HPV

Robot that can cut out hard-to-reach throat tumours through patients’ mouths: Pioneering operation reduces need for chemo and radiotherapy

Source: www.dailymail.co.uk
Author: Fiona McCrae, Roger Dobson

British surgeons are using a cutting-edge robot to remove difficult-to-reach throat tumours – through the mouths of patients.

The pioneering operation is designed to dramatically reduce the need for gruelling radiotherapy and chemotherapy, which can leave patients unable to swallow and dependent on a feeding tube for life.

With growing numbers of people developing throat cancer, it is more important than ever to have a range of effective treatments that lessen the impact on quality of life, says Asit Arora, consultant head and neck surgeon at Guy’s & St Thomas’ NHS Trust in London.

Once most common in elderly people with a history of drinking and smoking, rates of head and neck cancers have soared by 31 per cent in the past 25 years and are now as common in people in their 50s as in those in their 80s.

The 90 minute operation is designed to dramatically reduce the need for gruelling radiotherapy and chemotherapy, which can leave patients unable to swallow and dependent on a feeding tube for life

Much of the rise is attributed to HPV – a range of viruses that can be passed on during intimate and sexual contact. At least 80 per cent of the adult population carries some kinds of HPV on their skin, although most will never know it. In some cases, HPV can cause skin or genital warts, and other types are a known cause of cervical and anal cancers.

HPV can also infect the mouth and throat and is now to blame for at least half of throat cancers in the UK. Until a tumour occurs, the infection is typically symptomless.

Conventional treatment for early-stage throat cancer involves either powerful radiotherapy and chemotherapy to destroy the tumour, or laser surgery to cut it out.

Courses of radiotherapy and chemotherapy are time-consuming – some patients make up to 30 trips to hospital over a few months. The treatment can also damage the jaw and the swallowing muscles, meaning patients cannot eat without the help of a feeding tube.

Laser treatment is more gentle on the body but it can be difficult to cut out a hard-to-reach cancer completely and most patients need radiotherapy afterwards. Some also need chemotherapy.

Using the robot, the surgeon can zero in on the tumour and cut it away precisely. With the patient under general anaesthetic, the surgeon controls the robot with his hands and feet. One of the robot arms holds a 3D camera, while two others wield tiny instruments that can be passed through the mouth and into the throat, and turned and twisted in ways impossible with the human hand alone.

Surgery in the mouth and throat can be challenging because you are working in very small areas, manipulating surgical instruments in a tight space where there are important nerves and blood vessels to be avoided,’ says Mr Arora, who has pioneered robotic surgery for throat cancer in the UK.

‘With the latest robotic systems, we can be more targeted than ever before in how we treat these throat conditions in order to reduce unwanted side effects, particularly related to swallowing.’

Studies suggest that trans-oral robotic surgery (TORS) is at least as good as conventional surgery, although a definitive comparison has yet to be carried out, says Mr Arora. But importantly, by cutting out the tumour so precisely, it may reduce the amount of chemotherapy and radiotherapy patients need.

A £4.5 million Cancer Research UK trial into the procedure is now being carried out at Guy’s and hospitals around the country.

Mr Arora has used the method to remove about 30 throat tumours in the year since setting up the service with Jean-Pierre Jeannon, Guy’s clinical director for cancer.

The operation takes 90 minutes and patients are usually discharged after two days. They then undertake rehab, including speech therapy.

Retired policeman David Wonfor, 60, chose to take part in the trial after being diagnosed with early-stage throat cancer last summer. After his operation, David, 60, of Petts Wood, Kent, started on five weeks of low-dose radiotherapy. Although he lost weight and his sense of taste at first, he has now largely recovered, and says he is convinced that his recovery would have been very different if he had had chemotherapy.

March, 2019|Oral Cancer News|

HPV infection may be behind rise in vocal-cord cancers among young nonsmokers

Source: www.eurekalert.org
Author: Public Release Massachusetts General Hospital

A remarkable recent increase in the diagnosis of vocal-cord cancer in young adults appears to be the result of infection with strains of human papilloma virus (HPV) that also cause cervical cancer and other malignancies. Investigators from Massachusetts General Hospital (MGH) describe finding HPV infection in all tested samples of vocal-cord cancer from 10 patients diagnosed at age 30 or under, most of whom were non-smokers. Their report appears in a special supplement on innovations in laryngeal surgery that accompanies the March 2019 issue of Annals of Otology, Rhinology and Laryngology.

“Over the past 150 years, vocal-cord or glottic cancer has been almost exclusively a disease associated with smoking and almost entirely seen in patients over 40 years old,” says Steven Zeitels, MD, director of the MGH Division of Laryngeal Surgery, senior author of the report. “Today nonsmokers are approaching 50 percent of glottic cancer patients, and it is common for them to be diagnosed under the age of 40. This epidemiologic transformation of vocal-cord cancer is a significant public health issue, due to the diagnostic confusion it can create.”

