New risk factor for mouth cancer uncovered

Source: www.medicalnewstoday.com
Author: Tim Newman, fact checked by Paula Field

In some regions, mouth cancer incidence has risen. A recent study investigates a new risk factor for mouth cancer. In certain parts of the world, over the past couple of decades, mouth cancer rates have soared. For instance, in the United Kingdom, rates of mouth cancer have increased by 68 percent. They rose from eight cases per 100,0000 in 1992–1995 to 13 cases per 100,000 in 2012–2014.

In the United States, mouth cancer and mortality rates have declined overall. However, when examined at a state level, the data reveal a more complex picture. For instance, mouth cancer deaths have risen significantly in Nevada, North Carolina, Iowa, Ohio, Maine, Idaho, North Dakota, and Wyoming.

Some known risk factors for mouth cancer include smoking tobacco, drinking alcohol, human papillomavirus (HPV), and chewing betel quid, which is a mix of natural ingredients wrapped in a betel leaf that is popular in some parts of Southeast Asia.

In India, mouth cancers are the most common cause of cancer-related deaths in men aged 30–69 years old. Scientists think that chewing betel quid could be responsible for many of these deaths.

New risk factor for mouth cancer
Although scientists have confirmed some risk factors, there is still much to learn about how and why mouth cancer affects certain individuals and not others. Recently, scientists set out to investigate another potential risk factor: air pollution.

The researchers, funded by the Ministry of Science and Technology in Taiwan, published their findings this week in the Journal of Investigative Medicine.

In particular, the team focused on the impact of fine particulate matter, also known as PM2.5. These are particles of liquid or solid matter that measure 2.5 micrometers in diameter or under. Scientists already knew that PM2.5 has a negative impact on cardiovascular and respiratory health, but they wanted to find out whether exposure to higher levels of PM2.5 might also increase mouth cancer risk.

To investigate, they collated information from 482,659 men aged 40 years old or above. All participants had attended health services and given information about smoking and chewing betel quid.

The scientists next gathered data from 66 air quality-monitoring stations across Taiwan. By referring to the participants’ health records, the scientists could estimate each person’s exposure to PM2.5.

Risk increased by 43 percent
The researchers collected the data in 2012–2013. During this time, 1,617 men developed mouth cancer. As expected, both tobacco smoking and chewing betel quid increased mouth cancer risk. After taking a range of influencing factors into account, the scientists demonstrated that exposure to PM2.5 also increased mouth cancer risk.

The scientists compared PM2.5 levels of below 26.74 micrograms per cubic meter (ug/m3) with those above 40.37 ug/m3. They associated the higher levels of PM2.5 with a 43 percent increase in the risk of developing mouth cancer. According to the authors:

“This study, with a large sample size, is the first to associate mouth cancer with PM2.5. […] These findings add to the growing evidence on the adverse effects of PM2.5 on human health.”

Alongside PM2.5’s relationship with mouth cancer, the authors identified a correlation between higher levels of ozone and an increased risk of developing the disease.

The next challenge will be to understand how particulate matter might cause mouth cancer. Although this will require more detailed studies, some theorize that carcinogenic compounds found in PM2.5, including polycyclic aromatic hydrocarbons and heavy metals, might be part of the answer.

Because these particles have such a small diameter, the body absorbs them relatively easily, potentially causing damage as they travel through the body.

However, the authors also remind us to be cautious — this is an observational study, so it cannot definitively prove that pollution causes mouth cancer. Also, it is not clear exactly how much PM2.5 enters the mouth.

This interaction needs further investigation, but the large size of the current study makes their conclusions worthy of follow-up.

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October, 2018|Oral Cancer News|

FDA approves expanded use of Gardasil 9 to include individuals 27 through 45 years old

The U.S. Food and Drug Administration today approved a supplemental application for Gardasil 9 (Human Papillomavirus (HPV) 9-valent Vaccine, Recombinant) expanding the approved use of the vaccine to include women and men aged 27 through 45 years. Gardasil 9 prevents certain cancers and diseases caused by the nine HPV types covered by the vaccine.

“Today’s approval represents an important opportunity to help prevent HPV-related diseases and cancers in a broader age range,” said Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research. ”The Centers for Disease Control and Prevention has stated that HPV vaccination prior to becoming infected with the HPV types covered by the vaccine has the potential to prevent more than 90 percent of these cancers, or 31,200 cases every year, from ever developing.”

According to the CDC, every year about 14 million Americans become infected with HPV; about 12,000 women are diagnosed with and about 4,000 women die from cervical cancer caused by certain HPV viruses. Additionally, HPV viruses are associated with several other forms of cancer affecting men and women.

