Public urged to help cancer researchers by playing online game

Source: news.sky.com
Author: staff

Scientists have turned to the public to help with their latest cancer research in the form of an online citizen science game. The game is designed to train a computer algorithm to recognise oral cancers in medical images.

AcCELLerate tasks users with tracing the outline of a series of fluorescent dye-stained tongue images which become increasingly complex, using their computer mouse or finger on a smartphone.

It is designed to train a computer algorithm to recognise oral cancers in medical images, improving its ability to differentiate between healthy and cancerous cells.

“I’m really excited that the public will be contributing to my work on oral cancer,” said Dr Priyanka Bhosale, from King’s College London’s Centre for Stem Cells and Regenerative Medicine.

“The outcomes of the public training the AI will help me assess tumour tissue samples in a faster and more reliable way.”

It is hoped the tool can be used to advance research into other cancers.

The game forms part of the Royal Society Summer Science 2021 event and can be found at citizen.cellari.io.

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RowanSOM researcher begins human trials for cancer treatment drug

Source: today.rowan.edu
Author: news release

Could a targeted therapy derived from a plant used medicinally in China for centuries offer the next breakthrough in cancer treatment? Dr. Gary Goldberg, associate professor in the Department of Molecular Biology at Rowan University School of Osteopathic Medicine (RowanSOM), is undertaking a human clinical trial to find out.

Goldberg and his team are collaborating with a group at the Rutgers New Jersey Medical School headed by Dr. Mahnaz Fatazadeh, professor at Rutgers School of Dental Medicine, to test a new drug candidate called MASL. This novel compound has been trademarked and licensed from Rowan University by Sentrimed, a company founded by Goldberg. MASL is derived from Maackia amurensis, a legume tree native to the Amur River valley, which flows through parts of Russia and China.

The MASL human trial marks a milestone for RowanSOM, Goldberg noted.

“Coming up with a new drug and taking it to a clinical trial is an excellent example of investigator-initiated research from bench to bedside,” said Goldberg. “It has taken a lot of collaboration and work to get to this point.”

The FDA considers MASL an investigational new drug.

“This is a unique Phase I trial,” Goldberg said. “This study integrates investigation of patient safety, along with potential efficacy and proof of concept mechanistic studies.”

Goldberg and his team began the ongoing human trial, involving 20 cancer patients, in fall 2020. While MASL has the potential to treat many kinds of cancer, this trial will test MASL’s effects on oral cancer.

“Oral cancer is a horrible disease,” Goldberg said. “It kills as many people in this country as melanoma. In addition, survivors can suffer from decreased quality of life resulting from disfigurement and other consequences of surgery required for effective treatment.”

Since oral cancer causes lesions in the mouth, Goldberg and his team are administering MASL topically, with an oral lozenge, and systemically, as the compound enters the circulatory system after digestion.

Goldberg and his team aim to target cancer cells using specific proteins. Commonly used cancer treatments attack rapidly dividing cells, but not all of these cells are cancerous. This results in collateral damage, leading to a weakened immune system, as well as injury to digestive and other tissues.

MASL is different because, instead of harming all cells that divide rapidly—even normal and healthy ones—it targets the podoplanin (PDPN) protein receptor expressed on the surface of cancer cells.

Proteins are key in targeted cancer treatments, but thousands of proteins are turned on in the body of a cancer patient. Just a tiny fraction of these proteins are necessary for cancer to thrive.

“The most aggressive cancers tend to express high levels of PDPN,” Goldberg explained, including the vast majority of aggressive oral cancers. A normal cell may only have a little of this protein, but abnormal cells have a lot of it.

MASL’s potential goes beyond stopping the growth and spread of cancer cells, possibly even preventing precancerous lesions from turning malignant.

“The PDPN receptor offers exceptional opportunities as a powerful sentinel cancer biomarker and functionally relevant chemotherapeutic target,” Goldberg added.

Goldberg’s students have been heavily involved in developing knowledge of the basic science behind the drug’s efficacy, publishing findings in peer-reviewed journals and assisting directly with the human trial.

“I have seen firsthand the tumor-suppressive effects MASL has in cell culture and animal models,” said Stephanie Sheehan, a sixth-year Ph.D. student of cell and molecular biology who has assisted Goldberg in purifying, profiling and validating MASL in the lab for five years. “I am grateful this noninvasive and nontoxic therapy is being brought to patients.”

Learning about such cancer research drew seventh-year Ph.D. student Edward P. Retzbach to graduate school.

“As I learned more about MASL and the mechanisms behind how it worked, my interest grew,” Retzbach said. “For most preclinical and biomedical research, you don’t get to see the effects for a long time, so it is pretty great to actually see it happen in real time.”

