HPV

Immunotherapy drug a ‘gamechanger’ for head and neck cancer

Source: www.theguardian.com
Author: staff

An immunotherapy drug hailed as a potential gamechanger in the treatment of cancer could soon offer new hope to patients with currently untreatable forms of the disease.

Nivolumab outperformed chemotherapy significantly in keeping relapsed head and neck cancer patients alive. Photograph: Alamy

Nivolumab outperformed chemotherapy significantly in keeping relapsed head and neck cancer patients alive. Photograph: Alamy

Nivolumab was found to extend the lives of relapsed patients diagnosed with head and neck cancers who had run out of therapy options. After a year of treatment, 36% of trial patients treated with the drug were still alive compared with 17% of those given standard chemotherapy.

Trial participants treated with nivolumab typically survived for 7.5 months, and some for longer. Middle-range survival for patients on chemotherapy was 5.1 months. The phase-three study, the last stage in the testing process before a new treatment is licensed, provided the first evidence of a drug improving survival in this group of patients.

Prof Kevin Harrington, from the Institute of Cancer Research, London, who led the British arm of the international trial, said: “Nivolumab could be a real gamechanger for patients with advanced head and neck cancer. This trial found that it can greatly extend life among a group of patients who have no existing treatment options, without worsening quality of life.

“Once it has relapsed or spread, head and neck cancer is extremely difficult to treat. So it’s great news that these results indicate we now have a new treatment that can significantly extend life, and I’m keen to see it enter the clinic as soon as possible.”

Before it can be offered on the NHS, the treatment will have to be approved by the European Medicines Agency and the National Institute for Health and Care Excellence (Nice), which vets new therapies in England and Wales for cost-effectiveness.

Of the 361 patients enrolled in the trial, 240 were given nivolumab while the remaining 121 received one of three different chemotherapies. UK patients were assigned the chemotherapy drug docetaxel, the only treatment currently approved for advanced head and neck cancer by Nice.

Patients whose tumours tested positive for the HPV virus, which is linked to cervical cancer and may be spread by oral sex, did especially well. They typically survived for 9.1 months, compared with 4.4 months when treated with chemotherapy. More than half of patients relapse within three to five years.

Nivolumab is one of a new class of antibody drugs called checkpoint inhibitors that help the immune system fight cancer. It works by blocking signals from tumour cells that stop the immune system attacking.

The drug is already licensed for the treatment of advanced melanoma skin cancer and non-small-cell lung cancer in the UK. However while Nice has backed its use on the NHS for melanoma it has so far refused to recommend making the drug freely available to lung cancer patients.

Prof Paul Workman, chief executive of the Institute of Cancer Research, said: “Nivolumab is one of a new wave of immunotherapies that are beginning to have an impact across cancer treatment. This phase-three clinical trial expands the repertoire of nivolumab even further, showing that it is the first treatment to have significant benefits in relapsed head and neck cancer.

“We hope regulators can work with the manufacturer to avoid delays in getting this drug to patients who have no effective treatment options left to them.”

October, 2016|Oral Cancer News|

Particular HPV strain linked to improved prognosis for throat cancer

Source: medicalxpress.com
Author: provided by University of North Carolina Health Care

When it comes to cancer-causing viruses like human papillomavirus, or HPV, researchers are continuing to find that infection with one strain may be better than another.

In an analysis of survival data for patients with a particular type of head and neck cancer, researchers from the University of North Carolina Lineberger Comprehensive Cancer Center confirmed findings that a particular strain of HPV, a virus linked to a number of cancers, resulted in better overall survival for patients with oropharyngeal cancer than patients with other strains of the virus in their tumors.

They believe their findings, reported in the journal Oral Oncology, are particularly important as physicians move to lessen treatment intensity for patients with HPV-linked oropharyngeal cancer in clinical trials to try to spare them negative side effects of radiation or drugs. They also found that a test used widely to determine patients’ HPV status may not be sensitive enough to select patients for de-intensification.

“What we demonstrate in this study is that the type of HPV can help us to better determine a patient’s prognosis,” said the study’s senior author Jose P. Zevallos, MD, MPH, an associate member of UNC Lineberger and an associate professor in the UNC School of Medicine. “We think this is important because HPV positive patients do so well generally, and there’s been a huge move nationally to take treatment down a couple notches to limit morbidity and side effects. The risk is that if you de-intensify too much, and you happen to have a high-risk tumor because you have a different type of HPV, then this could be harmful to patients who don’t warrant it.”

The UNC study was based on an analysis of survival data for 238 patients in North Carolina diagnosed between January 2002 and February 2006 with oropharyngeal cancer, a type of head and neck cancer in the throat at the back of the mouth, as part of the Carolina Head and Neck Cancer Study, or CHANCE. The Centers for Disease Control and Prevention estimates that more than 15,600 cases of HPV-associated oropharyngeal cancer are diagnosed in the United States each year.

Previous studies have shown that patients with HPV-linked oropharyngeal cancer have higher survival and lower recurrence rates compared to those with HPV-negative oropharyngeal cancer. As those patients tend to respond better to treatment, researchers are studying whether patients with HPV-linked oropharyngeal cancer can receive less intensive treatment with good outcomes. The researchers point out, however, that there has been limited research that tracks outcomes for oropharyngeal cancer based on the particular strain of HPV that patients have.

Zevallos and his colleagues confirmed earlier findings that patients with oropharyngeal cancer tumors infected with HPV16 had improved overall survival. They also determined that patients whose cancer was infected with other HPV strains had similar survival rates as patients whose cancer did not have HPV at all.

