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|

There has to be more to dental hygiene than this: A systemic approach

Source: www.dentistryiq.com
Author: Michelle Strange, MSDH, RDH

Due to the COVID-19 pandemic, there will be added pressure on dental hygienists as patients return to our practices. During the lockdown, patients did not have access to our services. Now that the doors have reopened, patient treatments have begun with a renewed focus on protection from the virus.

Even though practices will be extra busy, now is a great time to make some changes to our services. What if we stop simply reacting to the apparent problems and instead make the shift from purely corrective to a preventive dental service, and from oral health to holistic health?

A holistic approach
Dentistry has the potential to assimilate and integrate into the holistic health approach. Until now, patients and other health professionals have considered a visit to a dental office as totally separate from other health care. Patients often view their twice-a-year visits as mandatory checkups and “cleanings” but fail to grasp the entire value we provide. Dental health is connected to our entire well-being and is even thought to be related to heart health.1

Poor dental hygiene may lead to a higher susceptibility to the human papillomavirus that can contribute to mouth and throat cancers.2 In 2013, a study from the University of Central Lancashire School of Medicine and Dentistry pinpointed a specific oral bacteria, Porphyromonas gingivalis, as present in the brains of four out of 10 participants with dementia.3 Research has found that erectile dysfunction,4 type 2 diabetes,5 irritable bowel syndrome,6 and sleep apnea7 may also be connected to poor oral hygiene.

This intertwined relationship between dental care and overall health care must carry through to the relationship between patients and dental professionals, both dentists and hygienists. Imagine the impact we could have if hygienists take up our deserved role as holistic health specialists!

The mouth is one of the mirrors of patient health, just like the skin, and we must use this information to guide our patients in their search for optimal well-being. We should take time to inform our patients about these connections with health and become client educators. If we take the holistic approach and help them become healthier, they will understand there is more to the role of the dental hygienist than just scaling their teeth.

Start the conversation
In a 2017 study, 64% of respondents between the ages of 18 and 64 visited the dentist in the last year,8 meaning that 36% did not. Moreover, of those who did, the majority walked in for their annual health insurance-covered prophies. In reality, dental hygienists offer and do so much more, including providing treatment of early-onset periodontal disease. We want the best for patients, but sometimes we don’t provide them with information and treatments that can help them become truly healthy. We might think they are not interested or they are only interested in a “free cleaning” from their insurance coverage. However, by not offering a more comprehensive package, a patient’s health journey may be compromised.

Instead, start a conversation with clients outlining the importance of dental health for their overall health and consider offering a set of standard tests. Implementation of tests similar to those provided by physicians, including blood pressure screening, heart rate, oxygen[KB2] , and checking other vital signs are all within the purview of hygienists. Include charting bleeding sites (using currently available software),9 oral cancer screenings,10 airway assessment, nutritional counseling, and salivary testing to help prevent patients from being susceptible to illnesses such as cardiovascular disease, dementia, and oral cancers through early diagnosis.11 Doing all this before picking up a scaler offers an unprecedented level of care.

Not only is this time in history an opportunity for us to expand our roles as health practitioners, but it is also our duty. Our patients have a right to an accurate, complete diagnosis and treatment plan. The American Dental Hygienists’ Association Standards for Clinical Dental Hygiene Practice outlines the importance of considering all aspects of a patient’s health.12 Hygienists are already highly trained and have the skills and access to procedures to offer the highest quality of care, but unfortunately, many fail to embrace this opportunity to provide comprehensive care adequately.

By offering such a high level of care, patients will see that dental hygienists are professionals who are a crucial part of their health journey, and they will feel more cared for, too.

References
1. Gum Disease and Heart Disease — What You … – WebMD. 25 Sep. 2009, https://www.webmd.com/oral-health/features/healthy-teeth-healthy-heart. Accessed Jun. 23, 2020.