Funding for Goldberg’s research has come from multiple organizations, including the National Institutes of Health, the Osteopathic Heritage Foundation, the N.J. Health Foundation, the Camden Health Research Initiative and the Northarvest Bean Growers Association, as well as Sentrimed and charitable donations.

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World’s first research centre for recurrent head and neck cancer

Source: www.nationalhealthexecutive.com
Author: Jasmine Jackson

The Royal Marsden NHS FT have launched the world’s first research centre for recurrent head and neck cancer, as a result of funding from the Royal Marsden Cancer Charity. It hopes to accelerate research into the disease, which will be carried out by a world-class team of clinicians and researchers.

The International Centre for Recurrent Head & Neck Cancer (IReC) also aims to improve patient outcomes in the UK and beyond, in the curative treatment, palliation, and supportive care of recurrent head and neck cancer.

The IReC announced a series of initiatives to help achieve these goals, including:

  • A national registry to improve understanding around recurrent head and neck cancer, whist capturing the different ways it is treated across the UK.
  • A tissue biobank to support laboratory and translational research.
  • An International Referral Centre to offer rapid second opinions for patients being treated in the UK and internationally.

This will also include the funding of three PhD research fellows, trial managers, a clinical trial nurse and a data manager, to increase research capacity.

Head and neck cancer is the 8th most common cancer in the UK, with more than 12,000 diagnoses each year. After treatment, it is estimated that between 20% and 40% of head and neck cancers will return, and in England, between 28% and 67% survive for five years or more.

IReC Director Professor Vinidh Paleri, Consultant Head and Neck Surgeon at The Royal Marsden, said: “Treating recurrent head and neck cancer is incredibly challenging as these patients have already been treated, often with surgery and radiotherapy, which can cause anatomical changes, scarring, and impaired healing. This means successfully treating the disease requires access to multi-specialty expertise, the latest drugs and surgical technology.

“However, patients with recurrent head and neck cancer in the UK face inconsistent access to treatment, with many treated palliatively not curatively. We also don’t know enough about the disease’s incidence or outcomes as national databases do not provide this information in detail, unlike for primary cancers.

“Through IReC, we aim to transform the treatment and care of recurrent head and neck cancer. From building a better understanding of how the disease is managed across the UK through a national registry, to funding research into novel treatments and minimally invasive surgery, our work will drive better outcomes for patients at The Royal Marsden and across the world.”

The IReC aims to launch more UK and international based projects over the next 10 years, to improve outcomes for patients. Part of this plan includes creating an international network of centres to roll out clinical trials quickly, and a genomics hub to enhance diagnostics and offer personalised treatment.

Charles Wilson, former Booker CEO and the founding donor of IReC, said: “Having been diagnosed with throat cancer three years ago, it is a privilege to support Professor Vinidh Paleri and his amazing team in helping found the International Centre for Recurrent Head & Neck Cancer.

“The need is great and the analytical, surgical and clinical expertise at The Royal Marsden is mind-blowing. The research could make a huge difference to patients around the world.”

The Royal Marsden’s Head and Neck Unit has been recognised as one of the largest of its kind in Europe and over the last two decades has helped pioneer numerous advances in the management of recurrent head and neck cancer.

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‘Vaccine for cancer’ trial begins in Liverpool and this is how it works

Source: www.liverpoolecho.co.uk
Author: Jonathan Humphries, Public Interest Reporter

The first human trials for a groundbreaking ‘vaccine for cancer’ have begun in Liverpool with the first patients recruited.

A team of cancer researchers from Liverpool Head & Neck Centre, The Clatterbridge Cancer Centre, Liverpool University Hospitals and the University of Liverpool are trialling new vaccines that aim to harness a patients own immune system to fight cancer.

Head and neck cancers, which include mouth, throat, tongue and sinus cancers, are particularly difficult to treat and carry a high risk of returning even after successful treatment.

The first UK patient has now been recruited in Liverpool and vaccine production has begun at the Transgene laboratory in France.

More patients will be recruited in coming months, with the aim of administering the first vaccine in a few months, when the usual treatment has been completed.

The Transgene trial will involve around 30 people who have just completed treatment for advanced, but still operable, HPV-negative (not linked to human papilloma virus) squamous cell carcinoma of the head and neck (SCCHN).

How does the vaccine work?

Head and neck cancer can involve many different kinds of gene mutations resulting in the production of new proteins, called ‘neoantigens’, that vary widely between patients.

The Transgene trial aims to produce individualised ‘therapeutic vaccines’, designed to trigger an immune response to the new antigen produced by a particular gene mutation linked to each patient’s own head and neck cancer.

