who visit the site, read the threads of discussion without becoming members or posting themselves, and over a quarter million archived threads of information, the forum has grown into the largest and most well curated databases of oral cancer information and emotional support on the internet. Members now span across the globe and dozens of countries. Even oncology researchers have looked to this online community to develop answers and insights into understanding the patient experience, and improving the ways in which they interact with patients, and anticipate their needs both physical and emotional.

When discussing the relationships he’s made on the forum, Ed Brown, now a 12-year oral cancer survivor says, “Finding each other is the greatest thing that has ever happened to us. When you feel like you’re some kind of freak and struggling alone with your issues, it’s the best feeling to find out there is someone else out there who has dealt with the same thing, someone who knows what it’s like, someone who understands the “work-arounds” for some of the complications of treatments that we all deal with. Thanks to the forum I now know 10,000 survivors who because of our shared experiences are a resource I can turn to.”  Few people can comprehend the pain and hardship of undergoing treatment for a life threatening illness, fewer are aware of the emotional isolation and lonesomeness that accompanies the disease. Only survivors, other patients, and their caregivers live the intimate struggles and battles of will that take place when fighting for your life.

“The support forum became a second family really, not just a bunch of patients or survivors, but a community that I was a part of. We’ve all shared a common experience, endured treatment, survival, complications, and funerals. The camaraderie in the community is the heart and soul of what OCF really is – a group of people helping other people,” says Hill. The individuals who use the support forum have made lifelong friendships and passed along their experiences and knowledge to others.  Brown says, “For every success I’ve had on this journey, likely a thousand people will have known about it.” Sharing in the successes of others and giving back to a community that has embraced you during your difficult times are important reasons why many of the thousands of forum users continue to use the site after they’ve been declared “disease free.”

Hill has called the patient support forum the “heart and soul” of the foundation. Given the foundations many diverse activities; from sponsoring research to advocacy, those that populate the OCF forum, who choose to spend part of their new lives in service to those behind them on the path, he feels they are the palpable core of what OCF is. Few face-to-face support groups can deal with the daily needs of patient ups and downs, as they most often meet once a month, and have less depth of experience to draw from as there are fewer individuals to share their experiences, and fewer survivors attending as they move on from their cancer experience. The OCF forum idea, created well before Google was the major search engine we know today, and before any social media companies like Facebook even existed, has a decade and a half of experience as an Internet based platform to help others… as often as they find a need for it.

Oral cancer is not fought with treatment staff and medicine alone, but in conjunction with reliable medical information to facilitate good decision making, and emotional support and guidance when the questions and weight of the experience seem overwhelming. OCF’s Patient Support Forum is a resource rich with answers, accessible anytime, from nearly anywhere, anonymous, monitored and safe, and free to anyone in need.

For more information about the Oral Cancer Foundation and the Patient Support Forum, please visit and

About the Oral Cancer Foundation:
The Oral Cancer Foundation, founded by oral cancer survivor Brian R. Hill, is an IRS registered non-profit 501(c)(3) public service charity that provides information, patient support, sponsorship of research, and advocacy related to oral cancer. Oral cancer is the largest group of those cancers that fall into the head and neck cancer category. Common names for it include such things as mouth cancer, tongue cancer, head and neck cancer, and throat cancer. The Oral Cancer Foundation maintains the web sites:,,, and, which receive millions of hits per month. Supporting the foundation’s goals is a scientific advisory board composed of leading cancer authorities from varied medical and dental specialties, and from prominent educational, treatment, and research institutions in the United States. The foundation also manages the Bruce Paltrow Oral Cancer Fund, a collaboration between the Paltrow family represented by Ms. Blythe Danner (Paltrow), Gwyneth Paltrow, Jake Paltrow and the Oral Cancer Foundation.

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“They don’t care:” Hamilton senior left five months without a voice

Wed, Sep 23, 2015


Author: Joanna Frketich

Donna Thombs has not uttered a word in five long months.

The east Hamilton senior is desperate to get her voice back, but has so far faced a waiting list with no room for compassion at St. Joseph’s hospital.

“It’s terrible,” mouths Thombs. “They don’t care.”