Gardasil, a vaccine approved by the FDA in 2006 to prevent certain cancers and diseases caused by four HPV types, is no longer distributed in the U.S. In 2014, the FDA approved Gardasil 9, which covers the same four HPV types as Gardasil, as well as an additional five HPV types. Gardasil 9 was approved for use in males and females aged 9 through 26 years.

The effectiveness of Gardasil is relevant to Gardasil 9 since the vaccines are manufactured similarly and cover four of the same HPV types. In a study in approximately 3,200 women 27 through 45 years of age, followed for an average of 3.5 years, Gardasil was 88 percent effective in the prevention of a combined endpoint of persistent infection, genital warts, vulvar and vaginal precancerous lesions, cervical precancerous lesions, and cervical cancer related to HPV types covered by the vaccine. The FDA’s approval of Gardasil 9 in women 27 through 45 years of age is based on these results and new data on long term follow-up from this study.

Effectiveness of Gardasil 9 in men 27 through 45 years of age is inferred from the data described above in women 27 through 45 years of age, as well as efficacy data from Gardasil in younger men (16 through 26 years of age) and immunogenicity data from a clinical trial in which 150 men, 27 through 45 years of age, received a 3-dose regimen of Gardasil over 6 months.

The safety of Gardasil 9 was evaluated in about a total of 13,000 males and females. The most commonly reported adverse reactions were injection site pain, swelling, redness and headaches.

The FDA granted the Gardasil 9 application priority review status. This program facilitates and expedites the review of medical products that address a serious or life-threatening condition.

The FDA granted approval of this supplement to the Gardasil 9 Biologics License Application to Merck, Sharp & Dohme Corp. a subsidiary of Merck & Co., Inc.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

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October, 2018|Oral Cancer News|

HPV vaccine expanded for people ages 27 to 45

Source: www.nytimes.com
Authors: Denise Grady and Jan Hoffman

About 14 million women and men become infected with the human papillomavirus each year in the United States, according to the Centers for Disease Control and Prevention. CreditCreditKeith Bedford/The Boston Globe, via Getty Images

The HPV vaccine, which prevents cervical cancer and other malignancies, is now approved for men and women from 27 to 45-years-old, the Food and Drug Administration said on Friday.

The vaccine is Gardasil 9, made by Merck, and had been previously approved for minors and people up to age 26.

It works against the human papillomavirus, HPV, which can also cause genital warts and cancers of the vulva, anus, penis and parts of the throat. The virus has many strains. It is sexually transmitted, and most adults encounter at least one strain at some point in their lives. The vaccine protects against nine strains, including those most likely to cause cancers and genital warts.

“Today’s approval represents an important opportunity to help prevent HPV-related diseases and cancers in a broader age range,” Dr. Peter Marks, director of the F.D.A.’s Center for Biologics Evaluation and Research, said in a statement.

The approval was based on a study in women ages 27 to 45, showing that an earlier version of the vaccine was highly effective in preventing persistent HPV infection, genital warts, vulvar and vaginal precancers, cervical precancers and cervical cancers related to the virus types covered by the vaccine.

The vaccine’s effectiveness in men ages 27 to 45 is inferred from the data in women, from its efficacy in younger men and from evidence that it created immunity in a study of men 27 to 45-years-old.

The most common side effects of the vaccine include soreness at the injection site, swelling, redness and headaches.

If a person has already been exposed to a particular strain of HPV, the vaccine will not work against that strain. For that reason, vaccination has been strongly recommended for young people before they become sexually active.

But even someone who has already been exposed to a few strains — but not to all nine in the vaccine — can still gain protection against the strains they have not encountered.

“This is great,” Dr. Lois M. Ramondetta, a professor of gynecologic oncology at MD Anderson Cancer Center in Houston, said in an interview. “It’s a prevention vaccine. The best time to get it is before you turn 13 and have any intimate activity at all. But, that said, it protects against nine types of HPV, so if you have one of the types, you still can be protected from other HPV types.”

She added: “There is a whole generation of people we were missing who didn’t know about it. Doctors weren’t good at talking about it.”

She and Dr. William Schaffner, an infectious disease expert at Vanderbilt University, said people over 26 began asking doctors about the vaccine. Some were leaving marriages or monogamous relationships, expected to begin dating and realized they might be exposed to the virus.

“They want to feel protected to some extent,” Dr. Ramondetta said. “Now they have the opportunity.”

Younger people need two shots, but the older ones will need three, spaced a few months apart.