2. Norton A. Poor oral hygiene tied to cancer-linked virus. WebMD. Aug. 21, 2013. https://www.webmd.com/oral-health/news/20130821/poor-oral-hygiene-tied-to-cancer-linked-virus-study-finds. Accessed Jun. 23, 2020.

3. Locke T. Can poor dental health cause dementia? WebMD. Jul. 31, 2013. https://www.webmd.com/oral-health/news/20130731/dental-health-dementia. Accessed Jun. 23, 2020.

4. Men’s sexual health may be linked to periodontal health. American Academy of Periodontology. Dec. 4, 2012. https://www.perio.org/consumer/erectile_dysfunction. Accessed Jun. 23, 2020.

5. Leite RS, Marlow MN, Fernandes JK. Oral health and type 2 diabetes. Am J Med Sci. 2013;345(4):271-273. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3623289/. Accessed Jun. 23, 2020.

6. Fourie NH, Wang D, Abey SK, et al. The microbiome of the oral mucosa in irritable bowel syndrome. Gut Microbes. 2016;7(4):286-301. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4988452/. Accessed Jun. 23, 2020.

7. Huang Y-S, Guilleminault C. Pediatric obstructive sleep apnea and the critical role of oral-facial growth: evidences. Front Neurol. 2013 Jan 22;3:184. ttps://pubmed.ncbi.nlm.nih.gov/23346072. Accessed Jun. 23, 2020.

8. Table 37. Dental visits in the past year, by selected characteristics: United States, selected years 1997-2017. Centers for Disease Control and Prevention. https://www.cdc.gov/nchs/data/hus/2018/037.pdf. Accessed Jun. 23, 2020.

9. Dental practice software. Capterra. https://www.capterra.com/dental-software/. Accessed Jun. 23, 2020.

10. Froum S. 10 steps to perform an oral cancer screening. Dentistry iQ. May 28, 2015. https://www.dentistryiq.com/dentistry/oral-cancer/article/16350620/10-steps-to-perform-an-oral-cancer-screening. Accessed Jun. 23, 2020.

11. LeBeau J. Dentistry’s proactive role in preventing disease. Compend. 2013;34(1). https://www.aegisdentalnetwork.com/cced/2013/01/dentistrys-proactive-role-in-preventing-disease. Accessed Jul. 13, 2020.

12. Standards for clinical dental hygiene practice – revised 2016. American Dental Hygienists’ Association. https://www.adha.org/resources-docs/2016-Revised-Standards-for-Clinical-Dental-Hygiene-Practice.pdf. Accessed Jul. 13, 2020.

2020-09-04T10:31:03-07:00September, 2020|Oral Cancer News|

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.

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.”

Less intense treatment safe for HPV+ throat cancer

Source: www.miragenews.com
Author: public release, University of Pittsburgh School of Medicine

A less intense treatment for human papillomavirus positive (HPV+) throat cancer—using robotic surgery followed by low-dose radiation—could provide as much benefit as standard higher-dose radiation and chemotherapy while preserving a patient’s throat function, and with potentially less toxicities, according to researchers at UPMC Hillman Cancer Center and Yale Cancer Center.

The results of their randomized phase two clinical trial will be presented virtually this week at the American Society of Clinical Oncology (ASCO) annual meeting during the Head and Neck Oral Abstract Session (Abstract 6500).

“These results present a promising deintensification approach that has proven to be safe in patients with intermediate risk, locally advanced oropharynx cancer,” said Robert Ferris, M.D., Ph.D., director, UPMC Hillman Cancer Center and a surgical oncologist specializing in head and neck cancer, who was lead investigator of the trial. The results are not yet published in a peer-reviewed journal.

About 60% of oropharynx cancer, in which cancer cells form in the back of the throat, base of the tongue and tonsils, is associated with HPV infection. The incidence has been increasing in recent years, especially in individuals under the age of 45.