Chief Investigator for the UK trial, Professor Christian Ottensmeier, a Consultant Medical Oncologist at The Clatterbridge Cancer Centre and Professor of Immuno-Oncology at the University of Liverpool, explained the process.

He said: “Cancer develops because of faulty cells.

“Cells in the body are constantly reproducing and sometimes a bit of the genetic code in a cell doesn’t get copied correctly. The new cells develop with faulty genetic code.

“Most of the time, this doesn’t matter because the faulty code doesn’t do anything important.

“Occasionally, however, the faulty code is important. If the body doesn’t spot the error, these faulty cells can continue to reproduce and the person develops cancer.

“The immune system is very good at recognising anything unusual such as viruses and bacteria, and the T-cells trigger antibodies to attack and destroy them.

“Cancer cells can be very good at hiding from the immune system because, apart from the faulty bit of genetic code, they are very similar to healthy cells.

“We are creating a cancer vaccine for each patient by turning the faulty genetic code into an Achilles heel for treatment.

“We already know that the vaccine technology is very effective at waking up the immune system. We hope this means that if the patient develops cells with the same faulty code in the future, their immune system will recognise them straight away and develop antibodies to destroy them before they develop into cancer.”

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Cancer survivors’ tongues less sensitive to tastes than those of healthy peers

Source: www.eurekalert.org
Author: University of Illinois at Urbana-Champaign, News Bureau

Most survivors of squamous cell head and neck cancers report that their sense of taste is dulled, changed or lost during radiation treatment, causing them to lose interest in eating and diminishing their quality of life.

In a study of taste and smell dysfunction with 40 cancer survivors, scientists at the University of Illinois Urbana-Champaign found that the tips of these individuals’ tongues were significantly less sensitive to bitter, salty or sweet tastes than peers in the control group who had never been diagnosed with cancer.

In a paper published in the journal Chemical Senses, the U. of I. team said this diminished taste sensitivity suggested that the taste buds on the front two-thirds of the cancer survivors’ tongues or a branch of the chorda tympani facial nerve, which carries signals from the tip of the tongue to the brain, may have been damaged during radiation therapy.

“While most studies suggest that patients’ ability to taste recovers within a few months of treatment, patients report that they continue to experience taste dysfunction for years after treatment ends,” said M. Yanina Pepino, a professor of food science and human nutrition at the U. of I. “Our primary goal in this study was to test the hypothesis that radiation therapy is associated with long-term alterations in patients’ senses of smell and taste.”

While undergoing radiation and/or chemotherapy, head and neck cancer patients may lose taste buds, triggering a transient reduction in their ability to taste – a condition called hypogeusia – or their perception of tastes may be altered, a condition called dysgeusia that can also occur when nerves are damaged during cancer surgery, she said.

“Taste buds’ average lifespan of about 10 days enables rapid recovery from injury if the stem cells are preserved, yet it also makes the short-lived and long-lived cells within taste buds particularly vulnerable to the direct cytotoxic and anti-proliferative effects of chemotherapy and radiotherapy,” Pepino said.

Prior studies that explored taste loss and perception in these patients showed mixed results. Many of these studies involved “whole mouth” experiments that may not have detected regional damage to the taste buds at the front of the tongue or to the chorda tympani section of the facial nerve, said graduate student Raul Alfaro, the lead author of the study.

The U. of I. team assessed participants’ smell and taste functions separately and explored whether sensory interactions between taste and retronasal odors – aromas from food and beverages that are perceived in the oral cavity while eating or drinking – differed for the cancer survivors and the people in the control group.

The team assessed participants’ ability to taste regionally by applying cotton swabs soaked in flavored solutions to the tips of their tongues.

They also evaluated participants’ whole-mouth taste function by having them swish solutions around in their mouths for five seconds and spit them out. For this test, the participants were presented with nine cups of liquids that contained both taste and smell sensory components. The cups contained two concentrations of strawberry extract in a sucrose solution, lemon extract in citric acid, salt in a vegetable broth and caffeinated instant coffee. They also received one cup of deionized water.

After sipping each sample, participants were asked to identify its taste quality – sweet, salty, bitter, umami (savory) or no sensation – and to rate the smell and taste intensity of the sample on a scale that ranged from “no sensation” to “strongest of any kind.”

Participants tasted the samples twice – once wearing a nose clip and once without – to determine whether their taste perception differed when the nose clip blocked their retronasal olfactory cues.

When participants’ sense of taste was assessed using the whole-mouth test with or without the nose clip, they similarly rated the taste and smell of nearly all of the samples.

However, when participants’ sense of taste was assessed regionally at the tip of the tongue, the cancer survivors were more likely to respond they did not perceive a taste or to misidentify the taste quality – such as bitter, salty or sweet – of multiple samples.

