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HPV Related Cancers Increase in Men

Wed, Feb 18, 2015

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Source: scientificamerican.com
Author: Robin Lloyd

A vaccine to protect against the most dangerous strains of human papillomavirus (HPV), which cause almost all cervical cancers, as well as many cases of other cancers and genital warts in both sexes, won the approval of the U.S. Food and Drug Administration nearly nine years ago. The Centers for Disease Control and Prevention now recommends that all boys and girls aged 11 or 12 receive the shots. Vaccination campaigns, aimed largely at girls and women, have fallen short of expectations. By 2013 just over half of U.S. females aged 13 to 17 had received at least one dose of either the Gardasil or Cervarix vaccine. For males, that figure was a disappointing 35 percent. Now head and neck cancers associated with the virus are on the rise, leading some experts to recommend that a gender-neutral or male-centric approach might be more effective.

HPV is the most prevalent sexually transmitted disease in the U.S. and worldwide, infecting just about all men and women at some point in their lives. Although most people clear the virus naturally, persistent infections with some strains can lead to cancer—usually cervical or oropharyngeal (affecting the back of the throat, tonsils and back of the tongue). HPV-associated cancers make up 3.3 percent of all cancer cases among women and 2 percent of all such cases among men annually in the latest available figures, yet the incidence of virally instigated oropharyngeal and anal cancers is increasing.

Ohio State University medical oncologist and epidemiologist Maura Gillison has studied men with oropharyngeal cancer in three different decades. She and other colleagues first noticed an odd shift in patient profiles in the late 1990s: younger men were showing up in her clinic, often with no significant history of smoking or heavy drinking, which are risk factors for head and neck cancers. She later found that whereas from 1984 to 1989 in the U.S. only 16 percent of oropharyngeal cancers tested positive for HPV, by 2005 that figure had skyrocketed to 73 percent. By 2020 experts project that such cancer diagnoses will exceed those for cervical cancer in the U.S., shifting the burden of HPV-associated cancers from women to men. Gillison reported these findings in October 2014 at the annual ScienceWriters meeting.

Based on these data, Gillison thinks that the female-centric approach to HPV-related cancers in the U.S. should switch to focus on both men and women. Nobel laureate Harald zur Hausen, who discovered 30 years ago that HPV causes cervical cancer, has gone further, saying that males should get the vaccine if only one sex were the focus. The vaccine is currently voluntary in most U.S. states, and only a smattering of vaccination coverage campaigns exist, such as those launched by the New York City Department of Health and the Minnesota Department of Health in the past year. Public health messages and even research literature often fail to mention male vaccination prominently or at all. Unfounded fear of vaccines and claims that the HPV shots would provoke early teen sexuality have hindered efforts to vaccinate broadly in much of the U.S.

No data exist to prove that the vaccines protect against HPV-positive oropharyngeal cancer. But such coverage is probable given that the same strains that cause most cervical, vaginal and vulval cancers also cause most head and neck cancers. If a shift in public health policy were to result in an increase in male vaccinations, experts say, at the very least rates of females’ HPV-associated cancers would decrease as a result of fewer infections acquired from men. And the rise in HPV-associated cancers in men would most likely decelerate, plateau or even reverse. A win for all of us.

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.
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HPV Vaccine Linked to Less-Risky Behavior

Wed, Feb 18, 2015

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Source: torontosun.com
Author: Roxanne Nelson, Reuters
 

Contrary to concerns that getting vaccinated against human papilloma virus (HPV) will lead young people to have more or riskier sex, a new study in England finds less risky behaviour among young women who got the HPV vaccine.

“To my knowledge no studies have shown that HPV vaccination increases risky sexual behavior among young women and some of these studies have shown this (less risky behaviour) is also the case outside of the UK,” said Dr. Laura Sadler of the University of Manchester, who led the study.

It’s possible that getting vaccinated led to better education about sexual health, Sadler and her colleagues write in the Journal of Family Planning and Reproductive Health Care.

Sadler and other experts say it’s also possible that young women who are already less likely to take risks are the ones who are more likely to get vaccinated.

HPV is one of the most common sexually transmitted infections and causes the majority of cervical cancers. The virus has also been linked to anal and throat cancers. Two vaccines, Cervarix and Gardasil, are now available that protect against strains of HPV that cause most cervical cancers.

Even though public health officials recommend that girls and young women be vaccinated against HPV, some parents have hesitated, fearing that it could encourage sexual activity or unsafe sex.

For their study, Sadler’s team reviewed the medical records of 363 women born in 1990 or later who attended an English clinic. Almost two-thirds of the young women in the group had received at least one dose of the vaccine. Full vaccination requires three vaccine shots.

The researchers compared the womens’ histories of behaviours that are risky in themselves or tend to be linked to risky sexual behaviour, such as not using condoms, having sex for the first time when they were 15 or younger, having six or more sexual partners and drinking alcohol two or more times a week.