The researchers note that the increase in vocal-cord cancer diagnosis appears to mimic an earlier increase in the diagnosis of throat cancer, which has been associated with infections by high-risk strains of HPV. After initially attributing incidents of vocal-cord cancer in nonsmokers, which they began to see about 15 years ago, to increased travel and exposure to infectious diseases, Zeitels and his colleagues decided to investigate whether HPV infection might explain the diagnosis in younger nonsmokers.

To do so they examined the records of patients treated by Zeitels either from July 1990 to June 2004 at Massachusetts Eye and Ear Infirmary or between July 2004 and June 2018 at MGH. Of 353 patients treated for vocal-cord cancer during the entire period, none of the 112 treated from 1990 to mid-2004 were age 30 or younger. But 11 of the 241 patients treated from 2004 to 2018 were 30 or younger – 3 were age 10 to 19 – and only 3 of the 11 were smokers. Analysis of tissue samples from the tumors of 10 of the 11 younger patients revealed high-risk strains of HPV in all of them.

The authors note that these high-risk-HPV-associated vocal-cord cancers greatly resemble recurrent respiratory papillomatosis (RRP), a benign condition caused by common, low-risk strains of HPV. One of the 11 patients treated by Zeitels had previously been diagnosed at another center with vocal-cord cancer, and when it recurred after being surgically removed, she was misdiagnosed with RRP and treated with a medication that made the cancer worse, leading to the need for a partial laryngectomy.

“Benign RRP of the vocal cords has been a well-known HPV disease for more than a century, and it is very remarkable that there is now an HPV malignancy that looks so similar, creating diagnostic and therapeutic confusion,” says Zeitels, the Eugene B. Casey Professor of Laryngeal Surgery at Harvard Medical School. “It should be noted that these HPV-associated vocal-cord carcinomas are not a malignant degeneration of the benign disease.”

Zeitels adds that HPV vocal-cord cancers are amenable to endoscopic treatment with the angiolytic KTP laser that he developed. “Large-scale studies are now needed to determine the pace of the increase in glottic cancer among nonsmokers, the incidence of high-risk HPV in these cancers and changes in the age and genders of those affected,” he says.

Note:
The lead author of the Annals of Otology, Rhinology and Laryngology paper is Semirra Bayan, MD, previously a fellow in laryngeal surgery at MGH and now at University of Chicago Medicine; William Faquin, MD, PhD, MGH Pathology, is a co-author. The study was supported by the Voice Health Institute, the National Philanthropic Trust, and the Eugene B. Casey Foundation.

March, 2019|Oral Cancer News|

The epidemic of throat cancer sweeping the industrialized world

Source: www.mercurynews.com
Author: Dr. Bryan Fong

Tonsils – Angina Pectoris

Over the past three decades, a dramatic increase in a new form of throat cancer has been observed throughout the industrialized world. The good news is that it’s potentially preventable — if parents get their children vaccinated.

The disease shows up primarily in men, typically between the ages of 45 and 70. Those who are affected often lead healthy lifestyles. They do not have extensive histories of smoking tobacco or consuming alcohol, which are risk factors for traditional throat cancers.

The rate of this new cancer has been increasing 5 percent per year and today, it is more than three times as common as in the mid-1980s. If you think this scenario sounds like a slow-moving infectious medical drama (think Contagion or World War Z), you would be right.

The source of this cancer is a virus, the human papillomavirus (HPV) — the same virus that causes most cervical cancer in women. It’s widely known that parents should get their girls vaccinated. Now, with the surge in oral HPV cancers, especially in men, parents should get their boys vaccinated too.

Currently, vaccination against HPV is recommended by the Centers for Disease Control for children and young adults ages 9-26. The vaccination includes a series of two or three injections; the side effects are mild.

Ideally, the vaccinations should be administered before someone becomes sexually active. That’s because HPV is spread via sexual activity. Risk of HPV infection and throat cancer increases with the number of lifetime partners.

Men have a lower immune response to the virus than women, which explains the predilection of this disease for men. It’s difficult to know if someone has an active oral HPV infection because there are no symptoms. Currently, there is no widely accepted test for HPV in men.

Chronic infection leads to cellular changes within the lymphatic tissues in the throat, specifically the tonsils and base of tongue. Over the course of 20-30 years, these changes can result in the formation of cancer.

Throat cancer caused by HPV is insidious. The primary tumor in the tonsil or base of tongue often causes little to no symptoms. Early signs of this cancer may be a mild sore throat, occasional blood-tinged oral saliva, or increased or new snoring.

Often, the first sign of the cancer is a lump in the neck after the cancer has spread into the lymphatic system. The lump may arise quickly and then shrink to varying degrees, lulling one into complacency.

Early stage cancer can be treated with surgery or radiation. More advanced cancers are treated with combined therapy such as surgery followed by radiation therapy, or chemotherapy in conjunction with radiation therapy.

Finally, some good news. Treatment for HPV-related throat cancer is successful in about 90 percent of cases and is significantly more successful than treatment of non-HPV related throat cancer.

But, as successful as medicine has been in treating this cancer, an even better alternative is prevention via vaccination. Initial studies have shown that vaccination produces an immune response to HPV and reduces the rate of HPV infection. Given time and good vaccination coverage, a decline in throat cancer is expected.