“Although the results from the whole-mouth taste test suggested that head and neck cancer survivors’ taste function was normal and well preserved, results from the regional tests indicated that they had some deficits,” Pepino said. “Subtle taste dysfunction in the tip of the tongue persisted for several months after they completed their oncology treatments.

“Taste dysfunction at the tip of the tongue might sound unimportant; however, there is an elegant cross-talk between the nerves that conveys signals from the tip and the back of the tongue, such that taste signals in the tip of the tongue inhibit signaling from the back. This system allows taste intensity to remain constant in the whole mouth, even when taste signaling coming from the tip of the tongue is reduced. However, reduced signal input can also lead to phantom tastes, metallic taste and other oral symptoms.”

Notes:
Additional co-authors of the study were food science and human nutrition professor Anna E. Arthur, who is also the Sylvia D. Stroup Scholar in Nutrition and Cancer, and an oncology dietitian with the Carle Cancer Center; Dr. Kalika P. Sarma, a radiation oncologist at Carle Foundation Hospital and a clinical assistant professor in the Carle Illinois College of Medicine; and then-research fellow Sylvia L. Crowder.

The work was supported by grants from the U.S. Department of Agriculture National Institute of Food and Agriculture, the Academy of Nutrition and Dietetics, and the Division of Nutritional Sciences at the U. of I.

Crowder’s work on the project was supported by a Carle Illinois Cancer Scholars for Translational and Applied Research Fellowship, as well as a grant from the National Cancer Institute.

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‘On the rise:’ Immunotherapy options for head and neck cancer

Source: www.curetoday.com
Author: Kristie L. Kahl

On behalf of the Head and Neck Cancer Alliance, Dr. Michael Moore spoke with CURE® about emerging therapies that potentially offer exciting new options for the future.

Although rates of head and neck cancer have risen, in part because of the human papillomavirus (HPV), emerging therapies such as targeted agents and immunotherapies are paving the way for future treatment of the disease, according to Dr. Michael Moore.

“I would say (immunotherapy) is probably one of the more exciting parts of what we’ve learned about head and neck cancer in recent years,” he told CURE® as a part of its “Speaking Out” video series.

On behalf of the Head and Neck Cancer Alliance, CURE® spoke with Moore, associate professor of otolaryngology-head and neck surgery and chief of head and neck surgery at Indiana University School of Medicine in Indianapolis, about targeted therapies, immunotherapy and how clinical trials are leading the way for future treatments.

How have genomics and targeted therapies played a role in head and neck cancer treatment?

Well, I would say it’s an emerging role. And it’s not used as commonly in head-neck cancer as it is in some other areas. So molecular testing or targeted therapies essentially are looking at a very specific part of the tumor to see if we can develop a specific drug that will target just that; (the goal is to) weaken the cancer’s defense — that is one way to say it — and try to very specifically treat that cancer in a way that will give us the best chance of getting rid of it and potentially try to limit the side effects related to the treatments. This has become a little bit more common now that the ability to analyze these tumors has become more widely available across the country. But still, the majority of these types of treatment approaches will be in the context of a clinical trial.

Do we have any currently approved targeted therapies for head and neck cancer?

That’s a great question. I think these are kind of different and are emerging all the time. There are ones that are focused on very specific mutations, such as what’s called the BRAF mutation, which is one that can be present in melanoma or certain aggressive cancers, such as thyroid cancer. And other ones will target things like tyrosine kinase inhibitors that have a more focused route to try to combat these tumors. And then there are ones that will be discussed a little later, such as immuno-oncology drugs that focus on the program cell death ligand and the receptor to try to turn the body’s immune system back on. Another example is what’s called Erbitux (cetuximab), which is focusing on a specific receptor on cancer cells, really trying to exploit this particular difference in cancer cells compared with normal tissue to try to give the best chance of getting rid of the tumor, but minimizing the side effects of the treatment.
What role has immunotherapy had in head and neck cancer treatment?

Cancer has a way of almost turning off the local immune system. It blocks many of the local immune responses to it. Normally, the body would say, “Yeah, that’s not part of our normal tissue, we want to get rid of it.” And some cancers have a way of blocking that. These immunotherapies have a way of almost inhibiting that blockage, if you will, or turning the immune system back on and allowing your own body’s immune system to fight these tumors. These can be incredibly effective. The challenge is if they’re only effective in a small minority of cancers. And so, when they do work, they can work extremely well and can give really good and long-lasting results. But in a high percentage of patients, the responses are much more modest or (patients) may not even respond at all.

Can you discuss the currently available immunotherapies for head and neck cancer?