They found that 71.4 percent of patients with HPV16-linked oropharyngeal cancer lived at least five years. Meanwhile, the five-year survival-rates for patients with other strains of the virus in their tumors, and for patients who were HPV-negative, were lower: 57 percent for patients with other types of HPV and 50 percent for HPV-negative patients.

Zevallos said the finding of a lower survival rate for patients positive for HPV strains other than HPV16 is important in that it indicates that those patients may not be good candidates for treatment de-intensification.

“The finding that non-HPV16 types are closer to the HPV-negative group in terms of survival differences suggests that those patients should definitely not be considered for anything other than standard aggressive therapy,” he said.

The researchers noted that additional research needs to be done in a larger sample size to rule out the possibility that characteristics other than HPV status are driving survival differences, and to clarify whether the patients found to have other HPV strains were not false-positives.

The also cautioned that based on their findings, a commonly used clinical test that measures for the presence of the p16 protein may not be specific enough to identify HPV-linked oropharyngeal cancer patients who are good candidates for treatment de-intensification. To determine whether patients had HPV-positive tumors, they compared the results of the p16 test with results of a more specific genetic test.

They found that 4.3 percent of the patients were positive for p16, but negative for HPV according to the genetic test. Another approximately 11 percent of p16-positive cases had HPV strains other than HPV16, according to the genetic tests. Zevallos said this is an important finding because patients whose cancer was not infected with HPV16 had a lower 5-year survival rate, meaning they would not be good candidates for treatment de-escalation.

Yet the researchers report that many of the clinical trials that de-intensify treatment use p16 expression alone to determine if a patient’s cancer is HPV-positive, and whether they should be considered for treatment de-intensification.

“Even though we rely almost exclusively around the country on p16 positivity as a surrogate for HPV16 presence, this sheds some light on the fact that maybe we should be considering HPV genotyping because of the survival differences we saw here,” Zevallos said.

September, 2016|Oral Cancer News|

Men with throat cancer will soon outnumber women with cervical cancer In The US

Source: www.houstonpublicmedia.org
Author: Carrie Feibel

The national increase in cases of oropharyngeal cancer related to the human papilloma virus is troubling, because there is no screening test to catch it early, like the Pap test for cervical cancer.

The oropharynx is the area of the throat behind the mouth, and includes the tonsils and the base of the tongue. Oropharyngeal cancer is increasing in both men and women, but for reasons that aren’t well understood, male patients are outnumbering female patients by five to one, according to Dr. Erich Sturgis, a head and neck surgeon at MD Anderson Cancer Center.

“It’s usually a man, and he notices it when he’s shaving. He notices a lump there,” Sturgis said. “That lump is actually the spread of the cancer from the tonsil or the base of the tongue to a lymph node. That means it’s already stage three at least.”

In the U.S., the number of oropharyngeal cancers caused by HPV are predicted to exceed the number of cervical cancers by 2020, Stugis said.

“With cervical cancer, we’ve seen declining numbers well before we had vaccination, and that’s due to the Pap smear being introduced back in the late 50s,” he said. “But we don’t have a screening mechanism for pharynx cancer.”

Research on an effective screening test for early-stage pharynx cancer is still underway. The reasons for the disproportionate effect on men are unknown. One theory is that people are engaging in more oral sex, but that doesn’t explain why men are more affected than women. Some suspect hormonal differences between men and women may be involved, and others hypothesize that it takes longer for women to “clear” the viral infection from their genitals, compared to men, according to Sturgis.

One of Sturgis’s patients, Bert Noojin, is an attorney in Alabama. He felt a little knot in his neck in early 2011. It took three trips to his primary care doctor, then a visit with an otolaryngologist before he was referred for a biopsy. Noojin was diagnosed with oropharyngeal cancer, but he still felt fine.

“It was still hard for me to believe I was sick in any way,” he recalled. “I didn’t even have a serious sore throat.”

After being diagnosed, Noojin came to MD Anderson Cancer Center in Houston for a second opinion and to pursue treatment. It was less than three months from when he first felt the knot, but an oncologist warned him the cancer was spreading fast.
“He said ‘Well, you need to start treatment right away’ and I said, ‘Well, do I have a week or 10 days to go home and get some things in order?’ and he said ‘No.’”

“He said ‘If you leave here, and you’re not part of our treatment plan when you leave here, I don’t think we’ll be able to help you.’ That is how far this disease had progressed, in such a very short time.”

The prognosis for HPV-related oropharyngeal cancer is good, especially compared to patients whose throat cancer is caused by heavy use of tobacco or alcohol, according to Sturgis. Between 75 and 80 percent of patients with the HPV-related type survive more than five years.

But the treatment is difficult, and can include “long-term swallowing problems, long-term problems with carotid artery narrowing, and long-term troubles with the teeth and jaw bone, and things that can cause a need for major surgeries later.”

In the summer of 2011, Noojin began chemotherapy and radiation at MD Anderson. He struggled with pain, nausea, and swallowing, and had to get a temporary feeding tube.

“Your throat just shuts down,” he said. “You’re burned on the inside. Just swallowing your own saliva, as an instinct, hurts.”

Noojin lost 45 pounds during treatment but feels lucky to have survived. He went back to his law practice in Alabama.

Noojin learned that cancers related to HPV, which is sexually transmitted, are cloaked in shame and guilt.

He experienced this first-hand when his marriage fell apart during his recovery. His wife was traumatized by the difficult months of treatment, he said. In addition, she irrationally blamed herself for giving him the virus, even though he was probably exposed many years earlier. He tried to comfort her and dispel her guilt, but they eventually divorced.

“I was married over two decades, but I was married previously, and she was married previously,” he said. “It just makes no sense for any of this to have a stigma.”

An estimated 80 percent of America women and 90 percent of men contract HPV at some point in their lives, usually when they’re young and first become sexually active. But the cancers caused by HPV can take years to develop.