In summary, here are a few simple take-home messages: If you have a lump in the neck or a chronic sore throat, don’t procrastinate. Have your doctor check it out. If you are a partner of someone with these symptoms, strongly encourage your partner to see his or her doctor.

If you have children ages 9-17, talk to your pediatrician about HPV vaccination. If you are 18-26 years old, talk to your primary care doctor about vaccination. These simple steps may save your life or the life of your loved one.

Note: Dr. Bryan Fong is the senior practicing head and neck surgical oncologist for Northern California Kaiser Permanente.

February, 2019|Oral Cancer News|

Why salivary diagnostics for dental practices?

Source: www.dentistryiq.com
Author: Barbara Kreuger, MA, RDH

I recently had the opportunity to visit OralDNA Labs and learn more about the process of running salivary diagnostic tests. Admittedly, when I first heard about salivary diagnostics, I didn’t immediately embrace the tests and what they had to offer. I was not convinced that they were necessary, believing they would not change how we treat dental disease.

However, we’ve been fortunate to use salivary diagnostics in practice and see the benefits in our patients firsthand. These tests have proven to be a great addition to our prevention tool box. Salivary diagnostics can play an important role in helping us produce high quality outcomes for patients and create awareness of their oral-systemic risk factors.

Bacterial identification
There are numerous salivary diagnostic tests available. The most widely used test from OralDNA Labs is MyPerioPath, which tests for the 11 pathogens that are known to contribute to periodontal destruction.(1) Once the test reveals which pathogens are contributing to the patient’s periodontal disease, it also offers antibiotic recommendations that target these specific bacteria.

When combined with periodontal maintenance visits and patient homecare, this test can lower a patient’s bacterial load, thus increasing positive outcomes. Retesting has shown that this reduction in bacteria can have a dramatic effect. We’ve seen tough cases—patients who were compliant with homecare but still exhibited clinical signs of periodontal disease—that improved dramatically after being treated with the test’s recommended systemic antibiotic. Periodic monitoring with MyPerioPath combined with periodontal maintenance treatment can help keep patients’ oral health stable.

Genetic predisposition
In addition to bacterial profile testing, various tests from OralDNA labs can tell us a patient’s genetic predisposition toward inflammation. This can reveal one of the reasons why some patients continue to experience periodontal destruction after treatment despite compliance and lower quantities of periodontal pathogens. In addition, much of the research connecting oral health to systemic conditions reveals that it is a patient’s total inflammatory burden that puts someone at risk for a host of health problems.(2,3)

While the patient’s genetic profile cannot be changed, the knowledge that the person has an overactive inflammatory response can help the practitioner and patient understand that there is a need for more frequent continuing care, adjunctive therapies, or treatment with a periodontist. This information can also help patients manage and control their systemic health with the help of their physician.

Caries risk assessment
When we look beyond the patient’s periodontal health, salivary diagnostics can also test for the bacteria that are known to contribute to caries. When we have an objective measure of the quantity and types of cariogenic bacteria in the patient’s mouth, we can once again tailor treatments to reduce his or her caries risk and motivate the patient toward behavioral change. If we then combine the test with a caries risk assessment tool, we can use the test to monitor the effectiveness of these behavior changes. Knowing the patient’s risk allows us to encourage the person to use interventions, such as fluoride to re-mineralize teeth and xylitol to inhibit the bacterial metabolism.

Oral cancer screening
Finally, salivary diagnostics can also test for the presence of various human papillomavirus (HPV) strains that have been shown to cause oral cancer. According to the American Cancer Society, oral cancer will take the lives of 10,860 people this year, and HPV is now seen as the leading cause.(4,5) Early diagnosis is key and increases survival from a dismal 20% when discovered after it has metastasized to distant sites, to 93% when discovered early.(6)

Knowing a patient’s HPV status may prompt us to increase the frequency of someone’s oral cancer screenings, or to use adjunctive diagnostic tools such as oral anomaly detection devices to more closely monitor the patient and potentially catch the cancer at an earlier stage.

More and more research studies are correlating the various bacteria that cause periodontal disease to systemic conditions. The more we understand about a patient’s bacterial load and risk factors, the better equipped we can be to help manage periodontal disease and improve overall health. Salivary diagnostics can help us provide optimal care for patients, increasing our ability to provide them with positive outcomes through tailored treatment and patient education.

Barbara Kreuger, MA, RDH, earned a Bachelor of Science in dental hygiene from the University of Minnesota and holds a Master of Arts in organizational leadership from St. Mary’s University of Minnesota. She spent more than 18 years as a clinical dental hygienist before moving to her current role as dental hygiene senior specialist for Pacific Dental Services. Barbara is currently serving as president of the Minnesota Dental Hygienists’ Association.