Following robotic surgery, patients with HPV-associated throat cancer would typically undergo high dose radiation and chemotherapy. While robotic surgery allows for more precise and optimal preservation of the organs and surrounding tissue, there is still concern with the toxicities from the chemotherapy and consequences of tissue damage from radiation therapy, particularly in a younger population.

“Most throat cancers caused by HPV have good outcomes, and the cancer doesn’t return or spread to other parts of the body after treatment,” said Ferris, who also is professor, Department of Otolaryngology, of Immunology, and of Radiation Oncology, University of Pittsburgh School of Medicine.

“In this trial, we studied the pathologic features of the tumors obtained at surgery to determine patients’ risk of recurrence—low, intermediate or high—to then administer the right amount of postoperative treatment for each risk group.”

Patients at low risk were observed. Patients at intermediate risk were randomized to two arms of radiation alone, at standard or lower doses of radiation. Patients at high risk were assigned to usual high-dose radiation therapy plus chemotherapy.

For patients at low and intermediate risk, the two-year, progression-free survival rate was approximately 95%, and reducing radiation or chemotherapy intensity did not increase the risk of recurrence.

“The tissue samples and imaging studies collected in the course of this trial are a rich resource for studying the biology of intermediate- and high-risk disease, in work that is ongoing,” said ECOG-ACRIN Head and Neck Committee Chair Barbara Burtness, M.D., professor of medicine, and co-leader, Developmental Therapeutics Program, Yale Cancer Center and Yale School of Medicine.

Note:
The ECOG-ACRIN Cancer Research Group designed and conducted the trial with funding from the National Cancer Institute, part of the National Institutes of Health.

World-first saliva test detects hidden throat cancer

Source: www.miragenews.com
Author: staff

A simple saliva test developed by Queensland University of Technology (QUT) biomedical scientists has detected early throat cancer in a person who had no symptoms, and no clinical signs of cancer. QUT researchers Associate Professor Chamindie Punyadeera and Dr Kai Tang.

  • A series of saliva HPV tests detected an asymptomatic throat cancer during a trial of a new saliva diagnostic
  • Further validation studies are needed to confirm this finding
  • It is a world-first discovery, previously there was no screening test for HPV-DNA oropharyngeal cancers
  • The patient had surgery in which a 2mm cancer was removed and has had no recurrence of HPV-DNA in his saliva.

In what is believed to be a world-first, the non-invasive test picked up HPV-DNA in a saliva sample from an infected healthy person. Persistent human papillomavirus (HPV) infection is now the leading cause of cancers in the oropharynx (tonsils and tongue base area of the throat).

“The series of saliva tests raised the alert and detected an early cancer before the person had any symptoms,” said QUT Faculty of Health’s Associate Professor Chamindie Punyadeera, who, with Dr Kai Tang developed the test.

“This enabled removal of the tonsil which had a 2mm cancer in it, by straightforward local surgery alone.

“The incidence of high-risk human papillomavirus (HPV)-driven throat cancers is on the rise in developed countries and, unfortunately, it is often discovered only when it more advanced, with patients needing complicated and highly impactful treatment.

“In the US, HPV-driven throat cancers have surpassed cervical cancers as the most common cancer caused by HPV but unlike cervical cancer, up until now, there has been no screening test for this type of oropharyngeal cancer.”

Professor Punyadeera said the discovery was made during an HPV-prevalence study which included 665 healthy individuals.

“To take the test all the person has to do is give a salivary oral rinse sample. When the test shows HPV-16 DNA, it is repeated and if the presence of HPV-16 is persistent over a period of time we would be suspicious that there may be underlying cancer.

“The person whom we reported in this study had been consistently HPV-16 DNA positive for 36 months, with a steadily rising count of HPV-16 DNA after testing at 6, 12 and 36 months.

“The patient was found to have a 2mm squamous cell carcinoma in the left tonsil, treated by tonsillectomy. This has given our patient a high chance of cure with very straightforward treatment.

