HPV

Blood test for HPV may help predict risk in cancer patients

Source: www.newswise.com
Author: University of North Carolina Health Care System

A blood test for the human papillomavirus, or HPV, may help researchers forecast whether patients with throat cancer linked to the sexually transmitted virus will respond to treatment, according to preliminary findings from the University of North Carolina Lineberger Comprehensive Cancer Center.

HPV can cause oropharyngeal cancer, which is a cancer of the throat behind the mouth, including the base of the tongue and tonsils. Studies have shown that patients with HPV-positive oropharyngeal cancer have better outcomes than patients whose cancer is not linked to the virus.

Preliminary findings presented at this year’s American Society for Radiation Oncology Annual Meeting suggest a genetic test for HPV16 in the blood could be useful to help assess risk for patients, and could help identify patients suitable for lower treatment doses.

“Our work on this blood test is ongoing, but we are optimistic that ‘liquid biopsy’ tests such as ours may be useful in the personalization of therapy for many patients with HPV-associated oropharyngeal cancer,” said the study’s senior author Gaorav P. Gupta, MD, PhD, UNC Lineberger member and assistant professor in the UNC School of Medicine Department of Radiation Oncology.

To avoid over-treating patients and to spare them from toxic treatment side effects, UNC Lineberger’s Bhisham Chera, MD, an associate professor in the radiation oncology department, led studies testing whether favorable-risk patients with HPV-positive oropharyngeal cancer can be treated successfully with lower doses of radiation and chemotherapy. A phase II clinical trial using this de-intensified regimen have shown “excellent” cancer control, Chera said.

The researchers used a number of selection criteria to identify patients who can benefit from lower-doses: patients had to be positive for HPV, and they had to have smoked fewer than 10 pack years. Chera said this system is not perfect, however. The researchers have seen cancer recur in non-smoking patients as well as “excellent” cancer control in longtime smokers.

“This has led us to question whether we can get better prognostication with other biomarkers,” Chera said.

They developed a test that can detect HPV16 circulating in the blood, and found that circulating HPV16 DNA was detectable using the test in the majority of a group of 47 favorable-risk oropharyngeal cancer patients.

In a finding that seems counterintuitive, they discovered that very low or undetectable HPV16 pretreatment levels in their blood actually had higher risk of persistent or recurrent disease for chemotherapy and radiation treatment. In contrast, patients with high pretreatment levels of HPV16 in their blood had 100 percent disease control.

They hypothesized that, potentially, the patients with undetectable/low pre-treatment HPV16 levels in the blood may have different, more radiation/chemotherapy resistant cancers.

“Our current theory is that these patients with low or undetectable levels of HPV16 have a different genetic makeup—one that is perhaps less driven purely by HPV, and thus potentially less sensitive to chemotherapy and radiation,” Gupta said. “We are performing next generation sequencing on these patients to search for additional genetic markers that may give us a clue regarding why they have a worse prognosis.”

They also identified a subset of patients who rapidly cleared the HPV16 from their blood. Researchers hypothesize that they could use their findings to further stratify patients who may be eligible for lower intensity treatment.

“A tantalizing – and yet currently untested – hypothesis is whether this subset of ultra-low risk patients may be treated with even lower doses of chemoradiotherapy,” Gupta said.

October, 2017|Oral Cancer News|

HPV and cancer: Key mechanism may suggest treatment

Source: www.medicalnewstoday.com
Author: Maria Cohut

New research from Georgetown University in Washington, D.C., investigates how the human papillomavirus promotes cancer. The findings might point to a potential new and improved strategy for targeted treatment.
The human papillomavirus (HPV) refers to a group of viruses transmitted through sexual contact. Some types of HPV cause various kinds of cancer, including mouth, anus, and cervical cancer.

According to data from the Centres for Disease Control and Prevention (CDC), around 1 in 4 people in the United States are infected with HPV.

Although treatments for HPV-related conditions do exist, they either target non-cancerous outcomes (such as genital warts) or they focus on the prevention of cancer through screening of abnormal cell activity.

Treatments for cancers caused by HPV include surgical interventions and chemotherapy, but at present, none of the options specifically address the viral source.

Researchers from Georgetown University Medical Center in Washington, D.C., have now identified the mechanism that promotes the survival of cancerous cells due to HPV. The study, which was led by Dr. Xuefeng Liu, describes a molecular apparatus that renders cancer cells “immortal.” Understanding how this apparatus works may lead to better targeted treatments in the future, the researcher suggests.

