Gardasil

The rise of HPV-related cancers in men

Source: www.tmc.edu
Author: Alexandra Becker

Scott Courville admired his full beard and round belly in the mirror: He was ready for the upcoming holiday season. It was November 2015 and Courville, who plays Santa Claus in Lafayette, Louisiana, was too excited about his favorite time of year to worry much about the pain developing in his jaw.

By February, though, the ache had worsened and was accompanied by new symptoms: white spots on his right tonsil, difficulty swallowing and lumps in his throat. He finally made his way to a walk-in clinic where he was diagnosed with tonsillitis and prescribed antibiotics.

“They sent me home and said, ‘In two weeks everything should clear up,’” Courville recalled.

But his symptoms only worsened. Courville made an appointment with a local ear, nose and throat (ENT) specialist who also diagnosed Courville with tonsillitis. The doctor prescribed more antibiotics and steroids, but two weeks later there were no improvements. Courville was referred to a dentist—“In case they see something we don’t”—but that, too, was a dead end.

Courville’s dentist insisted he return to his ENT, where he ultimately had a CT scan that revealed a mass in his throat. That was June 6, 2016. Two days later, Courville underwent a biopsy. When he awoke from the surgery, his doctor was standing over him.

Courville always gets choked up retelling this part of his story.

“The hardest part for me is always remembering when the doctor said, ‘I’m sorry, but you’ve got cancer.’”

Courville was referred to The University of Texas MD Anderson Cancer Center, where doctors confirmed that he had squamous cell carcinoma of the right tonsil. But there was more: Courville learned that his cancer had been caused by the human papillomavirus—HPV.

11 million men
Courville’s story is becoming increasingly common, with the annual incidence of HPV-related cancers of the throat, tonsils and the base of the tongue in men in the United States now outnumbering cases of cervical cancer in women, according to the U.S. Centers for Disease Control and Prevention (CDC). A 2017 research paper authored by scientists at Baylor College of Medicine and The University of Texas Health Science Center at Houston School of Public Health, among others, found the overall prevalence of oral HPV in men in the U.S. to be upwards of 11 million—much higher than previously believed.

“This has implications, because pretty much everyone is exposed to HPV,” said Andrew Sikora, M.D., Ph.D., one of the authors of the paper and vice chair for research and co-director of the Head and Neck Cancer Program at Baylor College of Medicine. “When we’re talking about the prevalence of oral HPV infection, we’re talking about that infection persisting inside the tonsils or on the base of the tongue of these men, and I think that’s what sets you up for cancer later in life—it may happen decades after you were exposed to HPV.”

That lag time, coupled with an absence of symptoms, is part of the reason HPV-related oropharyngeal cancers, also referred to as head and neck cancers, are increasing.

“What makes this cancer interesting is that it’s one of the only cancers in the body that we’re actually seeing more cases of year over year,” explained Ron J. Karni, M.D., who serves as chief of the division of Head and Neck Surgical Oncology at McGovern Medical School at UTHealth and Memorial Hermann-Texas Medical Center. “In the U.S., we can expect a certain number of breast cancer cases and lung cancer cases every year, but this is actually starting to look a bit like an epidemic in that we are seeing more every year. It’s alarming.”

Holy grail
HPV is the most common sexually transmitted disease in the U.S., with an estimated 79 million individuals infected. According to the CDC, HPV is so common that most people who are sexually active will get the virus at some point in their lives if they do not get the HPV vaccine.

The virus is spread through vaginal, anal and oral sexual activity, and often exhibits no signs or symptoms. In many cases, HPV is cleared by the immune system and does not cause health problems, but it can also persist and show up decades later alongside conditions such as genital warts and cancer—including cervical cancer, anal cancer and oropharyngeal cancers. For reasons not well understood, oropharyngeal cancers predominately affect men.

Currently, there is no annual screening test for men to determine whether they have the virus. Women, on the other hand, are advised to get regular pap smears.

The Papanicolaou test, commonly known as the pap smear, involves collecting cells from inside a woman’s cervix to detect pre-cancerous changes. It is performed during a woman’s annual exam and has been widely credited for detecting early signs of HPV-related cervical cancer and saving countless lives. No such screening test has been successfully developed for oropharyngeal cancer—another reason cited for its steady rise.

“We’re at a huge disadvantage,” said Sikora, who, in addition to his research, treats patients at the Michael E. DeBakey VA Medical Center in Houston. “The pap smear, in terms of global health impact, is probably one of the best, most cost-effective things ever invented in terms of just the sheer number of women who have not had cancers because of it. We have nothing like that for men.”

Sikora explained that anatomy is, in part, to blame. Whereas the cervix is easily sampled, the tonsils are full of “nooks and crannies,” he said, and scientists have yet to develop a reliable technique for obtaining a representative sample of cells inside the throat, tonsils and back of the tongue.

“It’s sort of a holy grail for researchers in the field,” Sikora said. “It would be a game-changer in terms of prevention and early detection of cancer.”

Scientists at MD Anderson, where Courville was treated, may be closing in on some answers. Researchers, including Erich M. Sturgis, M.D., MPH, the Christopher & Susan Damico Chair in Viral Associated Malignancies, are currently conducting a clinical trial for an antibody test that could be used to screen for HPV-related throat cancer.

The HOUSTON study, an acronym for “HPV-related Oropharyngeal and Uncommon Cancers Screening Trial of Men,” is looking to recruit 5,000 men ages 50 to 64 years to provide blood and saliva samples for serologic HPV testing and oral HPV testing, respectively. If a subject is found to have a positive antibody test, he will be asked to participate in a second phase of the study, which includes an intensive screening program run through MD Anderson’s oral pre-cancer clinic.

“A researcher at Arizona State University, Dr. Karen Anderson, developed a serologic test that predicts extremely well the risk for HPV-related oropharyngeal cancer,” Sturgis explained. “We have been able to show that serum antibodies to HPV early proteins, which are rare in the general population, are markers for oropharyngeal cancer. Specifically, we found that those who had antibodies to certain HPV antigens have a greater than 450-fold higher risk of oropharyngeal cancer compared with those who do not have the antibodies.”

The hope is that this study will reveal that serological HPV antibody testing is an effective screening tool for HPV-related cancer in men: the equivalent to a pap smear.

A lump in the neck
If and when HPV-related cancer does develop, men often notice a pain in their jaw or throat, trouble swallowing, change or loss of voice that lasts more than a week or two, a sore spot on the tongue and, most often, a lump in the neck.

“There’s often a very small, primary tumor, which is the tumor that is in the tongue or in the tonsil, and it travels early to the lymph nodes,” Sikora explained. “Depending on what your neck looks like, lymph nodes can get pretty big before they become noticeable. But a lump in the neck is by far the most common symptom, and unfortunately it’s often detected much later than we would like.”