“Since the surgery, the patient has had no evidence of HPV-16 DNA in his saliva.”

Professor Punyadeera said this was the first-ever case of histologically confirmed diagnosis of an asymptomatic, hidden throat cancer, diagnosed with a saliva screening test and that wider validation studies were required to confirm this finding.

“The presence of this pattern of elevated salivary HPV-DNA must be fully evaluated, as it may provide the critical marker for early cancer detection.

“We now have the promise of a screening test for oropharynx cancer and there is an urgent need to undertake a major study to validate this test and the appropriate assessment pathway for people with persisting salivary HPV-DNA.

This research is part of a collaboration with Royal Brisbane and Women’s Hospital’s Professor Liz Kenny, Dr Sarj Vasani, Dr Touraj Taheri and Associate Professor Brett Hughes and University of Queensland’s Professor Laurence J. Walsh.

Source:
The study, An Occult HPV-Driven Oropharyngeal Squamous Cell Carcinoma Discovered Through a Saliva Test (https://www.frontiersin.org/articles/10.3389/fonc.2020.00408/full), was published in Frontiers in Oncology.

Novel intervention looks to improve timeliness, equity of head and neck cancer care delivery

Source: www.miragenews.com
Author: staff report, Medical University of South Carolina

Many factors go into surviving cancer.

Hollings Cancer Center researcher Evan Graboyes, M.D., specializes in head and neck cancer, a disease with poor survival prospects despite intense therapy with combinations of surgery, radiation and chemotherapy. While head and neck cancer only accounts for 4% of all cancer cases each year in the US, it has a high mortality rate. The American Cancer Society estimates that more than 14,000 patients died from this disease in the U.S. in 2019.

Overall, only 50% of head and neck cancer patients are alive at five years. Unfortunately, the mortality rate is even worse for African American head and neck cancer patients. That’s why researchers are looking for new strategies to improve patient survival and decrease racial disparities in outcomes for these patients.

Graboyes and MUSC Hollings Cancer Center researchers Chanita Hughes-Halbert, Ph.D., Katherine Sterba, Ph.D., Hong Li, Ph.D., and Graham Warren, M.D., Ph.D., have teamed up to develop and test a novel intervention to improve the timeliness, equity and quality of head and neck cancer care delivery, which they think might one day be the key to improving survival for these patients.

Funded by a $1.3 million 5-year grant from the National Cancer Institute, their study – Improving the Timeliness and Equity of Adjuvant Therapy Following Surgery for Head and Neck Cancer-started in September 2019 and built upon important research funded by grants from Hollings Cancer Center.

Graboyes explained that for patients with advanced head and neck cancer who are treated with surgery, national guidelines recommend that postoperative radiation therapy should start within six weeks of surgery.

“However, we know from our research that despite national guidelines, over half of the patients nationally don’t get radiation started in a timely fashion. Patients who have delays with radiation are more likely to die and have their cancer recur,” he said. “We are trying to find new ways to deliver timely head and neck cancer care. It’s an appealing way to help improve survival for this group.”

Innovative approach
The study is designed in three parts. The first part aims to identify the underlying reasons for why delays starting postoperative radiation are so common for this patient population. The researchers then developed a new multilevel health care delivery intervention called NDURE (Navigation for Disparities and Untimely Radiation thErapy), that specifically targets the barriers that lead to delays.

In the second part of the grant, the researchers will pilot the NDURE intervention in a small group of patients to make sure that it’s feasible and acceptable and refine the intervention based on participant feedback. In the third and final part of the study, they will compare NDURE to standard care in a randomized controlled trial to see whether NDURE is effective at decreasing treatment delays.

