Oral Cancer News

World Trade Center responders might face greater risk of HPV throat and tongue cancer

Source: medicalxpress.com
Author: provided by Rutgers University

Firefighters at the World Trade Center were exposed to tons of toxic dust and debris that blanketed Manhattan on 9/11. Credit: Shutterstock

Researchers at Rutgers University – investigating the causes of head and neck cancers in World Trade Center rescue and recovery workers – will take the lead in a study to determine whether the responders are at a greater risk for human papillomavirus (HPV)-related throat and tongue cancer because of their exposure to toxic dust and debris.

“If we find that the prevalence of HPV is higher in World Trade Center exposed rescue workers it could mean that they have an increased likelihood of infection with HPV or have less of an ability to be able to clear this common infection naturally,” said Judith Graber, assistant professor of epidemiology in the School of Public Health.

HPV is the most common sexually transmitted infection in the United States, according to the Centers for Disease Control and Prevention, with most infections going away on their own. There is also now a vaccine to prevent HPV given to adolescents and teens. This is a new vaccine not given to adults and rates of vaccination have been low in the US.

While HPV-related oropharyngeal cancer, which includes throat, tonsils, back of tongue and soft palate, is relatively small, the number of HPV throat and tongue cancers are expected to increase and surpass HPV-related cervical cancers by 2020.

Graber said oropharyngeal cancer – which has a lower survival rate – is among the diseases which pose great risk for WTC rescue and recovery workers, who appear to have a greater incidence of throat and tongue cancer. Surviving patients, often left disfigured after treatments, are at a higher rate for depression, unemployment and suicide compared with other cancer patients, according to the study.

While the prevalence of HPV in the United States among people age 69 and younger is estimated at less than 10 percent, Graber said research indicates that 80 percent of all tumors found in this type of cancer are infected with HPV, some which can cause cancer.

“The symptoms, risk factors and exposure history could help in early prevention of this very devastating cancer,” said Graber.

The new Rutgers study will use tissue samples provided by the World Trade Center Biorepository at Mount Sinai from WTC workers diagnosed with oropharyngeal cancer and compare to tissue samples of people being treated for the disease at University Hospital in Newark.

This research is a spinoff of a two-year federally funded study examining risk factors for all head and neck cancers among WTC responders. Graber and her colleagues, including co-principal investigator, Mark Einstein, professor and chair department of OBGYN & Women’s Health at Rutgers New Jersey Medical School, are hoping to discover opportunities for early detection for these potentially debilitating diseases.

“HPV is very common, but cancers related to HPV are uncommon,” said Einstein. “Understanding the relationship between HPV and the development of oropharyngeal cancer is of critical importance so we can prevent and target this cancer better with novel therapies”.

What researchers need to determine in this new study, Graber said, is whether the higher incidence of the throat and tongue cancer is due to the fact that this group is being closely monitored, because of respiratory exposure after 9/11 or as a result of an HPV infection that creates a problem for a weakened immune system.

The information is critical, Graber said, in the quest to design a more definitive study to determine how and why these cancers are developing among those exposed during the rescue, recovery and clean-up efforts at the World Trade Cente

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September, 2017|Oral Cancer News|

What’s next after creating a cancer-prevention vaccine?

Source: www.scientificamerican.com
Author: Dina Fine Maron

A winner of this year’s Lasker Awards talks about his work with HPV

Imagine a vaccine that protects against more than a half-dozen types of cancer—and has a decade of data and experience behind it.

We have one. It’s the human papillomavirus (HPV) vaccine, and it was approved for the U.S. market back in June 2006. It can prevent almost all cervical cancers and protect against cancers of the mouth, throat and anus. It also combats the sexually transmitted genital warts that some forms of the virus can cause.

On Wednesday, two researchers who completed fundamental work on these vaccines received one of this year’s prestigious Lasker Awards, a group of medical prizes sometimes called the “American Nobels.” Douglas Lowy and John Schiller, whose research provided the basis for the HPV vaccine, were selected alongside a researcher who separately unraveled key aspects of metabolic control of cell growth. Planned Parenthood was also given an award, for its public service. Lowy and Schiller, who both work at the U.S. National Cancer Institute (NCI), received the Lasker for their research on animal and human papillomaviruses—work that enabled the development of a vaccine against HPV-16 type, a form of the virus that fuels many HPV malignancies. The duo’s experiments proved that the vaccine is effective in animals, and they also conducted the first clinical trial of an HPV-16 vaccine in humans. That gave pharmaceutical companies the evidence they needed to invest in their own vaccines designed to protect against multiple kinds of HPV, and ultimately led to the versions administered around the world today.

Yet HPV shots have had a difficult run. Despite overwhelming evidence of their safety and effectiveness, in some developed countries—including the U.S.—HPV inoculations face opposition from individuals and groups that fear the shots are still too new and unproved to use on their children. The HPV vaccine also faces another hurdle beyond other routine pediatric shots: the virus is transmitted via sexual contact—which some parents and communities believe teens should not or will not have, and thus that the shots should not be mandatory. (The U.S. Centers for Disease Control and Prevention [CDC] currently recommends administering two doses of the vaccines to children 11 to 12 years old, administered at least six months apart.)

Scientific American spoke with Schiller, a virologist, about his and Lowy’s award-winning HPV research, their future plans and how to combat anti-vaccine attitudes.

[An edited transcript of the interview follows.]

What’s the biggest hurdle to getting more coverage with the HPV vaccine?
The biggest problem is actually not in the West or most developed countries; it is in the lower- and middle-income countries because of availability there and vaccine prices that limit availability. In those settings vaccine acceptance is actually very high. But those settings present the biggest problem, since some 85 percent of cervical cancers occur in low-resource settings. In the more developed countries there are many different factors involved [in vaccine hesitancy], and they differ by country. In the U.S. it is more about fear of vaccines in general. And there are some issues with HPV vaccines specifically related to this being about a sexually transmitted disease.