The only sound is wheezing as she attempts to talk with gestures along with slowly mouthing out words using exaggerated movements. It takes multiple attempts to get across even the simplest words. Often, she shakes her head and just gives up.

amilton Spectator Donna Thombs has been living in silence for five months as she awaits an operation to restore her voice following surgery for throat cancer.

Credit: Hamilton Spectator
Donna Thombs has been living in silence for five months as she awaits an operation to restore her voice following surgery for throat cancer.

“Try not talking for one day,” she mouths. “I’ve done it for months. Now, it’s really starting to get to me.”

Thombs says the surgical procedure essential to giving her a voice takes roughly 20 minutes. She came achingly close when it was scheduled for Aug. 26, only to have it cancelled.

As of Friday, Thombs had been given no information by the office of head and neck surgeon Dr. Michael Gupta on how much longer she’d have to wait.

She’d been told her case was a low priority despite the safety concerns of a woman in her 80s living alone with no voice to call for help. Her relatives phone to check on her but her only way to communicate with them is to knock once to let them know she is well or twice if she needs them to come and help her out.

“I feel horrible she’s had to go through that kind of wait,” said Anne Marie MacDonald, director of surgery at St. Joseph’s. “We should have done better for this lady.”

MacDonald says she only became aware of Thombs’ plight after being contacted by The Spectator. She says she’s now working with the surgeon to get the procedure done “expeditiously.”

“It’s important to express our apologies,” she said. “We’ll be working with Dr. Gupta’s office to facilitate something to happen for her as soon as possible.”

It all started when Thombs was diagnosed with throat cancer in January. She had to go through a laryngectomy which removed all of her voice box and left her breathing through a hole in her throat.

Initially, she was expected to have received a tracheoesophageal voice prosthesis, a device that produces a sound source for the voice so she could speak again, by the end of May.

But a key tube that keeps open a space for the device to be put in fell out on a Saturday in May. Thombs said she had not been instructed on what to do if the tube fell out or told it would be an emergency that needed immediate treatment.

She was not in any pain or medical distress so she waited to call the surgeon’s office when it opened again on Monday. By that time the space had closed, requiring a surgical procedure to reopen it.

She has been waiting for that procedure ever since. She says every time she calls she’s told that the surgeon only has a limited amount of operating room time and it all goes to urgent cancer patients.

St. Joseph’s does have one of the shortest waits in the province for head and neck cancer surgery, with patients waiting far below the provincial target in the Ministry of Health’s public report for May to July.

“Our head and neck cancer physicians work hard to have patients wait the minimal time we can manage,” said MacDonald. “The surgeons themselves in their offices prioritize in order of acuity.”

But MacDonald said a “rare complication” like Thombs’ should have been given a higher priority.

Thombs said she’s been shocked by the “world of discrimination” she has faced since losing her voice. She says people treat her like she is “stupid” when she communicates at stores or the bank with handwritten notes.

“If they don’t do it soon, I’m going across the border,” she mouthed. “I’ll pay for it myself.”

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No definite symptom index for recurrence in head and neck cancer, small study suggests

Wed, Sep 23, 2015



In patients treated for head and neck squamous cell carcinoma (HNSCC), there was no definite index of symptoms that indicated local recurrence or second primary malignancy in a small Taiwanese study published online ahead of print in Head & Neck.1

In head and neck squamous cell carcinoma, there was no definite index of symptoms to indicate recurrence or second malignancy.

In head and neck squamous cell carcinoma, there was no definite index of symptoms to indicate recurrence or second malignancy.

Pei-Hsuan Lin, MD, and fellow researchers from the National Taiwan University examined 136 patients with HNSCC who were diagnosed between January 2010 and June 2014, 32 of whom had local recurrence and 14 of whom had second primary malignancy.

“The purposes of this study were to identify an index of symptoms and signs of swallowing disorders that indicate the occurrence of local recurrence or second primary malignancy,” the authors noted.

They found that common swallowing disorders and objective transnasal esophagoscopy findings were similar between patients with and without local recurrence or second primary malignancy.

“Routine transnasal esophagoscopy examination of patients treated for HNSCC with swallowing disorders is strongly recommended,” the authors concluded.

Lin P-H, Wang C-P, Lou P-J, et al. Evaluation of swallowing disorders by use of transnasal esophagoscopy in patients treated for head and neck cancer. [published online ahead of print September 2, 2015]. Head Neck. doi: 10.1002/hed.24174.