“There is no targeted treatment now for these cancers since German virologist Harald zur Hausen, Ph.D., discovered in 1983 that HPV can cause cervical cancer,” says Dr. Liu.

“Recently,” he adds, “the numbers of HPV-linked head and neck cancers have increased in the U.S. Now we have a chance to develop and test a very specific, potentially less toxic way to stop these cancers.”

The researchers’ findings are published in the journal Oncotarget.

October, 2017|Oral Cancer News|

B.C. to begin providing free HPV vaccines for Grade 6 boys

Source: ctvnews.ca
Author: Darcy Matheson
Date: September 26, 2017

For the first time in British Columbia, boys in Grade 6 will be receiving free vaccinations for the Human Papillomavirus.

HPV is one of the most commonly sexually transmitted infections and B.C. health authorities say three out of four sexually active people will get it at some point in their lives.

Often showing no physical symptoms, HPV can lead to cervical, vaginal, and vulvar cancers in women and penile cancer in men – and can also cause anal and throat cancer in both men and women.

Up until now, the vaccine to protect against HPV was only provided free to girls in Grade 6, with the assumption that boys would be indirectly protected through “herd immunity.”

Vancouver Coastal Health will soon be sending out letters to parents and caregivers through children’s schools regarding upcoming clinics for both girls and boys.

People can also be immunized through health-care providers, family doctors and local public health units.

Dr. Meena Dawar, medical health officer for Vancouver Coastal Health, said that immunizations are key because the symptom-less virus is often passed onto others without knowing it.

“Most often an HPV infection will clear on its own but sometimes HPV won’t go away and cells infected with the virus can become cancerous,” Dawar said in a statement.

Cancer survivor Sandy Yun had her 14-year-old daughter immunized as part of the B.C. program. She was going to pay for her 11-year-old son to get the vaccine but now she will be getting it for free.

“I wouldn’t want my kids, or anyone else, to go through what I went through,” the mom said in a statement.

“We have an easy way to protect our children from cancer, parents: this is a no-brainer.”

Each year in B.C. 200 women will get cervical cancer, and 50 will die from the disease.

B.C. joins Saskatchewan, Newfoundland and Labrador and New Brunswick in offering the vaccine for free to boys starting this month.

A study published this summer by the Canadian Medical Association Journal said the number of HPV-caused oral cancers has risen sharply in Canada — about 50 per cent between 2000 and 2012.

The majority of the cases featured in the CMAJ study – about 85 per cent – were men.

Researcher and co-author Sophie Huang, a research radiation therapist at Princess Margaret Cancer Centre in Toronto, said men have a weaker immune response to HPV than females, which may explain the higher incidence of oral cancers linked to the virus in men.

 

September, 2017|Oral Cancer News|

Treatment That’s Easy to Swallow in HPV+ Throat Cancer

Source: Medscape.com
Author: Nick Mulcahy
Date: September 27, 2017

SAN DIEGO, California ― Daniel Ma, MD, of the Mayo Clinic in Rochester, Minnesota, treats a lot of relatively young patients with human papillomavirus (HPV)-related oropharyngeal cancers who are cured by various standard combinations of surgery, radiation therapy and chemotherapy and then have “another 30 to 40 years of life ahead of them.”

But that life expectancy can be marred by the “potentially life-altering side effects” of standard treatment, including dry mouth, loss of taste, and, in about one half of patients, difficulty swallowing, he said.
These patients inspired the genesis of Dr. Ma’s phase 2 study of an “aggressive dose de-escalation” of adjuvant radiation in this setting, he said.

The investigators evaluated experimental radiation doses of 30 to 36 Gy, which is a 50% reduction from the current standard of 60 to 66 Gy.

At a median of 2 years’ follow-up among 80 patients, the treatment de-escalation has resulted in locoregional control rates comparable to historical controls, low toxicity, and, perhaps most notably, no decrement in swallowing function or quality of life, Dr. Ma reported here at the American Society for Radiation Oncology (ASTRO) 2016 Annual Meeting.

The toxicity and swallowing results are “the most exciting data,” Dr. Ma told a standing-room-only crowd at a meeting session today.