There are two. Opdivo (nivolumab) is one that can be used in patients who have not responded or progressed despite standard therapy, including recent treatment with chemotherapy, including cisplatin. And then Keytruda (pembrolizumab) is another similar amino therapy that can be used and has actually achieved approval for use in the primary setting. When cancer comes back in an area that can’t be treated with either definitive surgery or definitive radiation therapy, you can use that as a next avenue for treatment. These are the two (Food and Drug Administration)-approved drugs that are out there. They also have ongoing studies where they’re being combined with other standard-of- care, primary treatments for head and neck cancer. I think in the next five to 10 years, they’ll likely be integrated much more on the front end of cancer therapy, rather than just offering them to those who don’t have other treatment options.

How do clinical trials help to advance these therapies, and why should patients consider joining one?

These are really what allows us to make our cancer treatment better. We constantly are. It’s not just going out and experimenting on people but, rather, we’re comparing these treatments to see how we can improve on the current standard approach to therapy. If you were to look back 50 to 60 years ago, all we had were big, morbid surgeries that people were put through and possibly adding radiation therapy. And then we added cisplatin, which is a drug that can be effective in enhancing the effects of radiation therapy. Now, as we add these other treatments, such as immunotherapy and other targeted therapies, the only way we know if they have any advantage over what we have to offer, currently, is to compare them in a clinical trial.

And with these clinical trials, those who have designed them have been very thoughtful in trying to do so in a way that compares them and then looks to see: Does that give us a benefit in getting rid of the cancer or curing the cancer, or at a minimum, slowing it down or giving a longer life? And/or does it give better quality of life or reduce the level of side effects? That’s what many of these clinical trials are. Some are adding new agents to see if those work better than other ones. For example, in the HPV-related cancer, some of the clinical trials are saying these respond fairly well to treatment. Can we actually back off on the severity of treatment, give them just as good of a cancer cure but (with) fewer long-term side effects? I think they’re critical as the only way we’re going to figure out how best to manage these types of cancers.

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Personalized 3D-printed shields protect healthy tissue during radiotherapy

Source: physicsworld.com
Author: Jigar Dubal

Personalized 3D-printed devices for radioprotection of anatomical sites at high risk of radiation toxicity: intra-oral device (A), oesophageal device (B) and rectal device (C) generated from patient CT images. The area for protection is highlighted in red. (Courtesy: CC BY 4.0/Adv. Sci. 10.1002/advs.202100510)

One of the primary goals of radiation therapy is to deliver a large radiation dose to cancer cells whilst minimizing normal tissue toxicity. However, most cancer patients undergoing such treatments are likely to experience some side effects caused by irradiation of healthy tissue. The extent of this damage is dependent on the treatment location, with the most common toxicities involving the oral cavity and gastrointestinal tract.

Materials with a high atomic number (Z), often known as radiation-attenuating materials, can be used to shield normal tissue from radiation. However, integrating such materials into current patient treatment protocols has proven difficult due to the inability to rapidly create personalized shielding devices.

James Byrne and colleagues at Brigham and Women’s Hospital, Dana-Farber Cancer Institute, Massachusetts General Hospital and MIT have addressed this need. The team has developed 3D-printed radiation shields, based on patient CT scans, incorporating radiation-attenuating materials to reduce the toxicity to healthy tissue.

Producing personalized 3D-printed shielding
Before a patient undergoes radiotherapy, they undergo CT scans to provide anatomical information that is used to plan their treatment. Byrne and his colleagues utilize these CT images to design personalized radio-protective devices, which they produce through 3D printing.

To determine the most appropriate shielding materials for the device, the researchers tested various elements and alloys, including liquids, with a high Z number. They characterized these materials by measuring their relative mass attenuation coefficients. From this, the team determined that elemental materials demonstrated greater radiation shielding than alloys or composites, and that mercury largely outperformed all other liquids. They then incorporated the high-Z materials into the personalized 3D-printed devices. The devices were made such that the shielding material could be removed to reduce artefacts during CT imaging and replaced prior to treatment.

To evaluate the device’s ability to shield healthy tissue from radiation, the team treated 14 rats with single-dose irradiation, half with and half without radio-protective devices in place, and examined the incidence of toxicities such as oral mucositis and proctitis.

The group also simulated clinical radiation treatments by modelling the radio-protective devices in the treatment planning software. The dose distributions with and without shielding were compared to evaluate the dosimetric impact of the device. The researchers simulated treatments of prostate and head-and-neck cancer patients, selecting the appropriate positioning of the device based on the regions of increased radiation exposure.