“This study interests me because it is clinically important. To help patients with head and neck cancer live longer, you don’t need to invent a new drug. All you need to do is get them the treatment they’re supposed to be getting. If we can find a way to deliver timely guideline-recommended care, it could have such a large impact on their survival,” he said

“It’s also a scientifically important study. Head and neck cancer treated with surgery followed by radiation is a great model system for us to understand how we deliver cancer care. Right now, we spend a lot of time and effort helping get people in to initiate cancer care. However, we understand a lot less about how cancer patients move through complicated treatment plans.”

Graboyes said South Carolina is primarily a rural state with some geographic barriers that present obstacles for patients to navigate. “Many of the patients will have surgery at a regional center like MUSC, then because radiation is five days a week for six weeks, they’ll get radiation at a different facility closer to where they live. We have to coordinate cancer care across health care systems, which presents some barriers that can lead to treatment delays.”

Graboyes emphasized that head and neck cancer is a major concern for the state of South Carolina and Hollings Cancer Center, a National Cancer Institute-Designated Cancer Center. The two major causes of head and neck cancer are smoking and human papillomavirus (HPV). The state’s population is affected by both, due to high rates of tobacco use and very low rates of HPV vaccination.

“As a result, Hollings has recognized this issue and has really invested a lot in the clinical enterprise of head and neck cancer because it’s such a problem in South Carolina.”

Hollings also has a strong cancer control program dedicated to reducing issues of health disparities and equity in the state, he explained.

“We think that NDURE, our intervention targeting the multilevel barriers to timely head and neck postoperative radiation, will be an effective way to help improve timely cancer care delivery for these patients, which will lead to higher rates of survival and low recurrence and decrease racial disparities and outcomes. That’s very exciting to our team.”

Did you know?
About 70% of cancers in the oropharynx (which includes the tonsils, soft palate and base of the tongue) are linked to HPV.

Dedicated to the mission of raising HPV vaccination rates for teens and young adults, Hollings Cancer Center has initiated a $700,000 three-year project. The Centers for Disease Control and Prevention recommends speaking with a doctor about the HPV vaccination. The HPV vaccine can prevent new infections with the types of HPV that most often cause oropharyngeal and other cancers.

The YAP signal plays a crucial role in head-and-neck cancer onset

Source: www.eurekalert.org
Author: press release, Kobe University

Joint research between Kobe University and National Hospital Organization Kyushu Cancer Center has revealed that mice with mutations in the YAP signal pathway develop head-and-neck cancer over an extremely short period of time (world’s fastest cancer onset mouse model), indicating that this pathway plays a crucial role in the onset of these cancers. This discovery may shed light on the development of new drugs for head-and-neck cancer.

This research resulted from a collaboration between a research group led by Professor SUZUKI Akira and Associate Professor MAEHAMA Tomohiko at Kobe University Graduate School of Medicine, and Dr. MASUDA Muneyuki’s team at Kyushu Cancer Center.

These results were published in the American scientific journal ‘Science Advances‘ on March 18.

Main Points:
>Deletion of MOB1 (*1, which represses YAP) in mouse tongues causes strong activation of YAP (*2), leading to the early onset of cancer (in about 1 week).

>In humans, the expression of YAP increases during the development of dysplasia (pre-cancerous lesions), prior to the onset of head-and-neck cancer. YAP continues to increase with the development and progression of cancer. This high YAP activation is linked to poor patient prognosis.

>The onset and progression of head-and-neck cancer in the mice in this study, and the proliferation of stem cells in this cancer in humans, are dependent on YAP.

>These results suggest that cancer develops when the YAP activation exceeds a threshold. YAP may play a fundamental role in head-and-neck cancer onset and progression. These conclusions represent a paradigm shift in the understanding of these cancers.

>The mouse model developed in this study can be used in research to develop new drugs for head-and-neck cancer and, in addition, provides a beneficial resource for cancer research in general.

>By inhibiting YAP, the development and progression of head-and-neck cancer can be suppressed. Thus, the YAP pathway provides a good target for head-and-neck cancer treatments.