“It’s the first clinical trial in head and neck cancer to demonstrate no injury to swallowing function after radiation,” he told Medscape Medical News. In other words, patients’ ability to swallow was no worse post treatment. In fact, patients’ ability to swallow improved slightly at 1 year following radiation therapy compared to pretreatment (P = .03).

“It’s an exciting concept. Everyone’s going to want to hear more about it,” said Thomas Galloway, MD, of Fox Chase Cancer Center in Philadelphia, Pennsylvania, who was asked for comment about the trial.

The answer is not yet known, but the 2-year results from Dr. Ma are encouraging.

Two-year data indicate that after de-escalated treatment, the rate of locoregional tumor control was 95%, which is comparable to results with standard radiation (60 Gy) from the Radiation Therapy Oncology Group (RTOG) 0234 trial.

In the Mayo Clinic trial, three patients experienced local recurrence, and one patient experienced a nodal recurrence.

Fox Chase’s Dr. Galloway also observed that, in the new trial, patients received 30 Gy delivered in 1.5 Gy twice a day over 12 days (along with weekly docetaxel, 15 mg/m2, days 1 and 8). Twelve days is a lot shorter than the standard 6 weeks for 60-Gy therapy, but the twice-daily schedule may not be suitable for all patients, he pointed out.

De-escalation radiation therapy is experimental, but a phase 3 study that seeks to confirm the approach, known as the DART-HPV trial, is now underway.

“This is not incremental change,” he told Medscape Medical News. “It’s a stark change from the current standard of care.”

Dr. Galloway and Dr. Ma both said that HPV-positive head and neck cancers are necessitating change, because patients with these cancers are younger and healthier than patients without the virus, whose cancers are typically caused by smoking and alcohol consumption.

Some HPV-positive patients are now being treated without surgery. “What the perfect recipe for treatment is, no one knows for sure,” Dr. Galloway told Medscape Medical News about treatment combinations.

Paul Harari, MD, of the University of Wisconsin, Madison, said the HPV-positive head and neck cancers, including oropharyngeal cancers, “warrant different treatment approaches.” Standard treatment is toxic ― “make no mistake about it,” Dr Harari commented while acting as moderator at a press conference featuring the dose de-escalation trial.

However, cutting the radiation therapy dosage, he said, prompts a “tense question: can you maintain the cure rate?”

 

More Study Details, Including Toxicity

About half of the study patients, all of whom had oropharynx squamous cell carcinoma, had the above-described 2-week-long treatment schedule. But 43 patients had extracapsular extension, a marker of aggressive disease, and thus received an additional radiation boost to the affected areas, for a total dose of 36 Gy.

Data for both groups of patients were combined in the statistical tallies.

All of the study patients had no evidence of residual disease following surgery and a minimal smoking history (eg, less than one pack per day for 10 years or less). The median patient age was 60.5 years. All patients had stage III or IV disease.

There was also a “very dramatic reduction” in side effects, compared with standard treatment, said Dr. Ma. No patients required percutaneous endoscopic gastrostomy (PEG); by contrast, with traditional radiation therapy, one fifth to one third of patients undergo PEG.

The PEG feeding tube is inserted through the abdomen into the stomach. Typically, one fifth to one third of patients will receive such a feeding tube during standard treatment for oropharyngeal cancers, he said.

The rate of grade ≥2 toxicities 2 years post radiation therapy was 10%. Again, this compared favorably with 55% rate reported in RTOG 0234.

No patients had grade 3+ toxicity at 1 or 2 years following treatment.

All 14 patients (18%) who experienced cumulative grade 3+ toxicity did so within 3 months of treatment, and all cases resolved by 6 months post treatment. One patient experienced acute grade 4 toxicity related to a chemotherapy reaction, which quickly resolved.

Patient quality of life either improved or did not change following treatment, except with regard to xerostomia. Patients reported worse salivary flow following treatment (P < .0001).

Dr. Ma, his coinvestigators, Dr Galloway, and Dr. Harari have disclosed no relevant financial relationships.

American Society for Radiation Oncology (ASTRO) 2017 Annual Meeting. Abstract LBA-14, presented September 26, 2017.

 

 

 

 

September, 2017|Oral Cancer News|

British Columbia to begin providing free HPV vaccines for Grade 6 boys

Source: bc.ctvnews.ca
Author: Darcy Matheson, Senior Digital Producer, CTV Vancouver

For the first time in British Columbia, boys in Grade 6 will be receiving free vaccinations for the Human Papillomavirus. HPV is one of the most commonly sexually transmitted infections and B.C. health authorities say three out of four sexually active people will get it at some point in their lives.