They found five variables related to sexual behaviour that were significantly different between women who had been vaccinated and those who hadn’t.

Women who were not vaccinated were more likely to have had three sex partners in the last six months, to have attended the clinic with symptoms of a sexually transmitted disease, to have had anal intercourse with their last sexual contact and to have tested positive for Chlamydia (a common sexually transmitted infection) at their clinic visit.

Being vaccinated, in contrast, was associated with less-risky behaviours, such as using condoms.

“In this study, the lower prevalence of some risk outcomes among vaccinated women relative to unvaccinated women may be related to underlying differences in preventive care seeking and preventive health behaviors,” said Robert A. Bednarczyk, an assistant professor at the Rollins School of Public Health at Emory University, and who was not involved in the study.

“The women in our study were mainly from the catch-up vaccine program – older teens – and as in the other studies, it shows that among this group, vaccination was taken up by those demonstrating other types of preventive or less risky behaviors,” Sadler told Reuters Health by email.

While the findings are encouraging, and consistent with other research demonstrating that HPV vaccination does not lead to riskier behaviors, the study does not demonstrate that vaccination causes less risky behaviors, said Dr. Jessica Kahn, a professor of pediatrics at Cincinnati Children’s Hospital Medical Center.

“One explanation for the findings is that girls who are vaccinated receive education about sexual health and prevention which decreases riskier behaviors,” Kahn said in an email.

Another explanation is that girls who practice healthier and less risky behaviors are more likely to receive the vaccine, she noted. “Preventive health behaviors tend to cluster, so it makes sense that girls who practice safer behaviors are more likely to be vaccinated.”

 

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.
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New research shows possibility of cure for HPV positive throat cancer patients

Fri, Feb 13, 2015

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Source: Eurek Alert! The Global Source for Science News

Nice, France: Patients with cancer of the throat caused by the Human Papilloma virus (HPV+) have a better prognosis than those who are negative for the virus (HPV-). Now, for the first time, researchers have shown with convincing evidence that a group of patients with HPV+ cancer of the oropharynx (the part of the throat located behind the mouth, that makes up the region of the tonsils and the back part of the tongue where it connects to the swallowing part of the throat), can be cured in some cases even after disease has spread to distant organs in the body, like the lungs.

Dr Sophie Huang, Assistant Professor in the Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Canada, will tell the 5th International Conference on Innovative Approaches in Head and Neck Oncology (ICHNO) today (Friday) that her research has shown that, following intensive treatment, certain patients with HPV+ oropharyngeal cancer (OPC) and distant metastases (tumours appearing in an organ not directly related to the primary cancer site) can survive for more than two years without further evidence of disease. Such cancers are usually considered to be incurable, and the goal of treatment is usually limited to symptom control. “Our research, the largest study to date to explore survival predictors for metastatic HPV+ and HPV- oropharyngeal cancer patients, has shown that cure is a realistic goal in those patients with oligometastasis – metastases involving five or fewer lesions in one distant organ”, she will say.

Dr Huang and colleagues identified 934 patients with HPV+ OPC out of the 1238 OPC patients who had been treated at the Princess Margaret Cancer Centre between 2000 and 2011. Distant metastases were detected in 15% of these patients; 88 in the HPV+ group and 54 in those with HPV- disease. Oligometastasis was present in 24 HPV+ patients with distant metastases in a single organ.

The researchers found two types of distinct distant metastases in HPV(+) patients: “explosive” and “indolent” metastases. The explosive type metastasis, where more than ten lesions in one organ appear quickly in a short period (within three months of appearance of the first lesion), was present in 55% of the HPV+ group, as opposed to none in those who were HPV-. In both HPV+ and HPV- groups, lung was the most common metastatic site. The indolent type of metastases grow and spread at a much slower pace, most often manifesting as oligometastasis. This occurred in 24% of the HPV+ cases with metastases in a single organ as opposed to 26% of those who had HPV- cancer.

“In the HPV+ group of patients with oligometastases, when they were given definitive local treatment aimed at disease control – for example, a high radiation dose or surgical removal of the metastatic lesion, as opposed to a less aggressive treatment used to control symptoms -there was a long term disease-free period, suggesting that some may be cured,” Dr Huang will say. “In the HPV+ group with oligometases 25% were still alive after three years, whereas the percentage in the HPV- group was 15%.”

The survival advantage in HPV+ OPC patients is due to a number of factors, the researchers say. The cancer is more sensitive to radiotherapy and chemotherapy; the patients tend to be younger (an average age of 55 at diagnosis as opposed to 65) with fewer other health problems, including those caused by smoking-related illness, and this enables them to receive the more aggressive treatment necessary to eradicate metastatic disease.