Dr. Ramondetta noted that tumors affecting part of the throat — called oropharyngeal cancers — caused by HPV are rising, particularly in men. The vaccine is believed to help prevent them.

Dr. Schaffner said a panel that advises the Centers for Disease Control and Prevention has already been discussing the data on using the vaccine in older people, and is expected to make a recommendation about it. The recommendation could be universal, meaning that everyone in that age range should receive it, or it could be “permissive,” meaning that the decision is up to doctors and patients.

Once that group, the Advisory Committee on Immunization Practices, recommends a vaccine, insurers generally cover it.

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October, 2018|Oral Cancer News|

HPV16 vaccine yields added benefit in recurrent throat cancer

Source: www.medpagetoday.com
Author: Ian Ingram, Deputy Managing Editor, MedPage Today

Adding a tumor-specific vaccine to PD-1 checkpoint inhibition was safe and effective in HPV16-positive patients with recurrent or metastatic oropharyngeal cancer, a small phase II trial found.

Among 24 patients treated with nivolumab (Opdivo) and the ISA101 long peptide vaccine, 22 of whom had oropharyngeal cancer, 33% responded and median overall survival was 17.5 months, Cornelis Melief, PhD, of ISA Pharmaceuticals in the Netherlands, reported here at the 4th annual Cancer Immunotherapy Conference.

All eight of the responders had oropharyngeal cancer (36%), with two complete and six partial responses. The median duration of response among these patients was 10.3 months, and responses were seen in both platin- and cetuximab-refractory patients, and those refractory to both.

Melief noted that one of the partial responders had total clearance of the primary tumor, but a solitary lung metastasis remained, but was stable at 2.5 years.

Rate of overall survival at 6 and 12 months was 75% and 70%, respectively. The combination was well tolerated and safe, said Melief, with no increase in the rate of serious adverse events. A randomized trial is planned to confirm the findings.

“The results of our trial are among the first clinical data to support the general concept of combining cancer vaccination with immune checkpoint blockade to enhance efficacy of vaccine-activated T cells in the immunosuppressive tumor environment,” Melief’s group wrote in JAMA Oncology, where the findings were also published.

The findings compare favorably to outcomes in a larger group of p16-positive patients in CheckMate 141, which tested nivolumab in recurrent or metastatic, chemotherapy-refractory squamous cell head and neck cancer, and led to FDA approval in that setting.

Overall response among the 63 p16-positive patients in that trial was 15.9%, and median overall survival was 9.1 months.

Median progression-free survival (PFS) in the current study was just 2.7 months, similar to that in CheckMate 141: 2.0 months in nivolumab-treated patients, which was no different from the PFS with standard therapy at 2.3 months (HR 0.89, 95% CI 0.70-1.13, P=0.32).

“These findings are nearly double the response rate and median overall survival reported in the CheckMate 141, KEYNOTE-012, and KEYNOTE-055 trials,” said Theodoros Teknos, MD, of Seidman Cancer Center in Cleveland, calling the study an important incremental discovery in the burgeoning field of immunotherapy for head and neck cancer.

In KEYNOTE-012, the rate of overall response rate was 12% in a similar patient group (survival was not reported). In KEYNOTE-055, the rates were 20% and 8 months, respectively.

“Based on the findings reported in this study, additional investigation in the form of a larger randomized clinical trial evaluating the contribution of HPV16 vaccination to PD-L1 inhibition is warranted,” he told MedPage Today. “Nested in this trial, it would be advisable to perform robust analysis of immunologic subsets and cytokine profiling to identify biomarkers of response to this treatment approach.”

Teknos, who was not involved in the study, noted that the subgroup analysis again calls into question the use of PD-L1 as a biomarker. While 43% of the PD-L1 ≥1% group were responders, 18% of the PD-L1 < 1% group were as well.

Melief also presented data on the ISA101 vaccine in 62 late-stage HPV-positive cervical cancer patients treated with the ISA101 vaccine in combination with chemotherapy and highlighted the survival difference among those with a vaccine-induced T-cell response. Median overall survival was 22.7 months in those that had an HPV-specific response above the median versus 12.9 months for those with a response below the median (HR 0.286, 95% CI 0.149-0.551, P=0.0066).

He noted that this was not due just to immunocompetence differences between patients, as the effect was found to be independent of patients’ immune status.

The current study enrolled 24 patients from 2015 to 2016 — 20 men and four women. Outside of the oropharyngeal cancer patients, there was one patient with anal and cervical cancers each. Patients received three 100 μg doses of the subcutaneous ISA101 vaccine (days 1, 22, and 50). Starting on day 8, intravenous nivolumab was given every 2 weeks for a year or until disease progression or unacceptable toxicity.