Even more troubling, many individuals who have these symptoms are commonly misdiagnosed and handed antibiotics, as in Courville’s case.

“The most important message I can convey is that if you have a lump in your neck, go see an ear, nose and throat doctor,” Karni said, emphasizing the importance of an informed diagnosis and specialized care.

Treatment for oropharyngeal cancers varies depending on the case and often involves a multidisciplinary team of clinicians, as well as some form of combined modality therapy such as radiation and chemotherapy. In the future, Sturgis sees novel therapies, including immunotherapy options, changing the landscape of treatment protocols.

Karni hopes UTHealth’s dedicated HPV-related throat cancer program will carry patients through the entire arc of treatment by offering minimally invasive robotic surgery for qualifying cases, as well as annual community-wide screening clinics, rehabilitation therapists, and numerous other specialists.

“We want to think about cancer the way Target thinks about shopping or the way the best airlines think about flying,” Karni said. “We designed a program that is patient-centered. We asked, ‘What does the patient need on their fourth week of radiation? What do they need on their third month post-radiation? How can we get that into one clinic space?’ It’s a large team and it’s all centered around this one disease.”

47th in the nation
In 2006, an HPV vaccine named Gardasil hit the market. It was originally intended to prevent HPV in females and, ultimately, HPV-related cervical cancer. But as scientists learned more about HPV—first that males could be carriers and later that it causes cancer in men, as well—public health professionals and clinicians unanimously recommended the vaccine to everyone. The CDC recommends all young women through the age of 26 and all young men through age 21 receive two doses for the vaccine to be effective.

And it is. A recent report published in May by Cochrane, a global independent network of clinical researchers and health care professionals, concluded that the HPV vaccine protects against cervical cancer in young women, especially when they are vaccinated between the ages of 15 and 26.

Which begs the question: Will the vaccine protect young men against the development of oropharyngeal cancers?

“There is a lot more data on cervical cancer in women and the vaccine than there is on head and neck cancer in men and the vaccine, but what data exists suggests that it is going to be a very effective intervention,” Sikora said.

Yet despite scientific evidence that prophylactic HPV vaccination of children and young adults will drastically reduce HPV-related cancers, vaccination rates in the U.S. remain alarmingly low—and Texas ranks 47th. Even more, several generations did not have the vaccine available to them and are currently at risk for HPV-related cancer.

As Karni said, it is alarming.

“Because the median age of oropharynx cancer related to HPV is about 55 and, in some studies, 60, and because the vaccine does not seem to work in individuals who have already been exposed, the benefits of vaccination on HPV-related cancer will not be realized for several decades,” Sturgis said. “Even if we vaccinate 100 percent of our boys and girls tomorrow, we have a whole generation or two who are at risk for this cancer and cannot do anything about it.”

Courville endured six rounds of chemotherapy and 33 daily rounds of radiation to treat his cancer. He lost a year of his life, 100 pounds, his taste buds and salivary glands, and can no longer grow his full beard— but his therapy was successful. He has now made it his life’s mission to inform the public about the importance of the vaccine as well as ongoing advocacy and research surrounding HPV-related cancers.

“If you can educate the public and educate the parents, they will vaccinate their kids,” Courville said. “And if we can vaccinate this generation, we could eliminate these types of cancers.”

HPV is causing an oral cancer epidemic in men by outwitting natural defenses

Source: www.philly.com
Author: Marie McCullough, staff writer

Five years ago, when actor Michael Douglas candidly revealed that his throat cancer was linked to having oral sex, two things happened.

He made headlines that mortified his family. And he helped publicize the fact that a pervasive, sexually transmitted virus called HPV was unleashing an epidemic of oral cancer among men.

Since then, scientists have made headway in figuring out why HPV, the human papillomavirus, has this glaring gender bias. Men are four times more likely than women to be diagnosed with oral cancer, a hard-to-detect, hard-to-treat disease that has overtaken cervical cancer as the most common HPV-related malignancy in the United States.

To be sure, changes in sexual norms over the last few generations have played a role in this alarming trend. But research increasingly shows the real problem is something men have practically no control over: their immune response.

Compared with women, men are more likely to get infected with HPV — including “high-risk” cancer-causing strains. They also are less able to wipe out infection on their own, and more likely to get reinfected. The reasons are unclear.

“There is good evidence that men acquire oral infections more readily than women, even if they have similar sex practices,” said Ashish A. Deshmukh, a University of Florida HPV researcher. “And more than the acquisition, it’s the persistence of the virus. The clearance rate is not that fast in men.”

Michael Becker of Yardley has stepped up as the face of this immunological inequity. The 49-year-old former biotech executive is health-conscious, clean-living, happily married for 26 years – and battling terminal oropharyngeal cancer, the medical term for malignancies in parts of the mouth and throat.

He’s also battling the misconceptions and ignorance that keep too many parents from protecting their pubescent children — especially boys — against HPV-driven cancers. Two shots. That’s all it takes for the leading vaccine, Gardasil, to prevent most cervical cancers, less common genital malignancies, and the disease that is killing Becker.

“I can’t tell you how many emails I got from parents after the CBS segment,” he said, referring to a national television interview last month. “They said, ‘What do you mean this vaccine is for boys?’ and ‘What do you mean oral cancer incidence has eclipsed cervical cancer?’ ”

An inescapable virus
HPV is a family of more than 100 virus types that can live in the flat, thin cells on the surface of the skin, cervix, vagina, anus, vulva, penis, mouth, and throat. The virus is spread through contact with infected skin, mucous membranes, and bodily fluids. Some types can be passed during intercourse or — as Douglas pointed out — oral sex. While virtually all sexually active people will get infected at some point, the virus is usually wiped out by the immune system without so much as a symptom.

But not always.

In the cervix, persistent infection with high-risk HPV types can lead to precancerous changes that, left alone, slowly turn malignant. Fortunately, the Pap smear enables the detection and removal of abnormal cells before cancer develops. What’s more, age-related changes in cervical cells reduce the risk that HPV will take hold there as women get older.

No such screening test exists for oropharyngeal sites – the tongue, soft palate, tonsils, the throat behind the nasal cavity – and symptoms usually don’t appear until cancer is advanced. Becker, for example, had metastatic disease by the time he noticed a lump under his jaw line in late 2015.

Traditionally, smoking and heavy alcohol use are the big risk factors for oral cancer, but the non-HPV tumors linked to these bad habits have been declining in recent years. HPV-related tumors, in contrast, have increased more than 300 percent over the last 20 years. The virus is now found in 70 percent of all new oral cancers.

About 13,200 new HPV oral cancers are diagnosed in U.S. men each year, compared with 3,200 in women, according to federal data. Treatment — surgery, chemotherapy, radiation — can have disfiguring, disabling side effects. About half of late-stage patients die within five years.