The percentage of HPV positive to negative OPC cancers varies globally, depending on a number of factors, including the prevalence of smoking and the practice of oral sex. Overall the incidence of HPV+ throat cancers has increased over the past 20 years in developed countries, such as US, Canada, Japan, Australia, and some European countries. [1]

“This research has shown that metastatic HPV+ OPC patients who receive active treatment can survive considerably longer than those who did not receive treatment. One of the reasons patients with metastatic disease do not receive aggressive treatment is due to the physician and patient’s perception that this is an incurable state. We hope that these results will motivate researchers to optimise management strategies for these patients. This will not only help to produce a better quality of life and a return to work for them, but also reduce the cost to healthcare systems,” Dr Huang will say.

“We also hope that our study may trigger research to explore cost-effective methods for the early detection of metastases. Optimising and tailoring surveillance strategies for HPV+ patients are also important. For example, our research has shown that the surveillance period should be longer than the traditional two-year window, due to the possibility of later onset of metastases. Selecting the appropriate imaging method in order to detect asymptomatic oligometastasis (e.g. ultrasound for the early detection of liver metastasis) may allow salvage treatment of some patients before the cancer progresses. Finally, we hope that it will help clinicians identify patients who are best able to benefit from aggressive treatment, such as metastasectomy (surgical removal of the metastases) or stereotactic radiotherapy (highly focused high dose radiotherapy to small regions),” Dr Huang will say.

Whether it is possible to identify which patients at initial presentation are at high risk of developing distant metastasis, and which type of distant metastasis will subsequently develop are other important questions for future studies, say the researchers. “We know there is a degree of correlation between the initial stage and the risk of distant metastasis, but we did not find a strong relationship between this stage and the type of metastasis. The intensity of cigarette smoking in the years prior to the time of diagnosis is a possible factor. Being able to identify such relationships could be a huge help in deciding appropriate treatment at an early stage,” Dr Huang will say.

Although head and neck cancer is the sixth most common type of cancer worldwide, awareness of it is low, and hence the majority of diagnoses are not made until the disease is in an advanced stage, resulting in limited treatment choices and hence a reduction in the chance of survival.

Professor Jean Bourhis, co-chair of the conference scientific committee, said: This important piece of research adds substantially to what we know about the role and the importance of the Human Papilloma Virus (HPV) in oropharyngeal cancers and gives real hope of improvement in both diagnosis and treatment to those who are affected by the condition.”

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1Chaturvedi AK, Anderson WF, Lortet-Tieulent J, et al. Worldwide trends in incidence rates for oral cavity and oropharyngeal cancers. Journal of Clinical Oncology : official journal of the American Society of Clinical Oncology 2013;31(36):4550-9.

Abstract no OC-044: Proffered paper session, Auditorium Athena, Friday 16.00 hrs

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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

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A Study Finds Smoking’s Toll On Your Body and Health Worse Than Previously Thought

Thu, Feb 12, 2015

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Source: nytimes.com
Author: Denise Grady
 

However bad you thought smoking was, it’s even worse.

A new study adds at least five diseases and 60,000 deaths a year to the toll taken by tobacco in the United States. Before the study, smoking was already blamed for nearly half a million deaths a year in this country from 21 diseases, including 12 types of cancer.

The new findings are based on health data from nearly a million people who were followed for 10 years. In addition to the well-known hazards of lung cancer, artery disease, heart attacks, chronic lung disease and stroke, the researchers found that smoking was linked to significantly increased risks of infection, kidney disease, intestinal disease caused by inadequate blood flow, and heart and lung ailments not previously attributed to tobacco.

Even though people are already barraged with messages about the dangers of smoking, researchers say it is important to let the public know that there is yet more bad news.

“The smoking epidemic is still ongoing, and there is a need to evaluate how smoking is hurting us as a society, to support clinicians and policy making in public health,” said Brian D. Carter, an epidemiologist at the American Cancer Society and the first author of an article about the study, which appears in The New England Journal of Medicine. “It’s not a done story.”

In an editorial accompanying the article, Dr. Graham A. Colditz, from Washington University School of Medicine in St. Louis, said the new findings showed that officials in the United States had substantially underestimated the effect smoking has on public health. He said smokers, particularly those who depend on Medicaid, had not been receiving enough help to quit.

About 42 million Americans smoke — 15 percent of women and 21 percent of men — according to the Centers for Disease Control and Prevention. Research has shown that their death rates are two to three times higher than those of people who have never smoked, and that on average, they die more than a decade before nonsmokers. Smokers are more than 20 times as likely as nonsmokers to die of lung cancer. Poor people and those with less formal education are the most likely to smoke.

Mr. Carter said he had been inspired to dig deeper into the causes of death in smokers after taking an initial look at data from five large health surveys being conducted by other researchers. The participants were 421,378 men and 532,651 women 55 and older, including nearly 89,000 current smokers.

As expected, death rates were higher among the smokers. But diseases known to be caused by tobacco accounted for only 83 percent of the excess deaths in people who smoked.