Toxicities were of the expected variety: fever and injection site reactions with ISA101, and diarrhea, fatigue, and hepatoxicity with nivolumab. Two patients had grade 3 and 4 adverse events that led to discontinuation of nivolumab (an asymptomatic transaminase level elevation and a lipase elevation, respectively).

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October, 2018|Oral Cancer News|

Oral sex and ‘deep kissing’ linked to increase in HPV-positive head and neck cancer

Source: www.sbs.com.au
Author: Amelia Dunn

Jake Simpson was 22 when he started to get painful toothaches. Trips back and forth to the dentist couldn’t seem to fix the growing lump at the back of his mouth It came as a total surprise to Jake, his partner Carly, and their newborn son Noah, when oncologists in Brisbane told him he had stage four head and neck cancer, and would need to start treatment immediately.

“We didn’t know what any of it meant. He was so young and healthy, we couldn’t believe it,” Carly said.

Despite rigorous treatment and surgery that removed more than two-thirds of his tongue, Jake’s cancer was too aggressive and spread to his lungs. He died within eight months of his diagnosis.

These cancers, known as oropharyngeal cancers in the back of the tongue and tonsils, are on the rise in young men, and are caused by the sexually transmitted disease HPV – human papillomavirus. While doctors believe it is most commonly passed on through oral sex, some argue it’s now as easy as ‘deep kissing’.

“Jake wasn’t tested for HPV because it was too aggressive from the day one, but that age bracket that he fell in, more than likely, the cause was HPV,” Carly said.

HPV has been dubbed the ‘common cold’ of STDs. Over 80 per cent of Australian adults will get HPV at one point in their lives, and most will clear it without even knowing.

But two particular strains, P16 and P18 are closely linked with cancer, not just in the cervix like widely known, but increasingly in the head and neck.

Two strains of HPV, P16 and P18 are closely linked with cancer, not just in the cervix like widely known, but increasingly in the head and neck.
Source: The Feed

Researchers across the US, UK and Australia say changing sexual practices over the last 50 years, and an increase in sexual partners has prompted the rising incidence rate of this cancer.

Oncologist Brett Hughes has witnessed the significant shift in the patient demographic, who says nearly 80 per cent of his patients now have HPV positive cancers.

“We now see an age group of people who generally live very healthy lifestyles; that don’t necessarily have to have drunk or smoke and the other risk factors that we’d normally associate with cancers in the mouth or throat.”

The cancer is also eight times more likely to present in men. Dr Hughes said oropharyngeal cancers are now the most common HPV related cancer in Australia, trumping cervical cancer, and are continuing to rise.

“It’s predicted for Australia and it may even be as late as in the 2030s that we might see the peak incidence which is a little bit scary considering how common this cancer is becoming.”

While this cancer is increasing, many take comfort in Australia’s strong vaccination program to fight HPV related cancers.

The Gardasil vaccine, developed by Australian of the year Professor Ian Frazer, was first administered to Australian girls in 2007, and then to boys in 2013 after it became clear HPV was affecting them as well. But Professor Frazer said people need to be given the vaccine before they’re sexually active.

“All the vaccines that we currently use are vaccines to prevent infection. A vaccine to cure an infection is a different beast all together,” he said.

Without a therapeutic vaccine, sexually active adults who missed out on the vaccine at school are still at risk of contracting persisting HPV, with Prof Frazer insisting “the big challenge now is to get something for oropharyngeal cancer.”

Right now, there is no vaccine for adults and no way of testing or preventing HPV positive oropharyngeal cancers. But there are people out there trying to change that.

After Jake Simpson passed away in 2016, he donated $20,000 for research into early intervention for these cancers.

His family chose a saliva research program currently underway at the Institute of Health and Biomedical Innovation in Brisbane lead by Professor Chamindie Punyadeera. The lab work is aimed at creating a simple and easy test everyone can do to monitor their HPV status at the dentist or GP.

“What we want to do is early intervention and detection,” she said.

“If you detect early, 80 per cent of patients survive. If you detect late, 20 per cent of them survive.”

But as the technology is still five years away from public use, and a therapeutic vaccine is perhaps even further away, Carly and Professor Punyadeera agree young people just need to be aware that this cancer exists, and is on the rise.

“Young boys think it’s a women’s cancer type. It’s not at all,” Prof Punyadeera said.

“It’s really sad and we all need to be aware of HPV associated head and neck cancers.”