Natural defenses go awry
Oral HPV infection rates are skewed by gender, just like the resulting cancers. The latest national estimates of this disparity, published in October, come from Deshmukh and his University of Florida colleagues. They used a federal health survey that collected DNA specimens to estimate that 7.3 percent of men and 1.4 percent of women have oral infections with high-risk HPV types. That translates to 7 million men and 1.4 million women.

The chance of oral infection increases for women as well as men who have simultaneous genital HPV infections or a history of many sex partners, but male infection rates still far surpass female rates.

Patti Gravitt, an HPV researcher at George Washington University, believes these estimates are a bit oversimplified because women counted as uninfected may actually have undetectably low virus levels, or HPV may be hiding in a dormant state in their cells.

Still, Gravitt said the study is in line with others that suggest “men are more susceptible to HPV viral infection than women.”

In women, an HPV infection usually sets off the body’s defense mechanisms. The immune system makes antibodies that kill off the invader, then immune cells remain on guard, ready to attack if the virus reappears.

But in men, something goes awry. The HIM study — for HPV in Men — documented this by collecting genital, anal, and oral samples from 4,100 unvaccinated men in Florida, Mexico and Brazil between 2005 and 2009. The samples were tested for the presence of two high-risk HPV types and two that cause genital warts.

Among 384 men who developed infections during a 24-month period, only 8 percent produced antibodies. But this response rate varied depending on the site of infection; none of the small number of orally infected men produced antibodies.

Rather than putting the immune system on guard and protecting men from the virus, infection sharply increased the chance of getting infected again with the exact same HPV type. And many men who got reinfected were celibate at the time.

How could this be? Anna R. Giuliano, the researcher at the Moffitt Cancer Center in Tampa, Fla., who led the HIM study, said recurring infections may be due to reactivation of dormant virus, or to auto-inoculation – the man spreads infection from one part of his body to another. Or to something else entirely.

While the scientific understanding of this puzzle is evolving, one implication is clear. “HPV vaccination is the only reliable method to ensure immune protection against new HPV infections and subsequent disease in males,” Giuliano and her co-authors declared in a recent paper.

Becker hammers that message – when he is not being hammered by chemotherapy – using his self-published memoir and his blog. This week’s blog gave a shout-out to Sunday’s first-ever International HPV Awareness Day, declared by Giuliano and other members of the International Papillomavirus Society.

Becker realizes that the novelty of the vaccine, the complexity of HPV, and its link to sex are obstacles to immunization. But he focuses on the life-saving aspect.

“Parents are being asked to vaccinate their 11-year-old child and they can’t imagine 30 or 40 years down the line, it will prevent cancer,” Becker said. “If you don’t know it’s connected to six cancers, you’re not going to care. So it really should be cast as an anti-cancer vaccine.”

March, 2018|Oral Cancer News|

Young men should be required to get the HPV vaccine. It would have saved me from cancer.

Source: www.thedailybeast.com
Author: Michael Becker

In December 2015, at the age of 47, I was diagnosed with Stage IV oral squamous cell carcinoma.

More simply, I have advanced cancer of the head and neck. While initial treatment with grueling chemo-radiation appeared successful, the cancer returned one year later in both of my lungs. My prognosis shifted from potentially curable to terminal disease. The news was shocking and devastating—not just for me, but for my wife, two teenage daughters, and the rest of our family and friends.

Suddenly, my life revolved around regular appointments for chemotherapy, radiation therapy, imaging procedures, and frequent checkups. I made seemingly endless, unscheduled hospital emergency room visits—including one trip to the intensive care unit—to address some of the more severe toxicities from treatment.

All told, I suffered from more than a dozen side effects related to treatment and/or cancer progression. Some are temporary; others permanent. These include anxiety, depression, distorted sense of taste, clots forming in my blood vessels, dry mouth, weight loss, and many more.

My cancer started with a human papillomavirus (HPV) infection, a virus that is preventable with vaccines available for adolescent girls since 2006 and boys starting in 2011. The Food and Drug Administration (FDA) has approved three vaccines to prevent HPV infection: Gardasil®, Gardasil® 9, and Cervarix®. These vaccines provide strong protection against new HPV infections for young women through age 26, and young men through age 21, but they are not effective at treating established HPV infections. It was too late for me in 2011 when the HPV vaccine was made available to young men, and I was 43 years old.

According to the Centers for Disease Control and Prevention (CDC), more than 30,000 new cancers attributable to HPV are diagnosed each year. Unlike human immunodeficiency virus (HIV), which is spread by blood and semen, HPV is spread in the fluids of the mucosal membranes that line the mouth, throat, and genital tracts, and can be passed from one person to another simply via skin-to-skin contact.

While most HPV cases clear up on their own, infection with certain high-risk strains of HPV can cause changes in the body that lead to six different types of cancer, including cancers of the penis, cervix, vulva, vagina, anus, and head and neck (the last of which is what I have). Two of these, HPV strains 16 and 18, are responsible for most HPV-caused cancers.

Researchers believe that it can take between 10 and 30 years from the time of an initial HPV infection until a tumor forms. That’s why preventing HPV in the first place is so important and the HPV vaccine is so essential.

However, only 49.5 percent of girls and 37.5 percent of boys in the United States were up to date with this potentially lifesaving vaccination series, according to a 2017 CDC report. In sharp contrast, around 80 percent of adolescents receive two other recommended vaccines—a vaccine to prevent meningococcus (PDF), which causes bloodstream infections and meningitis, and the Tdap vaccine to prevent tetanus, diphtheria, and pertussis.

Even if you don’t think your child is at risk for HPV now, they almost certainly will be. HPV is extremely common. Nearly everyone gets it at some point; in fact, the CDC estimates that more than 90 percent and 80 percent of sexually active men and women, respectively, will be infected with at least one strain of HPV at some point in their lives. Around one-half of these infections are with a high-risk HPV strain.

As a cancer patient with a terminal prognosis, I find it infuriating that the HPV vaccine is tragically underutilized more than a decade since its introduction. Two simple shots administered in early adolescence can reduce a child’s risk of receiving a cancer diagnosis much later in life.

Parents who oppose the use of vaccines cite popular misconceptions that they are unsafe, ineffective, and that immunity is short-lived. Others argue that receiving the HPV vaccine may increase sexual promiscuity. Films like Vaxxed based on research that has been discredited, and directed by a researcher who fled the United Kingdom due to the misleading uproar he created, are still quoted as science.

Regardless, the fact remains that millions of adolescents aren’t getting a vaccine to prevent a virus known to cause cancer. We must counter untrue, exposed, and discredited research that keeps some parents from having their children vaccinated and put an end to the campaign of misinformation.