“I thought, ‘Wow, that’s really low,’ ” Mr. Carter said. “We have this huge cohort. Let’s get into the weeds, cast a wide net and see what is killing smokers that we don’t already know.”

The research was paid for by the American Cancer Society, and Mr. Carter worked with scientists from four universities and the National Cancer Institute.

The study was observational, meaning that it looked at people’s habits, like smoking, and noted statistical correlations between their behavior and their health. Correlation does not prove a cause-and-effect relationship, so this kind of research is not considered as strong as experiments in which participants are assigned at random to treatments or placebos and then compared. But people cannot ethically be instructed to smoke for a study, so a lot of the data on smoking’s effects on people comes from observational studies.

Analyzing deaths among the participants from 2000 to 2011, the researchers found that, compared with people who had never smoked, smokers were about twice as likely to die from infections, kidney disease, respiratory ailments not previously linked to tobacco, and hypertensive heart disease, in which high blood pressure leads to heart failure. Smokers were also six times more likely to die from a rare illness caused by insufficient blood flow to the intestines.

Mr. Carter said he had confidence in the findings because, biologically, it made sense that those conditions were related to tobacco. Smoking can weaken the immune system, increasing the risk of infection, he said. It is also known to cause diabetes, high blood pressure and artery disease, all of which can lead to kidney problems. Artery disease can also choke off the blood supply to the intestines. Lung damage from smoke, combined with increased vulnerability to infection, can lead to multiple respiratory illnesses.

Two other observations supported the findings, he said. One was that the more heavily a person smoked, the greater the added risks. The second was that among former smokers, the risks diminished over time. In general, such effects, known as a dose response, suggest that an observed correlation is more than a coincidence.

The study also found small increases in the risks of breast and prostate cancer among smokers. Mr. Carter said those findings were not as strong as the others, adding that additional research could help determine whether there were biological mechanisms that would support a connection.

A 2014 report by the surgeon general’s office said the evidence for a causal connection between smoking and breast cancer was “suggestive but not sufficient.” The same report found no evidence that smoking caused prostate cancer, but it noted that in men who did have prostate cancer, smoking seemed to worsen the outcome.

The diseases that had previously been established by the surgeon general as caused by smoking were cancers of the esophagus, stomach, colon, liver, pancreas, larynx, lung, bladder, kidney, cervix, lip and oral cavity; acute myeloid leukemia; diabetes; heart disease; stroke; atherosclerosis; aortic aneurysm; other artery diseases; chronic lung disease; pneumonia; influenza; and tuberculosis.

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.
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New Model Proposed for More Accurate Prediction of Treatment Outcomes for HPV Related Throat Cancer Patients

Wed, Feb 11, 2015

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Source: news-medical.net
Author: Researchers at Princess Margaret Cancer Centre, University Health Network

Researchers at the Princess Margaret Cancer Centre are proposing a new model to enable doctors to predict outcomes more accurately for patients with throat cancers specifically caused by Human Papillomavirus (HPV).

The findings are published online today in the Journal of Clinical Oncology. Study investigators, Dr. Brian O’Sullivan, Lead, Head and Neck Cancer Site Group and Shao-Hui Huang, Research and Clinical Radiation Therapist at Princess Margaret Cancer Centre, have determined that a new model for classifying the most frequently seen throat cancers in our geographic location is needed. This classification incorporates individual patient factors including age and their smoking status with the traditional classification of the extent of disease, to offer a more personalized approach to predict outcomes and guide treatment.

“Our study shows that the current model derived for smoking and alcohol related cancers is not suited for throat cancer caused by HPV, a burgeoning throat cancer population in the Western World, including Canada,” says Huang.

“This is the future of tumour staging. We need to consider the patient as a whole. Both individual factors, how extensive the disease is in the patient, and tumour biology should play a role in determining the best course of treatment.”

The purpose of a tumour staging system is to classify the disease into early, intermediate or advanced stage cancer. This classification helps determine treatment plans and can suggest what is likely to be the outcome. In recent years, it’s been discovered that throat cancer caused by HPV behaves differently than throat cancer caused by smoking and alcohol, yet both cancers use the same tumour classification model. Therefore, regardless of whether the cancer was caused by HPV or smoking, the treatment and perceived prognosis based on tumour staging has remained the same – even though patient outcomes, as this study demonstrates, vary considerably.

For example, a stage IV patient with HPV-related cancer has an 80 per cent survival rate while a stage IV smoking-related cancer patient has a 50-60 percent survival rate, but both are presently considered advanced stage – which is recognized as a life-threatening prognosis.

“When you tell a patient they have stage IV cancer, it’s an indication of advanced disease and they don’t expect it to be curable,” says Huang. “We need a staging system that more accurately reflects a patient’s prognosis – which in a case caused by HPV, is highly curable.”