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October, 2018|Oral Cancer News|

Vaccine, anti-PD1 drug show promise against incurable HPV-related cancers

A tumor-specific vaccine combined with an immune checkpoint inhibitor shrank tumors in one third of patients with incurable cancer related to the human papilloma virus (HPV) in a phase II clinical trial led by investigators at The University of Texas MD Anderson Cancer Center and reported in JAMA Oncology.

“That encouraging response rate is about twice the rate produced by PD1 checkpoint inhibitors in previous clinical trials, so these results will lead to larger, randomized clinical trials of this combination,” said principal investigator Bonnie Glisson, M.D., professor of Thoracic/Head and Neck Medical Oncology and Abell-Hanger Foundation Distinguished Professor at MD Anderson.

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

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

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

Of the 24 patients with recurrent HPV16-related cancers, 22 had oropharyngeal (back of the throat) cancer, one had cervical cancer and one had anal cancer.

  • Eight (33 percent) had a tumor response, two were complete. All eight had oropharyngeal cancer. Median duration of response was 10.3 months.
  • Overall median survival was 17.5 months, progression-free survival was 2.7 months and 70 percent of patients survived to 12 months.
  • Five of the eight responders remain in response.

“The median survival of 17.5 months for these patients is promising and provides further support for randomized trials testing the contribution of ISA101 to PD-1 inhibition,” Glisson said.

HPV causes nearly all cervical cancers, and most oropharyngeal, anal, penile, vulvar and vaginal cancers. HPV16 and HPV18 are the leading viral genotypes that increase cancer risk. Given the viral cause of these cancers, immunotherapy has been considered a strong potential approach. The researchers note that three previous clinical trials of PD1 inhibitors alone for recurrent HPV-related cancers yielded response rates ranging from 16 to 22 percent.

Two patients had grade 3 or 4 side effects—elevated enzyme levels—that required them to discontinue nivolumab. Glisson said the team observed side effects expected from the two treatments separately, but the researchers were encouraged to see no sign of synergistic side effects caused by the combination.

“That’s important as we develop rational combination immunotherapy,” Glisson said. This clinical trial was among the first to combine vaccination with PD1 inhibition.

Randomized clinical trials of the vaccine and anti-PD1 combination for cervical and oropharyngeal cancer are being organized.

The single-arm trial was an investigator-initiated effort originated at MD Anderson, Glisson noted.

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September, 2018|Oral Cancer News|

OCF’s Tobacco Cessation Spokesperson and Bradley Cooper’s Stunt Double Rides in Pendleton

You won’t find Cody Kiser at this year’s NFR, but you will find him working as a stuntman in the 2014 blockerbuster hit “American Sniper” starring Bradley Cooper.

The biographical war drama was directed by Clint Eastwood, and told the story of U.S. Navy Seal Chris Kyle.

Kiser, who rode Saturn Rocket for a 75.5-point score Friday at the Pendleton Round-Up, stepped in for Bradley during the scene that shows Kyle riding broncs during his rodeo days before he joined the Navy.

“That was the coolest thing I have ever done,” Kiser said. “I got to hang out for a day with Clint Eastwood and Bradley Cooper. Clint told me I looked a lot like Bradley. They said they wished they had me for the whole movie.”

A friend of Kiser’s who does stunt work in California put Kiser in touch with the people from the movie.

“They needed a bareback rider who had a certain look,” he said. “They had me and a saddle bronc rider, but he couldn’t ride bareback very well, so the job was mine.”

Kiser, 27, said he was living in Texas near where Kyle was shot in 2013, and that he had a friend working at the Rough Creek Ranch-Lodge in Erath County, Texas, where Kyle was shot.

“It’s such a small world,” he said.

Kiser earned a nice paycheck for his work, but said playing Kyle, even in a stunt role, was an honor.

“To be a part of that was unreal,” he said.

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September, 2018|OCF In The News|

New Book: Vaccines Have Always Had Haters

Date: 09/23/18
Source: National Public Radio
Author: Susan Brink

Vaccinations have saved millions, maybe billions, of lives, says Michael Kinch, associate vice chancellor and director of the Center for Research Innovation in Business at Washington University in St. Louis. Those routine shots every child is expected to get can fill parents with hope that they’re protecting their children from serious diseases.

But vaccines also inspire fear that something could go terribly wrong. That’s why Kinch’s new book is aptly named: Between Hope and Fear: A History of Vaccines and Human Immunity.

He wrote it, he says, to present the science behind vaccines and to highlight the fallacy of anti-vaccine movements. NPR talked with Kinch about vaccines. This interview has been edited for clarity and length.

The first attempts to control smallpox go back at least 1,000 years and didn’t involve vaccines. Can you describe those attempts?

