Timing and intensity of oral sex may affect risk of oropharyngeal cancer

Source: www.eurekalert.org
Author: Research News

Human papillomavirus (HPV) can infect the mouth and throat to cause cancers of the oropharynx. A new study published early online in CANCER, a peer-reviewed journal of the American Cancer Society, has found that having more than 10 prior oral sex partners was associated with a 4.3-times greater likelihood of having HPV-related oropharyngeal cancer. The study also shows that having oral sex at a younger age and more partners in a shorter time period (oral sex intensity) were associated with higher likelihoods of having HPV-related cancer of the mouth and throat.

Previous studies have shown that performing oral sex is a strong risk factor for HPV-related oropharyngeal cancer. To examine how behavior related to oral sex may affect risk, Virginia Drake, MD, of Johns Hopkins University, and her colleagues asked 163 individuals with and 345 without HPV-related oropharyngeal cancer to complete a behavioral survey.

In addition to timing and intensity of oral sex, individuals who had older sexual partners when they were young, and those with partners who had extramarital sex were more likely to have HPV-related oropharyngeal cancer.

“Our study builds on previous research to demonstrate that it is not only the number of oral sexual partners, but also other factors not previously appreciated that contribute to the risk of exposure to HPV orally and subsequent HPV-related oropharyngeal cancer,” said Dr. Drake. “As the incidence of HPV-related oropharyngeal cancer continues to rise in the United States, our study offers a contemporary evaluation of risk factors for this disease. We have uncovered additional nuances of how and why some people may develop this cancer, which may help identify those at greater risk.”

Full Citation:
“Timing, number, and type of sexual partners associated with risk of oropharyngeal cancer.” Virginia E. Drake, Carole Fakhry, Melina J. Windon, C. Matthew Stewart, Lee Akst, Alexander Hillel, Wade Chien, Patrick Ha, Brett Miles, Christine G. Gourin, Rajarsi Mandal, Wojciech K. Mydlarz, Lisa Rooper, Tanya Troy, Siddhartha Yavvari, Tim Waterboer Nicole Brenner, David W. Eisele, and Gypsyamber D’Souza. CANCER; Published Online: January 11, 2021 (DOI: 10.1002/cncr.33346).

Personalized vaccines: the new frontier in cancer treatment

Source: www.wildcat.arizona.edu
Author: Udbhav Venkataraman

Exciting results from a new clinical study showed that a personalized vaccine combined with an immunotherapy drug had a promising response rate in patients with advanced incurable head and neck cancer.

Dr. Julie Bauman, chief of Hematology and Oncology at the University of Arizona College of Medicine — Tucson, led a phase one clinical trial with the pharmaceutical company, Moderna, to test the combined use of personalized vaccines created from tumor DNA with the immunotherapy drug pembrolizumab.

Of the 10 patients involved in the study, five of the them responded to the treatment, meaning 30% of the cancer mass had decreased. Furthermore, two of the patients completely responded, meaning that cancer could not be detected.

Molly Cassidy is one of those two patients. What was initially determined to be a stress-related ear-ache turned out to be an aggressive case of squamous cell carcinoma, a form of head and neck cancer.

Head and neck cancers impact the linings of the mouth and throat. Risk factors for this disease include alcohol consumption, smoking and other environmental carcinogens that we are all exposed to. It can also be caused by human papillomavirus (HPV).

Cassidy did not fit this profile at all.

“I’m HPV-negative. I didn’t drink. I didn’t smoke. I’m a woman. I was the first person in my family to have cancer. I was 35 when I got my diagnosis,” Cassidy said. “I was also in really good health … To hear that I had cancer was really surprising.”

With an initial prognosis that the cancer was curable, Cassidy underwent a standard but invasive surgery followed by a grueling series of radiation and chemotherapy sessions over the next few months.

Just a week after completing Cassidy’s initial treatment plan, the cancer returned aggressively. She had several tumors in her neck and they were spreading to her lungs. Her prognosis became bleaker.

“Having such a quick recurrence was not a good sign … they put me on a palliative plan and I was told I need to get my affairs in order,” Cassidy said. “I wasn’t expected to live for more than a year.”

Cassidy now had advanced incurable head and neck cancer which occurs when an initial cancer treatment fails and the cancer returns. This combined with the fact that she was HPV negative made her eligible for Bauman’s clinical study.