“It’s a virus. It’s not anybody’s fault,” Noojin said.

He echoed the public health experts in calling for an end to the silence and shame, and a shift to a focus on prevention.

“All of what I went through, and all of what hundreds of thousands of men, and women, because of cervical cancer – what they have gone through is avoidable for the next many generations … if we just got serious about making sure our kids get vaccinated.”

The series of three shots can be given as early as age nine, but must be completed before the age of 26 to be effective. Currently, the completion rate for young women in the U.S. is less than 50 percent. Among young men, it’s less than 30 percent. That’s why experts warn these particular cancers will still be a problem decades from now.

September, 2016|Oral Cancer News|

Cancer-Preventing Vaccines Given To Less Than Half Of US Kids

Source: www.houstonpublicmedia.org
Author: Carrie Feibel

U.S. regulators approved a vaccine to protect against the human papilloma virus (HPV) in 2006, but cancer experts say misconceptions and stigma continue to hamper acceptance by both doctors and parents.

Eighty percent of Americans are exposed to the human papilloma virus in their lifetimes. Some strains of HPV can cause genital warts, but most people experience no symptoms and clear the virus from their systems within a year or two. But for an unlucky minority, the virus causes damage that, years later, leads to cervical cancer, throat cancer, and other types.

Researchers at MD Anderson are frustrated that ten years after the first vaccine arrived on the market, only 42 percent of U.S. girls, and 28 percent of boys, are getting the three-shot series.

The series can be given to girls and boys between the ages of 9 and 26, but the immune response is strongest at younger ages, before sexual activity begins.

n 2007, then-Texas governor Rick Perry proposed making the HPV vaccine mandatory for all preteen girls.  At the time, the vaccine was only approved and marketed for girls.

Dr. Lois Ramondetta, a cervical cancer specialist at MD Anderson, remembers the outcry.

“A lot of people felt that was the right idea, but the wrong way to go about it. Nobody really likes being told what to do, especially in Texas,” Ramondetta said. “I think there was a lot of backlash.”

Eventually, the legislature rejected Perry’s plan, even though it included an opt-out provision. Ramondetta said too many politicians focused on the fact that HPV is sexually transmitted. That had the unfortunate effect of skewing the conversation away from health care and into debates about morality and sexuality. She said the best and most accurate way to discuss the vaccine is to describe it as something that can prevent illness and death.

“I try to remove the whole concept of sexuality,” Ramondetta said. “When you’re talking about an infection that infects 80 percent of people, you’re really talking about something that is part of the human condition. Kind of like, it’s important to wash your hands because staph and strep are on all of us.”

Today, only Virginia, Rhode Island and Washington, D.C. mandate HPV vaccines.

“Our vaccination rates are really terrible right now,” Ramondetta said.

In Texas, only 41 percent of girls get all three of the required shots, and only 24 percent of boys.

hpv-kara-million-1200x788

Kara Million of League City finds those numbers upsetting.  Million survived two rounds of treatment for cervical cancer.

“Even if you had a chance that your kid could have any kind of cancer, and you could have given them two shots or three shots for it? To me, it’s a no-brainer,” Million said.

Million always got regular Pap tests. But she missed one appointment during a busy time following the birth of her second child. When she went back, it had been only 15 months since her last Pap test. But the doctor found cervical cancer, and it had already progressed to stage 3.

“That was a huge surprise,” Million recalled.

Million had chemotherapy and radiation at MD Anderson. But a year later the cancer returned.

The next step was surgery, a radical procedure called a total pelvic exenteration.

Million and her husband looked it up online.

“When I was reading it, I was just, like, ‘this is so barbaric, there is no way they are still doing this in this day and age,’” Million said. “‘For certain, in 2010 we have better surgeries to do than this.’”

But there weren’t better surgeries. This was her only option.

“I had a total hysterectomy; they pulled all the reproductive system out,” she explained. “They take your bladder out, they take part of your rectum, they take part of your colon, they take your vagina, all of that in your pelvic area comes out.”

The surgery took 13 hours, and left her with a permanent colostomy bag and urostomy bag.

“At that point, with two kids at that age – I think they were one-and-a-half and three – there’s no option. I’m a mom, so I’m going to do whatever it takes so they can have their mom.”

Most women survive cervical cancer if it’s caught early enough. But Million’s cancer was diagnosed at a later stage, where only a third of women make it past five years. She has already made it past that five-year anniversary, and she’s not wasting any time.

She now volunteers as a peer counselor at MD Anderson to other cervical cancer patients, and she urges parents to vaccinate their kids.

“If most of cervical cancer is caused by HPV, and now we have something that can help prevent what I went through, and what my friends went through, and the friends that I lost?” Million says, “I don’t understand why people don’t line up at the door to get their kids vaccinated for it.”

But Dr. Ramondetta said parents can’t consent to the vaccination if pediatricians or family doctors don’t offer it. And they’re not offering it nearly enough, she said.

Some doctors don’t know how to broach the topic, fearing it will lead to a difficult conversation about sexual behavior. Some mistakenly think boys don’t need it, although they do – not only to protect their partners from HPV, but to protect themselves against oropharyngeal and anal cancers, which are also caused by HPV.  Ramondetta added that some doctors incorrectly assume that giving the vaccine will promote promiscuity.

Ramondetta says extensive research actually shows it doesn’t.

“There should be this understanding of an ethical responsibility. That this is part of cancer screening and prevention, just like recommending mammograms and colonoscopies.”

In Texas, only 41 percent of girls get all three of the required shots, and only 24 percent of boys.

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

September, 2016|Oral Cancer News|

HPV symptoms and health consequences

Source: www.kristv.com
Author: Roland Rodriguez

No one dreams of walking into his or her doctor’s office and hearing the words “you have been diagnosed with human papillomavirus, or HPV.” Unfortunately, this scenario is all too real.