Smallpox was probably killing a half a million people a year in Europe alone. The medical community had adopted a practice called nasal insufflation. You could take a little bit of the material from a smallpox scab, turn it into a powder and have a child snort it into the nose. Or you could intentionally scrape the skin and put material from a smallpox pustule under the skin of a healthy individual. That was called variolation. Those procedures caused smallpox, and people got sick. But far fewer of them died because most people would get a less virulent form of disease than if they were infected through exposure to a smallpox patient. Those who survived were then immune to smallpox.

How do you suppose people even thought of doing those disgusting things with scabs and pus?

You have to make assumptions. Maybe someone who was caring for a person with smallpox got a cut, and the cut got infected with pus from the patient. Then the caretaker noticed that afterward, they were immune to smallpox infection.

Variolation and nasal insufflation worked reasonably well, but they were not vaccines. What is a vaccine?

A vaccine is an intentional procedure using killed or weakened germs to trigger an immune response. The exposure to the virus or bacteria allows your body’s defenses to work, clearing the germs from the body. With the next exposure to those germs, the body is ready to fight off infection. Vaccines are generally delivered in an injection in the muscle, because the vaccine stays in place long enough for the immune system to detect and fight it.

The development of the smallpox vaccine was a breakthrough by Edward Jenner in 1796. What did science learn from the smallpox vaccine?

It took about a century for all the lessons to be learned. The smallpox vaccine made people understand that, once you identify a pathogen, you can kill or weaken it. Inoculating people with those weakened or killed forms alerts their immune systems but without causing disease, without causing harm. But first, pathogens had to be identified. A whole slew of discoveries happened from the 1880s through the early 20th century. People discovered anthrax bacteria, discovered measles, mumps, rubella viruses, discovered diphtheria, pertussis and tetanus. Then scientists could weaken or kill the germs and create vaccines.

Which vaccines does the world most need now?

The two holy grails are an AIDS vaccine and a universal influenza vaccine. AIDS has proven particularly challenging because the virus mutates very rapidly, and AIDS has found really good ways to circumvent an immune response. And the influenza virus changes constantly. It kills 30,000 to 40,000 Americans a year, and every few generations, there’s a pandemic. Exactly 100 years ago, we had the Spanish flu that wiped out tens of millions of people.

There are others. The current scourge of the world is malaria. The organism that causes it can change and thus hide from a vaccine. New pathogens always arise, and with global warming they’re working their way north, where they haven’t been seen before.

The current anti-vaccination movement fears that vaccinations are linked to autism, though the original study suggesting the link has been roundly discredited. Were there always “anti-vaxers” throughout history?

The anti-vax movement is actually older than vaccines. There was a well-established anti-variolation movement when people were using scabs and pus to try to prevent smallpox. Lady Mary Wortley Montagu was the wife of the British ambassador to the Ottoman Empire and a progressive thinker. She strong-armed the embassy physician to perform variolation on her four-year-old son in 1715, but her husband was opposed to it and she had to do it behind his back.

For virtually any vaccine you can name, there was an anti-vax movement around it. An 1802 cartoon was titled “The Wonderful Effects of the New Inoculation.” It was a spoof, reflecting widespread fear and showing people sprouting cow’s heads and horns and tails after being vaccinated against smallpox. (Note: Smallpox vaccine was made with cowpox virus, which rendered people immune to both cowpox and smallpox.)

Have there been scientifically valid reasons for people to fear vaccines?

There have been mistakes. When Dr. Jonas Salk announced his polio vaccine in 1955, bells were rung around the country to celebrate. But as people started getting immunized, Cutter Laboratories, which manufactured the vaccine in California, didn’t properly prepare the vaccine. A lot of kids were unintentionally infected with polio, and the incident created a lot of fear. (According to the National Institutes of Health, 40,000 cases of polio were caused by 200,000 vaccinations from the bad batch; 10 children died and 40 were left with varying degrees of paralysis).

Vaccines aren’t perfect. But there’s no substance in the world, including water and oxygen, that is entirely safe.

Why did you write this book now?

I saw that things were getting worse. It’s becoming more expensive to develop vaccines and less profitable. We haven’t developed a novel vaccine in decades. Pharmaceutical companies are abandoning vaccines. The anti-vax movement, I would argue, is stronger than ever. They’re highly organized, highly motivated and well-funded.

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September, 2018|Oral Cancer News|

Penn-led study raises hopes for vaccine to treat head and neck cancer

Date: 09/21/18
Source: The Inquire, philly.com
Author: Marie McCullough

The patient’s head and neck cancer came roaring back, spreading to his lymph nodes and skin, which developed bleeding tumors. Yet despite a grim prognosis, that man is alive and cancer-free more than two years later.