One of the recent frontiers of cancer research has been immunotherapy — harnessing our immune systems to fight cancer. Our immune system is able to detect and attack foreign invaders in our bodies, including cancer cells. However, these cells develop ways to hide from the immune system.

Immunotherapy can involve using medication to activate and train the immune system to recognize and eliminate these cancer cells. When this treatment is effective, the response can be long-lived.

“I can give you chemo and drive you to a complete response, but as soon as chemo is not there, the cells that are left become resistant and grow back,” Bauman said. “Immunotherapy leaves behind an army of T-cells that if the cancer rears its ugly head again, will presumably kill it.”

According to Bauman, the current U.S. Food and Drug Administration-approved therapies are non-specific. These therapies generally activate the T-cells of the immune system which recognize foreign invaders. This method means that T-cells that recognize cancer cells would be activated. This method of therapy however has a low effectiveness rate.

“In head and neck cancer, this class of therapy is successful 10-15%of the time … We want that to be more often,” Bauman added.

Furthermore, there can be auto-immune side effects because T-cells that recognize our own healthy tissues may start attacking those very tissues.

This is where new and fascinating technology comes into the picture: personalized vaccines. This approach is a specific approach, where T-cells are activated based on the mutations of the patient’s cancer.

After taking a sample of cancer cells from the patient, those cells’ DNA is sequenced. Using a computational algorithm, the cancer DNA is compared to the patient’s healthy DNA to find the specific mutations present in that patient’s cancer. From all those mutations, Moderna is able to synthesize a messenger RNA vaccine, which can be used to train the appropriate T-cells to recognize abnormal proteins from these cancer cells.

A helpful video about the process can be found at the UA Health Sciences website. The clinical trial consisted of using both this personalized vaccine approach with the FDA approved T-cell activator pembrolizumab.

“The trial is the combination of using those mutations almost like a trojan horse … educating the immune system to see those mutated proteins at the same time as we give the unbridled T-cell activator,” Bauman said. “We’re awakening T-cells, but we’re saying this is the particular class of T-cells that we are calling.”

For the trial, each patient was given two doses of pembrolizumab over six weeks. During this time, the vaccine was developed by Moderna. After the vaccines were created, the patients received one dose of their vaccine every three weeks for nine weeks along with the pembrolizumab, and the cancer was monitored using a CAT scan.

And the results show that the vaccines are safe. This seems really promising and exciting to pursue.

“Although it is only 10 patients, and we have to not only overpromise … it is a really strong signal to expand the study and to see if we continue to see what we saw with these 10 patients,” Bauman said.

“When I was going into treatment, I was really ill and the treatments themselves were pretty hard on me. Cancer treatment is no walk in the park,” Cassidy said. “But once I got through the treatment’s initial side effects, I started to notice an increase in my energy and I wasn’t in as much pain.”

Having completely responded to her treatment, Cassidy is now able to live a normal life. She has spoken with various dentists and used her platform to help educate people about the prevalence and signs of oral cancers and the importance of understanding what the inside of our mouths are supposed to look like.

“It also brought forth what are the most important things for me — my son and husband and the importance of slowing down and enjoying my time with my family,” Cassidy said.

There are many new things that Bauman is looking into researching further. As they expand the trial to 40 participants for the next phase of trials, she is exploring how to optimize the vaccine.

“If we can selectively educate the immune system … we can have a therapy that is active, could drive a permanent response and not be toxic or harsh on the rest of the body,” Bauman said.

Bauman also mentioned that this optimization might mean potentially experimenting with a different drug than pembrolizumab for treatment, although this is a great start. They have also taken samples of the T-cells from the patients to see which types of mutations the T-cells respond best to.

“People who have advanced in cancer … have extraordinary suffering because cancer is uncontrolled in this area where things are critical to our humanity, like talking and breathing and eating and kissing and smiling. To be able to reverse that suffering and offer that hope is uniquely gratifying,” Bauman said.

2020-12-09T06:51:37-07:00December, 2020|Oral Cancer News|

Mouth cancer in the UK at record high

Source: www.hippocraticpost.com
Author: staff

New cases of mouth cancer in the UK have risen to a record high, according to the findings of a new report.