Viruses that are preventable, such as HPV, should be eradicated just like previous success with polio and smallpox. Cancers that are preventable through HPV vaccination should be prevented. The safety and efficacy of these vaccines are no longer subject to serious debate (PDF). Research has shown that vaccinations work; they keep children healthy, save lives, and protect future generations of Americans—but only when they are utilized.

The lesson: Don’t wait. Talk to your pediatrician about vaccinating your 11-year-old boys and girls against HPV today to eradicate this cancer-causing virus.

I only wish my parents had that opportunity when I was young, as it could have prevented the cancer that’s killing me.

December, 2017|Oral Cancer News|

Biotech exec facing death urges: Get the vaccine that prevents his cancer

Source: www.philly.com
Author: Michael D. Becker

Like most people who pen a new book, Michael D. Becker is eager for publicity.

But he has an unusual sense of urgency.

A former oncology biotech CEO, Becker has neck cancer. He expects his 49th birthday in November to be his last, if he makes it.

What also drives him to get his message out, however, is this: Children today can get a vaccine that prevents the kind of oropharyngeal cancer that is killing him.

As he collides with his mortality, Becker wants to share his story and raise awareness about the vaccine, which protects against dangerous strains of human papillomavirus, or HPV, the extremely common, sexually transmitted virus that caused his disease. His book, A Walk With Purpose: Memoir of a Bioentrepreneur (available on Amazon.com), was produced and self-published in a creative sprint between December, when his cancer recurred just a year after initial diagnosis and treatment, and April. He also has a blog, My Cancer Journey, and has been conducting media interviews.

“I had a lot of motivation to write the book quickly,” he said wryly at his home in Yardley.

In the final pages, he urges parents “to talk to their doctor about the HPV vaccine,” which “simply didn’t exist when I was a teenager, or it could have prevented my cancer.”

The leading vaccine brand, Gardasil, was hailed as a breakthrough when it was introduced in 2006. It is approved to prevent cervical cancer and less common genital malignancies, including anal cancer, that are driven by HPV infections. The vaccine was not clinically tested to prevent head and neck cancers, so it is not officially approved for that purpose, but research shows that it works. A study of young men presented last month found that vaccination reduced oral HPV infections by 88 percent.

Still, many adolescents are not getting the shots, for various reasons.

“It just kills me,” Becker says without a trace of irony, “that it’s underutilized. There are parents debating about whether to vaccinate their children. I’ve talked to immunologists about the safety. I had to make the decision to vaccinate my own kids. I was 100 percent convinced.”

From dropout to go-getter:
Becker describes his own youth as a bit misspent. He left home and dropped out of high school in his junior year, soon after his parents divorced.

“During my teens, I had experimented with sex, drugs, and alcohol while teaching myself how to play guitar and dreaming of becoming the next Eddie van Halen,” he writes in his book. “Making it through a number of near-death and reckless experiences during that period now seemed like a minor miracle.”

In his late teens, he wised up, got his equivalency diploma, and went to work for his father’s investment firm, where he discovered a talent for computer programming. Next came a job as a stock broker in Chicago, where he met and soon married Lorie Statland, an elementary school teacher who inspired him to get a college degree. The couple had two children, Rosie, now 19, and Megan, 16.

Becker went on to have a prolific career in biotechnology, complete with the occasional setbacks (lawsuits and soured partnerships) that are part of that high-stakes world. His resume includes Wall Street securities analyst, portfolio manager, founder of his own communications firm, and top executive of three biotech companies, two of which developed oncology products. During his cancer treatment, he used a prescription medicine that he played a major role in developing while at New Jersey-based Cytogen Corp: Caphosol, an electrolyte mouthwash that treats mouth ulcers caused by radiation therapy.

His diagnosis followed his discovery of a lump under his jaw line on the day before Thanksgiving in 2015. Tests revealed cancer that had spread from a tonsil to a lymph node and surrounding tissue.

At Memorial Sloan Kettering Cancer Center in New York, he opted for chemotherapy and radiation instead of surgery. The operation, he explains, can damage speech and swallowing, and if it doesn’t get all the cancer, chemo and radiation are still necessary.

He describes the main side effects of treatment – constant dry mouth and changes in taste – as manageable. And he says he was not unhappy to lose 30 pounds.

Although he sounds almost too stoic, he is frank about “the one major issue I tried to ignore … namely, depression.”

“On more than one occasion I burst into a crying session,” he writes. “I’m not talking about the quiet episode with sniffles and a tear or two. I mean full-fledged bawling your eyes out accompanied by nasal discharge and the near inability to speak normally.”

A sensitive subject:
Conspicuously missing from his book, though, is information about head and neck cancer. Over the last 30 years, the epidemiology has changed dramatically in the United States, with a decline in cases related to smoking and alcohol use, and a steady increase in HPV-related cancers. Men are three times more likely than women to develop these malignancies. Of an estimated 63,000 new head and neck cancer diagnoses this year, 11,600 will likely be caused by HPV, according to the U.S. Centers for Disease Control and Prevention.

This surge reflects changes in sexual practices, especially oral sex, research suggests. That’s a sensitive issue, as actor Michael Douglas discovered when his candor about his throat cancer and cunnilingus turned him into fodder for tweeters and late-night comics. The thing is, genital strains of HPV are so ubiquitous that almost all sexually active people — not just promiscuous ones — will be infected at some point. It is not clear why, for a fraction of these people, the immune system fails to wipe out the infection.

Becker says he did not wade into this subject in his book because of the scientific uncertainties.

In a recent blog post, he quoted the CDC: “Only a few studies have looked at how people get oral HPV, and some show conflicting results. Some studies suggest that oral HPV may be passed on during oral sex or simply open-mouthed (“French”) kissing, others have not. More research is needed to understand exactly how people get and give oral HPV infections.”

After his cancer recurred, Becker explored his options and entered a National Cancer Institute clinical trial of an experimental immunotherapy. It seems to have slowed, but not stopped, his cancer, which has spread to his lungs.

He is philosophical about his plight.

“I get up each morning feeling fine. It’s not a bad quality of life at the moment,” he said. “And I’ve had just a fabulous life. I’ve worked very hard, but the fruits of those labors were phenomenal. Being able to travel. Being able to give my daughters what they wanted. I wanted them to have a better youth than I had. I’ve got the best wife in the world. I’ve had 25 fabulous years with her. It’s hard to look at my situation and have a lot of self-pity.”

But he does have a hope: “That by sharing this experience freely, I can help create greater awareness for the disease and its impact.”

HPV vaccine; cancer prevention

Source: www.nujournal.com
Author: staff

Human papillomavirus (HPV) is a sexually transmitted infection, of several strains, most associated with cervical cancers. The virus is so common that nearly all males and females have been infected at some time in their life. One in four is currently infected in the nation.