Research Background

Head-and-neck cancer in humans
Head-and-neck cancer is the sixth most common type of cancer in the world, affecting 600,000 people annually. In Japan there are around 22,500 new cases every year. This ‘head and neck’ includes the oral cavity and areas of the throat (pharynx and larynx). Among these, mouth cancers (especially tongue cancer) are the most prevalent.

It is understood that exposure to carcinogens, such as those found in cigarettes and alcohol, as well as mechanical irritation of the mucous membranes in the mouth, tooth decay and improperly fitted dentures, are risk factors for the development of head-and-neck cancer.

In addition, 15% of head-and-neck cancer is caused by Human Papillomavirus (HPV), which in particular causes oropharynx cancer.

The prognosis for patients who are HPV-positive is relatively good. Conversely, prognosis is poor for HPV negative patients and in most cases, mutations are found in the tumor suppressor gene TP53 (p53). However, mutations in this gene alone are not sufficient to cause head-and-neck cancer. It has been thought that changes in other molecules are also necessary for cancer development, however these causes remain elusive.

From comprehensive cancer genome analyses, it is known that PTEN/P13K (46%), FAT1 (32%), EGFR (15%) gene mutations are also found in HPV-negative head-and-neck cancer. However, the genetic pathway of these molecules in relation to head-and-neck cancer development has not been sufficiently understood.

Mouse models of cancer
Up until now, research using mouse models of head-and-neck cancer has discovered that if both the p53 and Akt genes are mutated, 50% of mice will develop this type of cancer about 9 months after the mutation (the average mouse lifespan is 2 years).

The onset of cancer begins after many genetic mutations have accumulated (multistep carcinogenesis). Mice with a mutation in one important molecule usually develop cancer within 4 to 24 months (with the majority showing signs between 6 to 12 months).

The YAP pathway
The function of the transcriptional co-activator YAP is to turn ‘on’ the transcription of gene clusters related to cell growth. The LATS/MOB1 complex phosphorylates YAP, thereby excluding YAP from the nucleus, leading to the subsequent degradation of YAP proteins. In other words, MOB1 and LATS act as a ‘brake’ (tumor suppressor) to inhibit cell proliferation facilitated by YAP. It has been reported that in 8% of human head-and-neck cancer cases, the YAP gene is amplified and there is a connection between YAP activation, cancer progression and poor prognosis.

This research group produced mice with MOB1 deletion in their tongues (so that YAP would be intrinsically activated) in order to perform a detailed analysis in vivo of the role that the YAP pathway plays in head-and-neck cancer.

Research Methodology

Mice with MOB1 deletion exhibit rapid onset tongue cancer
This research group developed mice with MOB1 deletion in their tongues by applying the drug tamoxifen to their tongues and then modifying them genetically using the Cre-loxP system (*4).

Three days after applying tamoxifen, the amount of MOB1 had barely decreased, however by day 7, the vast majority of these proteins had disappeared. At this point, a third of the mice demonstrated rapid onset head-and-neck cancer (intraepithelial tongue cancer), with all mice developing the disease by day 14. The cancer had progressed in all mice by day 28 (invasive tongue cancer). The team succeeded in developing the world’s fastest mouse model of cancer onset. Both domestic and international patents for this model have been applied for.

This mouse model showed that head-and-neck cancer develops quickly (within a week) when the YAP pathway is strongly activated, suggesting that this pathway plays an extremely important role in head-and-neck cancer onset.

YAP activation and tumorigenic properties of the tongue epithelium in MOB1 deletion mice.
The epithelial cells (on the surface of the tongues) of MOB1 deletion mice exhibited the following properties characteristic of tumor development: increased cell proliferation and cell saturation density, impaired cell polarity, low levels of apoptosis (cell death), increase in undifferentiated cells, and chromosomal instability (characterized by increases in aneuploid cells (*5)), multipolar spindles (*6) and micronucleated cells). On a biochemical level, activation of YAP and a decrease in LATS proteins was evident due to MOB1 deletion.