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Vaccine law should cover HPV cancers

Wed, Sep 23, 2015


Author: Brandon Brown

Vaccines are the most effective way to prevent infectious diseases. Gov. Jerry Brown rightly signed a law that requires, starting July 1, 2016, that all children enrolled in public or private schools or day care be vaccinated against whooping cough, measles, polio and other diseases, regardless of parents’ religious or personal beliefs. But frustratingly, the California mandate does not include the vaccine to protect against cervical, anal and oral cancers, and genital warts.

HPV vaccines have been around for 10 years. Three types exist, with the newest providing the highest protection against chronic infection and precancerous conditions among boys and girls. Despite the recommendations of major health groups, national data show only 57 percent of adolescent females and 35 percent of males received at least one dose of the three-dose HPV vaccine series in 2013. HPV vaccine has the lowest completion rate of any vaccine in the United States.

There may be several explanations for this. One is the short time that providers have available to stress the need for early vaccination during a normal medical visit, much less to address parents’ concerns about implicitly sanctioning sexual activity. But the vaccine is linked to age rather than sexual activity, and postponing it until after boys and girls start having sex decreases its effectiveness.

Another reason for low vaccination rates is that it requires tremendous work, including training health care providers on how to promote HPV vaccine as a cancer-prevention tool similar to hepatitis B vaccine, which has a similar route of transmission. With hepatitis B, sex is not part of the discussion, and HPV should be treated the same way.

We must applaud Rhode Island for recently joining Washington, D.C., and Virginia for incorporating all vaccines recommended by pediatricians and the Centers for Disease Control and Prevention, including HPV, into their school immunization regulations.

More than 14 million HPV infections occur annually in the United States. With such a sobering statistic, no sound justification can be made for HPV vaccines to be treated differently than other recommended vaccines. It’s time for solutions instead of excuses.

Author: Brandon Brown is an assistant professor at the University of California, Riverside, School of Medicine.

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Spreading awareness and saving lives — Oral Cancer Foundation’s Walk for Awareness may be coming to a city near you!

Tue, Sep 22, 2015


Author: press release

Oral cancer has historically existed outside the awareness of much of the public, yet in the U.S. it claims one life every hour of every day of the year. This year alone, approximately 45,750 Americans will be diagnosed with oral cancer. This number is on the rise and The Oral Cancer Foundation (OCF) needs help spreading awareness about this devastating disease. OCF is working in communities across the country to bring “Walk for Awareness” events to the public, and with them the opportunity to engage in a conversation that too few people are having.

These events raise awareness of a disease that far too many Americans have never even heard of. Most events also incorporate free to the public oral cancer screenings, providing the opportunity to educate attendees about the early signs and symptoms of oral cancer while also instilling the importance of early detection and need for annual oral cancer screenings. To see if an OCF Walk for Awareness is taking place near you, visit and click support to view an interactive map of the organization’s upcoming events.

OCF has been raising awareness and providing support in communities for 16 years in cities scattered across the US. Here are a just a few of the remaining Fall 2015 events:

  • The 5th Annual Oral Cancer Foundation Walk/Fun Run for Awareness – Twin Cities, Minnesota, will take place this Sunday, September 27, 2015 at City of Eagan Community Center. For more details, to register and donate please visit,
  • The 9th Annual Oral Cancer Foundation Walk/Run for Awareness – Boston, Massachusetts, will take place on Sunday, October 4, 2015. This event has been taking place for nearly a decade! Please join OCF this year at the Chestnut Hill Reservoir in Brighton, Massachusetts. For more information about this event, to register or donate please visit,
  • The 2nd Annual Oral Cancer Walk/Run for Awareness – Southern California will take place on Saturday, October 10, 2015 at Mile Square Park in Fountain Valley, CA. Please visit, to find out more.

Participating in and supporting an OCF event helps the foundation accomplish many of its important missions. As a national public-service, 501c3 non-profit entity, OCF’s mission is to reduce suffering and save lives through prevention, education, research, advocacy, and patient support activities. In addition to OCF’s community outreach activities, the foundation hosts the websites and to deliver free and vetted oral cancer health information to the public including the risk factors that lead to oral cancer, signs and symptoms, treatments, current research, complications of treatment, nutrition, related clinical trials, and current oral cancer related news.