The study also highlights the fact that many HPV-related throat cancer patients are over-treated due to the stage IV tumour classification. High dose chemotherapy combined with high dose radiation is often given to this patient population when radiation therapy alone or other less intensive strategies can probably cure many of them.

Clinical trials have now begun to address these questions but their descriptions and design are hindered by inadequacies of the current stage classification. A new tumour staging model will help to separate patients with promising prognoses from those with negative prognoses to design the most appropriate treatment strategies for each group.

“This work has several interesting characteristics, and not just relating to the management of head and neck cancer. Providing a relevant stage classification for a rapidly emerging disease is important, but the additional feature of the classification is that it provides the opportunity to include factors beyond just the traditional description of disease extent into the prognostic classification we are trying to develop to assist in treating patients,” says Dr. O’Sullivan.

“The structure used for the classification follows a template we developed at the Union for International Cancer Control (UICC) and is relevant to all cancers. Important factors that are emerging throughout oncology are not currently included in the international classifications. This needs to change to facilitate our goal of providing personalized approaches to patients with cancer.”

The Princess Margaret is collaborating with six major cancer centres across the world to validate these findings, which will provide solid evidence for a new tumour staging system that offers a personalized approach to medicine.

 

 *This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.
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HPV vaccination does not increase promiscuity among adolescents: It’s a vaccine against sexually transmitted cancer

Wed, Feb 11, 2015

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Source: reason.com
Author: Ronald Bailey

On February 3, 2015, libertarian radio host Andrew Wilkow invited me to discuss the risks and benefits of vaccination. We disagreed: Mr. Wilkow is considerably more worried about the risks than is warranted by the scientific evidence. During the segment, Mr. Wilkow stated that he did not plan to have his two-year old daughter vaccinated against the human papilloma virus (HPV).

Infection with human papilloma virus is responsible for about 11,967 new cases of HPV-associated cervical cancer and for about 2,370 new cases of HPV-associated oropharyngeal cancers in women and nearly 9,356 new cases in men each year in the United States. During the radio segment, I mentioned that a male friend had recently died of HPV-associated head-and-neck cancer. I failed to mention that another male friend is being treated for that cancer now.

Mr. Wilkow argued that since the vaccine immunizes against a sexually transmitted disease that he saw no reason to have his daughter vaccinated against it. The series of three HPV injections is recommended to start after age 9, so Mr. Wilkow has time to reconsider.

Mr. Wilkow is, however, not alone in his opposition to HPV vaccination. A 2014 study in Clinical Pediatrics reported the results of a survey of parents’ actions regarding HPV vaccination. The researchers found:

A significantly higher proportion of parents of girls who were non-Hispanic white, lived in households with higher incomes, and had mothers with higher education levels, delayed and/or refused vaccination.

Another of the early concerns by some opponents of HPV vaccine is that it might encourage sexual promiscuity by lessening adolescent fears of getting sexually transmitted diseases. Several studies have looked at this issue and all have found no such link. The latest study just published in the journal JAMA Internal Medicine is reassuring on that account. The researchers compared the sexually transmitted disease incidence (STI) among vaccinated and unvaccinated adolescent females. The study found:

Human papillomavirus vaccination was not associated with increases in STIs in a large cohort of females, suggesting that vaccination is unlikely to promote unsafe sexual activity.

If you could immunize your kids against breast or prostate cancer you would, wouldn’t you? So why not vaccinate against these cancers?

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Harnessing the immune system to fight cancer

Wed, Feb 11, 2015

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Source: www.npr.org
Author: staff

When Barbara Marder was diagnosed with lung cancer three years ago, she had part of her right lung removed, went through a round of chemotherapy and tried to move on with her life.

“I had hoped that everything was fine — that I would not create difficulty for my children, that I would get to see my grandchildren grow up,” says Marder, 73, of Arnold, Md.

But a routine scan a year later found bad news: The cancer was back — this time in her other lung.

“I was very disappointed,” says Marder. She knew her prognosis was grim. “I decided at that point that … I should think about the fact that perhaps this was going to advance rapidly at this point. And check and make sure: Is my will in order? What should I do so that my children aren’t left with a mess to clean up in my house?”

But Marder didn’t give up. She started exploring her options, which eventually brought her to Johns Hopkins in Baltimore, where doctors are testing a new type of cancer treatment known as immunotherapy.

“Immunotherapy for cancer means developing treatments to harness your immune system and using your own immune system to fight the cancer,” says Dr. Julie Brahmer, an associate professor of oncology and Marder’s doctor.

Scientists have been trying to do this for decades. After all, our immune systems can fight off all kinds of health threats. So, why not cancer? But nothing seemed to really work.

“It’s been very frustrating,” Brahmer says.

But scientists recently discovered that cancer takes a page from Harry Potter: It puts on a kind of invisibility cloak.