The epithelial cells acquired the characteristics of tumor cells due to the YAP activation caused by the deletion of MOB1.

YAP activation in the stages of tongue cancer in humans
The development of human tongue cancer can be divided to the following stages; the normal stage, the dysplasia stage, the intraepithelial cancer stage (*8) and the invasive cancer stage (*9).

If we look at YAP activation across all these stages, we can see that YAP is enhanced in the dysplasia stage which proceeds the onset of cancer. YAP activation shows continued increase during the subsequent stages of cancer progression. In cases where YAP is highly activated, overall survival is decreased and the likelihood of cancer relapse is high.

In other words, YAP increases before the onset of cancer and continues to increase as the cancer develops and progresses. Accumulation of YAP is linked to poor patient prognosis.

Cancer formation is dependent on YAP when MOB1 is deleted
Invasive cancer occurred in MOB1 deletion mice. However, when both YAP and MOB1 are deleted from mice, cancer onset is halted at the dysplasia stage, showing that the onset of head-and-neck cancer is dependent on YAP (Figure 2).

Among current YAP pathway inhibitors, the SRC inhibitor Dasatinib (*10) was shown to be the most effective (SRC has been previously shown to activate YAP both directly and indirectly). Dasatinib was shown to prevent the onset of intraepithelial head-and-neck cancer in the MOB1 deletion mice. It also suppressed the development of invasive cancer in MOB1 deletion mice that had reached the intraepithelial head-and-neck cancer stage.

In human head-and-neck cancer stem cells, it is possible to suppress cell proliferation either by inhibiting YAP gene expression or by adding YAP inhibitors. Cisplatin, which is commonly used to treat head-and-neck cancer, is augmented when YAP is suppressed.

In mice, head-and-neck cancer onset and progression was suppressed when YAP was inhibited. In the same way, it was shown that in human tongue cancer stem cells, cell proliferation was also suppressed when YAP was inhibited.

Known genetic mutations in human head-and-neck cancer and YAP activation
Genetic mutations in p53, PTEN/PI3K, FAT1, and EGFR have been identified in HPV-negative head-and-neck cancer.

This research group showed that EGF signal activation and mutations in p53, PTEN and FAT1 each play a role in YAP activation. Furthermore, YAP activation gradually increases as these genetic mutations accumulate.

Normally, cancer takes time to develop as it is a multistep process. However, in this study, intraepithelial head-and-neck cancer rapidly developed just from highly strengthening YAP activation.

In conclusion, this study raises the possibility that the following process for head-and-neck cancer development takes place: A. Cancer develops when the YAP activation exceeds a threshold due to the accumulation of genetic mutations in p53, PTEN/PI3K, FAT1 and EGFR (Figure 3). B. Subsequently, YAP continues to accumulate after cancer has developed, resulting in cancer progression.

Conclusion and Further Developments
YAP is frequently activated in cancer cells although genetic mutations in the YAP pathway are not frequently found. It is thought that this is why the importance of the YAP pathway in the onset of head-and-neck cancer was unclear until now.

1. YAP activation levels are high before the onset of head-and-neck cancer in humans.
2. YAP is further activated as the cancer progresses.
3. The high frequency of mutations in p53, PTEN/PI3K, FAT1 and EGFR all activate YAP.
4. The accumulation of these molecular mutations gradually leads to high YAP activation:
4a. The accumulation of genetic mutations in p53, PTEN/PI3K, FAT1 and EGFR cause YAP to reach its threshold, culminating the onset of cancer.
4b. YAP continues to accumulate after the cancer onset, resulting in further cancer progression.

It is necessary to consider YAP as a basis for head-and-neck cancer onset and progression. This represents a paradigm shift in our understanding of these cancers.