In a study led by the University of Pennsylvania and published Friday, researchers hypothesize that his remarkable remission is due to a promising combination: an experimental cancer vaccine that activated his disease-fighting T cells, plus Opdivo, one of the revolutionary “checkpoint inhibitor” drugs that cut a brake on the immune system.

“Of course, I’m biased,” said Charu Aggarwal, the Penn oncologist who led the study. “In my career, I haven’t seen a vaccine as impactful as this.”

However, the remission may have been due to Opdivo alone; the study lacks data to rule out that possibility.

Robert Ferris, director of the University of Pittsburgh Medical Center’s Hillman Cancer Center and head of the pivotal study leading to approval of Opdivo, called the Penn-led study “an important intermediate step exploring a strategy that we hope will work.”

Conventional vaccines prevent diseases by priming the immune system to recognize the distinctive “antigens” on invading microbes. Therapeutic cancer vaccines, like the one in this study, are intended to work after cancer develops by provoking a heightened immune response.

Despite decades of research, this approach remains experimental. The only approved product, the prostate cancer vaccine Provenge, was barely effective; the maker filed for bankruptcy in 2015.

A major obstacle to treatment vaccines is the fact that cancer arises from the body’s own cells. Although cancer cells produce antigens as they mutate, using these telltale proteins as targets for the immune system has proved to be very difficult.

Even so, at least four pharmaceutical groups are developing therapeutic vaccines that target human papillomavirus, HPV, the sexually transmitted virus that causes cervical cancer, head and neck cancer, and some rare genital cancers.

These diseases can be warded off with the preventive HPV vaccine that is recommended for all adolescents, but it didn’t exist until 12 years ago. Much to the dismay of public health authorities, vaccination rates remain low. And while screening can detect and treat cervical precancers, there are no early detection methods for head and neck cancers; experts call the surging incidence of these malignancies an “epidemic.”

The vaccine in the new study, called MEDI0457, was originally developed by Inovio with technology pioneered at Penn. In 2015, MedImmune, which is part of AstraZeneca, acquired exclusive rights to the drug.

MEDI0457 contains a DNA ring called a plasmid that programs the patient’s cells to produce two HPV antigens. The vaccine is injected into the patient’s muscle and enters cells with the help of a small electrical pulse applied to the skin. When the cells make the antigens, this triggers the immune system to activate disease-fighting white blood cells, so-called “killer” T cells.

For the study, published Friday in Clinical Cancer Research, 22 patients with head and neck cancer received conventional treatment — either surgery or chemotherapy and radiation — that eliminated all signs of cancer. This was supplemented by four doses of the experimental vaccine, which caused no serious side effects.

Eighteen patients, or 80 percent, showed elevated T cell activity that lasted at least three months after the final vaccine dose. While that is an encouraging sign, the study was too preliminary to detect clinical effectiveness such as tumor shrinkage or improved survival.

In the one patient who relapsed, cancer recurred seven months after vaccine treatment and spread to his lymph nodes and skin. He was given Opdivo and, eight weeks later, the cancer was gone.

Aggarwal and her co-authors note that such remarkable remissions do occasionally occur with checkpoint inhibitors. But they speculate that the vaccine revved up the patient’s T cells, then Opdivo removed the immune brake, enabling the T cells to attack the cancer.

“The response suggests the vaccine may in some manner prime the immune system, potentially boosting the effects of subsequent [checkpoint inhibitor] therapy,” Aggarwal said.

Rajarsi Mandal, director of the head and neck cancer immunotherapy research program at Johns Hopkins University, took a more conservative view: “They demonstrated vaccine specific T cell proliferation very nicely. But there is not a lot of data to suggest the vaccine is inducing any clinical response in these patients. Overall, it’s very interesting, but future studies are needed to demonstrate definitive clinical responses to the vaccine.”

Still, the combination approach is sufficiently promising that MedImmune is now funding a Penn-led clinical trial of MEDI0457 and MedImmune’s own experimental checkpoint inhibitor.

Ferris, meanwhile, said he is part of a trial of a competing experimental vaccine for HPV-related cancers, plus the approved checkpoint inhibitor Keytruda.

“The preventive HPV vaccine works really well,” he said. “But if you’re too old to get it, there is hope that you can stimulate the immune system to fight the cancer. This [new study] suggests the next logical step.”