Evaluation of radio-protective devices
Histopathological analysis revealed that only one of seven rats with radio-protective devices in place during treatment suffered ulceration on the surface of the tongue. In contrast, all seven control rats, with no device in place, experienced extensive ulcerations on the tongue surface.

The clinical simulations identified that using radio-protective devices during prostate cancer treatment could reduce the dose to healthy tissue by 15% without reducing the dose delivered to the tumour. For the head-and-neck cancer treatment, the dose absorbed by inner-cheek tissue was reduced by 30%.

The results clearly show that the radio-protective devices may improve patient comfort throughout the course of treatment. “Our results support the feasibility of personalized devices for reduction of radiation dose and associated side effects” claims Byrne.

Future clinical implementation
The benefits of using 3D-printed radio-protective devices in the clinic are clear. “This personalized approach could be applicable to a variety of cancers that respond to radiation therapy,” says Byrne.

The researchers acknowledge that full clinical translation of 3D-printed shielding devices will require further development. “Given the small sample size of our dosimetric studies, further investigation in larger cohorts is needed to validate these approaches,” they say.

The researchers publish their findings in Advanced Science.

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Five reasons boys and young men need the HPV vaccine, too

Source: www.mskcc.org
Author: Memorial Sloan Kettering Cancer Center, News and Information

Rich Delgrosso found the lump while shaving. It was on the left side of his neck and it seemed to grow bigger by the day. He made an appointment with his ear, nose, and throat doctor.

“He said the odds were 50/50 that it was an infection,” recalls the 56-year-old father of two from Pleasantville, New York. “I asked, ‘What’s the other 50?’”

It was a possibility no one wanted to hear: Cancer. Rich underwent a biopsy and learned he had squamous cell carcinoma that had originated on the base of his tongue. His cancer, the doctor told him, was caused by the human papillomavirus (HPV).

Rich was shocked. “I knew HPV could cause cancer,” he says, “but I thought it was only cervical cancer in women.”

It’s true that HPV, a sexually transmitted virus, does cause the majority of cervical cancer cases in women. But it can also cause a variety of cancers in men, too, some of which are on the rise.

HPV led to a five-fold increase of head and neck cancers in young men from 2001 to 2017, according to data released at the 2021 American Society for Clinical Oncology annual meeting.

Memorial Sloan Kettering’s David Pfister, a medical oncologist who cares for people with head and neck cancer, says these cancer cases are just now emerging in people infected with the virus many years ago.

“Once the association between HPV infection and throat cancers was established, we better understood the significant increase in the rate of these cancers,” he says. “There is a delay between infection and the development of cancer, so there is a big reservoir of people already potentially at risk.”

But there is a way to prevent more than 90% of cancers caused by this virus: Get the HPV vaccine. It protects against head and neck cancers as well as anal cancer in both men and women. In men, it also protects against penile cancer, and in women, cervical cancer, vaginal cancer, and vulvar cancer. The vaccine is recommended for all children and can be given as early as age 9. It’s also approved for adults up to age 45.

Amidst growing concern about falling vaccination rates, MSK joined other National Cancer Institute-designated cancer centers in a May 2021 statement urging physicians, parents, and young adults to begin or keep up with HPV vaccinations, after they were interrupted by COVID-19. Early in the pandemic, HPV vaccination rates among adolescents fell by 75%. Since March 2020, an estimated one million doses of HPV vaccine have been missed by adolescents who have public insurance. That’s a decline of 21% from pre-pandemic levels.

Moreover, parents of boys are increasingly hesitant to have their sons vaccinated, according to a study in the journal Pediatrics.

MSK’s HPV Center is working to increase vaccination rates for everyone. Here are five reasons why it’s especially important for males.

1. Men get cancers caused by HPV in large numbers, too.
From 2013 to 2017, there were approximately 25,000 cases of HPV-associated cancers in women and 19,000 in men, according to the Centers for Disease Control and Prevention. More than four out of every ten cases of cancer caused by HPV are in men.

“HPV should be of concern to all since men and women are affected virtually the same by this virus,” says Abraham Aragones, an MSK physician who also studies public health.

2. There are now more cases of head and neck cancers than cervical cancers in America; HPV causes 70% of them, according to the CDC.
“My doctor told me that tumors of the neck and throat were getting more common in men,” Rich recalls.

Head and neck cancers are four times as common in men as they are in women.

3. There is no test for HPV cancers in males.
A Pap test detects early-stage cervical cancer in women. No such test exists for penile, anal, or head and neck cancers.

“Developing something like a Pap test for throat cancer would be a game-changer,” says Dr. Pfister. “When you compare the throat to the cervix, the anatomy of sites like the tonsils and the base of the tongue have hard-to-reach crevices the virus can hide in. Until an effective and reliable screening test is developed, patients should stay up to date on their HPV vaccines, know how the disease is acquired, and take any suspicious symptoms like a lump in the neck or blood in the phlegm to their doctor or dentist.”