In addition, it has also been shown that risk factors for head-and-neck cancer, such as cigarette smoking, mechanical irritation of mucous membranes and HPV infection, also play a part in YAP activation.

The mouse model in this study: 1. Is the fastest mouse model in the world for showing the natural onset of cancer. 2. Can be used to visualize cancer onset and progression. 3. Allows cancers to be developed naturally at the same time. 4. Allows cancer onset and progression to be analyzed in mice immediately after birth, allowing drug tests to be conducted in a shorter period of time and in small quantities. The results suggest that this mouse model would be ideal, not only for research into developing new treatments for head-and-neck cancer, but also for cancer research in general.

It is expected that the YAP pathway will provide a good target for drugs used in the treatment of head-and-neck cancer because inhibiting YAP not only suppresses the cancer onset but can also prevent its progression.

Researchers from all over the world, including this research group, are currently trying to find new drugs that target the YAP pathway. We have shown one factor that is effective against head-and-neck cancer. It is also expected that the mouse model will become an indispensable tool for evaluating their results and for head-and-neck cancer research.

Glossary
1. MOB1 (Mps One Binder 1): MOB1 is necessary for activating the LATS kinase and acts as a brake (tumor suppressor) on downstream, negatively-controlled YAP. Deletion of MOB1 exacerbates cell proliferation and leads to cancer.
2. YAP (Yes-associated Protein): YAP is a transcriptional coactivator. It forms a complex with multiple transcription factors inside the nucleus to control the expression of various genes. YAP is phosphorylated by the LATS kinase, causing YAP to be excluded from the nucleus and inactivated.
3. Human Papillomavirus (HPV): A type of papillomavirus, there are over a hundred genotypes or varieties of HPV. The virus is linked to genital warts, head-and-neck cancer and cervical cancer.
4. Cre-loxP system: A genetic modification system using Cre recombinase, which catalyze DNA recombination between two loxP sites (a 34-base pair nucleotide sequence). If Cre is expressed in a cell where chromosomal DNA has been artificially inserted into two loxP sites, the intervening DNA segment is deleted.
5. Aneuploid Cells: contain an abnormal number of individual chromosomes. This does not include a difference of one or more complete sets of chromosomes.
6. Multipolar Spindle: Spindles are formed during cell division to separate chromosomes between daughter cells. In normal cells, a pair of centrosomes forms prior to cell division to organize proteins called microtubules into a spindle between the two centrosomes. However, in cancer cells there are more than two centrosomes, and so-called multipolar spindles form. This can cause chromosomal instability and lead to the formation of aneuploid cells because the chromosomes were not correctly allocated at the time of cell division.
7. Dysplasia: The presence of cells of an abnormal type within a tissue. In medical diagnosis, the presence of abnormal-looking cells (dysplasia) observed under a microscope can signify an increased chance of a patient developing cancer (pre-cancerous symptoms).
8. Intraepithelial cancer: This is where cancer cells are found within the intraepithelial layer of cells which form on an organ’s surface. At this point, cancer cells have not been able to penetrate the basement membrane and have not spread deeply. Related terms include Carcinoma in Situ (CIS), intraepithelial tumor and intraepithelial neoplasia.
9. Invasive cancer: is where cancer cells penetrate the basement membrane, a thin membrane separating them from other tissues. From there, cancer can spread to the surrounding area.
10. Dasatinib: a chemotherapy drug that inhibits the SRC kinase family, which can cause malignant transformation in cells. SRC is both directly and indirectly connected to YAP activation, so dasatinib can also inhibit YAP. It is currently used to treat leukemia but is not prescribed for head-and-neck cancer treatment.

Acknowledgements:
This research was made possible primarily through funding to the project ‘The development of cancer treatment methods targeting cancer suppression genes.’ (Lead researcher: Suzuki Akira) as part of the Japanese Agency for Medical Research and Development’s Project for Cancer Research and Therapeutic Evolution (AMED P-CREATE).

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