  • New figures show there have been 8,722 new cases of mouth cancer in the UK last year.
  • This is an increase of 58% compared to ten years ago and 97% compared to 20 years ago.
  • Data released in a new report to coincide with November’s Mouth Cancer Action Month.

Figures collected by the Oral Health Foundation show that 8,722 people in the UK were diagnosed with the disease last year, increasing by 97% since 2000.

Mouth cancer cases in the UK have soared for the 11th year in a row and have more than doubled within the last generation.

The findings are part of the charity’s new State of Mouth Cancer UK Report 2020/21 and have been released to coincide with November’s Mouth Cancer Action Month.

Dr Nigel Carter OBE, Chief Executive of the Oral Health Foundation, believes with mouth cancer cases continuing to rise, more must be done to raise awareness of the disease.

Dr Carter says: “While many cancers are seeing a reduction in the number of people affected, mouth cancer is one of very few that is sadly going the other way. Established risk factors like smoking and excessive alcohol have been joined by emerging causes like the human papillomavirus (HPV). This has changed the profile of the disease quite considerably over recent years and mouth cancer can now affect anybody.

“The disease can have a devastating and lasting effect on a person’s life. It can change how somebody speaks, it makes eating and drinking more difficult, and often leads to changes to a person’s physical appearance. Because of this, it also takes a heavy toll on a person’s mental health too.

“One of the biggest challenges we face regarding mouth cancer is how little educational support it receives from government and public health bodies. As part of Mouth Cancer Action Month, we will be working with thousands of organisations to improve awareness of the disease so that more people are able to recognise the early warning signs.”

Statistics from governing health bodies across the UK show around two-in-three (67%) mouth cancers are recorded in men while three-in-four (78%) are in the over 55’s.

Mouth cancer is most likely to occur in the tongue, contributing to more than one-in-three (34%) cases. Mouth cancer can also appear in the tonsils, the roof and floor of the mouth, lips and gums.

The early warning signs of the disease include mouth ulcers that do not heal within three weeks, red or white patches in the mouth, or unusual lumps and swellings. Persistent hoarseness could also be a symptom.

Dr Catherine Rutland, Clinical Director at Denplan, part of Simplyhealth, speaks about the importance of knowing how to spot mouth cancer early and acting quickly if you notice anything out of the ordinary.

Dr Rutland says: “Self-checks and regular dental visits are extremely important for spotting mouth cancer in its initial stages, yet public awareness of mouth cancer actually remains very poor – around 3 out of 4 people said they did not know what the symptoms of mouth cancer are in the Oral Health Foundation’s latest research. Many mouth cancer cases are caught far too late. For a significant proportion of patients, a delay of three to six months in diagnosis and treatment will affect the likelihood of achieving long-term survival.

“Be ‘mouthaware’ and alert to any unusual changes to the mouth, head or neck. Mouth ulcers lasting more than three weeks, unexplained persistent lumps, red patches and white patches are all signs that should be checked by a dentist. If you notice anything out of the ordinary, don’t wait. Book an appointment with your dentist so that they can examine you.

“For Mouth Cancer Action Month this November, make sure you know the basics. Learn how to perform a quick self-check (visit mouthcancer.org), know what to look for and where mouth cancer occurs. By doing this, you give yourself the best possible chance of overcoming mouth cancer.”

Roy Templeton (59) from Beauly, Inverness, was diagnosed with mouth cancer of the tonsils. Now given the all clear, Roy says his experience of mouth cancer will never leave him.

Roy says: “Although I had heard of mouth cancer, I wasn’t aware how terribly common it was, and I didn’t know anybody personally who had had it. Any conversations I’d heard about people with mouth cancer had given me the impression it happens to much older people and especially those who heavily drank or smoke. I didn’t smoke and I was a moderate drinker, so the diagnosis really came as a shock.

“Going through cancer treatment had a big effect on me mentally. It crystallised in my own mind that life is quite precious. When it comes to opportunities arising in your life, either in work or your personal life, you want to grab every moment more than ever before.

“I was quite fortunate that I went to my GP early when I found something not right. If you have any inkling something is wrong, I would urge you to get it looked at. Getting checked out early could save your life.”

Spotting mouth cancer early is crucial for beating the disease. Early detection boosts the chances of survival from 50% to 90% while also dramatically improving a person’s quality of life.