So far, more than 270 million doses of HPV vaccines have been distributed worldwide. But in the United States, by 2015 only 28 percent of teen males and 42 percent of teen girls had received the full course of three shots then recommended by the CDC. How can the science community help combat HPV vaccine hesitancy?
There are quite a few studies that show one of the biggest issues is that the vaccine is not being promoted sufficiently by pediatricians and general practitioners. If you look at other vaccines like for meningitis and hepatitis B—which are also administered to adolescents and could be given in the same visit as HPV—they are given at greater rates than HPV. So, there is some disconnect in communication between pediatricians and parents there. Part of the problem here is that the HPV vaccine is a prophylactic vaccine to prevent a disease—cervical cancer—that those providers never see. Obstetrician-gynecologists see it, but pediatricians don’t, which is the opposite of most other childhood or pediatric vaccines. Right now it’s being singled out as something special instead of treated as a routine childhood or adolescent vaccine. But we’ve had this vaccine for 10 years now and it’s not the new kid on the block anymore.

Mounting evidence suggests that among people who feel vaccines are unsafe, any new data showing that they arereally safe does not move the needle to convince them. So, what can be done?
My feeling is that there is a certain percentage of people who, no matter what facts you present to them, they are just not going to be convinced. Quite frankly it doesn’t pay to spend a lot of resources trying to convince that relatively small fraction. What we need to focus on is a much larger fraction of the population who aren’t having their kids vaccinated for reasons like convenience—like it’s a hassle—or they just need a bit more information to make them comfortable. People against all vaccines, those people would not be convinced to get an HPV vaccine so it’s not worth spending a lot of resources on them. I think one of the things that would increase HPV vaccine coverage would be allowing people to get them at their local CVS. I’m not an expert on this, but I have a daughter who as a teen spent much more time at the local CVS than at her local Kaiser clinic. Different states have different laws about which vaccines can and can’t be delivered at pharmacies—but if someone could go get an HPV vaccine at the same place they get their flu vaccine, presumably it would lead to an uptick.

I see you studied molecular biology as an undergrad at the University of Wisconsin–Madison. Did you always want to work on vaccines?
No, absolutely not. When I first started out I was an academic purist and thought you should study knowledge for its own sake. I was fascinated by molecular biology. When I first heard about the way metabolism works in bacteria, plants and humans, that just wowed me because that was a common feature of all life. I just wanted to study that. I thought people who did translational work were sort of selling out to the man—this was in the 1970s. I didn’t get interested in vaccines until much later. Now, I’m very fascinated with translational research.

So, what changed?
It was a very gradual thing. To this day we still do basic research, and it’s still intrinsically valuable to do basic research because you don’t know when it will lead to a transformational breakthrough.

What led you to work on HPV?
When I had just joined the field, suddenly there was this discovery that made papilloma viruses important for human health as opposed to just an understanding of how cells become cancerous. I had joined Doug Lowy’s lab at the National Cancer Institute as a postdoc back in 1983, and the second lecture I went to there was by Harald zur Hausen—who later won the Nobel Prize—and his lecture was saying “eureka! We found a virus that seems to cause 50 percent of cervical cancers”—and that virus turned out to be a human papilloma virus strain, HPV-16. So basically we went from looking at a model about how a normal cell transforms to become carcinogenic to something probably involved in causing human cancer. It was somewhat serendipitous.

What are you working on now?
One thing we are doing at the NCI, and cosponsored by the Bill & Melinda Gates Foundation, is testing if one dose of HPV vaccine is enough to provide long-term protection. It would be transformative, especially in the developing country setting, if you could just have one dose at a younger age. This new trial is going to be done in Costa Rica in collaboration with the Costa Rican government. That’s the site where we had done a prior pilot trial that suggested one dose may be enough.

We are also looking into cancer immunotherapy work. It turns out that these virus-like particles that we work with for the HPV vaccine—these are typically the outer shell of a virus, like from the HPV-16 strain or other animal, or human papilloma virus particles—have a unique ability to infect tumor cells and bind to them specifically. So we are using that knowledge to develop cancer therapies that are broad-spectrum. It turns out these cancers, like melanoma, do bind these particles, specifically.

One other thing we are doing is trying to develop vaccines that would treat herpes simplex infections and HPV infections in the female genital tract. Again, this would take advantage of these virus-like particles’ structures.

Last year I interviewed Michael Sofia, who won a Lasker Award for his hepatitis C vaccine work. The name of that vaccine, sofosbuvir—brand name Sovaldi—is a nod to his last name. But the National Institutes of Health (NIH) do a lot of early-stage research, and then it’s passed off to private companies that develop it further. Your name isn’t part of the HPV vaccines Gardasil or Cervarix, for example. Is it frustrating doing a lot of that behind-the-scenes work?
It’s funny because I would never have thought of that. It would have never entered my mind to name a vaccine after ourselves. We are so used to doing this translational work. My job is to move a project along so it’s interesting enough for a company to invest hundreds of millions of dollars for the benefit of large numbers of people. NIH doesn’t have the money to do phase III trials for lots of drugs, and even if they did it wouldn’t lead to all the drugs we need—because NIH wouldn’t have the money to develop them. This translational and basic research is what NIH does best. That work is way too fraught with failure for companies to do it all. It has to be done in the public sector, and then when things look more promising companies can take it over.

What advice would you offer someone considering becoming a scientist now?