References

1. Oral DNA tests. OralDNA website. https://www.oraldna.com/tests.html. Accessed February 1, 2019.
2. Hunter P. The inflammation theory of disease. The growing realization that chronic inflammation is crucial in many diseases opens new avenues for treatment. EMBO Rep. 2012;13(11):968-70.
3. Minihane AM, et al. Low-grade inflammation, diet composition and health: current research evidence and its translation. Brit Jour Nutrition. 2015;114(7):999–1012.
4. Key Statistics for Oral Cavity and Oropharyngeal Cancers. American Cancer Society website. https://www.cancer.org/cancer/oral-cavity-and-oropharyngeal-cancer/about/key-statistics.html. Accessed February 1, 2019.
5. HPV/Oral Cancer Facts. Oral Cancer Foundation website. https://oralcancerfoundation.org/understanding/hpv/hpv-oral-cancer-facts/. Accessed February 1, 2019.
6. Survival Rates for Oral Cavity and Oropharyngeal Cancer. American Cancer Society website. https://www.cancer.org/cancer/oral-cavity-and-oropharyngeal-cancer/detection-diagnosis-staging/survival-rates.html. Accessed February 1, 2019.

February, 2019|Oral Cancer News|

CDC: Top HPV-Associated Cancer Is Now Oropharyngeal

Date: 08/23/18
Source: medscape.com
Author: Nick Mulcahy

Oropharyngeal squamous cell carcinoma (SCC) is now the most common HPV-associated cancer in the United States, according to a new report from the Centers for Disease Control and Prevention (CDC) that covers the years 1999 to 2015.

During that period, cervical cancer dropped from being the top HPV-associated cancer and oropharyngeal SCC took its place.

The transition happened because cervical carcinoma incidence rates decreased 1.6% per year, and oropharyngeal SCC incidence rates increased 2.7% per year among men and 0.8% per year among women.

In 2015, there were a total of 11,788 cervical cancers compared with 18,917 oropharyngeal SCCs.

The decline in cervical cancer is a “continued trend since the 1950s as a result of cancer screening,” write the report authors, led by Elizabeth Van Dyne, MD, MPH, an epidemic intelligence service officer at the CDC.

The uptick in oropharyngeal SCC could be due in part to “changing sexual behaviors,” including unprotected oral sex, especially among white men, who report having the highest number of sexual partners and performing oral sex at a younger age compared with other racial/ethnic groups, the authors say.

Oropharyngeal SCCs include those at the base of tongue, pharyngeal tonsils, anterior and posterior tonsillar pillars, glos­sotonsillar sulci, anterior surface of soft palate and uvula, and lateral and posterior pharyngeal walls.

The new report was published August 24 in the Morbidity and Mortality Weekly Report.

The study authors defined HPV-associated cancer as “an invasive malignancy in which HPV DNA was frequently found in special studies.” In other words, the new study data reveal the total number of certain cancers that are associated with — but not necessarily caused by — HPV.

A total of 30,115 new cases of HPV-associated cancers were reported in 1999 and 43,371 in 2015.

Overall, the rate of HPV-associated cancers dropped among women (change, –0.4%) during the study period and rose among men (change, 2.4%).

The CDC analyzed data from their National Program of Cancer Registries and the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program for all years from 1999 to 2015. “These data cover approximately 97.8% of the US population,” say the authors.

However, these two population-based cancer registries have a limitation: They tally invasive cancers but not the HPV status of cancers.

The authors point out HPV causes cervical cancer and “some oropharyngeal, vulvar, vaginal, penile, and anal cancers.”

Table. Annual Change in Type of Cancer From 1999 to 2015

Cancer Type Average Annual Change (%)
Cervical –1.6
Vaginal –0.6
Oropharyngeal in men 2.7
Oropharyngeal in women 0.8
Anal in men 2.1
Anal in women 2.9
Vulvar 1.3

Penile cancer rates remained stable during the study period.

The study authors say that the public health implication of the study is that HPV vaccination “can prevent infection with the HPV types most strongly associated with cancer.”

January, 2019|Oral Cancer News|

HPV discovery raises hope for new cervical cancer treatments

Source: www.eurekalert.org
Author: press release – University of Virginia Health Syste

Researchers at the University of Virginia School of Medicine have made a discovery about human papillomavirus (HPV) that could lead to new treatments for cervical cancer and other cancers caused by the virus.

HPV is responsible for nearly all cases of cervical cancer and 95 percent of anal cancers. It is the most common sexually transmitted disease, infecting more than 79 million Americans. Most have no idea that are infected or that they could be spreading it.

“Human papillomavirus causes a lot of cancers. Literally thousands upon thousands of people get cervical cancer and die from it all over the world. Cancers of the mouth and anal cancers are also caused by human papillomaviruses,” said UVA researcher Anindya Dutta, PhD, of the UVA Cancer Center. “Now there’s a vaccine for HPV, so we’re hopeful the incidences will decrease. But that vaccine is not available all around the world, and because of religious sensitivity, not everybody is taking it. The vaccine is expensive, so I think the human papillomavirus cancers are here to stay. They’re not going to disappear. So we need new therapies.”

HPV and Cancer
HPV has been a stubborn foe for scientists, even though researchers have a solid grasp of how it causes cancer: by producing proteins that shut down healthy cells’ natural ability to prevent tumors. Blocking one of those proteins, called oncoprotein E6, seemed like an obvious solution, but decades of attempts to do so have proved unsuccessful.