Vaccines exist to prevent HPV, which is a common sexually transmitted infection.

Often showing no physical symptoms, HPV can lead to cervical, vaginal, and vulvar cancers in women and penile cancer in men – and can also cause anal and throat cancer in both men and women. Up until now, the vaccine to protect against HPV was only provided free to girls in Grade 6, with the assumption that boys would be indirectly protected through “herd immunity.”

Vancouver Coastal Health will soon be sending out letters to parents and caregivers through children’s schools regarding upcoming clinics for both girls and boys. People can also be immunized through health-care providers, family doctors and local public health units.

Dr. Meena Dawar, medical health officer for Vancouver Coastal Health, said that immunizations are key because the symptom-less virus is often passed onto others without knowing it.

“Most often an HPV infection will clear on its own but sometimes HPV won’t go away and cells infected with the virus can become cancerous,” Dawar said in a statement.

Cancer survivor Sandy Yun had her 14-year-old daughter immunized as part of the B.C. program. She was going to pay for her 11-year-old son to get the vaccine but now she will be getting it for free.

“I wouldn’t want my kids, or anyone else, to go through what I went through,” the mom said in a statement.

“We have an easy way to protect our children from cancer, parents: this is a no-brainer.”

Each year in B.C. 200 women will get cervical cancer, and 50 will die from the disease. B.C. joins Saskatchewan, Newfoundland and Labrador and New Brunswick in offering the vaccine for free to boys starting this month.

A study published this summer by the Canadian Medical Association Journal said the number of HPV-caused oral cancers has risen sharply in Canada — about 50 per cent between 2000 and 2012.

The majority of the cases featured in the CMAJ study – about 85 per cent – were men.

Researcher and co-author Sophie Huang, a research radiation therapist at Princess Margaret Cancer Centre in Toronto, said men have a weaker immune response to HPV than females, which may explain the higher incidence of oral cancers linked to the virus in men.

September, 2017|Oral Cancer News|

Halving radiation therapy for HPV-related throat cancer offers fewer side effects, similar outcomes

Source: www.eurekalert.org
Author: Mayo Clinic press release

Mayo Clinic researchers have found that a 50 percent reduction in the intensity and dose of radiation therapy for patients with HPV-related throat cancer reduced side effects with no loss in survival and no decrease in cure rates. Results of a phase II study were presented today at the 59th Annual Meeting of the American Society for Radiation Oncology in San Diego by Daniel Ma, M.D. a radiation oncologist at Mayo Clinic.

“A common approach for treating HPV-related throat cancer is a combination of surgery followed by daily radiation therapy for six to 6½ weeks,” says Dr. Ma. “However, the radiation treatment can cause a high degree of side effects, including altered taste, difficulty swallowing, dry mouth, stiff neck and damage to the jaw bone.” Dr. Ma says that patients with HPV-related throat cancer tend to be young and, once treated, are likely to live a long time with possibly life-altering side effects from the standard treatment. “The goal of our trial was to see if an aggressive reduction of radiation therapy (two weeks of radiation twice daily) could maintain excellent cure rates, while significantly reducing posttreatment side effects, improving quality of life and lowering treatment costs.”

Researchers followed 80 patients with HPV-related oropharyngeal squamous cell cancer with no evidence of residual disease following surgery and a smoking history of 10 or fewer pack years. That’s the number of years smoking multiplied by the average packs of cigarettes smoked per day.

At two years following the aggressively de-escalated treatment, the rate of tumor control in the oropharynx (throat) and surrounding region was 95 percent. Of the 80 patients in the trial, only three experienced a local cancer recurrence. One patient experienced a regional cancer recurrence. Patient quality of life largely improved or did not change following treatment, except for some dry mouth.

“Patients in our trial had a very dramatic reduction in side effects, compared with standard treatment,” says Dr. Ma. “For example, no patient in our trial needed a feeding tube placed during dose-reduced treatment; whereas, close to a third of patients had feeding tubes placed with traditional radiation therapy doses on other recent clinical trials.” Dr. Ma says the reduction in side effects did not lead to any reduction in cure rate, as survival rates were similar to traditional survival rates for HPV-related throat cancer.

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.

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?”

September, 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.”