Sadly, far too many mouth cancers are caught in the late stages of the disease. Latest annual reports show mouth cancer claims 2,702 lives a year, which on average is one person every hour.

2020-11-04T11:53:47-07:00November, 2020|Oral Cancer News|

Smell of a person’s breath may help identify early cancers

Source: www.theweek.in
Author: staff

Cancer researchers from Flinders University have reported significant progress in developing a method to test exhaled breath profiles which accurately differentiate head and neck cancer from non-cancer patients.

Previous studies elsewhere have indicated that the exhaled breath condensate can reveal gene mutations or DNA abnormalities in patients with lung cancer.

The global quest to use a person’s breath analysis for rapid, inexpensive and accurate early-stage testing for cancer and other diseases has taken a leap forward.

The Australian researchers collected breath samples from 181 patients suspected of having early-stage head and neck squamous cell carcinoma (HNSCC) before any treatment began.

“We sought to determine the diagnostic accuracy of breath analysis as a non-invasive test for detecting head and neck cancer, which in time may result in a simple method to improve treatment outcomes and patient morbidity,” says lead researchers Dr Roger Yazbek and Associate Professor Eng Ooi.

Worldwide, head and neck cancer accounts for 6 percent of all cancers, killing more than 300,000 people per year globally. Tobacco, alcohol and poor oral hygiene are known major risk factors for this cancer.

A surge in human papilloma virus (HPV)-associated head and neck cancers is seeing these cancers affecting a much younger population, the researchers say.

Current therapies are effective at treating early-stage disease, however late-stage presentations are common, and often associated with poor prognosis and high treatment-related morbidity.

In the Australian study, a selected ion flow-tube mass spectrometer was used to analyse breath for volatile organic compounds. Using statistical modelling, the Flinders researchers were able to develop a breath test that could differentiate cancer and control (benign disease) patients, with an average sensitivity and specificity of 85 percent.

Diagnosis was confirmed by analysis of tissue biopsies.

“With these strong results, we hope to trial the method in primary care settings, such as GP clinics, to further develop its use in early-stage screening for HNSCC in the community,” says co-lead author Dr Nuwan Dharmawardana.

The study has been published in the British Journal of Cancer.

Most parents of unvaccinated teens have no intention of getting HPV vaccine for their kids, study finds

Source: www.newstribune.com
Author: Kasra Zarei, The Philadelphia Inquirer

The human papillomavirus (HPV) vaccine has been proven to prevent certain types of oral and genital cancers and other health problems. However, in a study published this week in Lancet Public Health, researchers found that more than half of the parents of adolescents who have not received the HPV vaccine had no intention to initiate the vaccine series for their children.

Using data from a nationally representative survey of U.S. adolescents, the study authors estimated national-level and state-level parental intent to initiate and complete the HPV vaccine series for their kids. In states including Idaho, Montana, Nebraska, North Dakota, Oklahoma, and Utah, more than 65 percent of parents of unvaccinated adolescents had no intention to initiate the HPV vaccine series.

According to the most recent data by the Centers for Disease Control and Prevention, Wyoming and Mississippi have the lowest HPV vaccine rates at roughly 50 percent. The new study found of parents of unvaccinated adolescents in these states, almost 62 percent and 57 percent, respectively, did not intend to initiate the HPV vaccine for them.

Lack of parental intent to complete the vaccine series was lowest in the District of Columbia, at nearly 11 percent, and Rhode Island, at 20 percent. HPV vaccination is mandated in both regions.

In Philadelphia, HPV vaccine coverage is among the highest in the country — roughly 71 percent in 2018, according to CDC data. Still, in Pennsylvania, between 60-65 percent of the parents of unvaccinated adolescents do not intend to have their kids start the vaccine.

“I was surprised that the intent to vaccinate (for HPV) is this low,” said Cynthia DeMuth, a primary-care pediatrician in Harrisburg and the Pennsylvania chapter immunization representative for the American Academy of Pediatrics, who was not involved with the study.

The HPV vaccine guidelines recommend adolescents who start the vaccine series before their 15th birthday receive two doses, or three doses if they start after their 15th birthday.

But even among kids who receive the first dose, many parents don’t intend to have their child complete the series, the study found. Nationally, almost a quarter of the parents of adolescents who received the first dose of the vaccine had no intention to complete the series. In states like Arkansas, Florida, Georgia, Hawaii, Idaho, Utah, and West Virginia, that percentage was even higher at more than 30 percent.