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September, 2018|Oral Cancer News|

Youth vaping has soared in 2018, new data show

Source: www.wsj.com
Authors: Betsy McKay and Jennifer Maloney

Number of high schoolers who used e-cigarettes in the past 30 days has risen some 75% in 2018

Teen use of e-cigarettes has soared this year, according to new research conducted in 2018 that suggest fast-changing youth habits will pose a challenge for public-health officials, schools and parents.

The number of high-school students who used e-cigarettes in the past 30 days has risen roughly 75% since last year, according to a person who has seen new preliminary federal data.

That would equate to about three million, or about 20% of high-school students, up from 1.73 million, or 11.7% of high-school students in the most recently published federal numbers from 2017.

Nearly a third of 13-to-18-year-olds who responded to a separate survey conducted by The Wall Street Journal with research firm Mercury Analytics said they currently vape.

The new numbers offer a rare look at evolving teen vaping habits. Sales of e-cigarettes are expected nearly to double this year over 2017, and researchers have wondered how much of that increase is because of teen use. But there can be a long lag time between the collection of data and public reports.

Most of the teens who vape said they are doing it for reasons other than to quit smoking, according to the Journal’s survey conducted in 49 states in May. More than half said they do it because they like the flavors that e-cigarette liquids come in and they think vaping is fun. More than two-thirds said they believe vaping can be part of a “healthy life.”

U.S. Food and Drug Commissioner Scott Gottlieb said last week that teen use “has reached an epidemic proportion.” He announced new measures to curb teen vaping and warned he is considering banning flavored products.

The preliminary federal numbers from 2018 are from the government’s latest National Youth Tobacco Survey, according to the person familiar with the data. The survey was conducted in the spring.

The number of high-school users of combustible, or traditional, cigarettes increased slightly from the 2017 survey, this person said.

Monitoring the Future, a long-running youth survey conducted by the University of Michigan, found in 2017 that 16.6% of 12th-graders and 13.1% of 10th-graders had vaped nicotine, marijuana or flavoring in the previous 30 days. Richard Miech, the survey’s principal investigator, said he believes there has been a “considerable jump” in adolescent vaping this year.

This year’s sales growth has been driven largely by the Juul, a slim device that resembles a flash drive and has become a status symbol among teens, who often vape sweet-flavored liquids like mango. Juul has a 72.8% dollar share of the estimated $2.5 billion market in channels measured by market-research firm Nielsen, according to a Wells Fargo analysis.

Health officials are concerned that the high levels of nicotine in some liquids can alter the chemistry of developing brains, making them more sensitive to addiction.

Juul Labs Inc. says its device is intended to help adult smokers quit. “We cannot be more emphatic on this point: No minor or non-nicotine user should ever try JUUL,” a spokeswoman said. “Our packaging includes a prominent nicotine label and clearly states for adult smokers.”

Parents and educators say they are trying to do more to combat vaping with children back to school. “There is a lot more that needs to be done because at this point there are so many thousands of kids who are addicted to nicotine,” said Meredith Berkman, a founder of Parents Against Vaping E-Cigarettes, which advocates for action to restrict e-cigarette access.

Trinity School in New York City, for example, plans this year to incorporate more material on e-cigarettes into its health-education program for students, said John Allman, head of school. “Parents are letting us know about this,” he said of teen use.

The Journal survey was conducted online with 1,722 participants initially, and most of the survey questions focused on 1,007 participants who said they either vape, used to vape, or know someone who vapes. Nearly three-quarters of the 1,007 participants were 17 or 18 years old; 62% were white, 21% were African-American and 18% were Hispanic. Rates of e-cigarette use are higher in older than younger teens.

A total of 501 participants said they vape: 153 regularly, and 348 occasionally. Their most common reasons for vaping were for the flavors, and because they think it’s cool. “I just enjoy the flavor and blowing really big clouds,” one participant wrote.

“It made me feel good the first time I tried it, and I got hooked,” wrote another.

When asked what they were inhaling, 71% said flavors, and 61% said nicotine.

More than two-thirds of the current vapers said they believe vaping can be part of a healthy life, though they believe there are some risks. More than half said their views of vaping had been influenced by posts on social media, an issue that has public-health experts concerned.

The percentage of respondents who said they vape is unusually high, and should be interpreted with caution, said David Abrams, a professor in the College of Global Public Health at New York University. “We can’t make too much of it,” he said, because the survey was conducted online, and the questions weren’t all asked the way they are asked on large academic or government surveys.

Measures taken by the FDA, Juul, schools and parents to limit underage access to vaping devices since this spring may also be having an effect, some experts say. “It’s possible that prevalence and use may decline over time,” said Jidong Huang, an associate professor of health management and policy at Georgia State University who studies e-cigarette use.

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September, 2018|Oral Cancer News|