Signs and symptoms of HPV are variable. Most will recover from the virus within two years without ever knowing they were infected, making HPV easy to spread. Occasionally, the virus lasts much longer in the body which can cause cells to change and lead to cancer. Fortunately, we have a vaccine to prevent cancer caused by HPV.

The Food and Drug Administration (FDA) has approved three vaccines for HPV; Cervarix, Gardasil, and Gardasil 9. These vaccines are tested and proven to be safe and effective.

Prevention is important with HPV. The vaccine should be administered before exposure to the virus for stronger protection against cervical, vaginal, vulvar, penile, and some mouth or throat cancers. (Gardasil and Gardasil 9 also prevent genital warts and anal cancer.) The best age to obtain maximum potential of the vaccine is at 11 or 12 years old. At this age, the body’s immune system is the most receptive to the vaccination’s virus-like particles and the body produces higher amounts of antibodies in defense, protecting the adolescent for his or her future. Both girls and boys should get the HPV vaccine. For ages 9-14, two doses – six to twelve months apart, are recommended. For 15-26 year olds, three doses are recommended. Side effects may include brief soreness, or redness or swelling at the injection site.

The HPV vaccine does prevent cancer, limiting biopsies and invasive procedures thus cutting potential health care costs. Most private insurance companies cover preventive vaccinations, it is best to call your carrier for more information. The HPV vaccine is covered by Minnesota Health Plans. Uninsured individuals may be eligible to get the vaccine at their local public health office.

Schedule your adolescent’s annual health exam today and ask which HPV vaccine is best for the child in your life.

“Every year in the United States, HPV causes 30,700 cancers in men and women. HPV vaccination can prevent most of the cancers (about 28,000) from occurring.” (CDC, December, 2016)

Learn more at www.cdc.gov/hpv or www.cancer.gov

April, 2017|Oral Cancer News|

GlaxoSmithKline pulls Cervarix from U.S. market

Source: www.managedcaremag.com
Author: staff

In response to “a very low market demand,” GlaxoSmithKline has decided to stop selling its human papillomavirus (HPV) vaccine Cervarix in the United States, according to FiercePharma. The move gives Merck’s Gardasil unchallenged dominance of the HPV vaccine market in this country.

Last year, Cervarix earned only about $3.7 million in the U.S. out of a $107 million worldwide total. In contrast, the global total for Merck’s Gardasil franchise was $1.9 billion.

Figures from the Centers for Disease Control and Prevention (CDC) last year placed HPV vaccination rates at 42% of girls and 28% of boys ages 13 to 17 years––far short of the U.S. Department of Health and Human Services’ goal of 80% for both boys and girls by 2020.

To combat the public’s lukewarm response, the CDC and other cancer organizations are urging health care providers to promote the cancer-prevention benefits of HPV vaccines rather than stressing that they protect against sexually transmitted infections, which puts off some parents who worry the vaccine will promote promiscuity or who feel that their preteens are too young to need the shots, according to the Wall Street Journal.

HPV, which is transmitted sexually, can cause at least six types of cancer as well as genital warts. The vaccine is recommended for boy and girls at age 11 or 12 and is also given at other ages.

Experts are urging pediatricians to present the vaccine as routine, rather than different from other preteen shots. They are also stressing completion of the vaccine series by age 13.

Merck, the maker of Gardasil, is currently airing an ad on national television that puts the onus on parents to get their children vaccinated.

Sources: FiercePharma; October 21, 2016; and Wall Street Journal; October 17, 2016.

October, 2016|Oral Cancer News|

Pre-Teens need just two doses of HPV vaccine, not three: Feds

Source: www.nbcnews.com/health
Author: Maggie Fox

There’s good news for kids who haven’t received all their HPV vaccines yet – they only need two doses of the vaccine instead of three, federal government advisers said Wednesday. The new recommendations should make it easier to get more children vaccinated against the human papillomavirus (HPV), which causes a range of cancers including cervical cancer, throat cancer and mouth cancer, officials said.

“It’s not often you get a recommendation simplifying vaccine schedules,” said Dr. Nancy Messonnier, Director of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention.

The CDC immediately accepted the recommendations from its Advisory Committee on Immunization Practices.

“Safe, effective, and long-lasting protection against HPV cancers with two visits instead of three means more Americans will be protected from cancer,” said CDC Director Dr. Tom Frieden. “This recommendation will make it simpler for parents to get their children protected in time.”

The CDC says every pre-teen boy and girl should get the vaccine, but fewer than a third have received all three doses.

Messonnier says the three-dose schedule was based on the earliest studies of the vaccine. New studies show that two doses protect people for decades from the cancer-causing virus. And studies also suggest that spacing the two doses a year apart is at least as effective, if not more effective than giving them more closely together – something that could also make it easier to get kids fully vaccinated.

Older teens who have not been vaccinated at all before age 15 should still get three doses, because there’s not enough evidence to show whether two doses fully protect them, ACIP said.

Adults can also get the HPV vaccine. “Young women can get HPV vaccine through age 26, and young men can get vaccinated through age 21,” the CDC says.

“The vaccine is also recommended for any man who has sex with men through age 26, and for men with compromised immune systems (including HIV) through age 26, if they did not get HPV vaccine when they were younger.”

HPV is extremely common, but rates of HPV-related disease have fallen among vaccinated people.

“About 14 million people, including teens, become infected with HPV each year. HPV infection can cause cervical,vaginal, and vulvar cancers in women; penile cancer in men; and anal cancer, cancer of the back of the throat (oropharynx), and genital warts in both men and women,” the CDC says.

The original two vaccines on the market protected against either two or four of the strains of HPV known to cause cancer. Now the only vaccine available in the U.S. is Merck’s Gardasil 9, which protect against 9 strains of HPV.

Messonnier says it’s too soon to say whether teens vaccinated with the older vaccines should get a top-up dose with the new formulation.

October, 2016|Oral Cancer News|

Mouth, throat cancers caused by HPV on the rise, especially among Canadian men

Source: www.ctvnews.ca
Author: Sonja Puzic, CTVNews.ca Staff

Mouth and throat cancers caused by the human papilloma virus have been rising steadily over the past two decades, with a “dramatic” increase among Canadian men, according to a new report from the Canadian Cancer Society.

The special report on HPV-associated cancers, released Wednesday as part of the 2016 Canadian Cancer Statistics breakdown, says the rate of mouth and throat cancers in men is poised to surpass the rate of cervical cancer diagnoses in women.

Researchers and doctors have known for decades that certain strains of HPV – the most commonly sexually transmitted disease in Canada and the world — cause cervical cancer. But the latest Canadian cancer statistics show that only 35 per cent of HPV cancers are cervical, and that about 33 per cent of HPV cancers occur in males.

The latest data show that about one-third of all HPV cancers in Canada are found in the mouth and throat.