Through the small event registration fees and community fundraising, OCF’s national walk events pay for the many missions of the foundation related to this disease. The money funds researchers working on various components of the problem, pays for advocacy work at places as diverse as the National Institutes of Health, National Cancer Institute, The Centers for Disease Control, and even in the political components of our government. By participating in an OCF event, you can help further progress against a disease that takes far too many lives.

About the Oral Cancer Foundation:
The Oral Cancer Foundation is a 501 (c) 3 national public service, non-profit entity designed to reduce suffering and save lives through prevention, education, research, advocacy, and support activities. Visit to learn more about risk factors, signs and symptoms, treatments, current research and current oral cancer related news, among other important information.

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Vaccine clears some precancerous cervical lesions in clinical trial

Mon, Sep 21, 2015


Author: Mark L Bagarazzi, MD et al.

Scientists have used a genetically engineered vaccine to successfully eradicate high-grade precancerous cervical lesions in nearly one-half of women who received the vaccine in a clinical trial. The goal, say the scientists, was to find nonsurgical ways to treat precancerous lesions caused by HPV.

“Every standard therapeutic option for women with these lesions destroys part of the cervix, which is particularly relevant for women of childbearing age, who may then be at risk for preterm birth due to a weakened cervix,” says Cornelia Trimble, M.D., professor of gynecology and obstetrics, oncology, and pathology at the Johns Hopkins University School of Medicine, and first author of the new report, which appears online Sept. 17 in The Lancet. “A vaccine able to cure precancerous lesions could eventually be one way women can avoid surgery that is invasive and can also harm their fertility.”

High-grade cervical lesions, termed CIN2/3, occur most often in women 40 or younger, according to Trimble, a member of Johns Hopkins’ Kelly Gynecologic Oncology Service and Kimmel Cancer Center. Because the lesions can progress to cancer, they are usually removed by surgery, freezing or laser. The procedures are successful in removing the precancerous areas in approximately 80 percent of women, says Trimble. Less troublesome lesions, called low-grade dysplasia, are usually monitored by physicians rather than immediately removed because they pose less of a risk for cancer and usually regress on their own.

For the study, the scientists used a vaccine, originally developed by University of Pennsylvania scientist David Weiner, Ph.D., which is engineered to teach immune system cells to recognize precancerous and cancerous cells. Those cells are coated with proteins linked to an infection with two strains of HPV — 16 and 18 — that cause cervical cancer. The vaccine, given by injection into the arm, is made by Inovio Pharmaceuticals Inc., which funded the clinical trial, and whose employees co-authored the report with Trimble.

Between 2011 and 2013, the scientists recruited 167 women, ages 18 to 55, with newly diagnosed, high-grade precancerous cervical lesions. The women were randomly assigned to receive either three doses of the vaccine or saline injections over a 12-week period at 36 hospitals and private gynecology practices in the U.S. and six other countries.

After each of the injections, the scientists gave the women a small electric pulse at the site of the injection. Cells near the electric pulse open their pores, says Trimble, increasing the likelihood that the vaccine will be taken up by immune system cells.

Of 114 women who received at least one vaccine dose, 55 (48.2 percent) had a regression of their precancerous lesion, meaning their lesions disappeared or converted to low-grade lesions, compared with 12 of 40 (30 percent) who received saline injections. Of the 114, 107 received all three vaccine doses, and 53 of them (49.5 percent) had regression of their lesions. Of the 40 in the saline group, 36 got all three injections, and 11 of them (30.6 percent) had regression of their lesions. Thirteen women dropped out of the study after enrollment.

Two patients discontinued the study because of pain at the injection site. Skin redness was more common in the vaccine group compared with saline.

Among women who completed all three injections, scientists could find no trace of HPV in the cervixes of 56 of the 107 women who received the vaccine, compared with only nine of 35 saline recipients.

“In many of these women, the vaccine not only made their lesions disappear, but it also cleared the virus from their cervix,” says Trimble. “In most unvaccinated patients whose lesions went away, the virus was still present, and many still had low-grade lesions.”

Trimble says clearance of the virus is a “significant bonus” from receiving the vaccine because persistent HPV infection is a major risk factor for recurrence of cervical lesions.