Research suggests parents’ main driver is perceived safety of the vaccine, which may be due to past reports of adverse effects since the vaccine’s approval in 2006.

“It’s a safe and effective vaccine, and there haven’t been any serious adverse events related to the vaccine,” DeMuth said.

Studies have since proven rates of cancers that are prevented by the HPV vaccine have greatly decreased. Experts estimate widespread HPV vaccination has the potential to reduce new cervical cancer cases around the world by as much as 90 percent.

Lack of knowledge about the vaccine and lack of recommendations from health-care providers are also reasons expressed by parents with no intent to vaccinate their kids.

“Adults between the ages of 18 to 45 don’t even know what HPV is, and there is a vaccine to protect it,” said Kalyani Sonawane, professor in the department of management, policy, and community health at the University of Texas Health Science Center and lead author of the study.

There are also perceptions the vaccine is not needed for younger teens who may not be sexually active, as HPV is mainly sexually transmitted.

When declining the HPV vaccine, “sometimes parents say their child is too young and isn’t sexually active, and they’ll think about it for next year,” DeMuth said. “But the vaccine works better at young ages — the antibody levels are higher at a younger age with two shots compared to three shots at older ages.”

These trends worry experts who say it could cause a rise in HPV-related cancer rates.

“Particularly among girls, the coverage rate has not improved. If parents are not intending to vaccinate their kids, in the future, we could expect to see an increase in HPV-associated cancers,” Sonawane said.

Sonawane said while people may not think about HPV like measles, for which low vaccine coverage can lead to outbreaks, HPV is still an infectious disease and can remain in the body for years. HPV-related cancers are already on the rise by almost 3 percent. Experts caution if vaccine coverage doesn’t improve, increases in HPV-related cancers are only going to get worse.

Health care professionals and pediatricians can play an immediate role in addressing these potential health concerns.

“A strong recommendation from the provider is one of the most significant things providers can do,” DeMuth said. “The longer it’s been out, the more confident I am it’s safe, and the better I feel about giving a strong recommendation for the vaccine.”

Researchers take head and neck cancer by the throat

Source: www.brisbanetimes.com.au
Author: Stuart Layt

Research has identified more weak spots in a deadly type of head and neck cancer that it is hoped will lead to more effective treatments.

Oropharyngeal cancer can affect the base of the tongue, the tonsils, soft palate and parts of the throat, and almost half of all cases in Australia are caused by the human papillomavirus (HPV).

Current immunotherapies target two protein receptors on the cancer; however, they have had mixed success.

Lead researcher Professor Rajiv Khanna from QIMR Berghofer said they had identified four more spots on the genome of the cancer that they believed could be targeted by immunotherapy.

“Everybody has been trying to make immunotherapies that target those two antigens, but what we have found is that while those two are important, we were ignoring some of the other antigens,” Professor Khanna said.

“We took immune cells out of our patients and effectively asked them what they could “see” other than [the two proteins] E6 and E7, and actually they could see others.”

The study analysed immune cells taken from 66 oropharyngeal cancer patients at the Royal Brisbane and Women’s Hospital and the Princess Alexandra Hospital.

Co-lead author Professor Sandro Porceddu, the director of radiation oncology research at the Princess Alexandra Hospital, said they were now developing therapies based on the research.

“We’re already working on developing better killer T-cell immunotherapies that recognise all, or a combination, of these proteins,” Professor Porceddu said.

“Different combinations of the proteins are present on different patients’ cancer cells, so we will develop immunotherapies with different bunches of keys for different patients.”

At present, the cancer is treated with a combination of chemotherapy and radiation therapy, but it is hoped an effective immunotherapy will eventually become the standard treatment.

Oropharyngeal cancers are the sixth-most-common type of cancer worldwide, with US actor Michael Douglas diagnosed with stage four oral cancer in 2010, before going into remission after aggressive radiation treatment and chemotherapy.

Douglas credited HPV for his cancer but later said he was a heavy smoker and drinker, habits that also increase the risk of developing the disease.

In Queensland the incidence rate for the cancer type has increased by 162 per cent in men and 40 per cent in women over a 15-year period, according to data from the Cancer Alliance Queensland.