It’s got to be a passion because being a scientist—especially early in your career—is more a lifestyle than occupation. You have to really want to do it, because there is a lot of uncertainty—especially about running your own lab and getting funding. Success and failure can be on a knife’s edge sometimes. The other thing is that you need to be strategic about thinking of what you want to go into, and that’s hard for young people because they don’t have the perspective: There are some fields just opening up ripe for discoveries. And there are some areas that are very mature, that we have been working on for a long time, where there are a lot of scientists working already—so the chances of making a big impact are lower. From my own life, this is like when we started with human papilloma viruses. When I went into this field, we had just been given the tools to study them and so it seemed like a great opportunity to get involved. In some ways it’s best if you can pick an emerging field with new tools to answer big questions. But you have to pick something you are really interested in and go with it.

The other thing I’d say is read a lot. Now with PubMed and access to all these journals there is no excuse for not knowing the background in something that basically has already been done. Young people tend to want to get out and do experiments, but a few days searching PubMed may save someone years of work trying to reinvent the wheel.

Right now, what would you say is the biggest challenge—or one of the biggest challenges—that needs to be solved?
That’s a really tough one. I think as scientists we are all sort of locked into the things we study. I could say cancer, obviously. But Alzheimer’s is something we obviously need to solve. HIV infection. All these different things. One of the things that really needs to be solved in terms of the whole scientific enterprise now is stable funding. Right now we are in a situation where there are too many good scientists—especially young scientists—competing for a limited pot of money. So you lose some good people because there’s not enough money to go around. Also, people are forced to do relatively mundane things that are really a methodological extension of something they’ve done before instead of something truly transformative that would have a large chance of failure. Grant reviewers are looking at something likely to succeed and move the field incrementally, or something transformative that may have a high chance of failure, and have to make those decisions. This is an issue across the sciences. The obvious solution would be to have more funding, but then that raises the question about how to do that. And I’m not a politician.

What, if anything, does this Lasker Award do for your work?
Quite honestly, probably nothing, because one of the nice things about being part of intramural research [at NIH] is that I have stable funding. I’ve had six people in my lab for the last 25 years, so this won’t lead to more grants or me doubling the size of my lab, or anything like that. I’m happy with my moderate-sized lab and collaborations with a lot of great people. That’s why I’m here. Every four years we have a site visit, which is a retrospective review of “what have you done for us lately,” and if it’s reasonable I will continue to get funding. So the award won’t affect my research career much at all.

Right now, some in the scientific community fear amid this political climate that facts matter less than they once did and thus science matters less. What’s your take on that?
Obviously, my perspective is science matters a lot. I really can’t comment on what’s happening in the country overall—and whether this is something that is pervasive where science is really held in less esteem, or it’s that there is a vocal minority being heard a lot now. I would hope it’s the latter.

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September, 2017|Oral Cancer News|

Personalised cancer treatment

Source: medicalxpress.com
Author: University of Oslo

In Norway, more and more people are being affected by cancer of the mouth and throat. In recent years, the incidence has increased but the mortality has remained the same. Cisplatin is one of the most commonly administered cytostatics for this patient group. At the start of treatment, the drug works well. Gradually, though, most patients experience that the tumour develops resistance against this drug and the prognosis for survival then becomes very poor.

In her PhD thesis, Jian Gao wanted to find out how the cancer cells could protect themselves against this cytostatic i.e. what is the underlying mechanism of resistance.

She therefore cultured various cancer cell lines derived from oral cavity which were given differing doses of the cytostatic cisplatin. A cancer cell line is cultured from patients’ cancerous tumours and can live indefinitely in the laboratory. These types of cell lines are used to examine the biology and the changes that have resulted in the development of cancer. Because the cancer cell lines divide in the laboratory, they can also adapt to new growth conditions, for example by becoming resistant to the cytostatic cisplatin in the same way as the cancer tissue in the patients.

“First, I had to find those cancer cells that were sensitive to the cytostatic,” explains Jian Gao. By identifying the sensitive cancer cell lines that I could make resistant in the laboratory, I could then study which changes took place in the cells as they changed from being sensitive to being resistant,” clarifies Gao.

Cytostatic for cancer cell lines

“During this process I found two different cancer cell lines. At the beginning, I gave them a dose of cytostatic that was strong enough to kill half of the cancer cells. This dose was increased each week, and after eight months both types of cancer cells were resistant to the cytostatic, cisplatin,” explains Gao.

Next, these cells had a resting period from any type of treatment. Gao wanted to see whether this resistance could be reversed by the pause in cytostatic treatment. However, it became apparent that the pause did not have any effect and the cells were permanently resistant to cisplatin. The resistant cell lines had changed permanently.

“Since I have two cell types that I knew were resistant, and I could now compare these cell lines with the original sensitive cancer cell lines,” comments Gao.

To compare gene expression in the cells, Gao used a technique that studies the expression of about 21,000 genes, a so-called mRNA microarray. This technique was used to look at changes in gene expression in the resistant cancer cell lines and then compare them with the gene expression in the original sensitive cancer cell lines.

Up-regulated genes

Only three genes were found to be up-regulated in both of the resistant cell lines. Of these genes, Gao decided to look at a cytokin, interleukin 6 (IL-6), which is a signal molecule that is often up-regulated in cancer, and which is associated with a poor prognosis and cisplatin resistance in several types of cancer.

By investigating expression of the IL-6 gene in head and throat cancers in 399 patients and then comparing this with survival, Gao and her co-workers found that, after treatment with the cytostatic cisplatin, the patients with cancer tumours with the up-regulated interleukin 6 gene did not have a better prognosis for survival.

Apparently, such cancer tumours were resistant to cisplatin. However, detailed mapping of the resistant cancer cell lines revealed that IL-6 in itself did not make the cancer cisplatin resistant. The effect had to be exerted via currently unknown mechanisms, possibly in the interaction between the cancer and IL-6 stimulation in the surrounding connective tissue.