“Cancer can keep the immune system from recognizing that it’s bad and keep it from attacking itself,” Brahmer says.

Now scientists have found a way around this.

“The breakthrough is in therapies called ‘checkpoint inhibitors,’ ” Brahmer says.

Checkpoint inhibitors are drugs that pull off cancer’s invisibility cloak by blocking the switch that turns it on.

“It prevents that invisibility cloak or that force field or shield … from going up,” Brahmer says, “so it can’t shield itself from the immune system.”

And these drugs seem to be working, at least for some patients — melting away the toughest tumors, such as some melanomas, the deadliest kind of skin cancer.

npr-immuno

Click image to animate

“They seem to be working quite well for multiple different cancers,” Brahmer says, including kidney cancer, bladder cancer, head and neck cancers, lymphoma and even perhaps breast and lung cancers.

So Marder volunteered for one of Brahmer’s studies testing a checkpoint inhibitor called nivolumab, or Opdivo, for lung cancer. Within weeks of starting her infusions, the tumors in her left lung began to disappear.

“That was very, very exciting. It really changed my perspective. I thought, ‘Jeepers,’ ” Marder says.

Checkpoint inhibitors can cause serious side effects when the immune system attacks healthy cells, causing dangerous, even sometimes life-threatening organ damage. But so far that appears to be relatively rare.

Most patients just get a little tired. Some, like Marder, get an itchy rash. But compared with traditional chemotherapy, it’s easier in most cases.

“You can live a great life,” Brahmer says, “travel and try to live your life as normally as possible. That’s definitely different than chemotherapy.”

One big question is, how long will these drugs keep working? Traditional chemotherapy often stops working with time — the length of effectiveness varies depending on the patient, the type of cancer and the stage at which it was diagnosed. But so far checkpoint inhibitors seem to keep going a lot longer, even in patients who have stopped responding to standard chemotherapy. No one knows yet how much longer.

But Brahmer says so far it looks promising.

“We’re reporting three-year survival rates in [lung cancer] patients who we would say typically should not be around,” Brahmer says.

For melanoma, researchers have followed patients for even longer, she says.

When Marder went back for a checkup more than a year after starting her treatment, there was still no sign of her cancer. Marder was thrilled.

“I’m very fortunate,” she says.

But another big question about these drugs is how much they cost: more than $120,000 for each round. That has drawn some intense criticism.

“Cancer immunotherapy is the most exciting thing we have going on in the field,” says Dr. Peter Bach, director of the Center for Health Policy and Outcomes at the Memorial Sloan Kettering Cancer Center in New York. “It’s frustrating that the companies are gouging the U.S. system with their prices.”

The companies that make checkpoint inhibitors defend their price tags and say they will help make sure patients can afford them.

“Any patient who needs access to a checkpoint inhibitor made by Bristol-Myers Squibb will have access through a robust patient-assistance program,” says Michael Giordano, who heads oncology drug development at the company.

Brahmer hopes doctors will figure out a way to cut the costs and says patients may not have to stay on the drugs indefinitely. That’s because when patients stop taking them, immune system cells known as T-cells seem to remember how to keep the body cancer-free.

“We think that over time your immune system creates memory,” Brahmer says.

The T-cells remember how to attack the tumor and stop the cancer from putting up a shield. “So those T-cells continually keep that cancer under control. Even without treatment,” Brahmer says.

Brahmer might try that for Marder. But for now, she’s coming back every two weeks to receive infusions, and because she is in a study, Marder doesn’t have to pay for the drug.

Brahmer knows she and other researchers will have to treat many more patients for a lot longer to really know just how well these checkpoint inhibitors work, and for how long. Many scientists suspect it will take a combination of checkpoint inhibitors to get the most out of our immune systems to fight cancer.

“We’re trying to figure out how to personalize this treatment,” Brahmer says. “Who needs just one checkpoint inhibitor? Who needs a combination to really unleash the immune system? That’s where this is probably headed.”

NPR’s documentary Cancer: The Emperor of All Maladies will air on PBS in March.

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New model proposed for predicting outcomes more accurately in HPV-related throat cancer patients

Wed, Feb 11, 2015

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Source: www.news-medical.net
Author: staff

Researchers at the Princess Margaret Cancer Centre are proposing a new model to enable doctors to predict outcomes more accurately for patients with throat cancers specifically caused by Human Papillomavirus (HPV).

The findings are published online today in the Journal of Clinical Oncology. Study investigators, Dr. Brian O’Sullivan, Lead, Head and Neck Cancer Site Group and Shao-Hui Huang, Research and Clinical Radiation Therapist at Princess Margaret Cancer Centre, have determined that a new model for classifying the most frequently seen throat cancers in our geographic location is needed. This classification incorporates individual patient factors including age and their smoking status with the traditional classification of the extent of disease, to offer a more personalized approach to predict outcomes and guide treatment.