HPV is the most common sexually-transmitted infection (STI) in the United States. In fact, it’s so common that nearly all sexually active men and women get it at some point in their lives.

There are over 100 different kinds of HPV but only some of them can cause serious health problems like genital warts or cancer of the cervix, vagina, vulva or anus.

Testing positive for HPV does not automatically mean you will get cancer. Some studies estimate that 50 percent of those infected with HPV will clear the virus within eight months— and 90 percent will be cured within two years. It’s only when your immune system isn’t able to fight off the infection that some strains of HPV can persist and possibly lead to cancer.

The number of human papilloma virus (HPV)-associated cancers in the United States has increased by 17 percent, to nearly 39,000 cases a year, according to a report released from the Centers for Disease Control and Prevention.

While men cannot get HPV-linked cervical cancers, they are particularly vulnerable to HPV-related cancers of the mouth, tongue and throat, called oropharyngeal cancers. According to the new CDC report, the rates of mouth and throat cancers are more than four times higher among males than females.

In the past, people always felt that the boys needed to be vaccinated to protect the girls but, truthfully, the most effective way to prevent HPV: early vaccination.

Boys and girls are supposed to get three doses of the HPV vaccine — starting at age 11 or 12 because the vaccine works best before sexual activity begins.

The other benefit of giving it early is that our immune response is better, and that it may last longer.

Yet the latest statistic from the CDC shows that in 2014, only 40 percent of teenage girls received all three doses of the vaccine needed. In boys, that number is even lower: Only 22 percent of boys between 13 and 17 are properly vaccinated against HPV, increasing their chances for HPV-caused cancers later in life.

According to the CDC, the HPV vaccine — which is usually covered by insurance — is safe and not associated with serious side-effects of the HPV.

What are the signs, symptoms and health consequences of HPV?

In most cases, HPV goes away on its own and does not cause any health problems. But when HPV does not go away, it can cause health problems like genital warts and cancer.

Genital warts usually appear as a small bump or groups of bumps in the genital area. They can be small or large, raised or flat, or shaped like a cauliflower. A healthcare provider can usually diagnose warts by looking at the genital area.

Cervical cancer usually does not have symptoms until it is quite advanced, very serious and hard to treat. For this reason, it is important for women to get regular screening for cervical cancer. Screening tests can find early signs of disease so that problems can be treated early, before they ever turn into cancer.

Other HPV-related cancers might not have signs or symptoms until they are advanced and hard to treat. These include cancers of the vulva, vagina, penis, anus, and oropharynx (cancers of the back of the throat, including the base of the tongue and tonsils.

September, 2016|Oral Cancer News|

Incisionless robotic surgery offers promising outcomes for oropharyngeal cancer patients

Source: medicalxpress.com
Author: press release, Henry Ford Health System

A new study from researchers at Henry Ford Hospital finds an incisionless robotic surgery – done alone or in conjunction with chemotherapy or radiation – may offer oropharyngeal cancer patients good outcomes and survival, without significant pain and disfigurement.

Patients with cancers of the base of tongue, tonsils, soft palate and pharynx who underwent TransOral Robotic Surgery, or TORS, as the first line of treatment experienced an average three-year survival from time of diagnosis.

Most notably, the study’s preliminary results reveal oropharyngeal cancer patients who are p16 negative – a marker for the human papilloma virus, or HPV, that affects how well cancer will respond to treatment – have good outcomes with TORS in combination with radiation and/or chemotherapy.

“For non-surgical patients, several studies have shown that p16 positive throat cancers, or HPV- related throat cancers, have better survival and less recurrence than p16 negative throat cancers,” says study lead author Tamer Ghanem, M.D., Ph.D., director of Head and Neck Oncology and Reconstructive Surgery Division in the Department of Otolaryngology-Head & Neck Surgery at Henry Ford Hospital.

“Within our study, patients treated with robotic surgery had excellent results and survival, irrespective of their p16 status.”

Study results will be presented Sunday, Sept. 18 at the 2016 American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) annual meeting in San Diego.

Led by Dr. Ghanem, Henry Ford Hospital in Detroit was among the first in the country to perform TORS using the da Vinci Surgical System. TORS offers patients an option to remove certain head and neck cancer tumors without visible scarring, while preserving speech and the ability to eat.

With TORS, surgeons can access tumors through the mouth using the slender operating arms of the da Vinci, thus not requiring an open skin incision.

Unlike traditional surgical approaches to head and neck cancer that require a large incision and long recovery, TORS patients are able to return to their normal lives only a few days after surgery without significant pain and disfigurement.

For the study, Dr. Ghanem and his colleagues wanted to take a closer look at the effectiveness of TORS for oropharyngeal cancer patients. They reviewed overall three-year survival, cancer control and metastasis, as well as the effect of p16 status on these variables.

The study included 53 Henry Ford oropharyngeal cancer patients who had TORS. Among them, 83 percent were male, 77 percent were Caucasian, and the mean age was 60.8 years. Thirty-seven percent had TORS alone, while more than 11 percent had TORS with radiation therapy, and more than half received chemotherapy and radiation therapy.

Thirty-seven percent had TORS alone, 11.4 percent received radiation therapy, and 50 percent received chemotherapy and radiation therapy. Eighty-one percent of patients had p16+ disease.

The study shows patients with a p16 negative marker had high survival (100 percent) and low cancer recurrence when TORS was the first line of treatment, as well as when TORS was followed by chemotherapy or radiation therapy.

The majority of patients (63 percent) were able to receive a lower dose of radiation after TORS, which reduces the risk of radiation side effects.