Growth factors

Connective tissue can produce growth factors which cause the cancer to grow. There are a number of different growth factors and, of the eight known epithelial growth factors, Gao and her co-workers could demonstrate a relationship between the tumour’s gene expression in four of these epithelial growth factors and survival. The four growth factors were: Amphiregulin, epidermal, heparin-binding EGF-like growth factor and betacellulin. Could increased production of these growth factors explain cisplatin resistance?

Jian Gao’s research showed that if these growth factors were up-regulated, there was a high probability that the patient would not survive. At the same time, no relationship was found between cisplatin resistance in the cancer cell lines and the production of these growth factors.

However, the researchers could demonstrate that the more of these four growth factors a tumour expressed, the poorer the prognosis for the patient. By quantifying the amount of mRNA in the tumour tissue, Gao and co-workers could predict the patient’s prognosis considerably more accurately than the TNM system, which is the traditional method used to determine the stage of a cancer. The level of these four growth factors could predict how long even the most ill patients with distant metastases would live.

These growth factors have a common receptor in the so-called EGF receptor family. Currently, there are a number of drugs in use in patient treatment that can block this receptor. For patients whose cancers demonstrate high expression of these growth factors, it could potentially be particularly appropriate to use these medicines to reduce the growth of the cancer and increase the patient’s chances of survival.

In the last part of her PhD thesis, Gao tried to find the various “inhibitors” that could affect cisplatin resistance. After several trials with various signal and receptor inhibitors, she finally found that a drug called AG825, which inhibits the activity of an EGF receptor family member (HER 2), could reduce cisplatin resistance in four different cancer cell lines. This occurred by increasing the ability of cisplatin to trigger the cells’ self-destruct programme (apoptosis).

These drugs are already in use to treat patients with other types of cancer and, even though the details of the mechanism must be investigated in more detail, Gao and co-workers have demonstrated the probability that treatment with a cytostatic combined with “inhibitors” of the cancer cells’ protective mechanism will be advantageous. This could considerably improve the effect of the cytostatic cisplatin and thereby improve the prognosis for survival for patients with cancer of the head or throat.

But a lot of work still remains, and the journey from cell line reactions in the laboratory to how cancer cells in patients react to the same type of combined therapy is often long. Only more research can provide the answer to whether this is a navigable route to a more effective, personalised treatment of cancer of the head and throat.

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September, 2017|Oral Cancer News|

Why HPV Vaccination Rates Remain Low in Rural States

Source: TechnologyReview.com
Author: Emily Mullin
Date: September 1, 2017

 

Mandi Price never thought she’d be diagnosed with cancer at age 24. She was a healthy college student finishing her senior year when, during a regular Pap smear, her gynecologist found abnormal cells in her cervix. It was stage II cervical cancer.

Even more devastating was the fact that her cancer was preventable. Doctors detected a strain of human papillomavirus, the most common sexually transmitted infection in the U.S., in Price’s cancer cells. That strain of HPV is targeted by a vaccine called Gardasil. But Price never got the vaccine. Her primary care doctor didn’t recommend it when she was a teenager growing up in Washington state. Had she received it before becoming infected with HPV, she wouldn’t have gotten cancer.

Price dropped out of her classes to get treatment. She needed surgery to remove the tumor from her cervix, then underwent chemotherapy and radiation to kill any remaining cancerous tissue. At her one-year follow-up appointment, doctors found that the cancer had spread. She endured chemotherapy for another six months. Now, at 29, Price is in remission and is working in Los Angeles. “Most of my 20s comprised being in a hospital. It was isolating,” she says.

Merck’s Gardasil vaccine was considered a breakthrough when it was approved by the U.S. Food and Drug Administration in June 2006. It was the first vaccine to protect against several cancers. But more than a decade after the vaccine came out, vaccination rates in many places in the U.S., especially in the South, Midwest, and Appalachian states, still remain much lower than rates for other childhood vaccines—too low to stop transmission of the most dangerous HPV strains.

In 2016, only about 50 percent of girls and 38 percent of boys had all the required doses of the HPV vaccine needed to be fully protected, according to data released last week by the U.S. Centers for Disease Control and Prevention. Those figures are up slightly from last year, but still not close to the 80 percent that public health experts want to achieve.

Gardasil is approved to protect against cervical, vulvar, and vaginal cancers in girls and women ages 9 through 26, as well as anal cancer for the same age group in both girls and boys. Recently, the vaccine has also been shown to protect against oral cancers in men. HPV causes about 32,000 cancers every year, with cervical cancer the most common for women and oral cancers the most frequent in men.

Electra Paskett, a cancer epidemiologist at Ohio State University, says she is still surprised that the vaccine’s uptake has been so slow. “It’s crazy that there’s not a line around the corner. If we said we have a vaccine for breast cancer, we’d be vaccinating day and night,” she says.

The problem the vaccine has faced is its link to a taboo in American culture: sexual activity among teenagers. About one in four people in the U.S., including teens, are currently infected with HPV. Health-care providers are the biggest hurdle to getting more children vaccinated. Some primary care physicians, like in Price’s case, may not recommend it at all.

For Merck, the world’s largest vaccine maker, Gardasil has been a profit generator even though the company admits the uptake of the vaccine has been surprisingly slow. The company says it’s trying to increase rates by educating health-care providers.

William Schaffner, a professor of preventive medicine and infectious diseases at Vanderbilt University, remembers the initial excitement in the medical community when Gardasil first came out. “I thought the advent of our first explicitly anti-cancer vaccine, and the fact that it was so incredibly successful and safe, would be immediately embraced with pizzazz and rose petals,” he says.