4. The odds of getting HPV-related cancer increases with age.
“Today’s men are living longer than ever before, and that gives cancer more time to develop,” Dr. Aragones says. “Vaccination protects men from HPV-related cancers in the short and long term.”

5. The vaccine is just as safe for boys as it is girls.
The HPV vaccine went through years of rigorous safety testing before it was approved in 2006 to prevent cervical cancer in women and in 2009 to prevent HPV-related cancers in males. Since then, more than 100 million doses of the HPV vaccine have been given in the United States. Like any vaccine, there can be side effects, but they are minor, like arm soreness and fatigue. “The benefits of vaccinating against HPV far outweigh any potential risk of side effects,” says Dr. Aragones.

Rich made sure his teenage son got the HPV vaccine and says his younger daughter will follow suit.

“I didn’t want them to go through what I went through,” he says. After radiation and chemotherapy three years ago, Rich thankfully has shown no evidence of disease.

HPV-related cancers are usually able to be treated successfully. But preventing a cancer is far better than treating it, which makes the HPV vaccine a valuable weapon against cancer.

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Study finds major anti-inflammatory immune activity that favors oral cancer tumors

Source: medicalxpress.com
Author: MELISA Institute

A collaborative research led by immunologist Estefania Nova-Lamperti from the Universidad de Concepción (Chile), with a branch of researchers from MELISA Institute and other international academic centers, made progress in the understanding of molecular mechanisms preventing an effective antitumor immune response in oral cancer; The latter due to the production of chemical mediators that induce an anti-inflammatory regulatory response that favors tumor development through the vitamin D signaling pathway. The study was published in Frontiers in Immunology on May 7, 2021.

Oral cancer, 90% of which corresponds to the squamous cell type, is a neoplasm with a high mortality and morbidity rate, mainly because the diagnosis is made in late stages when metastases already exist, and where treatment produces serious physical and functional sequel among survivors.

It is well known that the immune system plays a key role in the development of cancer, either by stimulating pathways that play an anti-tumor role or, conversely, by generating an anti-inflammatory environment that allows the tumor to grow and be spread.

The main biological agents of the immune system are lymphocytes or T cells, which have different functions or phenotypes. In cancer, the presence of regulatory T cells (Tregs) and helper T cells type 2 (Th2) are associated with a worse prognosis, whereas the responses of helper T cells type 1 (Th1) within tumors, in general, show a better prognosis.

Dr. Nova-Lamperti points out that a key question in oral cancer is how an anti-inflammatory microenvironment is induced, boosting tumors growth. To date, “the immunoregulatory mechanisms associated with this change in the immune response are unknown and it is not acknowledged whether they come from or are external to the tumor,” explains the immunologist.

Using flow cytometry techniques, the research team was able to feature the T-cell phenotypes predominant in biopsies of 15 patients with oral cancer and compared them with the T-cell populations found in biopsies of 16 disease-free controls. Thus, they identified a predominant distribution of T cells expressing CCR8+ receptors (generally abundant in skin tissues), Th2-like regulatory T cells, and a small population of Th1 cells.

Based on these new findings, the researchers hypothesized that the tumor microenvironment obtained from biopsy cultures of patients with oral cancer, which contains the factors secreted by tumor cells (known as secretome), had the ability to induce an anti-inflammatory phenotype itself. To test this assumption, Nova-Lamperti and her colleagues challenged immune T cells subpopulations with the cancer secretome and, using genomics and proteomics techniques, determined how the mRNA transcripts and proteins expressed by these cells are modified.

Notably, transcriptomics showed that oral cancer secretome induced the expression of a group of genes that control the vitamin D (VitD) signaling pathway in T cells. Moreover, the proteomics study, through high-resolution mass spectrometry, revealed the presence of several proteins associated with the production of prostaglandin E2 (PGE2) linked to VitD rapid signaling in cell membranes. In addition, the researchers found a reduction in the proteins that carry VitD into the cell.

Based on these findings, the researchers suggested that the decrease in the mobility of VitD promotes an increase in its concentration in the tumor microenvironment, inducing an anti-inflammatory phenotype favorable to the tumor. In new experiments, the researchers challenged T-cell cultures with VitD and PEG2, confirming that VitD induces a Th2 regulatory response with expression of CCR8, while the combination of VitD and PEG2 inhibited the production of small proteins called cytokines. The latter are important for the activation of the immune system. Additionally, the study showed that a cytokine that binds to the CCR8 receptor, known as chemokine CCL18, was overexpressed in tumors, favoring a vicious circle that stimulates the Tregs cells to ‘stagnate’ in the tumor microenvironment.