Dutta and his colleagues, however, have found a new way forward. They have determined that the virus takes the help of a protein present in our cells, an enzyme called USP46, which becomes essential for HPV-induced tumor formation and growth. And USP46 enzyme promises to be very susceptible to drugs. Dutta calls it “eminently druggable.”

“It’s an enzyme, and because it’s an enzyme, it has a small pocket essential for its activity, and because drug companies are very good at producing small chemicals that will jam that pocket and make enzymes like USP46 inactive,” said Dutta, chairman of UVA’s Department of Biochemistry and Molecular Genetics. “So we are very excited by this possibility that by inactivating USP46 we’ll have a way to treat HPV-caused cancers.”

Curiously, HPV uses USP46 for an activity that is opposite to what the oncoprotein E6 was known to do. E6 has been known for more than two decades to recruit another cellular enzyme to degrade the cell’s tumor suppressor, while Dutta’s new finding shows that E6 uses USP46 to stabilize other cellular proteins and prevent them from being degraded. Both activities of E6 are critical to the growth of cancer.

The researchers note that enzyme USP46 is specific to HPV strains that cause cancer. It is not used by other strains of HPV that do not cause cancer, they report.

Notes:
(1) The researchers have published their findings in the scientific journal Molecular Cell. The team included Shashi Kiran, Ashraf Dar, Samarendra K. Singh, Kyung Yong Lee and Dutta. All are from UVA’s Department of Biochemistry and Molecular Genetics.

(2)The work was supported by the National Institutes of Health, grant R01 GM084465.

December, 2018|Oral Cancer News|

New guidelines from NCCN help people with mouth cancers understand treatment options

Source: www.heraldmailmedia.com
Author: press release

The National Comprehensive Cancer Network® ( NCCN ®) has published the first of three guidelines for patients with head and neck cancers, focused on oral cavity (mouth and lip) cancers. The guidebook offers treatment explanations based on the recommendations from the NCCN Clinical Practice Guidelines in Oncology ( NCCN Guidelines ®) used by clinicians, put into plain language with accompanying glossary and background. This free online resource is also available in print through Amazon.com for a nominal fee. The publication was made possible thanks to funding through the NCCN Foundation ®, and sponsorship from the Head and Neck Cancer Alliance ( HNCA ) and Support for People with Oral and Head and Neck Cancer ( SPOHNC ).

“These guidelines will help to decrease the anxieties associated with a cancer diagnosis,” explained Mary Ann Caputo, Executive Director, SPOHNC. “You will learn and empower yourself with the necessary knowledge of the disease and its treatment. These tools will enable one to go forward with a strong conviction of moving on and living a full life.”

“When I was first diagnosed, I was surprised, overwhelmed and scared. I was completely focused on the treatment for my cancer, and so initially I was less aware of all the information shared with me during my medical appointments about my particular diagnosis,” said Jason Mendelsohn, HNCA Board Member and Survivor. “These guidelines are a great resource that patients, their caregivers, and families can read when they’re ready and able to focus on everything they need to know. We believe they will be a great resource for head and neck cancer patients everywhere.”

Ellie Maghami, MD, FACS, Chief and Professor, Division of Otolaryngology/Head and Neck Surgery, City of Hope National Medical Center, and Member, NCCN Guidelines Panel for Head and Neck Cancers says Mendelsohn’s experience is one she’s seen again and again. She emphasized that while smoking and other tobacco use is by far the most common cause of mouth cancer, it can happen to anybody.

“It’s not just an old person’s disease or just a smoker’s disease,” said Dr. Maghami. “For instance, incidences of tongue cancer — which is a type of oral cancer — are on the rise in non-smoking young people.” She also explained that HPV, despite its common link to throat cancer, is actually responsible for fewer than five percent of tongue cancer occurrences.

The NCCN Guidelines for Patients explain that there are several different types of cancers that can originate in all different parts of the mouth. They are generally treated first by surgery, including immediate reconstruction as needed and followed by rehabilitation of speech and swallow functions. It can be beneficial to receive treatment at a high-volume cancer center with highly-experienced specialists who frequently treat these rarer types of cancers. The NCCN Guidelines® also recommend enrollment in clinical trials whenever possible, and advocate for asking questions and seeking second opinions.

As with most cancers, early detection can make a huge difference. According to Dr. Maghami, these cancers are often caught early, thanks to the high visibility of the mouth location.

“It’s relatively easy to do a self-exam for oral cavity cancers. If you see something in your mouth that looks abnormal or feels strange for more than a few days, talk to a doctor about it.”

NCCN Guidelines for Patients currently cover disease types that account for approximately 90% of all cancer diagnoses. Patient guidelines for both Non-Invasive and Metastatic Breast Cancer have been recently updated, along with those for Colon and Prostate Cancer. The next two books in the Head and Neck series will cover oropharynx and nasopharynx cancers. The NCCN Guidelines for Patients: Thyroid Cancer already exists as a separate publication. All patient guidelines are available for free online at NCCN.org/patients or by app.