Regional differences
State vaccination rates were as high as 73 percent among girls in Rhode Island and as low as 31 percent in South Carolina for all three doses in 2016. Among boys, Wyoming had the lowest rate, with only 20 percent getting the full round of shots.

Overall, teens living in major metropolitan areas were far more likely to get the vaccine than those living in rural areas, which may be more socially conservative and lack access to certain health-care services. In some of these places, average household incomes are lower than the national average, and parents might not be able to afford to take their pre-teens or teens to get the vaccine.

In some states with low vaccination rates, HPV-caused cancers are the among the highest. In Mississippi, for example, only about 34 percent of girls and 25 percent of boys get all required doses of the vaccine. The state also has one of the highest rates of HPV-related cervical cancer in the country. Wyoming tells a similar story, with high rates of HPV-associated cancers in both men and women.

Of course, those cancer rates can’t yet be tied to the states’ low vaccination rates. Gardasil was introduced just over a decade ago, and many of these cancer cases are in people who were too old to get the vaccine when it came out. But it means that these disparities could grow if more people there don’t get the vaccine.

HPV vaccination for boys is especially lagging in some areas. Paskett, who has studied cancer in Appalachia, say there’s a perception that HPV only causes cancers in women. “A lot of parents don’t know that boys should be vaccinated,” she says. Boys and men not only carry HPV but can get HPV-related cancers, like anal, penile, throat, and tongue cancers.

Price says shortly after her cancer diagnosis, she urged her parents to get her two younger brothers vaccinated.

Doctor hesitancy
A 2015 study found that a little over a quarter of the 776 pediatricians and family physicians surveyed do not strongly endorse the HPV vaccine. About one-third of the total doctors surveyed also said that having to talk about a sexually transmitted infection makes them uncomfortable.

Nneka Holder, associate professor of adolescent medicine at University of Mississippi Medical Center, says she is frustrated that so many doctors don’t recommend the HPV vaccine because they think it means they have to talk to parents about sex.

“We don’t usually explain to patients how they get hepatitis or meningitis,” she says. “So why should HPV be different?” Instead, she says health-care providers should focus on the cancer prevention aspect of the vaccine, rather than how HPV is spread.

Even health-care providers who do talk to parents about the vaccine aren’t always effective at getting their message across. A study from 2014 found that 47 percent of Minnesota health-care physicians and nurses that did ask parents about their concerns with the vaccine said they lacked time to probe the issue further, and 55 percent felt they couldn’t change parents’ minds.

Schaffner says doctors that are most successful with getting parents on board with the HPV vaccine are the ones who don’t call special attention to it. He says the best tactic is for physicians to sandwich in the HPV vaccine with other recommended vaccines—as in, “It’s time for your son to get the meningococcal, HPV, and Tdap vaccines.”

Parent concerns
Since the vaccine is just over 10 years old, it’s too early to know how many cases of cancer it has prevented so far. But clinical trials have showed that the vaccine provides nearly 100 percent protection against cervical infections caused by certain strains of HPV. These infections have fallen by 64 percent among teen girls in the U.S. since 2006, when the vaccine was introduced. Large clinical trials of the HPV vaccine have also shown it’s safe for both boys and girls.

These benefits have led Virginia, Rhode Island, and Washington, D.C., to adopt public school mandates for HPV vaccination. But some parents are still uncomfortable about the HPV vaccine’s association with sex and think their children don’t need it because they’re not sexually active. That has led parents to form groups in opposition to such mandates.

Aimee Gardiner, director of one such group called Rhode Island Against Mandated HPV Vaccine, says she doesn’t see HPV as the “epidemic” she thinks the CDC has made it out to be. “For me the risk of developing a cancer from any HPV is so insignificantly small that I do not feel like the vaccine is a necessity,” she says. Gardiner has two children, one of whom isn’t old enough to receive the vaccine and the other who hasn’t received it. She says she doesn’t plan to vaccinate them with Gardasil.

It’s true that for most people, the immune system clears the virus from their systems naturally. But for a small number of people, HPV persists and can turn cancerous. For those patients, like Price, cancer can be a major life ordeal, not to mention much more expensive than a vaccine that costs about $150 per dose.

Looking ahead
HPV vaccination rates continue to increase steadily, but the problems associated with its uptake could spell trouble for other vaccines in the future. For example, researchers for years have been working on a vaccine that would protect people from contracting HIV, the virus that causes AIDS. If a vaccine for HIV were ever to be successful, it could run into the same problems. HIV’s risk factors—unprotected sex and intravenous drug use—make it even more taboo.

Another worry is that rising anti-vaccine sentiments causing parents to opt out of vaccinating their children will hurt efforts to expand HPV vaccine coverage.

One factor that may increase vaccination rates is a new guideline from the CDC announced in October 2016. Children ages 11 to 14 now only need two doses of the HPV vaccine at least six months apart instead of three, which was previously recommended. Teens 15 and older still need to complete the three-dose series. This change may increase uptake of the vaccine, as vaccination rates drop off after each dose.

For Price and other cancer patients, the thought of not getting a vaccine that could prevent something so terrible is unimaginable. “I am a huge proponent of it,” she says. “If you had the chance to prevent cancer in your son or daughter, why wouldn’t you do that?”

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September, 2017|Oral Cancer News|

FDA Approves First Gene Therapy For Leukemia

Source: npr.org
Author: Rob Stein
Date: August 30, 2017

The Food and Drug Administration on Wednesday announced what the agency calls a “historic action” — the first approval of a cell-based gene therapy in the United States.

The FDA approved Kymriah, which scientists refer to as a “living drug” because it involves using genetically modified immune cells from patients to attack their cancer.

The drug was approved to treat children and young adults up to age 25 suffering from a form of acute lymphoblastic leukemia who do not respond to standard treatment or have suffered relapses.