Between 1992 and 2012, the incidence of HPV-related mouth and throat cancers increased 56 per cent in males and 17 per cent in females. In 1992, the age-standardized incidence rate (or ASIR) of those cancers was 4.1 per 100,000 Canadian males. In 2012, it was 6.4 per 100,000 males. In females, the rate was 1.2 in 1992 and 1.4 in 2012.

‘I thought I was done’
Three years ago, Dan Antoniuk noticed a lump on his neck and initially thought that it was just a swollen gland. But when the Edmonton father went to see a doctor, he was diagnosed with Stage 4 throat cancer, caused by HPV.

“I was devastated. I thought I was done,” Antoniuk, 61, told CTV News. “It shattered me, it shattered my family and affected everybody sitting in the waiting room.”

Antoniuk said that until his diagnosis, he had never heard of HPV cancers in men. His doctors told him that, despite the late stage of his cancer, his prognosis was still good with the right treatment. He underwent surgery, radiation and chemotherapy and although the treatments took a toll on his body, he’s now doing well.

“The end result is I am here, I am healthy and I can do most of the same things I have done before,” he said. “The ultimate message is: Be aware of your body and be aware of the fact that this could be something more serious and there is hope now.”

Dr. Hadi Seikaly, a professor and oncology surgeon at the University of Alberta, said doctors are seeing more HPV-related cancers in both men and women.

“The surprising thing is that we’re just seeing the front end of the epidemic,” he told CTV News. “And it is an epidemic … cervical cancer rates are coming down and head, neck cancer rates are going up.”

Doctors say that oropharyngeal cancers (which include the back of the throat, the base of the tongue and the tonsils) and cancers of the mouth used to be mostly found in older patients who smoked, drank heavily or had other health issues. But it’s now more common to see HPV-related throat and mouth cancers in younger, otherwise healthy patients.

“HPV is without question driving the dramatic increase we are seeing in oropharyngeal squamous cell carcinoma (OPSCC),” Dr. Joseph Dort, the chief of otolaryngology head and neck surgery at the Foothills Medical Centre in Calgary, told CTV News.

“Our most recent data shows that about 70 per cent of our new cases of this cancer are HPV positive. Recent studies suggest that oropharyngeal cancer will become the most common HPV-associated malignancy by the year 2020, surpassing cancer of the cervix,” he said in an email.

The changing face of the disease
Jennifer Cicci was shocked to learn that she had oral cancer caused by HPV after a lump appeared on the side of her neck in the fall of 2013.

The dental hygienist and mother of four from Brampton, Ont., said she was an otherwise healthy woman in her 40s who didn’t have any of the typical risk factors associated with head and neck cancers.

Cicci’s surgeon removed a baseball-sized mass of tissue from the back of her throat and a section from the back of her tongue. She also underwent laser surgery and radiation, with painful side effects. Still, she feels she “got off easy,” despite the entire ordeal.

In some cases, mouth and neck cancer treatments can have devastating effects on a patient’s ability to speak and eat. Some patients have had parts of their tongues and even their voice boxes removed.

The good news, doctors say, is that HPV-related cancers seem to be more treatable. More than 80 per cent of patients will survive if the cancer is caught in time.

“I felt like having this gave me an opportunity to raise awareness of something that I felt was becoming an epidemic,” Cicci said.

Dr. Brian O’Sullivan, a head and neck cancer specialist at Princess Margaret Hospital in Toronto, said that HPV infections in the throat and mouth are largely linked to sexual contact, but he has also seen patients who have had very few sexual partners and little experience with oral sex.

Calls for more widespread HPV immunization
The Canadian Cancer Society estimates that nearly 4,400 Canadians will be diagnosed with an HPV-caused cancer (that can include cervical, vaginal, anal and oral) and about 1,200 will die from it in 2016.

The society is focusing its messaging on cancer prevention and informing the public about the HPV vaccine. The two HPV vaccines approved by Health Canada are Gardasil and Cervarix.

HPV immunization is already available through publicly-funded school programs across the country, starting between Grades 4 and 7, up to age 13. But while the vaccine is offered to girls in all provinces and territories, only six provinces — Alberta, Manitoba, Nova Scotia, Ontario, Prince Edward Island and Quebec – also offer it to boys.

The Canadian Cancer Society is calling on the remaining provinces and territories to expand HPV immunization to boys.

Robert Nuttall, the society’s assistant director of health policy, also said that adults should talk to their doctors to see whether they can benefit from the HPV vaccine. However, there is currently no scientific evidence showing the benefits of HPV vaccines in older adults.

In Canada, Gardasil is approved for use in females aged 9 to 45, and males aged 9 to 26. Cervarix is approved for use in females between the ages of 10 and 25, but is currently not approved for boys and young men.

The vaccine works best in people who have not been exposed to HPV. That’s why it is given to school-aged children and teens as a preventative measure.

It will be a while before scientists can conclusively determine whether HPV vaccines can prevent throat and neck cancers, since it can take many years for an HPV infection to cause malignancies.

In the meantime, Dr. Seikaly says it’s important for Canadians to understand this disease could happen to anybody, because the modes of HPV transmission aren’t fully understood.

“They need to understand the signs and symptoms of it. And those include pain in your throat, difficulty swallowing, neck masses, ulcers in your mouth and throat,” he said. “And they need to make sure during their physical that doctors do look in their mouth and their throat.”

Early symptoms of mouth and throat cancers can often be vague, but they also include white or red patches inside the mouth or on the lips, persistent earaches and loose teeth.

As a dental hygienist who was also a cancer patient, Cicci urges regular exams of the mouth and throat during dental visits.

“What I try to do is to break down the stigma that is attached to (HPV),” she said. “The fact of the matter is, while most of the time it is still being sexually transmitted … we don’t know all the modes of transmission.”

October, 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.”

HPV is changing the face of head and neck cancers

Source: www.healio.com
Author: Christine Cona
 

A drastic increase in the number of HPV-associated oropharynx cancers, particularly those of the tonsil and base of tongue, has captured the attention of head and neck oncologists worldwide.

In February, at the Multidisciplinary Head and Neck Cancer Symposium in Chandler, Ariz., Maura Gillison, MD, PhD, professor and Jeg Coughlin Chair of Cancer Research at The Ohio State University in Columbus, presented data that showed that the proportion of all head and neck squamous cell cancers that were of the oropharynx — which are most commonly HPV-positive cancers — increased from 18% in 1973 to 32% in 2005.

9ea467bbf8646a69da2a432f8fcc5452Maura Gillison, MD, PhD, Jeg Coughlin Chair of Cancer Research at The Ohio State University, said screening for HPV in the head and neck is years behind cervical screening for HPV.

 

In addition, studies from the United States, Europe, Denmark and Australia indicate that HPV-positive patients have a more than twofold increased cancer survival than HPV-negative patients, according to Gillison.