After 12 weeks, doctors surgically removed lesions that did not regress and took biopsies of each study participant’s cervix. In the surgically removed lesions, scientists found miniscule cancers in two of the women who received the vaccine. Trimble says these microinvasive cancers are rarely diagnosed by a biopsy but are found in surgical specimens.

n the biopsy samples, the scientists found that patients whose lesions completely regressed after treatment had more immune cells, called T cells, present in the tissue. “It’s important that T cells capable of recognizing HPV stay in the cervix and fight off any recurrence of the infection,” says Trimble.

“This is a great first step,” says Trimble. “We showed that the vaccine may enable an immune response in a person whose immune system was initially not adequately engaged or was hampered in some way so as to let the lesion occur.”

Trimble says that precancerous lesions are unlikely to progress to cancer during the vaccine treatment period, and monitoring of high-grade lesions is done routinely for pregnant women. “It typically takes about 10 or more years for precancerous cells to become cancer, so there is a window of opportunity to intervene with nonsurgical approaches to reverse the process of viral-associated cancers,” says Trimble.

Trimble says she and her colleagues are now working to identify biomarkers from cervical tissue that can predict which lesions are more likely to persist and eventually progress to cancer. The research team will be monitoring this initial group of study participants to see whether they have fewer recurrences than unvaccinated patients. Trimble is also studying other types of vaccines to prevent the progression of high-grade cervical lesions to cancer.


Trimble received an unrestricted grant from Inovio Pharmaceuticals Inc., but she has no other financial or consulting arrangements with the company.

In addition to Trimble, scientists who contributed to the research include Lance Edwards from Suffolk Obstetrics and Gynecology in Port Jefferson, New York; R. Lamar Parker from Lyndhurst Gynecologic Associates in Winston-Salem, North Carolina; Lynette Denny from the University of Cape Town’s Groote Schuur Hospital in South Africa; David B. Weiner from the University of Pennsylvania; and Matthew P. Morrow, Kimberly A. Kraynyak, Xuefei Shen, Michael Dallas, Jian Yan, Mary Giffear, Ami Shah Brown, Kathleen Marcozzi-Pierce, Divya Shah, Anna M. Slager, Albert J. Sylvester, Amir Khan, Kate E. Broderick, Robert J. Juba, Timothy A. Herring, Jean Boyer, Jessica Lee, Niranjan Y. Sardesai, David B. Weiner and Mark L Bagarazzi from Inovio Pharmaceuticals Inc.

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

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Imaging method has potential to stratify head and neck cancer patients

Sat, Sep 19, 2015


Author: press release

Manchester researchers have identified a potential new way to predict which patients with head and neck cancer may benefit most from chemotherapy.

These patients commonly receive pre-treatment induction chemotherapy, before either surgery or radiotherapy, to reduce the risk of disease spread. However the effectiveness of such treatment is reduced in tumours with poor blood flow.

Previous studies have shown that CT scans can be used to assess tumour blood flow. Now researchers at The University of Manchester and The Christie NHS Foundation Trust – both part of the Manchester Cancer Research Centre – have explored the use of MRI scans in predicting which patients would benefit from induction chemotherapy.

Professor Catharine West, who led the study, said: “It’s also important to identify those patients who are unlikely to respond to induction therapy so that we can skip ahead in the treatment pathway and offer them potentially more effective treatments and hopefully improve their outcome.”

The team used an imaging technique known as dynamic contrast-enhanced MRI (DCE-MRI), where a contrast agent tracer is injected into a patient’s vein whilst they have a series of MRI scans taken. This allows scientists and doctors to investigate the blood flow and vessel structure of a patient’s tumour.

They found that the blood flow of a patient’s tumour before they received induction therapy could predict response to treatment. In a paper recently published in the journal Oral Oncology, the group report that those with high tumour blood flow were more likely to respond.

Jonathan Bernstein, a co-author on the paper, said: “Delivery and effectiveness of chemotherapy appears to be better in tumours with higher blood flow. However, amongst those patients with lower measured tumour blood flow, more work is needed to determine those who will and won’t respond.”