The disease is a cancer of blood and bone marrow that is the most common childhood cancer in the United States. About 3,100 patients who are 20 and younger are diagnosed with ALL each year.

“We’re entering a new frontier in medical innovation with the ability to reprogram a patient’s own cells to attack a deadly cancer,” FDA Commissioner Scott Gottlieb said in a written statement.

“New technologies such as gene and cell therapies hold out the potential to transform medicine and create an inflection point in our ability to treat and even cure many intractable illnesses,” Gottlieb said.

The treatment involves removing immune system cells known as T cells from each patient and genetically modifying the cells in the laboratory to attack and kill leukemia cells. The genetically modified cells are then infused back into patients. It’s also known as CAR-T cell therapy.

“Kymriah is a first-of-its-kind treatment approach that fills an important unmet need for children and young adults with this serious disease,” said Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research.

“Not only does Kymriah provide these patients with a new treatment option where very limited options existed, but a treatment option that has shown promising remission and survival rates in clinical trials,” Marks said in the FDA statement.

The treatment, which is also called CTL019, produced remission within three months in 83 percent of 63 pediatric and young adult patients. The patients had failed to respond to standard treatments or had suffered relapses. Based on those results, an FDA advisory panel recommended the approval in July.

The treatment does carry risks, however, including a dangerous overreaction by the immune system known as cytokine-release syndrome. As a result, the FDA is requiring strong warnings.

In addition, the treatment will be initially available only at 32 hospitals and clinics that have been specially trained in administering the therapy.

Novartis, which developed the drug, says the one-time treatment will cost $475,000 for patients who respond. People who do not respond within a month would not be charged, and the company said it is taking additional steps to make sure everyone who needs the drug can afford it

But some patient advocates criticized the cost nevertheless.

“While Novartis’ decision to set a price at $475,000 per treatment may be seen by some as restraint, we believe it is excessive,” says David Mitchell, founder and president of Patients For Affordable Drugs. “Let’s remember, American taxpayers invested over $200 million in CAR-T’s discovery.”

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August, 2017|Oral Cancer News|

Gliknik announces dosing of first patient in phase 2 trial targeting prevention of recurrence of high-risk oral cavity cancer

Source: www.prnewswire.com
Author: press release

Gliknik Inc. today announced that clinicians have enrolled and dosed the first of 80 patients in the company’s phase 2 clinical trial assessing the efficacy and safety of biropepimut-S (GL-0817), an immunomodulatory therapeutic targeting the prevention of recurrence of squamous cell cancer of the oral cavity in patients at high risk of recurrence after surgery, chemotherapy, and radiation.

“We are pleased to enroll the first patient in this phase 2 trial of biropepimut-S, which will further our understanding of the potential role of this advanced-design cancer vaccine with immune enhancing adjuvants in high-risk oral cavity cancer,” said Jeff Herpst, Senior Director of Clinical Development at Gliknik.

High-risk oral cavity cancer is associated with a recurrence rate of approximately 70% within three years of the time of surgical resection despite adjuvant chemoradiotherapy. Unfortunately, only a small percent of patients respond to the clinical options currently available for physicians to use in treating such patients who recur.

“With recurrent oral cavity cancer being so difficult to treat, now is an opportune time to assess how useful and safe biropepimut-S may be in protecting individuals from recurrence of high-risk oral cavity cancer,” said David Block, CEO of Gliknik. “The goal of the study is to see if we can activate the individual’s immune system to eliminate residual cancer cells that cannot be seen by current imaging methods, thereby avoiding clinical recurrence. We are finding that physicians and patients are interested in clinical trials addressing this significant unmet medical need.”

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August, 2017|Oral Cancer News|

More U.S. Teens Getting Vaccinated Against HPV

Source: http://health.usnews.com
Date: 8/24/17

THURSDAY, Aug. 24, 2017 (HealthDay News) — Six out of 10 U.S. parents are choosing to get their children vaccinated against the cancer-causing human papillomavirus (HPV), which is spread by sexual contact, federal health officials reported Thursday.

The bad news: while most children are getting their first dose of HPV vaccine, many aren’t completing the full vaccination schedule, the officials said.

“I’m pleased with the progress, but too many teens are still not receiving the HPV vaccine — which leaves them vulnerable to cancers caused by HPV infection,” CDC director Dr. Brenda Fitzgerald said in an agency news release. “We need to do more to increase the vaccination rate and protect American youth today from future cancers tomorrow.”

An estimated 14 million Americans, including teens, become infected with HPV each year. The infection can cause cervical, vaginal and vulvar cancers in women, and penile cancer in men. It can also cause anal cancer, throat cancer and genital warts in both men and women, according to the CDC.

The CDC recommends two doses of HPV vaccine for children at ages 11 or 12. Teens who get the first vaccine dose before their 15th birthday need two doses to be protected. Teens and young adults who start the vaccine series between ages 15 through 26 need three doses, according to the agency.

In its new report, the CDC said 60 percent of teens aged 13 to 17 received one or more doses of HPV vaccine in 2016 — an increase of 4 percentage points from 2015.

And the report found that HPV vaccination is becoming more common among boys. An estimated 65 percent of girls received their first dose of HPV vaccine in 2016, compared to 56 percent of boys. That represents a 6 percentage point increase for boys from 2015. Rates for girls were about the same as 2015, the CDC said.

But agency officials said they’re concerned because, while most teens have received the first dose of HPV vaccine, only 43 percent are up to date on all recommended doses. Vaccination rates tend to be lower in rural and less urban areas compared to more urban areas, the CDC said.