While Dr. Ghanem notes the study’s results are not enough to change clinical practice, it does demonstrate that TORS alone or in conjunction with adjuvant radiation or chemotherapy is an acceptable treatment option for oropharyngeal cancer patients regardless of p16 status.

September, 2016|Oral Cancer News|

Why men need to start caring about HPV

Source: www.refinery29.com
Author: Sarah Jacoby

The human papillomavirus (HPV) is one of very few STIs that we have a vaccine for. And — bonus! — that vaccine prevents cancer. But a report from the U.S. Centers for Disease Control and Prevention (CDC) released last month indicated that although we’ve made some improvements in the vaccination rates, they still aren’t where we want them — especially for boys. This is despite the fact that pretty much everyone who’s sexually active will get the virus at some point and men are at risk for their own unique set of HPV-related health consequences.

Let’s start with the basics: “HPV is a virus that’s sexually transmitted, but it’s incredibly common,” explains Kathleen Schmeler, MD, of the University of Texas MD Anderson Cancer Center. Up to 80% of people get it at some point in their lives, she says, which is why some doctors refer to it as the “common cold” of STIs. For most people, the virus goes away on its own, without causing symptoms or needing treatment. Some people develop genital warts that can be treated with medication. But in some rare instances, the virus can go on to cause more serious health issues — including some types of cancer.

“The problem is we don’t know who’s going to clear it and who won’t,” Dr. Schmeler says. Most notably, HPV is known to cause cervical cancer. In fact, nearly all cases of cervical cancer are attributed to HPV. In 2013, the most recent year with available data, almost 12,000 women were diagnosed with cervical cancer in the U.S. and about 4,200 women died from the disease.

In addition to the risks of passing on the virus to their partners, men may face other consequences of HPV. Some types of HPV-related cancer, including throat cancer, are actually more common among men than women. “The rates for that are increasing significantly,” says Dr. Schmeler. “That’s been a huge deal recently.”

However, there is currently no accepted test for HPV-related cancers in men. Women are recommended to get a routine Pap screening, which can detect abnormal cervical cells that may be a result of an HPV infection. But similar screening for anal, penile, and throat cancers in men isn’t recommended.

“The common story that we hear is that [men are] shaving and they find a big lump in their neck,” says Dr. Schmeler. “But by then, it’s advanced disease because it’s spread to the lymph nodes.”

So although Dr. Schmeler’s team is working to find one, there’s no early or precancerous-stage test to detect HPV-related cancer in men.

Because they can’t be tested, it’s that much more important for boys to get the vaccine. Currently, the vaccine is recommended for boys and girls ages 11 to 12 to make sure they get it before they come in contact with the virus. But according to that August report, only about 50% of boys and 63% of girls actually got the vaccine in 2015. While the rates are improving quickly, they’re still nowhere near where they should be.

So why is it that the already-low vaccination rate is even lower for boys than girls? Part of that appears to be due to the way the vaccine was originally marketed: “When it first came out [in 2006], it was recommended only for girls because the primary focus was cervical cancer,” explains Dr. Schmeler. Since then, the CDC has expanded its recommendations to include boys, too. Parents may simply be unaware of the update.

According to research from the CDC, another big problem is that parents don’t believe their kids are (or are about to be) sexually active at that age. Doctors may be reluctant to push the issue or, in some cases, even bring it up.

“Everyone’s so obsessed with the fact that it’s a sexually transmitted disease,” says Dr. Schmeler. “[And in the process, we’re] forgetting that, with this vaccine, we can prevent cancer.”

It may be too late for adult men to get the most out of vaccination — it’s recommended that everyone get the vaccine by age 26. But for it to be it’s most effective, you should ideally get the vaccine before you’re exposed to the virus. And if you’ve already had multiple sexual partners, it’s likely that you’ve already been exposed.

But that doesn’t mean men don’t have to worry about this. In addition to the risk of spreading the virus to their partners, men are at risk for various cancers, as well. The bottom line is that HPV affects everyone, so we should all be equally sharing the burden of stopping the virus — and its associated cancers.

September, 2016|Oral Cancer News|

Expert says Nivolumab Poised to Change Standard of Care in SCCHN

Source: www.onclive.com
Author: Laura Panjwani

Robert-Ferris

Nivolumab (Opdivo) is a game-changing agent for the treatment of patients with squamous cell carcinoma of the head and neck (SCCHN), according to Robert L. Ferris, MD, PhD.

“Recent findings have shown us that this agent is really the new standard-of-care option for all platinum-refractory patients with head and neck cancer,” says Ferris, vice chair for Clinical Operations, associate director for Translational Research, and co-leader of the Cancer Immunology Program at the University of Pittsburgh Cancer Institute. “This is regardless of whether patients are PD-L1–positive or negative or whether they are HPV-positive or negative.”

The PD-L1 inhibitor received a priority review designation by the FDA in July 2016 based on the CheckMate-141 study, which demonstrated a median overall survival (OS) with nivolumab of 7.5 months compared with 5.1 months with investigator’s choice of therapy (HR, 0.70; 95% CI, 0.51-0.96; P = .0101) in patients with recurrent or metastatic SCCHN.

The objective response rate (ORR) was 13.3% with nivolumab and 5.8% for investigator’s choice. The FDA is scheduled to make a decision on the application for the PD-1 inhibitor by November 11, 2016, as part of the Prescription Drug User Fee Act.

Ferris was the lead author on an analysis that further evaluated preliminary data from CheckMate-141, which was presented at the 2016 ASCO Annual Meeting. In an interview with OncLive, he discusses the findings of this study, potential biomarkers for nivolumab, and questions that remain regarding the use of the immunotherapy in SCCHN.