That is despite the development of the HPV vaccine from Professor Ian Frazer and his team at the University of Queensland in the early 2000s.

However, experts warn the impact of widespread immunisation programs for HPV will not be felt for decades.

The research has been published in the Journal of Experimental Medicine.

FDA approves Gardasil 9, the HPV vaccine, to prevent head-and-neck cancer

For the past decade, evidence has suggested that Gardasil, the HPV vaccine, could stem an epidemic of throat cancer. But it has also never received approval from the Food and Drug Administration for that use — and it was unclear if it ever would.

On Friday, the agency granted that approval, clearing the latest version of the vaccine, Gardasil 9, to prevent a cancer that affects 13,500 Americans annually. The decision was announced by Gardasil’s maker, Merck.

The decision doesn’t change recommendations about who should get the vaccine, which is already recommended for females and males ages 9 through 45 to prevent cervical, vulvar, vaginal, and anal cancer as well as genital warts. But cancers of the head and neck — mainly those of the tonsils and throat — have been left off the list.

It’s a striking omission, because head and neck cancer, mostly cancer of the throat, is the most common malignancy caused by HPV, the human papilloma virus, in the U.S. According to the Centers for Disease Control and Prevention, there are 35,000 cases of HPV-related cancer in the U.S. annually. On top of the 13,500 cases in the throat, 10,900 are cases of cervical cancer.

“That’s excellent news,” said Stewart Lyman, a pharmaceutical consultant whose doctors discovered a tumor in his throat in 2016. It was removed surgically, and was caused by HPV. “To have this extended to head and neck cancer is really very helpful for helping to inform the public that this serious disease, which has significant morbidity and mortality associated with it, can be prevented with the vaccine,” Lyman said.

Marshall Posner, the director of head and neck medical oncology at the Tisch Cancer Institute, said the approval is “a good thing for the FDA to do” and that he would be “thrilled” if head and neck cancer cases could be reduced through vaccination in coming decades. He said he has “every expectation” that an HPV vaccine would reduce cancer rates.

The original version of the Gardasil vaccine was approved in 2006 for girls and women between the ages of 9 and 26 based on data from clinical trials showing that the vaccine, by preventing HPV infection, could also prevent precancerous cervical lesions. But such lesions don’t exist in head and neck cancer, and it was not clear how to prove the vaccine’s efficacy.

Maura Gillison, now a professor at M.D. Anderson Cancer Center, first connected a subset of head-and-neck cancers to HPV in 1999. But then she and other epidemiologists noticed something: The number of head and neck cancers was rising rapidly, and HPV seemed to be a culprit. What’s more, these sexually transmitted cases seemed different — and somewhat easier to treat. The most common victims were middle-aged men who had contracted the virus decades before.

The FDA is granting what’s known as an accelerated approval, meaning that the decision is contingent on the production of more data and is based on what’s known as a “surrogate endpoint” — an indication that a medicine works that is not foolproof. In this case, the FDA is approving the drug based on data on preventing anogenital infection. In February, Merck began a study of  6,000 men that will test whether patients who receive the vaccine are less likely to get persistent HPV infections in their throats.

Adding another disease to the approval does impact what Merck can say to doctors and patients about HPV and head and neck cancer. “It’s something that was missing in the label,” said Alain Luxembourg, director, clinical research, Merck Research Laboratories. “It is something missing in the conversation between patients and doctors.”

Otis Brawley, an oncology and epidemiology professor at Johns Hopkins University, said that while he is usually opposed to surrogate endpoints, in this case he is comfortable with the decision. “There’s already enough reasons to vaccinate for HPV in men,” he said, adding that doing so broadly might make it possible to eradicate the virus, and the cancers it causes.

For Gillison, who spotted the emergence of HPV throat cancer, it came too late. She pushed Merck to do a study, and said that the one that started in February is coming “10 years plus after when it would have really mattered.” She also thinks that the real reason for the decision is the weight of epidemiologic evidence that she and others produced.

“The fact of the matter is that this approval probably has little whatsoever to do with the anal data per se,” Gillison wrote via text message. “It is because the FDA is made more comfortable with inference because of all the data that has been generated regarding the relationship between oral HPV infection and HPV vaccination outside of vaccine trials in the last 10 years.”