“Recent changes to the vaccine recommendations mean preventing cancer is easier now than ever before,” said Dr. Nancy Messonnier, who directs the CDC’s National Center for Immunization and Respiratory Diseases. “Now is the time for parents to protect their children from cancers caused by HPV.”

Latest statistics show that HPV vaccination has led to significant drops in HPV infections: HPV-related cancers and genital warts have decreased by 71 percent among teen girls and 61 percent among young women, the CDC said.

The CDC findings were published in the Aug. 25 issue of the agency’s Morbidity and Mortality Weekly Report.

Dr. Lois Ramondetta is a professor of gynecologic oncology and reproductive medicine at the University of Texas MD Anderson Cancer Center in Houston.

She said the new CDC report shows that education and outreach efforts to parents about the HPV vaccine are working, with vaccination rates moving in the right direction, albeit slowly.

Ramondetta said it’s also encouraging to see that the vaccination gap between boys and girls is shrinking.

“However, the data also show that we have a long way to go, particularly with children completing the vaccine series,” she added. “It is concerning that more parents and physicians aren’t taking advantage of this safe and effective vaccine to prevent several cancers in their children. I recently vaccinated my own daughter, and I’m thankful to have the opportunity to protect her in this way.”

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August, 2017|Oral Cancer News|

Big tobacco fuels nicotine replacement addiction, UCSF study shows

Source: http://www.sfgate.com
Author: Lizzie Johnson
Date: August 17, 2017

Nicotine patches, lozenges, inhalers and gum have long been marketed as ways of helping addicts break the habit. But such products by themselves won’t do the job — something tobacco companies themselves have taken advantage of to boost their profits, new research from UCSF says.

Nicotine replacement therapy products, which have been sold over the counter at drugstores since 1996, are effective only when paired with counseling, according to a UCSF study released Thursday. Without that, relying on such products can actually make it harder to kick tobacco, the study found.

UCSF researchers who reviewed millions of pages of internal tobacco company documents said the firms have long known that such products by themselves don’t wean users off cigarettes, and market their own smokeless nicotine to keep users addicted.

“Those products should not be used unless they are done in the proper way,” said Stanton Glantz, an author of the study, professor of medicine at UCSF and the director of the Center for Tobacco Control Research and Education.

“The problem is, without the behavioral support, they actually inhibit quitting,” he said. “Unfortunately, a lot of people think they are making progress and quitting when that’s not so. That’s what tobacco companies have known for decades. They’re developing products under the guise of nicotine replacement therapy.”

Some of the biggest tobacco companies, including RJ Reynolds, Philip Morris and British American Tobacco, have developed nicotine accessories. Many corner stores stock the products, some of them in brightly colored packages, next to chocolate bars and other candy near the cash register.

Medi-Cal and many private health insurance policies cover the cost of quitting aids. State-subsidized insurance will pay for two annual courses of treatment with pills such as Chantix and Zyban, Nicorette lozenges, Nicorette gum and NicoDerm CQ Patches.

But people are more likely to use those products as complements to smoking — at work or in airplanes when cigarettes are banned — instead of as a tool to quit, the UCSF study found. Nicotine replacement products can be effective if people combine them with counseling and consultation with a doctor, but the majority of consumers don’t use them that way, researchers said.

Randomized clinical trials cited in the study showed that people who went to counseling and tapered their use of nicotine replacement therapy products over time were successful. Those who didn’t were not.

A 2009 study in the BMJ — formerly known as the British Medical Journal — found that of the 2,767 smokers tested, only 6.75 percent were able to abstain from cigarettes for six months while using nicotine replacement therapy products.

Nicotine patches and gum were first approved by the U.S. Food and Drug Administration in 1984, and the tobacco industry originally saw them as a threat, the UCSF study said. By 1992, however, company executives determined such products would not help smokers quit, and that there was money to be made from them. By 2009, tobacco companies were selling their own nicotine patches, lozenges and e-cigarettes.

“It was surprising to discover the industry came to view NRT (nicotine replacement therapy) as just another product,” said Dorie Apollonio, an associate professor in clinical pharmacy at UCSF and lead author of the study. “The tobacco companies want people to get nicotine — and they’re open-minded about how they get it.”

Representatives of RJ Reynolds, Philip Morris and British American Tobacco did not respond to requests for comment.

Apollonio’s researchers analyzed 90 million pages of documents from seven tobacco companies dating back as far as 1960, obtained in litigation against the tobacco industry.

Those papers showed that the tobacco industry began developing its own nicotine replacement products after its research showed that some smokers used them in addition to tobacco.

“The way the marketing is framed, it is explicitly discouraging quitting,” Glantz said. “The tobacco companies know more about tobacco products than anybody else. Now they are selling these products in a way that protects their market. I do not think most health professionals are aware of this.”

But some are. Derek Smith, director of the San Francisco Department of Public Health’s Tobacco Free Project, said he encourages smokers to check with their pharmacists or doctors before trying a nicotine replacement therapy like a patch or pill.

“You can’t plop on a patch and expect to quit smoking,” he said. “It’s part of the arsenal to tackle this complicated addiction. Smokers know better than anyone how hard it is to quit. It takes eight or 10 times before it sticks. In my experience, they are really aware what a tough addiction it is and how a patch isn’t the magical solution.”

A free smoking cessation program offered by the city at San Francisco General Hospital funnels smokers through a seven-class session. The weekly meetings teach participants how to create a plan with a quit date and identify stressful situations that lead to smoking. Instructors teach them to drink more water and improve their diet to help cope with cravings.

Patches, gum and e-cigarettes can be useful tools, Smith said. It didn’t surprise him that the tobacco industry had started creating its own products.

“Those internal documents reveal their intentions,” he said. “It’s always fascinating to see how the tobacco industry is thinking. They have an opportunistic assessment of the market. It never ceases to amaze me.”