“Patients need reliable, accurate, up-to-date information presented in an easy to understand fashion,” said Dr. Maghami. “And that’s exactly what NCCN provides.”

NCCN Guidelines for Patients and NCCN Quick Guide™ sheets DO NOT replace the expertise and clinical judgment of the clinician.

November, 2018|Oral Cancer News|

Standard chemotherapy treatment for HPV-positive throat cancer remains the most effective, study finds

Source: www.eurekalert.org
Author: press release, University of Birmingham

A new study funded by Cancer Research UK and led by the University of Birmingham has found that the standard chemotherapy used to treat a specific type of throat cancer remains the most effective.

The findings of the trial, which aimed to compare for the first time the outcomes of using two different kinds of treatment for patients with Human papillomavirus (HPV)-positive throat cancer, are published today (November 15th) in The Lancet.

Throat cancer is one of the fastest rising cancers in Western countries. In the UK, incidence was unchanged between 1970 and 1995, then doubled between 1996 and 2006, and doubled again between 2006 and 2010. The rise has been attributed to HPV, which is often a sexually transmitted infection. Most throat cancers were previously caused by smoking and alcohol and affected 65 to 70 year old working class men. Today, HPV is the main cause of throat cancer and patients are middle class, working, have young children and are aged around 55.

HPV-positive throat cancer responds well to a combination of cisplatin chemotherapy and radiotherapy, and patients can survive for 30 to 40 years, but the treatment causes lifelong side effects including dry mouth, difficulty swallowing, and loss of taste.

The De-ESCALaTE HPV study, which was sponsored by the University of Warwick, compared the side effects and survival of 164 patients who were treated with radiotherapy and cisplatin, and 162 who were given radiotherapy and cetuximab. The patients were enrolled between 2012 and 2016 at 32 centres in the UK, Ireland, and the Netherlands. Patients were randomly allocated to be treated with radiotherapy and either cisplatin or cetuximab. Eight in ten patients were male and the average age was 57 years.

Importantly, the results found that there was very little difference between the two drugs in terms of toxicity in patients and side effects such as dry mouth, however, there was a significant difference in the survival rates and recurrences of cancer in patients taking part in the trial.

They found that the patients who received the current standard chemotherapy cisplatin had a significantly higher two-year overall survival rate (97.5%) than those on cetuximab (89.4%). During the six-year study, there were 29 recurrences and 20 deaths with cetuximab, compared to 10 recurrences of cancer and six deaths in patients who were treated with the current standard chemotherapy cisplatin.

And cancer was three times more likely to recur in two years following treatment with cetuximab compared to cisplatin, with recurrence rates of 16.1 per cent versus six per cent, respectively.

Study lead Professor Hisham Mehanna, Director of the University of Birmingham’s Institute of Head and Neck Studies and Education, said: “Many patients have been receiving cetuximab with radiotherapy on the assumption that it was as effective as cisplatin chemotherapy with radiotherapy and caused fewer side effects but there has been no head-to-head comparison of the two treatments.

“Cetuximab did not cause less toxicity and resulted in worse overall survival and more cancer recurrence than cisplatin.

“This was a surprise – we thought it would lead to the same survival rates but better toxicity. Patients with throat cancer who are HPV positive should be given cisplatin, and not cetuximab, where possible.”

Dr Emma King, Cancer Research UK Associate Professor in head and neck surgery at the University of Southampton, said: “Studies like this are essential for us to optimise treatments for patients. We now know that for HPV-positive throat cancer, the standard chemotherapy treatment remains the most effective option.

“However, we must keep testing new alternatives to ensure patients always have access to cutting-edge and kinder treatments. Chemotherapy and radiotherapy can leave head and neck cancer patients with long term pain and difficulties swallowing, so we should always strive to minimise side effects.”

Professor Janet Dunn from the University of Warwick, whose team ran the De-ESCALaTE HPV trial, said: “In the current trend for de-escalation of treatment, the results of the De-ESCALaTE HPV trial are very important as they were not as we expected. They do highlight the need for academic clinical trials and are an acknowledgement of the key role played by Warwick Clinical Trials Unit at the University of Warwick as the co-ordination and analysis centre for this important international trial.”

The patients on the De-ESCALaTE trial Steering Committee endorsed the importance of research findings.

Malcom Babb, who is also President of the National Association of Laryngectomee Clubs, said: “From a patient perspective, De-ESCALaTE has been a success by providing definitive information about the comparative effectiveness of treatment choices.”

November, 2018|Oral Cancer News|

Early detection, treatment helps conquer oral cancer

Source: www.newsbug.info
Author: Bob Moulesong

According to the Oral Cancer Foundation, almost 50,000 cases of oral cancer will be diagnosed in the U.S. in 2018. The American Cancer Society reports that 10,000 people will die from the disease this year. Half of all people diagnosed with oral cancer will be alive in five years, according to both sources.

While those are disquieting statistics, Region physicians say routine checkups and early diagnosis improve the odds.

Oral cancer
Oral cancer includes cancers of the lips, tongue, cheeks, floor of the mouth, hard and soft palate, sinuses, saliva glands, and throat.