FDA approves Gardasil 9, the HPV vaccine, to prevent head-and-neck cancer

Source: www.statnews.com
Author: Matthew Herper

For the past decade, evidence has suggested that Gardasil, the HPV vaccine, could stem an epidemic of throat cancer. But it has also never received approval from the Food and Drug Administration for that use — and it was unclear if it ever would.

Charles Rex Arbogast/AP

On Friday, the agency granted that approval, clearing the latest version of the vaccine, Gardasil 9, to prevent a cancer that affects 13,500 Americans annually. The decision was announced by Gardasil’s maker, Merck.

The decision doesn’t change recommendations about who should get the vaccine, which is already recommended for females and males ages 9 through 45 to prevent cervical, vulvar, vaginal, and anal cancer as well as genital warts. But cancers of the head and neck — mainly those of the tonsils and throat — have been left off the list.

It’s a striking omission, because head and neck cancer, mostly cancer of the throat, is the most common malignancy caused by HPV, the human papilloma virus, in the U.S. According to the Centers for Disease Control and Prevention, there are 35,000 cases of HPV-related cancer in the U.S. annually. On top of the 13,500 cases in the throat, 10,900 are cases of cervical cancer.

“That’s excellent news,” said Stewart Lyman, a pharmaceutical consultant whose doctors discovered a tumor in his throat in 2016. It was removed surgically, and was caused by HPV. “To have this extended to head and neck cancer is really very helpful for helping to inform the public that this serious disease, which has significant morbidity and mortality associated with it, can be prevented with the vaccine,” Lyman said.

Marshall Posner, the director of head and neck medical oncology at the Tisch Cancer Institute, said the approval is “a good thing for the FDA to do” and that he would be “thrilled” if head and neck cancer cases could be reduced through vaccination in coming decades. He said he has “every expectation” that an HPV vaccine would reduce cancer rates.

The original version of the Gardasil vaccine was approved in 2006 for girls and women between the ages of 9 and 26 based on data from clinical trials showing that the vaccine, by preventing HPV infection, could also prevent precancerous cervical lesions. But such lesions don’t exist in head and neck cancer, and it was not clear how to prove the vaccine’s efficacy.

Maura Gillison, now a professor at M.D. Anderson Cancer Center, first connected a subset of head-and-neck cancers to HPV in 1999. But then she and other epidemiologists noticed something: The number of head and neck cancers was rising rapidly, and HPV seemed to be a culprit. What’s more, these sexually transmitted cases seemed different — and somewhat easier to treat. The most common victims were middle-aged men who had contracted the virus decades before.

The FDA is granting what’s known as an accelerated approval, meaning that the decision is contingent on the production of more data and is based on what’s known as a “surrogate endpoint” — an indication that a medicine works that is not foolproof. In this case, the FDA is approving the drug based on data on preventing anogenital infection. In February, Merck began a study of 6,000 men that will test whether patients who receive the vaccine are less likely to get persistent HPV infections in their throats.

Adding another disease to the approval does impact what Merck can say to doctors and patients about HPV and head and neck cancer. “It’s something that was missing in the label,” said Alain Luxembourg, director, clinical research, Merck Research Laboratories. “It is something missing in the conversation between patients and doctors.”

Otis Brawley, an oncology and epidemiology professor at Johns Hopkins University, said that while he is usually opposed to surrogate endpoints, in this case he is comfortable with the decision. “There’s already enough reasons to vaccinate for HPV in men,” he said, adding that doing so broadly might make it possible to eradicate the virus, and the cancers it causes.

For Gillison, who spotted the emergence of HPV throat cancer, it came too late. She pushed Merck to do a study, and said that the one that started in February is coming “10 years plus after when it would have really mattered.” She also thinks that the real reason for the decision is the weight of epidemiologic evidence that she and others produced.

“The fact of the matter is that this approval probably has little whatsoever to do with the anal data per se,” Gillison wrote via text message. “It is because the FDA is made more comfortable with inference because of all the data that has been generated regarding the relationship between oral HPV infection and HPV vaccination outside of vaccine trials in the last 10 years.”

Fighting throat cancer with T cells

Source: www.miragenews.com
Author: press release, Centenary Institute

Research led by the Centenary Institute has discovered that immune cells accumulating within the tumor environment, called tumor-resident T cells, are a critical determinant in survival rates of patients suffering from throat cancer.