Regarding the effect of the study, the immunologist noted that “findings could be interesting for the development of biological therapies centered on antibodies capable of blocking the action of specific molecules that favor tumor growth. For example, in the case of oral cancer, a therapy that selectively blocks the CCR8 receptor or that normalizes the vitamin D signaling pathway could eventually slow tumor growth, decrease the sequel of surgical resections, and improve survival in these patients.” The researcher stressed the need to continue doing research in this regard.

Researcher Mauricio Hernández, a mass spectrometry expert at the MELISA Institute, stated that “collaborating in this research was challenging; the proteomics for this study required several time-consuming procedures to obtain optimal results. For example, because we dealt with cell culture media, each sample had to be depleted of abundant proteins such as albumin that ‘shield’ or make it difficult to detect smaller, less abundant proteins; then we performed an off-line fractionation to increase our identification capability. This encompasses a chromatography step to subdivide each sample, which substantially multiplies the number of runs on our mass spectrometer and increases the time in subsequent bioinformatic analysis.”

Finally, Prof. Elard Koch, senior researcher and Chairman at the MELISA Institute, said that they were pleased to be invited to participate in the study led by Dr. Nova-Lamperti; “Collaborating with our multi omics capabilities in research as relevant as this one is encouraging for our researchers and a key goal for our institute” Koch remarked.

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More women being diagnosed with mouth cancer, researchers say

Source: www.9news.com.au
Author: Gabriella Rogers, Health Reporter

Head and neck surgeons say more women are being diagnosed with mouth cancer and research is underway to help unravel what’s fuelling the alarming trend.

“These mouth cancers historically occur in older men, particularly smokers and drinkers,” said Associate Professor Carsten Palme, Director of Head and Neck Surgery at Chris O’Brien Lifehouse.

But surgeons here and overseas have identified a rise in the number of women being diagnosed with cases increasing about 5 per cent each year.

Those women are not presenting with traditional risk factors and their diagnosis usually “comes out of the blue”.

“A lot of research at the moment at our institutions is being done to try and identify exactly what is happening and why,” Dr Palme said.

Dr Palme said his youngest patient had just finished her HSC.

“She was 18 she presented with an ulcer at the right side of her tongue which was initially thought to be a benign traumatic ulcer and she ended up having a stage three tongue cancer,” he said.

“We are commonly seeing women between the ages of 20 and 40 present to our clinics, pretty well on a weekly basis,” he said.

According to the Australian Institute of Health and Welfare, more than 5,000 Australians are diagnosed with head and neck cancers each year.

Doctors at Chris O’Brien Lifehouse are now routinely using innovative approaches to remove and rebuild a patient’s jaw to help cure their cancer.

Tara Flannery, aged 49, was diagnosed with squamous cell cancer in her gum and doctors said removing the entire top jaw would give her the best chance of a cure.

On its own, the surgery would cause significant cosmetic deformities and would make eating, swallowing and speaking extremely difficult.

Surgeons used skin grafts grown in the woman’s leg to form the upper gum. (9News)

The teacher feared she would have to stand up in front of 30 kids with a disfigured face.

“I didn’t want to stop teaching,” Ms Flannery said.

The Lifehouse team created a 3D model of Ms Flannery’s jaw which enabled them to virtually map out her complex operation.

“It means what we plan on the computer can then be executed at surgery. And for something as complicated as the jaw, it’s absolutely critical,” said Dr David Leinkram, Lifehouse Oral and Maxillofacial Surgeon.

The doctors used the position of Tara’s top and bottom teeth as a starting point for the reconstruction and worked backwards.

“So we want to keep those teeth exactly where they were before and then we plan the reconstruction and the immediate dental implant at that time,” Dr Palme said.

Six weeks before the major surgery, they placed titanium implants and skin grafts inside her calf bone called the fibula. The skin grafts would form her new upper gum. Three segments of that bone and nearby blood vessels would eventually be removed to build her new jaw.

During the pre-fabrication process in the leg, specialist dentists take a mould to help build a bridge for her new acrylic teeth.

“Tara is a phenomenal example of what we can achieve in this day and age,” said Dr Palme.

“Within the last few years we’ve been able to really automate this process, speed up this process and really make it part of our routine care delivery for these patients,” said Dr Palme.

Ms Flannery is now back in the classroom doing what she loves doing best, teaching. She doesn’t look like she has had her jaw removed and is ecstatic with the result.

“I get blown away when I think about it,” she said.

“Tara’s a rock star. You would hardly know she’s had such incredibly destructive surgery,” said Dr Palme.

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