With the rising incidence of HPV-related oropharynx cancers, it will soon be the predominant type of cancer in the oral or head and neck region, according to Andy Trotti, MD, director of radiation oncology clinical research, H. Lee Moffitt Cancer Center & Research Institute, in Tampa, Fla.

“We should be focusing on HPV-related oropharyngeal cancer because it will dominate the field of head and neck cancers for many years,” he said during an interview with HemOnc Today. “It is certainly an important population for which to continue to conduct research.”

Because HPV-associated oropharyngeal cancer is emerging as a distinct biological entity, the recent rise in incidence will significantly affect treatment, and prevention and screening techniques, essentially reshaping current clinical practice.

Social change driving incidence

In the analysis performed by Gillison and colleagues, trends demonstrated that change in the rates of head and neck cancers was largely due to birth cohort effects, meaning that one of the greatest determinants of risk was the year in which patients were born.

The increased incidence of HPV-related oropharyngeal squamous cell carcinoma started to occur in birth cohorts born after 1935, indicating that people who were aged in their teens and twenties in the 1960s were demonstrating increased incidence, Gillison said.

“Two important and probably related events happened in the 1960s. In 1964, the surgeon general published a report citing smoking as a risk factor for lung cancer, and public health policy began promoting smoking cessation along with encouragement not to start smoking,” she told HemOnc Today.

If you were 40 years old between 2000 and 2005, your risk for having HPV-related cancer is more than someone who was between the age of 40 and 45 years in 1970, according to Gillison. Social changes that occurred among people born after 1935, for example, a reduction in the number of smokers, is consistent with the increasing proportion of oropharyngeal cancers that were HPV-related.

“The rates for HPV-related cancers began to increase and the rates for HPV-unrelated cancers started to decline, consistent with the known decline in tobacco use in the U.S. population,” she said.

Now, most cases of head and neck squamous cell carcinoma in non-smokers are HPV-related; however, oral HPV infection is common and is a cause of oropharyngeal cancer in both smokers and non-smokers, research shows.

In addition to a decrease in tobacco use reducing HPV-unrelated oral cavity cancers, the number of sexual partners may have increased during this time and have helped to increase HPV-related oropharyngeal cancers, according to Gillison.

Determining the cause of the elevated incidence is only a small piece of the puzzle. Screening, establishing who is at risk, and weighing vaccination and treatment options are all relevant issues that must be addressed.

Screening is problematic

A critical area for examination and research is the issue of screening for oral cancers. In contrast to cervical cancer, there is no accepted screening that has been shown to reduce incidence or death from oropharyngeal cancer, according to Gillison.

Not many studies have examined the issue of screening for HPV-unrelated oral cancers, and the few that have, tend to include design flaws.

Gillison said there is a hope that dentists would examine the oral cavity and palpate the lymph nodes in the neck as a front-line screen for oral cancer; however, in her experience, and from her perspective as a scientist, this has never been shown to provide benefit for oral cancer as a whole.

Another caveat with regard to HPV detection is that head and neck HPV screening is about 20 years behind the cervical field.

“Clinicians screening for HPV in the field of gynecology were incredibly fortunate because Pap smear screening was already an accepted cervical cancer screening method before HPV was even identified,” she said. “There was already a treatment algorithm: If there were cytologic abnormalities, patients were referred to the gynecologist, who in turn did a colposcopy and biopsy.”

A similar infrastructure does not exist for oropharyngeal cancer. People with HPV16 oral infection are at a 15-fold higher risk for oropharynx cancer and a 50-fold increased risk for HPV-positive head and neck cancer, yet there is no algorithm for treatment and management of these at-risk individuals, Gillison said.

In 2007, WHO said there was sufficient evidence to conclude that HPV16 was the cause of oropharynx cancer, but with no clinical algorithm already established, progress in this area is much further behind.

Another problematic aspect of HPV-related oropharyngeal cancer screening is that the site where the cancer arises is not accessible to a brush sampling, according to Gillison.

“To try to find this incredibly small lesion in the submucosal area that you cannot see and cannot get access to with a brush, highlights that we need to develop new techniques, new technologies and new approaches,” she said.

The near future consists of establishing the actual rates of infection in the oral cavity and oropharynx, and then screening for early diagnosis, according to Erich Madison Sturgis, MD, MPH, associate professor in the department of head and neck surgery and the department of epidemiology at The University of Texas M.D. Anderson Cancer Center.

“I am not extremely hopeful because the oropharyngeal anatomy makes screening complicated, and these cancers likely begin in small areas within the tonsils and the base of the tongue,” Sturgis told HemOnc Today. “I am hopeful, however, that preventive vaccines will eventually, at a population level, start to prevent these cancers by helping people avoid initial infection by immunity through vaccination earlier in life.”

Much of the currently known information surrounding the issue of HPV-related oral cancers is new, so researchers continue to conduct research in various relevant areas. One key question to answer is who may be at higher risk for HPV-related oropharynx cancers.

Who is at risk?

As mentioned earlier, the number of oral sex partners seems to play a role in the risk for contracting the HPV virus.

In one study published in The New England Journal of Medicine in 2007, findings demonstrated that a high lifetime number of oral sex partners (at least six partners) was associated with an increased risk for oropharyngeal cancer (OR=3.4; 95% CI, 1.3-8.8).

In addition to a higher number of oral sex partners, other still unknown factors may be contributing to risk. This is an area that needs further research, according to Barbara Burtness, MD, chief of head and neck oncology, and professor of medical oncology at Fox Chase Cancer Center in Philadelphia.

The effect of smoking status is another area that needs further research. According to Burtness, smokers with HPV-associated oropharynx cancer have less favorable outcomes.

When discussing the prognosis of HPV-associated cancers, Sturgis said low risk is defined as low or no tobacco exposure and positive HPV status, and intermediate risk is defined as significant tobacco exposure but an HPV-positive tumor, and the highest risk group appears to be the HPV-negative group.

Although HPV-negative cancers are overwhelmingly tobacco-related cancers and tend to have multiple mutations, it appears that HPV-positive cancers, particularly those in patients with low tobacco and alcohol exposure, tend to lack mutations and to have a better prognosis, and this may ultimately help to guide treatment practices, according to Sturgis. Yet, there is still much to learn about HPV-related oropharyngeal cancers on various fronts.

Vaccination a hopeful ally

In HPV-related head and neck cancer, particularly oropharynx cancers, more than 90% of patients who have an HPV-type DNA identified, have type 16, according to Sturgis.

The two current HPV vaccines, Gardasil (Merck) and Cervarix (GlaxoSmithKline), which are approved for cervical cancers, include HPV types 16 and 18; therefore, in theory, they should be protective against the development of infections in the oropharynx and protective at preventing these HPV-associated cancers from occurring.