OncLive: What were the updated findings from CheckMate-141 presented at ASCO?

Ferris: The data that were presented at the 2016 ASCO Annual Meeting were further evaluations and follow-up on some preliminary data—originally presented at the 2016 AACR Annual Meeting—that listed the OS results.

At ASCO, we recapped the primary endpoint of OS as an important endpoint for immunotherapies because response rate and progression-free survival may not be as accurate. Ultimately, the FDA and people at large want OS. In this study, OS was 36% at 1 year in the nivolumab-treated arm and 16.6% in the comparator arm, which was investigator’s choice of single-agent chemotherapy, consisting of methotrexate, docetaxel, or cetuximab. In this phase III randomized trial, nivolumab was given in a 2:1 randomization: 240 patients received nivolumab and 120 received investigator’s choice.

Also at ASCO, we presented further evaluations consisting of what the regimens are in the comparator arm. There was about 20% each of docetaxel and methotrexate and 12% of cetuximab. Approximately 60% of the patients had prior cetuximab exposure and we stratified by cetuximab as a prior therapy. We also demonstrated the ORR, which was 13.3% in the nivolumab-treated arm versus 5.8% in the investigator’s choice arm.

Therefore, there was an improvement in overall response, but the difference seemed more modest than the OS benefit—which was a doubling—with 20% more patients alive at 1 year. This reinforces the concept that perhaps response rate may not be the best endpoint. Progression-free survival (PFS) was double at 6 months, with about 20% in the nivolumab arm versus about 9.9% in the investigator’s choice arm. The median PFS was not different, but the 6-month PFS was twice as high. The time to response was about 2 months in each arm at the first assessment.

Your analysis also looked at biomarkers. Can you discuss these findings and their significance?

The p16 or HPV-positive group had a better hazard ratio for OS than the overall study population. The hazard ratio was .73 for the overall population, using a preplanned interim analysis. With the HPV-positive group, we had a hazard ratio of .55 and the HPV-negative group had a hazard ratio of .99. It is still favoring the nivolumab-treated patients but, with the curves separated earlier in the HPV-positive group, one could see the improvement with nivolumab at about 1 to 2 months. It took 7 or 8 months with the HPV-negative group to show a separation of the curves in favor of nivolumab.

We looked at PD-L1 levels, and PD-L1—using a 1% or above level—had an improvement in the PD-L1–positive patients in favor of nivolumab in terms of OS and ORR. When we looked at 5% and 10% thresholds of PD-L1, the OS did not seem to improve. Therefore, in all levels above 1%, the OS was similarly beneficial over the PD-L1 less-than-1% group. However, essentially all levels of PD-L1–positivity and PD-L1–negativity still favored nivolumab, but the benefit was more when its levels were greater than 1%.

We could combine HPV status with PD-L1 status and look at subsets; however, essentially every subset benefited, whether it was PD-L1–negative or positive. This indicates that, in this group of patients, who progress within 6 months of platinum-based therapy, that no current systemic therapeutic options benefit patients as well as nivolumab.

With regard to these findings, what are you most excited about?

Head and neck cancer is a difficult disease. Until recently, we didn’t know the impact of this enrichment for HPV-positive virus-induced subsets and we didn’t know if this was an immune responsive cancer. Clearly, it is. We have all of the hallmarks that we have seen for a bright future—based on the melanoma data—and a series of other cancers indicating response rates in the 15% to 20% range, suggesting that we now have a platform of the PD-1 pathway to combine with other checkpoints and to integrate earlier in disease with radiation and chemotherapy.

We have a demonstration of head and neck cancer as an immune-responsive cancer. We are beginning to get an idea of the biomarkers and starting to be able to segment patients who will benefit. Now, we have a large comparative trial with an OS endpoint and tissue to look at biomarkers to try and understand what the best future combinations will be.

What are some questions that you still hope to answer regarding nivolumab in head and neck cancer?

We have to get down deeper into the nonresponders. We should acknowledge that the majority of patients neither had a response nor benefited. Understanding who is more likely to benefit is useful, but we also need to understand the levels of alternative checkpoint receptors or other biomarkers of resistance.

We have sequential lymphocyte specimens from the peripheral blood, tissues, and serum so those are intensively under evaluation. There are interferon gamma signatures that have risen from the melanoma checkpoint field that will certainty be applied, as well.

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

August, 2016|Oral Cancer News|

Despite medical backing, HPV vaccine rates remain low amid sexual and moral controversy

Source: www.omaha.com
Author: Rick Ruggles, World-Herald staff writer

pharynx_cancer

The HPV vaccine can reduce the rates of certain cancers, including many cervical and oral cancers, physicians and medical organizations say. But opposition by some individuals is strong, and HPV vaccination rates remain low when compared with other kinds of vaccinations recommended for adolescents.

Because the human papillomavirus is sexually transmitted and seventh grade is considered the ideal time to receive the three-dose vaccine regimen, the issue is rife with sexual and moral implications. Perhaps more potent today, though, are Internet horror stories and concerns about side effects.

A World-Herald Facebook request for views on the HPV vaccine generated far more negatives than positives. “NO NO & NO!! There is NO reason for this vaccine,” one wrote. Another called it a “deadly shot.”

Two Omaha mothers who were interviewed expressed their belief that it’s wise to have children vaccinated, and said their kids suffered no side effects. But an Iowa man described health problems suffered by his daughter, and he and an Ohio physician believe the girl was injured by the HPV vaccinations.

So mediocre are HPV vaccination rates that GSK, the maker of Cervarix, plans to cease distribution of its HPV vaccine in the United States in September. It will continue to supply it in many other nations, such as Great Britain, Germany, France and Mexico. The departure of Cervarix leaves the market to Gardasil, a vaccine produced by Merck.