Source: ‘Tumor plasma flow determined by dynamic contrast-enhanced MRI predicts response to induction chemotherapy in head and neck cancer’, Bernstein et al. (2015) Oral Oncology

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FDA Grant Forwards Listeria-Based Throat Cancer Vaccine

Thu, Sep 17, 2015


Author: Sandra Kear

An experimental immunotherapy for human papillomavirus-, or HPV-, related throat cancers, which is driven by the Listeria bacteria (that wreaks havoc when ingested), may now move forward due to a $1.1 million dollar grant from the FDA to researchers at Baylor College of Medicine.

“Immunotherapy, such as axalimogene filolisbac, which targets HPV proteins expressed in cancer cells is a great example of using a cancer’s own unique biology against it.” said principal investigator Andrew Sikora, MD, PhD, leader of the head and neck cancer program in the NCI Comprehensive Designated Dan L. Duncan Cancer Center and an associate professor of otolaryngology at Baylor College, in an interview with Targeted Oncology.


“This is hopefully the first step toward development of more targeted treatment approaches that reduce side effects and cancer treatment-related morbidity by uniquely targeting only virus-infected cells.” 
The Listeria-based HPV immunotherapy, axalimogene filolisbac (ADXS11-001), is developed by Advaxis, and functions by stimulating an immune response against HPV proteins, thus killing infected cells.

The drug is currently being evaluated in phase I-II study3 alone or in combination with MedImmune’s durvalumab, in patients with cervical or HPV-positive head and neck cancer. The study has online games for real money three arms: axalimogene filolisbac alone, durvalumab alone, and the two drugs combined. Primary outcomes established for the study are: number of subjects with adverse events (AEs) in each dose level, number of subjects with AEs in the combination dose, and progression-free survival.

Patients must have measurable disease by RECIST criteria, as well as histologically diagnosed squamous cell cancer of the head and neck or squamous, nonsquamous, adenosquamous, carcinoma, or adenocarcinoma of the cervix. HPV positivity is not required for cervical cancer. Enrolled patients must be ≥18 years of age with a performance status of 0 or 1. Females must have a negative pregnancy test, and patients must agree to use two methods of birth control 120 days after the last treatment dose. The estimated study completion date is December 2019.

“We continue to accrue patients for this trial and collect blood and tumor specimens. Immune studies are best done in batches, so every time we have the specimens from 5 to 6 patients available, we can start another round of studies looking at things like T-cell responses, changes in immune cell profiles, altered serum cytokines, etc.” Sikora said. “At the end of it, each different assay provides a different snapshot of how the immune system works, and we hope to put them together to comprehensively understand what is happening to the immune system in these patients and how to use this information to put together the next round of clinical trials.”

Sikora will collaborate with the Icahn School of Medicine at Mount Sinai in New York City and with Advaxis. The grant was given by the FDA’s Orphan Products Grants Program, which supports clinical development of new treatments for rare diseases or conditions where no current treatment exists or superior treatments are needed.

“The grant from the FDA is a total game changer, because not only does it make it possible for us to fully complete accrual of the trial, but it gives us the opportunity to perform really cutting-edge analyses on the samples collected. We now have the opportunity to use nearly every tool at our disposal to meticulously profile and understand how this therapy drives antitumor immune responses,” said Sikora.

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

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Smokeless tobacco use on the rise among high school athletes

Sun, Sep 13, 2015


Author: Jeron Rennie

A new Centers for Disease Control and Prevention (CDC) report shows a trend they don’t want to see.

A Morbidity and Mortality Weekly Report (MMWR) shows that from 2001-2013, smokeless tobacco use increased significantly among high school athletes, but not with non-athletes.

The report also found there was lower use of combustible tobacco products among athletes than non-athletes. The CDC said that could be due, in part, to an awareness of the negative consequences on athletic performance. However, they say the use of smokeless tobacco suggests they find those products as being harmless.

“When you see it in the media and you see all those athletes that you’re looking up to as a younger student and trying to reach some of the goals that they’ve reached,” said Freeborn County Drug-Free Coalition Prevention Coordinator Lana Howe. “It definitely plays a large impact on you as a youth.”

The CDC said using smokeless tobacco can, however, adversely impact athletic performance and lead to disease and early death since they contain nicotine, toxins and carcinogens.

Several athletes with a history of smokeless tobacco use have been diagnosed with, or died from, oral cancer.

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