“People we see usually come to us for a lesion or ulcer found in the mouth or throat,” says Dr. Akta Kakodkar, an ear, nose and throat specialist with Community Healthcare System. “Some of them experience no pain but notice a growth or patch of discolored tissue in their mouth, cheek or gum.”

Kakodkar, who with her husband and fellow Community ENT physician, Dr. Kedar Kakodkar, treats oral cancer patients, is quick to point out that not every lesion, ulcer or mouth sore is cancer.

“We see hundreds of nervous patients who have bacterial or fungal infections,” she says. “Treatment with antibiotics or antifungal medications clear up many of these lesions. There are also many white and red patches that clear up on their own.”

The only way to know is a thorough examination.

Types and risk factors
“Most cases of oral cancer are linked to use of tobacco, alcohol and betel nuts, or infection with HPV,” Kakodkar says. “There are major risks associated with tobacco use, whether it’s smoking or chewing.”

There are two main types of oral cancer. Most prevalent is squamous cell carcinoma, accounting for more than 90 percent of cancers that occur in the oral cavity and oropharynx. Slow-growing verrucous carcinoma makes up more than 5 percent of oral cavity tumors.

First steps
Kakodkar says prevention is the best defense. “Your primary care physician may examine your head, neck, mouth and throat for abnormalities,” she says.

Self-exam may uncover a lesion or sore. “Remember, many of these are very treatable and are not cancer,” Kakodkar says. “But don’t wait. Cancer never goes away by itself.”

When Kakodkar discovers a suspicious lesion, she recommends a biopsy: “Depending on several variables, we might do the biopsy in clinic, or we may do it in a hospital setting.”

Once the results return, a plan of action can be established. “Usually, the next steps include imaging, such as a CT scan,” she says. “We also order a PET scan, which tells us what stage the cancer is in and whether or not it has spread.”

Treatment
Kakodkar says she prefers to go straight to surgery. “Many oral cancers are still small and local,” she explains. “Removing them completely is the best way to stop the spread of the cancer.”

Depending on the type and stage of the cancer, radiation and/or chemotherapy may be used.

“I want people to know that surgery for oral cancer is frequently a simple procedure,” Kakodkar says. “Oral cancer is frequently found early due to its visibility. Almost 90 percent of cancer patients in stage 1 or 2 recover and survive.”

A dental checkup
“Oral cancer screening is crucial during a dental examination,” says Dr. Ami Pandya, dentist at Family Dental Care in Valparaiso. “Recognizing abnormal tissue in a patient’s mouth could indicate precancerous tissues, and when identified early could save your life.”

A dentist will perform a thorough head and neck exam, which includes an oral cancer screening. “Dentists will complete extraoral examinations by palpating your jaw line to feel for any suspicious lumps that are not routinely present in these areas,” Pandya says.

A dentist will examine the intraoral tissues of your mouth and look for any suspicious lesions. “We examine the patient’s tongue, the floor of their mouth, and their gingival tissue,” Pandya says. Red and/or white patches can become cancerous.

Many doctors including Pandya have begun using VELscope, a light-based technology to detect precancerous tissues. It’s a wireless hand-held device that scans tissue, with abnormalities showing up as a dark black color.

“VELscope can detect abnormalities before they have a clinical presentation,” Pandya says. “It’s an incredible aid with oral cancer screening.”

Pandya recommends an annual VELscope examination for low-risk adults. Higher risk patients should get a VELscope exam each appointment.

Under the VELscope, cancer shows up as black, says Dr. Ami Pandya

If the dentist detects an abnormality, he or she informs the patient, noting the size, color and location of the lesion. A two-week follow-up is standard. “Oftentimes, these lesions resolve,” Pandya says. If it doesn’t resolve after two weeks, the patient is referred for further evaluation.

Note: This article originally ran on nwitimes.com.

November, 2018|Oral Cancer News|

Research Update: Vaccine Plus Checkpoint Inhibitor Combos for HPV-related Cancers

Source: MedPage Today
Author: Mark L. Feurst

Two new studies show the profound impact of a combined vaccine and anti-programmed death-1 (PD-1) antibody approach in the treatment of human papilloma virus (HPV)-related cancers.

HPV causes nearly all cervical cancers, as well as most oropharyngeal, anal, penile, vulvar, and vaginal cancers. HPV16 and HPV18 are the leading viral genotypes that increase cancer risk. Given the viral cause of these cancers, immunotherapy has been considered a strong potential approach.

Many patients with the HPV16 and HPV18 subtypes of head and neck squamous cell carcinoma have good outcomes from treatment that includes surgery or chemotherapy and radiation. Although anti-PD-1 therapy is approved for patients who do not respond to treatment or who develop metastatic disease, it benefits only about 15% of patients. The theory, therefore, is that a vaccine could potentially boost the immune systems of patients with HPV-related head and neck cancer, opening the door for better responses to other existing therapies.

Vaccine + Nivolumab in Phase II Study

In the first study, a phase II trial, a tumor-specific vaccine combined with the immune checkpoint inhibitor nivolumab was found to shrink tumors in patients with incurable HPV-related cancers.