Reported in the prestigious ‘Journal for ImmunoTherapy of Cancer’, the research suggests that strategies aiming to boost these T-cells at tumor sites could be beneficial to patients.

“Oropharyngeal squamous cell carcinoma (OPSCC) is a form of throat cancer. It can be caused by environmental factors such as smoking or by human papillomavirus infection (HPV), the same virus that causes cervical cancer in women,” said Ms Rehana Hewavisenti, lead author of the study and researcher at the Centenary Institute and the University of Sydney.

“We knew that patients with HPV-related OPSCC had far better clinical outcomes compared to other OPSCC patients but we didn’t know why,” she said.

In examining over sixty patient samples, Ms Hewavisenti and her colleagues discovered that increased levels of tumor-resident T cells, whether in HPV or non-HPV OPSCC cases, was clearly associated with improved patient survival outcomes.

“It was the accumulation of these immune T-cells, in and around the tumour site that appeared to be key,” said Ms Hewavisenti.

The researchers also found in their study that HPV OPSCC patients generally had far higher levels of tumour-resident T cells compared to their non-HPV OPSCC patient counterparts.

“We think these HPV positive patients tended to have better clinical outcomes as HPV infection is likely to favor the accumulation of these beneficial T-cells within the tumor area,” she said.

Dr Mainthan Palendira, Head of the Centenary Institute’s Human Viral and Cancer Immunology Laboratory and senior author on the research paper believes the research findings have major implications.

“Now that we understand how important this immune response is in relation to OPSCC, we can begin developing new treatment strategies focused on recruiting these favourable tumor-resident T cells directly to tumors,” he said.

Dr Palendira believes that looking at the amount of these T-cells in cancer could help clinicians to personalize the best treatment approach for individual patients.

“We also think that our research demonstrating viral (HPV) links with this tumor-resident T cell accumulation could help in future cancer vaccine development efforts too,” he said.

Experts release new guidelines for studies into most effective treatments for HPV-positive throat cancer

Source: en.brinkwire.com
Author: provided by University of Birmingham, United Kingdom

Heightened caution is needed when considering de-escalation trials for patients with Human papillomavirus (HPV)-positive oropharyngeal cancer (OPC), to ensure minimal harm to patients, new guidelines from a group of international head and neck cancer experts have suggested.

HPV-positive oropharyngeal cancer is a cancer of the throat caused by the human papillomavirus—a common, but symptomless group of sexually transmitted viruses. Instances of many throat and neck cancers have declined as smoking rates have fallen, whereas HPV-positive OPC has increased, largely affecting younger patients.

The standard course of treatment for this disease is a combination of cisplatin (a common chemotherapy drug) and radiotherapy. The younger age of the patient population, significantly improved prognosis, and relatively minimal morbidities caused by the standard treatment pathway have led to the popularisation of the concept of treatment de-escalation as a way to improve the quality of life of patients by reducing dosage or frequency of treatment.

These new recommendations, published today in the Journal of Clinical Oncology have been created by the Head and Neck Cancer International Group, a group of experts from nineteen countries, led by the University of Birmingham, UK. The guidelines have been prompted by the recent results of the first three randomised de-escalation trials which suggested a clear detriment in survival when cisplatin is omitted or substituted to minimise side effects.

After a review of available HPV-positive OPC literature, the guidelines recommend an overall need for caution when considering de-escalation options, even in instances where there appears to be possible favourable disease outcomes. Experts also recommend a revised approach to how findings are evaluated during phase II studies to ensure that any potential risks to survival are identified and only if none are present should phase III trials follow.

The guidelines also recommend that de-escalation trials should only be considered for well-defined, very low risk groups and only when there is a strong rationale for investigating a particular treatment strategy. Additionally harm-minimisation techniques should be considered as an alternative. Importantly, treatments should not be implemented into clinical practice before high level evidence is available.

Corresponding author Professor Hisham Mehanna, Director, Institute of Head and Neck Studies and Education (InHANSE) at the University of Birmingham said: “Clinicians and researchers have to be careful when planning and undertaking de-escalation studies, as trials to date have that harm can befall patient. Very controlled and small strides need to be taken when evaluating a possible de-escalation strategy, especially one that removes cisplatin.”

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