“GSK has made the decision to stop supplying Cervarix … in the U.S. due to very low market demand,” the company told The World-Herald last week by email.

Many doctors in the Omaha area express disappointment with the low HPV vaccination rates but are optimistic that the situation will improve.

“As pediatricians, we’re trying to change that,” said Dr. Katrena Lacey, a Methodist Physicians Clinic pediatrician in Gretna. “I think we’re on the right track.”

A survey of adolescents reported last year by the federal Centers for Disease Control and Prevention found that 39.7 percent of girls ages 13 to 17 had received the three-dose regimen of the HPV vaccine in 2014, and 21.6 percent of boys.

This compares with 87.6 percent of boys and girls who had received the tetanus-diphtheria-pertussis vaccination and 79.3 percent who had received the meningococcal vaccine.

Dr. Megann Sauer, a pediatrician with Boys Town Pediatrics, said parents accept use of the vaccine if it’s explained well and described as a cancer-prevention strategy. “It’s a huge responsibility for us as providers to offer this to our patients,” Sauer said. “My job is to keep my patients healthy.”

Gardasil was approved in the United States 10 years ago. It was met with concern that having a child vaccinated for HPV, which is the most common sexually transmitted infection, would promote promiscuity.

Today, the global Christian ministry Focus on the Family says it “supports universal availability of HPV vaccines,” but it opposes government-mandated HPV vaccinations for public-school enrollment. The mandates are in place in Virginia, Rhode Island and Washington, D.C.

Tom Venzor of the Nebraska Catholic Conference said the vaccine itself isn’t morally problematic. But “the promotion of chastity and parental consent should never be undermined in the promotion of the HPV vaccine,” Venzor said in an email.

The Kaiser Family Foundation estimates that there are more than 14 million new human papillomavirus infections annually in the U.S. Most resolve on their own, but some chronic HPV infections can embed in tissues and lead to cervical cancers and tongue, tonsil, anal, vulvar, vaginal and penile cancers.

The American Cancer Society estimated there will be close to 13,000 new cases of cervical cancer this year and 4,120 deaths. HPV was detected in more than 90 percent of cervical cancers, a 2015 study reported in the Journal of the National Cancer Institute said.

“If you’ve ever seen anyone die of cervical cancer, it will tear you apart, because it’s a nasty, nasty disease,” said Dr. Steve Remmenga, a specialist in gynecologic oncology at the University of Nebraska Medical Center. Remmenga advocates getting the vaccination.

The CDC recommends routine HPV vaccinations beginning at 11 or 12 years of age for girls and boys, but the series can start as early as 9 years of age. The second dose should be given a month or two later and the third at least six months after the first. The vaccinations may be completed by 26 years of age. The recommendations have been adopted by the American Cancer Society and other medical organizations.

The recommendations suggest children receive the vaccinations “so they are protected before ever being exposed to the virus,” the CDC said. The agency said clinical trials indicate the vaccination provides “limited or no protection” against HPV-related diseases for women older than 26.

The CDC says the vaccine has repeatedly been shown to be safe.

Kari Nelson, a biology instructor at the University of Nebraska at Omaha, said two of her daughters, Claire and Emma, have had the full regimen and her third daughter, Gretchen, is about to get her second shot.

“I definitely believe in protecting my kids as much as possible,” Nelson said. “I do always try to weigh the pros and cons of anything. I just feel that the pros far outweigh the cons in this case.”

The Nelsons’ pediatrician, Dr. Tina Scott-Mordhorst, supports children and adolescents receiving the HPV vaccine. Why, she asked, would anyone not get a shot that might prevent cancer? “It works,” said Scott-Mordhorst, a clinical professor in UNMC’s department of pediatrics.

A study reported this year in the journal Pediatrics found that among sexually active females ages 14 to 24, the prevalence of four key HPV types was 16.9 percent among the unvaccinated and 2.1 percent among the vaccinated.

Scientists say it can take many years for chronic HPV to turn cancerous.

Dr. Bill Lydiatt, a head and neck cancer surgeon at Methodist Hospital, said oral sex and the sexual revolution of the late 1960s have contributed to an increase in cancers of the pharynx, or tonsil and back of tongue. The cancer society reported there will be 16,420 cases of cancer of the pharynx this year, most of them in men, compared with 8,950 in 2006. More than 3,000 will die this year from that kind of cancer, the society says.

Lydiatt said scientists only about 10 years ago made the clear link between HPV and cancers of the pharynx and tonsils.

There are more than 150 strains of HPV and more than 40 that can cause cancer, the Kaiser Family Foundation reported. The first form of Gardasil protected against four strains, including the two believed to be most prevalent in cancers. Two years ago the FDA approved a Gardasil vaccine that protected against nine strains. The study in the Journal of the National Cancer Institute says that “current vaccines will reduce most HPV-associated cancers.”

The vaccines are expensive. The Gardasil nine-strain vaccine is close to $250 per dose at Kohll’s Pharmacy if a family pays out of pocket. But many insurers, such as Blue Cross Blue Shield of Nebraska, Aetna/Coventry and UnitedHealthcare, participate in the payment.

A Merck spokeswoman said GSK’s decision to cease supplying Cervarix to the U.S. market hasn’t affected Gardasil prices as of now. An Omaha pharmacist said it wouldn’t be unusual to see prices go up with the departure of a competitor. “The reality is that they can,” Mohamed Jalloh said. “I’m not saying they’re going to.”

Merck has applied to the Food and Drug Administration to market a two-dose regimen of Gardasil, which would reduce the overall price of the series.

Facebook posts and the Internet contain scathing reviews of Gardasil, including stories of children being hurt and families being scared of the vaccination.