“Our study shows that the current model derived for smoking and alcohol related cancers is not suited for throat cancer caused by HPV, a burgeoning throat cancer population in the Western World, including Canada,” says Huang.

“This is the future of tumour staging. We need to consider the patient as a whole. Both individual factors, how extensive the disease is in the patient, and tumour biology should play a role in determining the best course of treatment.”

The purpose of a tumour staging system is to classify the disease into early, intermediate or advanced stage cancer. This classification helps determine treatment plans and can suggest what is likely to be the outcome. In recent years, it’s been discovered that throat cancer caused by HPV behaves differently than throat cancer caused by smoking and alcohol, yet both cancers use the same tumour classification model. Therefore, regardless of whether the cancer was caused by HPV or smoking, the treatment and perceived prognosis based on tumour staging has remained the same – even though patient outcomes, as this study demonstrates, vary considerably.

For example, a stage IV patient with HPV-related cancer has an 80 per cent survival rate while a stage IV smoking-related cancer patient has a 50-60 percent survival rate, but both are presently considered advanced stage – which is recognized as a life-threatening prognosis.

“When you tell a patient they have stage IV cancer, it’s an indication of advanced disease and they don’t expect it to be curable,” says Huang. “We need a staging system that more accurately reflects a patient’s prognosis – which in a case caused by HPV, is highly curable.”

The study also highlights the fact that many HPV-related throat cancer patients are over-treated due to the stage IV tumour classification. High dose chemotherapy combined with high dose radiation is often given to this patient population when radiation therapy alone or other less intensive strategies can probably cure many of them.

Clinical trials have now begun to address these questions but their descriptions and design are hindered by inadequacies of the current stage classification. A new tumour staging model will help to separate patients with promising prognoses from those with negative prognoses to design the most appropriate treatment strategies for each group.

“This work has several interesting characteristics, and not just relating to the management of head and neck cancer. Providing a relevant stage classification for a rapidly emerging disease is important, but the additional feature of the classification is that it provides the opportunity to include factors beyond just the traditional description of disease extent into the prognostic classification we are trying to develop to assist in treating patients,” says Dr. O’Sullivan.

“The structure used for the classification follows a template we developed at the Union for International Cancer Control (UICC) and is relevant to all cancers. Important factors that are emerging throughout oncology are not currently included in the international classifications. This needs to change to facilitate our goal of providing personalized approaches to patients with cancer.”

The Princess Margaret is collaborating with six major cancer centres across the world to validate these findings, which will provide solid evidence for a new tumour staging system that offers a personalized approach to medicine.

Source:
Princess Margaret Cancer Centre, University Health Network

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Integrative and Comparative Genomic Analysis of HPV-Positive and HPV-Negative Head and Neck Squamous Cell Carcinomas

Thu, Feb 5, 2015

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Source: http://clincancerres.aacrjournals.org/
Authors:
Tanguy Y. Seiwert, Zhixiang Zuo, Michaela K. Keck, Arun Khattri, Chandra S. Pedamallu, Thomas Stricker, Christopher Brown, Trevor J. Pugh, Petar Stojanov, Juok Cho, Michael S. Lawrence, Gad Getz, Johannes Brägelmann, Rebecca DeBoer, Ralph R. Weichselbau, Alexander Langerman, Louis Portugal, Elizabeth Blair, Kerstin Stenson, Mark W. Lingen, Ezra E.W. Cohen, Everett E. Vokes, Kevin P. White, and Peter S. Hammerman
 

Abstract

Purpose: The genetic differences between human papilloma virus (HPV)–positive and –negative head and neck squamous cell carcinomas (HNSCC) remain largely unknown. To identify differential biology and novel therapeutic targets for both entities, we determined mutations and copy-number aberrations in a large cohort of locoregionally advanced HNSCC.

Experimental Design: We performed massively parallel sequencing of 617 cancer-associated genes in 120 matched tumor/normal samples (42.5% HPV-positive). Mutations and copy-number aberrations were determined and results validated with a secondary method.

Results: The overall mutational burden in HPV-negative and HPV-positive HNSCC was similar with an average of 15.2 versus 14.4 somatic exonic mutations in the targeted cancer-associated genes. HPV-negative tumors showed a mutational spectrum concordant with published lung squamous cell carcinoma analyses with enrichment for mutations in TP53, CDKN2A, MLL2, CUL3, NSD1, PIK3CA, and NOTCH genes. HPV-positive tumors showed unique mutations in DDX3X, FGFR2/3 and aberrations in PIK3CA, KRAS, MLL2/3, and NOTCH1 were enriched in HPV-positive tumors. Currently targetable genomic alterations were identified in FGFR1, DDR2, EGFR, FGFR2/3, EPHA2, and PIK3CA. EGFR, CCND1, and FGFR1 amplifications occurred in HPV-negative tumors, whereas 17.6% of HPV-positive tumors harbored mutations in fibroblast growth factor receptor genes (FGFR2/3), including six recurrent FGFR3 S249C mutations. HPV-positive tumors showed a 5.8% incidence of KRAS mutations, and DNA-repair gene aberrations, including 7.8% BRCA1/2 mutations, were identified.