August, 2017|Oral Cancer News|

No HPV Vaccination for Boys in UK

Source: Peter Russell
Date: July 20, 2017
Source: www.medscape.com

Health bodies are condemning a decision not to include boys in the human papilloma virus (HPV) vaccination programme as “shameful” and a “missed opportunity”.

The Joint Committee on Vaccination and Immunisation (JCVI) has concluded that it “did not recommend vaccinating boys at this time as it was considered unlikely to be cost-effective”.

Girls aged 12 to 13 have routinely been offered the HPV jab since September 2008 as part of the NHS childhood vaccination programme.

The JCVI has been considering whether to include boys on the scheme since 2014.

Protection Against Some Cancers

HPV is the name for a group of viruses that are most commonly passed on through genital contact between straight and same-sex partners.

It is a very common infection. Almost every sexually active person will get HPV at some time in their lives.

Most people who get HPV never develop symptoms or health problems, but for some it can lead to cancer of the cervix, vulva, vagina, penis, anus, and head and neck, as well as cause genital warts.

According to health professionals, the virus has been linked to 1 in 20 cases of cancer in the UK.

Campaigners in favour of giving boys the jab argue that HPV does not discriminate between the sexes and that offering the vaccine to boys in school would save lives.

‘Few Additional Benefits’

The JCVI has decided that a high take-up of the vaccine among girls would provide ‘herd protection’ to boys, and that vaccination of boys “would generate little additional benefit to the prevention of cervical cancer, which was the main aim of the programme”.

Additionally, the committee found insufficient evidence that the jab would protect against cancers affecting males such as anal, head and neck cancers. However, it agreed to keep evidence under review, particularly for men who have sex with men.

‘An Astonishing Decision’

Several health bodies have issued statements criticising the JCVI’s decision. The Faculty of Sexual and Reproductive Healthcare says it’s a “missed opportunity” and is urging it to reconsider its stance in October after a period of public consultation. Peter Baker, HPV action campaign director, says: “It is astonishing that the government’s vaccination advisory committee has ignored advice from patient organisations, doctors treating men with HPV-related cancers, public health experts and those whose lives have been devastated by HPV.

“The interim decision not to vaccinate boys is about saving money not public health or equity.”

Dentists are also condemning the decision. Mick Armstrong, chair of the British Dental Association, says: “HPV has emerged as the leading cause of oropharyngeal cancers, so JCVI’s unwillingness to expand the vaccination programme to boys is frankly indefensible. The state has a responsibility to offer all our children the best possible defence.

Dentists are also condemning the decision. Mick Armstrong, chair of the British Dental Association, says: “HPV has emerged as the leading cause of oropharyngeal cancers, so JCVI’s unwillingness to expand the vaccination programme to boys is frankly indefensible. The state has a responsibility to offer all our children the best possible defence.

“Dentists are on the front line in the battle against oral cancer, a condition with heart-breaking and life-changing results. Ministers can choose to sit this one out, or show they really believe in prevention.”

‘Shameful’

Emma Greenwood, Cancer Research UK’s director of policy, comments: “We’re disappointed to hear that the JCVI has made an interim recommendation not to offer the HPV vaccine to boys. If boys were included in the vaccination programme, it would help reduce the risk of HPV related cancers for the whole population, compared to vaccinating girls alone.”

The Terrence Higgins Trust describes the JCVIs decision as “shameful”. Its chief executive, Ian Green, says: “A gender neutral policy on HPV vaccination is long overdue and would protect boys from cancers caused by untreated HPV, including penile, anal and some types of head and neck cancer.”.

Jonathan Ball, professor of molecular virology at the University of Nottingham, says: “As increasing numbers of girls take up the vaccine then risk of heterosexual transmission decreases and the benefit of vaccinating boys diminishes.

“But of course, this reliance on herd immunity doesn’t provide optimal benefit for boys who go onto have sex with other men in adulthood.  There is a pilot vaccination programme running for men who have sex with men, but not all men at risk are likely to enrol in this, and we know the vaccine is most effective before someone becomes sexually active.

Limited Health Resources

“Unfortunately, it isn’t a question of science – it’s one of cost – and at the moment the Vaccination and Immunisation Committee doesn’t consider that the benefits are worth the investment.”

Dr David Elliman, consultant in community child health, adds: “Although it always seems hard to have to consider cost, it is important to make sure that we spend the money available to the NHS in a way that gets us best value.”

August, 2017|Oral Cancer News|