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August, 2017|Oral Cancer News|

Cancer patients who use alternative medicine more than twice as likely to die

Source: http://www.independent.co.uk/
Date: August 15, 2017

After five years, 78.3 per cent of people who opted for medical treatment were still alive compared to just 54.7 percent of people who opted for alternative therapies.

A new study has shown that cancer sufferers who turn to alternative therapies in preference to conventional medicine are more than twice as likely to die.

Scientists from America’s prestigious Yale University found that patients were more likely to be cured through conventional medicine, despite anecdotal evidence from some who say their cancer was cured by turning to natural or alternative remedies, .

Researchers sifted through the National Cancer Database for their study “Use of Alternative Medicine for Cancer and its Impact on Survival”.

They tracked 280 people who were diagnosed with the disease in 2004 and opted for alternative medicine and 560 “control” cancer patients who underwent conventional treatments such as chemotherapy, radiotherapy and surgery.

After five years, 78.3 per cent of people who opted for medical treatment were still alive compared to just 54.7 percent of people who opted for alternative therapies.

The study also looked at different types of cancer including breast, lung, prostate and colorectal.

They found those with lung cancer were twice as likely to die after five years if they had opted for alternative therapies.

Breast cancer patients who used alternative therapies were five times as likely to have lost their lives to the disease.Colorectal cancer patients were four times more likely to die if they rejected conventional medicine in favour of alternative treatment.

Alternative medicine, advocated by some outside the medical profession to treat cancer includes chiropractic treatment, homeopathy, acupuncture and juice diets.

The researchers could not specifically identify which alternative medicines subjects were using.

Other limitations of the data include unmeasured confounders or selection bias that could impact survival, the researchers noted.

”However, because patients receiving alternative medicine were more likely to be younger, more affluent, more well-educated, and less burdened with comorbidities, this would not likely account for the observed survival differences,” they concluded.

The researchers concluded that patients who chose treatment alongside alternative medicine were more likely to die and urged for greater scrutiny of the use of alternative medicine for the initial treatment of cancer.

“We now have evidence to suggest that using alternative medicine in place of proven cancer therapies results in worse survival,” said lead author Skyler Johnson.

“It is our hope that this information can be used by patients and physicians when discussing the impact of cancer treatment decisions on survival.”

The findings were published in the Journal of the National Cancer Institute.

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August, 2017|Oral Cancer News|

HPV-related oral cancers have risen significantly in Canada

Source: www.ctvnews.ca
Author: Sheryl Ubelacker, The Canadian Press

The proportion of oral cancers caused by the human papillomavirus has risen significantly in Canada, say researchers, who suggest the infection is now behind an estimated three-quarters of all such malignancies. In a cross-Canada study, published Monday in the Canadian Medical Association Journal, the researchers found the incidence of HPV-related oropharyngeal cancers increased by about 50 per cent between 2000 and 2012.

“It’s a snapshot of looking at the disease burden and the time trend to see how the speed of the increase of this disease (is changing),” said co-author Sophie Huang, a research radiation therapist at Princess Margaret Cancer Centre in Toronto.

Researchers looked at data from specialized cancer centres in British Columbia, Alberta, Ontario and Nova Scotia to determine rates of HPV-related tumours among 3,643 patients aged 18 years or older who had been diagnosed with squamous cell oropharyngeal cancer between 2000 and 2012.

HPV is the most common sexually transmitted infection worldwide. Most people never develop symptoms and the infection resolves on its own within about two years.

“In 2000, the proportion of throat cancer caused by HPV was estimated at 47 per cent,” said Huang. “But in 2012, the proportion became 74 per cent … about a 50 per cent increase.”

Statistics from a Canadian Cancer Society report last fall showed 1,335 Canadians were diagnosed in 2012 with HPV-related oropharyngeal cancer and 372 died from the disease.

HPV is the most common sexually transmitted infection worldwide. Most people never develop symptoms and the infection resolves on its own within about two years. But in some people, the infection can persist, leading to cervical cancer in women, penile cancer in men and oropharyngeal cancer in both sexes.

Most cases of HPV-related oral cancer are linked to oral sex, said Huang, noting that about 85 per cent of the cases in the CMAJ study were men.

HPV-related tumours respond better to treatment and have a higher survival rate than those linked to tobacco and alcohol use, the other major cause of oral cancer, she said, adding that early identification of a tumour’s cause is important to ensure appropriate and effective treatment.

While some centres in Canada routinely test oral tumours to determine their HPV status, such testing is not consistent across the country, the researchers say.

In the past, physicians generally tended to reserve tumour testing for cases most likely to be caused by HPV – among them younger males with no history of smoking and with light alcohol consumption – to prevent an unnecessary burden on pathology labs.

“Only as accumulating data have supported the clinical importance of HPV testing has routine testing been implemented in most (though not all) Canadian centres,” the researchers write.

The study showed that the proportion of new HPV-related oral cancers rose as those caused by non-HPV-related tumours fell between 2000 and 2012 – likely the result of steadily declining smoking rates.

Huang said males tend to have a weaker immune response to HPV than do females, which may in part explain the higher incidence of oral cancers linked to the virus in men.

HPV vaccines given to young people before they become sexually active can prevent infection – and the researchers say both boys and girls should be inoculated.

Currently, six provinces provide HPV immunization to Grade 6 boys as well as girls, with the other four provinces set to add males to vaccination programs this fall, said Huang.

“So vaccinating boys is very important because, if you look at Canadian Cancer Society statistics (for 2012), HPV- related oropharyngeal cancer in total numbers has already surpassed cervical cancers,” she said.
“The increase of HPV-related cancer is real, and it’s striking that there’s no sign of a slowdown.”

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August, 2017|Oral Cancer News|