Conclusions: The mutational makeup of HPV-positive and HPV-negative HNSCC differs significantly, including targetable genes. HNSCC harbors multiple therapeutically important genetic aberrations, including frequent aberrations in the FGFR and PI3K pathway genes. Clin Cancer Res; 21(3); 632–41. ©2014 AACR.

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.
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How green tea can kill cancer cells: compound destroys disease while leaving healthy cells unscathed

Wed, Feb 4, 2015

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Source: www.dailymail.co.uk
Author: Lizzie Parry

A compound in green tea has been found to kill mouth cancer cells while leaving healthy cells undamaged. While it was known the drink could help fight the disease, scientists say they have now worked out why. The breakthrough involved identifying the process by which the substance attacks cancer cells. This, it is hoped, will lead to new treatments for oral cancer, as well as other forms of the disease.

A compound found in green tea has been found to kill off oral cancer cells, while leaving healthy cells undamaged. Scientists at Penn State have now identified how the process targets the disease

A compound found in green tea has been found to kill off oral cancer cells, while leaving healthy cells undamaged. Scientists at Penn State have now identified how the process targets the disease

Scientists at Penn State University, in the US, explored the specific mechanism by which the green tea compound is able to target the diseased cells. Earlier studies have shown that epigallocatechin-3-gallate (EGCG), a compound found in green tea, killed mouth cancer cells without harming normal cells. But researchers did not understand the reasons behind the substance’s ability to kill the cancer cells. Scientists now believe EGCG may trigger a process in the mitochondria – the powerhouse of a cell that produces energy – that leads to cell death.

Professor Joshua Lambert, a specialist in food science and co-director of Penn State’s Center for Plant and Mushroom Foods for Health, said: ‘EGCG is doing something to damage the mitochondria.

‘That mitochondrial damage sets up a cycle causing more damage and it spirals out, until the cell undergoes programmed cell death.

‘It looks like EGCG causes the formation of reactive oxygen species in cancer cells, which damages the mitochondria, and the mitochondria responds by making more reactive oxygen species.’

Reactive oxygen species are chemically reactive molecules containing oxygen. They play an important role in cell signalling and homeostatsis – the control of internal conditions including temperature. When reactive oxygen species levels increase dramatically, it can cause significant damage to cell structures – this is known as oxidative stress. As this mitochondrial demise continues, the cancer cell also reduces the expression of antioxidant genes, further lowering its defences.

‘So, it’s turning off its mechanism of protection at the same time that EGCG is causing this oxidative stress,’ Professor Lambert added.

His team discovered the EGCG did not cause the same reaction in normal cells. In fact, the compound appeared to increase the healthy cell’s protective capabilities.

The researchers studied normal human oral cells, alongside human oral cancer cells, to determine how the compound was targeting the cancer cells differently to those healthy tissues. They grew the normal and cancer cells on petri dishes, before exposing them to EGCG – the major polyphenol found in green tea. They used concentrations of the compound typically found in the saliva after a person chews green tea gum. At specific times the scientists collected the cells to check for oxidative stress and signs of antioxidant response.

Professor Lambert, said: ‘We also took a lot of pictures, so we could use fluorescent dyes that measure mitochondrial function and oxidative stress and actually see these things develop.’

His team identified a protein called sirtuin 3 (SIRT3) is critical to the process.

‘It plays an important role in mitochondrial function and in antioxidant response in lots of tissues in the body, so the idea that EGCG might selectively affect the activity of sirtuin 3 in cancer cells – to turn it off – and in normal cells – to turn it on – is probably applicable in multiple kinds of cancers,’ said Professor Lambert.

This study builds on past research into how the compound affects oral cancer, a disease expected to kill more than 8,000 people in the US this year.

‘We’ve published one paper previously just looking at the effect of these green tea polyphenols on oral cancer cells in cultures,’ said Professor Lambert.

‘And there have been other papers published using oral cancer cells and at least a couple of animal model studies that have looked at oral cancer and prevention of oral cancer.’

He said the next step would be to study the mechanism in animals. If those tests and human trials were then successful, the scientists hope to create cancer treatments that are as effective as current ones, but without the harmful side effects.

Professor Lambert added: ‘The problem with a lot of chemotherapy drugs – especially early chemotherapy drugs – is that they really just target rapidly dividing cells, so cancer divides rapidly, but so do cells in your hair follicles and cells in your intestines, so you have a lot of side effects.

‘But you don’t see these sorts of side effects with green tea consumption.’

The study, supported by the American Institute for Cancer Research, was published in the online issue of Molecular Nutrition and Food Research.

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