The presumption is that if there was a population-wide vaccination against HPV, there would be less person-to-person transmission, and this would lead to fewer oropharynx cancers, according to Burtness, who said this theory still needs further research.

There is excitement at the possibility that therapeutic vaccines could be developed, and various groups are investigating this, Burtness added.

“There is reason to think that the vaccines may be helpful; however, when HPV infects the tonsillar tissues, it exerts control in the host cells by making two proteins: E6 and E7; so another potentially exciting therapeutic avenue would be to target those specific viral proteins,” she told HemOnc Today.

Anxiety about protection from the HPV virus is palpable, according to Sturgis. He described the worry that many patients experience about contracting and transmitting HPV infection.

“Many patients are concerned they will put their spouses and/or children at risk in ways such as kissing them; and we need to tone down those worries until we have better data,” he said.

Screening and vaccination are fundamental aspects of current ongoing research, but of equal importance is determining what clinicians should do to treat a population of patients with HPV-related oropharyngeal cancers.

HPV status may influence treatment

With rates of HPV-related cancers escalating, determining the appropriate treatment for these patients is crucial.

During the past 10 years, findings from retrospective studies have shown that patients with HPV-related cancers have a much better prognosis than patients who test negative for HPV. Findings from several retrospective analyses from clinical trials conducted during the past 2 years have come to the same conclusion, according to Gillison: HPV-positive patients have half the risk for death compared with patients negative for HPV.

Therefore, there may be several alternative treatment options, including the possibility of reducing the dose of radiation given to patients after chemotherapy, thereby reducing toxicity.

Comparing HPV-negative and HPV-positive patients may not be enough to determine proper treatment, researchers said. Data between different cohorts of HPV-positive patients also needs to be examined. Smoking, for example, may play a role in patient outcome.

In a prospective Radiation Therapy Oncology Group clinical trial (RTOG 0129), presented by Gillison at the 2009 ASCO Annual Meeting and recently published in The New England Journal of Medicine (see page 53), researchers conducted a subanalysis of the effect of smoking on outcome in uniformly staged and treated HPV-positive and HPV-negative patients while accounting for a number of potential confounders. HPV-positive patients who were never smokers had a 3-year OS of 93% compared with heavy smoking HPV-negative patients who had an OS of 46%.

The study found that smoking was independently associated with OS and PFS. Patients had a 1% increased risk for death and cancer relapse for each additional pack-year of smoking. This risk was evident in both HPV-positive and HPV-negative patients. Gillison said smoking data must be paid attention to, and she encouraged cooperative group research on the topic.

Most of the findings demonstrate improved outcomes for patients with HPV-positive oropharyngeal cancers vs. patients with HPV-negative oropharyngeal cancers, according to the experts interviewed by HemOnc Today.

Dose de-intensification for less toxicity

To date, there is no evidence that HPV-related cancers should be managed differently than HPV-unrelated cancers, but it is a hot topic among clinicians in the field, according to Burtness.

The superior outcomes for HPV-associated oropharynx cancer have suggested the possibility of treatment de-intensification. The use of effective induction chemotherapy may permit definitive treatment with a lower total radiation dose. In theory, this would reduce the severity of late toxic effects of radiation, such as swallowing dysfunction. Such a trial is being conducted by the Eastern Cooperative Oncology Group. Burtness said this is currently pure research question.

“There is still much research that needs to be done before clinicians can safely reduce the dose of radiation administered to HPV-positive patients,” Burtness said.

Currently, she and colleagues in the ECOG are conducting a study of patients with HPV-associated stage III or IV oropharynx cancers to examine the possibility of tailoring therapy to these patients. Patients are assigned to one of two groups: low-dose intensity-modulated radiotherapy 5 days per week for 5 weeks (27 fractions) plus IV cetuximab (Erbitux, ImClone) once weekly for 6 weeks, or standard-dose intensity-modulated radiotherapy 5 days per week for 6 weeks (33 fractions) plus IV cetuximab once weekly for 7 weeks.

If patients have a very good clinical response to chemotherapy, which is likely to happen with HPV-associated cancers, they are eligible to receive a reduced dose of radiation, and hopefully, they would experience less adverse effects, Burtness said.

“Patients who are treated with the full course of radiation for head and neck cancer are now getting 70 Gy, and they are often left with dry mouth, and speech and swallowing difficulty,” she said. “We are hopeful that if these particular cancers are treatment responsive to chemotherapy, we may be able to spare the patient the last 14 Gy of radiation.”

Immunotherapy a viable treatment

Another possible treatment technique that may benefit patients with HPV-related cancers is immunotherapy. One form of immunotherapy uses lymphocytes collected from the patient, and training the cells in the laboratory to recognize in this case a virus that is associated with a tumor and consequently attack it. This approach potentially may be used to treat HPV-related oropharynx cancers, according to Carlos A. Ramos, MD, assistant professor at the Center for Cell and Gene Therapy at Baylor College of Medicine, Houston.

“With some infections that lead to cancer, even though the virus is present in the tumor cells, the proteins shown to the immune system are limited; therefore, they do not drive a very strong immune response,” Ramos told HemOnc Today. “Training the immune system cells, T lymphocytes, may make them respond better to antigens.”

Data from ongoing trials that are taking T lymphocytes from patients and educating them to recognize antigens in patients with the Epstein-Barr virus associated tumors have shown some activity against them, according to Ramos. This adoptive transfer appears to be safe and may have the same effect on the HPV virus associated tumors. Immunotherapy does not cause the usual toxicities associated with chemotherapy, he said.

“There are currently no trials showing whether we can prevent more recurrences with this approach, but the results of trials examining viruses such as Epstein-Barr are good so far, in both patients who have no evidence of disease and in those who still have disease,” he said.

Even patients with active disease who have not responded to other therapies have responded to this therapy, Ramos said. He and colleagues are working toward compiling preclinical data to study the possibility of using immunotherapy to treat patients with HPV-related cancers.

Journey is just beginning

Much of what is known about risk, screening, prevention and treatment of HPV-related oropharynx cancers is in the early stages of discovery and much is still theoretical, according to Sturgis.

“As far as we can tell, these infections are transmitted sexually; the hope is that as we have better vaccines for prevention of cervical dysplasia, the downstream effect will help prevent other HPV-related cancers, such as anal cancers and penile cancers and oropharyngeal cancers,” he said.

Several recent studies examining new therapies that may reduce the intensity of traditional treatments while maintaining survival rates would have a major effect on the field, according to Sturgis.

Gillison said the rise in the number of cases of HPV-related cancers is changing the patient population considered to be at risk, and more research is vital.

“The most important thing for clinicians to do is be aware that trials are being developed and strongly encourage their patients to participate,” she said.  Christen Cona

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

June, 2016|Oral Cancer News|