Laura Hansen, a cancer researcher at Creighton University, said she wishes she could find the words to persuade people to get their kids vaccinated.

“About all of us have family members impacted by cancer,” said Hansen, a professor of biomedical sciences. By having their kids vaccinated, she said, “Every parent could make an impact on cancer deaths.”

She said it’s hard to fight Internet scare stories and “anecdotal science” as opposed to real science and legitimate studies. The discussion should be “more about facts and less about hysteria,” said Hansen, who saw to it that her two teen-age sons, Charlie and Jack, were vaccinated.

Jeff Weggen of Muscatine, Iowa, has an entirely different view. Weggen said his daughter, Sydney, had the vaccines about four years ago. Soon after, she began to lose weight, suffered back pain and became pale. Over a period of months she was hospitalized and saw specialists in state and out-of-state. She was eventually found to have a fungal infection and a large tissue mass in her chest.

Weggen eventually linked Sydney’s ongoing medical problems to Gardasil, he said. Online groups, other parents and the timeline of her vaccines and her illness helped lead him to this opinion, he said. An anti-Gardasil Facebook post introduced him to a doctor in Ohio who early this year generally confirmed Weggen’s suspicions.

Dr. Phillip DeMio of the Cleveland area said he has several patients he believes were sickened by Gardasil. DeMio, a general practitioner who said his practice focuses on chronically ill people, said some of his patients have been injured by other vaccines, too.

“These are challenging situations, no two ways about it,” he said. Most people have received a variety of vaccinations, he said, and he believes the aluminum in Gardasil and other vaccines can be a problem for some people.

He saw Sydney early this year. Based on the extensive testing that ruled out other diseases, the severity of her illness, the timing of vaccination and other factors, he said he believes “there’s a component of vaccine damage for her and for many of my patients.”

He said there are good reasons to have an adolescent receive Gardasil and mentioned the likelihood that some individuals will be sexually active. But it makes no sense to have a 9-year-old get it, he said. He said parents should be well-informed of the risks and benefits of Gardasil and other vaccines.

“I think people should have a choice,” he said. “I’m not saying I’m against the vaccine.”

The CDC sent a written statement saying that millions of doses of Gardasil have been administered.

Scientific studies have detected no link to “unusual or unexpected adverse reactions,” the CDC said.

Side effects can include pain from the shot and occasionally a patient might faint after any injectable vaccine, the CDC said. But “the benefits of vaccination far outweigh any risks.”

Rate of HPV-associated cancers on the rise in U.S., according to new CDC report

Source: www.curetoday.com
Author: Andrew J. Roth

Though the first preventive human papilloma virus (HPV) vaccine was approved by the U.S. Food and Drug Administration 10 years ago, the incidence of HPV-associated cancers is on the rise.

From 2008 to 2012, the number of HPV-associated cancers diagnosed per year increased by approximately 16 percent compared with the previous five-year period, according to a new report by the Centers for Disease Control and Prevention (CDC).

Nearly all sexually active individuals in the U.S. will get at least one type of HPV in their lifetime, making it the most common sexually-transmitted infection in the country. And though about 90 percent of HPV infections will clear a person’s system within two years, some infections persist and can cause cervical cancers and some types of vulvar, oropharyngeal, penile, rectal and cancers.

There are over 40 HPV types, and vaccines are available for HPV types 16 and 18 (which account for 63 percent of HPV-associated cancers), as well as for types 31, 33, 45, 52 and 58 (which account for an additional 10 percent). Type 16 is the most likely to persist and develop into cancer.

In this new report, the CDC analyzed data from its own National Program of Cancer Registries as well as the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) database. In total, 38,793 HPV-associated cancers (11.7 per 100,000 persons), on average, were diagnosed annually from 2008 to 2012 compared with 33,369 diagnoses (10.8 per 100,000 persons) from 2004 to 2008. Researchers then multiplied the number of cancers that could have been associated with HPV by the rate actually believed to be attributable to HPV, and found that an estimated 30,700 (79 percent) of the cancers could have been attributed to the virus.

The report highlights numerous challenges to controlling HPV-related cancers. First, not enough adolescents are receiving all three HPV vaccines. The CDC recommends that all males and females should start the HPV vaccine series at the age of 11 or 12 years. The CDC also notes that males can receive the series through age 21 and females can receive it through age 26.

According to this CDC report, though, in 2014, just 60 percent of females aged 13 to 17 received at least one dose, 50.3 percent received at least two doses and 39.7 percent received three doses. Among males, the rates were worse: 41.7 percent received at least one dose, 31.4 percent received at least two doses and 21.6 percent received three doses.

Additionally, differences exist between races. In the 2008 to 2012 study, rates of cervical cancer were higher among blacks compared with whites and higher among Hispanics compared with non-Hispanics. Rates of both vulvar and oropharyngeal cancers were lower, however, among blacks and Hispanics versus whites and non-Hispanics, respectively. Rates of anal cancer were lower among black women and Hispanics, but higher among black men, compared with their counterparts.

HPV-associated cancer rates also differed based on geographic location: Utah had the lowest rate (7.5 per 100,000 persons) while Kentucky had the highest rate (14.7 per 100,000). The study’s authors noted that most states with rates higher than the overall U.S. rate (11.7 per 100,000) were located in the South.

Study authors pointed out that most cervical cancers can be prevented by regularly screening women aged 21 to 65 for precancerous lesions, though there are no effective population-based screening tools for other HPV-associated cancers.

The authors also reviewed two challenges with the report itself. Though the CDC and SEER databases are reliable, the authors wrote, “no registry routinely collects or reports information on HPV DNA status in cancer tissue, so the HPV-attributable cancers are only estimates.” The authors also noted that race and ethnicity data came from medical records and may be inaccurate in a small number of cases.