“Ours are the first results with this particular approach,” Bonnie Glisson, MD, of the Department of Thoracic Head and Neck Medical Oncology at the University of Texas MD Anderson Cancer Center in Houston, told the Reading Room. “The rates of response and survival are approximately double what have been observed with nivolumab given alone to similar patients. These results will lead to larger, randomized clinical trials of this combination.”

Vaccines specific to HPV antigens found on tumors had previously sparked a strong immune response, but had not by themselves been active against established cancers, she noted.

“Vaccines are revving up the immune system, but the immunosuppressive tumor microenvironment probably prevents them from working. Our thinking was that inhibition of programmed death-1 (PD-1) would address one mechanism of immunosuppression, empowering the vaccine-activated T lymphocytes to attack the cancer.”

Glisson and colleagues combined the vaccine ISA101, which targets peptides produced by the strongly cancer-promoting HPV16 genotype of the virus, along with nivolumab, a checkpoint inhibitor that blocks activation of PD-1 on T cells.

The single-arm, single-center clinical trial included 24 patients with incurable HPV-16–positive cancer who were followed for 12.2 months. The vaccine was given subcutaneously on days 1, 22, and 50. A nivolumab dose of 3 mg/kg was given intravenously every 2 weeks beginning on day 8 for up to 1 year. Of the 24 patients with recurrent HPV16-related cancers, 22 had oropharyngeal cancer, one had cervical cancer, and one had anal cancer. The overall response rate was 33% (eight patients), and the median duration of response was 10.3 months. Five of eight patients remain in response, the team reported.

The overall median survival was 17.5 months, progression-free survival was 2.7 months, and 70% of patients survived to 12 months.

Grades 3 to 4 toxicity occurred in two patients (asymptomatic grade 3 transaminase level elevation in one patient and grade 4 lipase elevation in one patient), requiring discontinuation of nivolumab therapy. The researchers observed side effects expected from the two treatments separately, but said they were encouraged to see no sign of synergistic side effects caused by the combination.

“The combination was very well tolerated as opposed to other immunotherapy combinations such as combined blockade of PD-1 and CTLA-4,” Glisson said. “The vaccine did stimulate a strong HPV-specific immune response in peripheral blood T cells, although this was not correlated with response or survival. This suggests that other immune-suppressive factors in the tumor environment are contributing to immune evasion.”

Randomized clinical trials of the vaccine and anti-PD1 combinations for cervical and oropharyngeal cancer are ongoing, she added. “These are promising data that will be confirmed in a randomized trial. Positive results could lead to marketing of the first therapeutic HPV vaccine.”

Vaccine Helps T cells Infiltrate HPV-related Head and Neck Cancer

In the second study, another vaccine was shown to boost antibodies and T cells to help them infiltrate tumors and fight off HPV-related head and neck cancer. This approach might complement PD-1 or programmed death-ligand 1 inhibition in HPV-associated head and neck cancers to improve therapeutic outcomes, explained the study’s lead author, Charu Aggarwal, MD, MPH, of the Perelman School of Medicine at the University of Pennsylvania.

“We wanted to know if this vaccine can boost the immune systems of patients with HPV-related head and neck cancer, potentially opening the door for better response rates to other existing therapies. Our findings show that we can.”

Aggarwal and colleagues conducted a Phase Ib/II safety, tolerability, and immunogenicity study of immunotherapy with MEDI0457, a DNA immunotherapy targeting HPV16/18 E6/E7 with interleukin-12 encoding plasmids. The vaccine was delivered via electroporation to 21 patients. One group of patients received one dose before surgery, followed by three doses after surgery. The second group received four doses following chemotherapy and radiation.

Eighteen of the 21 patients (86%) showed elevated T cell activity that lasted at least 3 months after the final vaccine dose, the team reported. Five tumors were biopsied both before and after one dose of the vaccine, and there was evidence of T cells reacting with antigens contained in the vaccine in all five of these samples. One patient who developed metastatic disease and was treated with anti-PD-1 therapy developed a rapid and durable complete response that has lasted more than 2 years.

“We have not seen that kind of infiltration with just one dose of a vaccine before. These findings open the door for utilizing targeted immunotherapy approaches against specific cancer-causing targets like HPV,” said Aggarwal, adding that the vaccine was well tolerated, with no serious side effects reported.

“This response suggests that the vaccine may, in some manner, prime the immune system, potentially boosting the effects of subsequent anti-PD-1 therapy,” she explained, noting that a multi-site clinical trial is now open to patients with metastatic HPV-associated head and neck cancer, who will receive a combination of the vaccine with anti-PD-1 therapy.

Previously, the CheckMate-141 trial tested nivolumab in 361 patients with recurrent or metastatic, chemotherapy-refractory squamous cell head and neck cancer, and the results led to FDA approval in that setting. Sixty three of these patients were HPV16-positive, and the overall response rate among this group was 15.9%, with a median overall survival of 9.1 months.

 

November, 2018|Oral Cancer News|