Monthly Archives: November 2018

Israeli company set to begin testing new radiation cancer therapy

Source: www.forbes.com
Author: Robin Seaton Jefferson

An Israeli medical technology company is set to begin testing its new radiation cancer therapy in leading medical centers in Italy. The Alpha DaRT (Dіffusіng Alpha-emіtters Radіatіon Therapy) device delivers high-precision alpha radiation that is released when radioactive substances decay inside the tumor and kills cancer cells while sparing the surrounding healthy tissue, the company says.

The company hopes to get approval from the European Commission by next year for the therapy.

Early results from an ongoing pre-clinical trial on patients with squamous cell carcinoma (SCC) tumors at the Rabin Medical Center in Israel and the IRST (Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori) in Italy showed a reduction in all tumor sizes and more than 70 percent of the tumors completely disappearing within a few weeks after treatment, NoCamels reported.

The therapy has already been tested on more than 6,000 animals and has been found “to be effective and safe for various indications, including tumors considered to be resistant to standard radiotherapy.” according to the breakthrough innovation news site NoCamels.

Alpha Tau Medical was founded in 2016 to focus on research and development as well as commercialization of its Alpha DaRT cancer treatment. The therapy was initially developed in 2003 by Professors Itzhak Kelson and Yona Keisari at Tel Aviv University.

According to the National Cancer Institute (NCI), cancers that are known collectively as head and neck cancers, or squamous cell carcinomas of the head and neck, usually begin in the squamous cells that line the moist, mucosal surfaces inside the head and neck (for example, inside the mouth, the nose, and the throat).

Head and neck cancers account for about 4% of all cancers in the United States, are more than twice as common among men as they are among women, and are more often diagnosed among people over age 50.

Cancers of the head and neck are further categorized by the area of the head or neck in which they begin including the oral cavity, pharynx (throat), larynx, paranasal sinuses and nasal cavity, and salivary glands. They can include hypopharyngeal cancer, laryngeal cancer, lip and oral, cavity cancer, metastatic squamous neck cancer with occult primary, nasopharyngeal cancer, oropharyngeal cancer, paranasal sinus and nasal cavity cancer, salivary gland cancer.

The Alpha DaRT treatment can be applied under local anesthesia in a short single session and can be combined with chemotherapy and immunotherapy to increase effectiveness, according to Alpha Tau Medical. The company reports Alpha DaRT can even trigger anti-tumor immunity for the elimination of distant metastases, NoCamels reported.

Clinical trials for Alpha DaRT will be conducted at the Sapienza University of Rome, which is initiating Alpha Tau’s clinical trial protocol for squamous cell carcinomas of the skin and oral cavity, and the IFO (Istituti Fisioterapici Ospitalieri), which is conducting its first study of Alpha DaRT for the treatment of cutaneous and mucosal malignant neoplasia (CMN).

Alpha Tau is also collaborating with key cancer physicians worldwide to investigate the Alpha DaRT as a treatment for other cancers, including pancreatic, breast and prostate, NoCamels reported.

November, 2018|Oral Cancer News|

Scientists Confirm There’s Nothing But Misinformation On Anti-Vax Sites

Source: Huffington Post, LIFE
Author: Agata Blaszczak-Boxe
Date: 11/04/18

Many websites that promote unscientific views about vaccinations use pseudoscience and misinformation to spread the idea that vaccines are dangerous, according to a new study.

For example, of the nearly 500 anti-vaccination websites examined in the study, nearly two-thirds claimed that vaccines cause autism, the researchers found. However, multiple studies have shown that there is no link between vaccines and autism.

About two-thirds of the websites used information that they represented as scientific evidence, but in fact was not, to support their claims that vaccines are dangerous, and about one-third used people’s anecdotes to reinforce those claims, the scientists found.

Some websites also cited actual peer-reviewed studies as their sources of information, but they misinterpreted and misrepresented the findings of these studies.

“So the science itself was strong, but the way it was being interpreted was not very accurate,” said study author Meghan Moran, an associate professor in Johns Hopkins University Bloomberg School’s Department of Health, Behavior and Society. “It was being distorted to support an anti-vaccine agenda.”

In the study, the researchers looked at websites with content about childhood vaccines. They used four search engines to find the sites — Google, Bing, Yahoo and Ask Jeeves — and searched for terms including “immunization dangers” and “vaccine danger” as well as other phrases. Their final sample of 480 anti-vaccination websites included a mix of personal websites, blogs, Facebook pages and health websites. The researchers examined the content of the websites, looking for vaccine misinformation, the sources of the misinformation and the types of persuasive tactics that the sites used to convince people that vaccines are dangerous.

In examining the websites, the researchers also observed a lot of misunderstanding and misinterpretation of epidemiological principles, Moran told Live Science.

For example, epidemiologists know that correlation does not imply causation. “Just because two things happen at the same time, that doesn’t mean that one is causing the other,” Moran said. But some of the websites presented timelines that showed that, as rates of immunization went up over a certain period of time, so did autism diagnoses, Moran said.

Although it is true that both have increased over the same period, the anti-vaccine websites frequently implied that “it must be that the immunizations were causing autism, which we know is not true,” Moran said.

Another tactic commonly employed by the websites in the study was the use of anecdotes and stories of parents of children with autism, the researchers said. Because such stories are easy for other parents to connect to, they help to make the anti-vaccine agenda that these sites are promoting appear “a lot more vivid and powerful,” Moran said.

Some of the sites also included information promoting positive health behaviors, the researchers said. For example, 18.5 percent of them promoted eating healthy, about 5 percent promoted eating organic food and 5.5 percent recommended breast-feeding.

The biggest takeaway from the findings is that researchers and health officials “need to communicate to the vaccine-hesitant parent in a way that resonates with them and is sensitive to their concerns,” Moran said in a statement. “In our review, we saw communication for things we consider healthy, such as breast-feeding, eating organic, the types of behavior public health officials want to encourage. I think we can leverage these good things and reframe our communication in a way that makes sense to those parents resisting vaccines for their children.”

The new findings were presented today (Nov. 3) at the American Public Health Association’s Annual Meeting in Chicago.

 

November, 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|

Call for closer links between GPs and dentists

Source: www.onmedica.com
Author: Adrian O’Dowd

GPs must work more closely and liaise better with dentists if the rising number of patients with oral cancer are to be helped properly, according to a new action plan.

The action plan launched by trade union the British Dental Association (BDA) calls for better coordination between health professionals, checks to ensure patients have regular dental check-ups, and better detection and prevention of the disease.

The document Oral Cancer: A Plan for Action was launched in Edinburgh by BDA Scotland at a Stand Up to Oral Cancer event held to coincide with Mouth Cancer Action Month in November.

New cases of oral cancer in the UK have reached 8,302 per year and this has increased by 49% in the last decade. Cancer Research UK estimates that incidence rates for oral cancers will rise by a further 33% in the UK by 2035.

In the UK last year, 2,722 people died after developing oral cancer. The 10-year survival rate is between 19% and 58%, depending on where the cancer strikes and how early it is diagnosed.

The plan focuses on prevention, early detection and having better referral pathways to ensure good links between dentists, GPs and pharmacists.

It follows the publication of the Scottish Government’s Oral Health Improvement Plan (OHIP) earlier this year, which proposed extending the dental recall interval for some patients to 24 months – a move strongly opposed by the BDA.

Anas Sarwar MSP (member of the Scottish Parliament) has tabled a motion in the Scottish Parliament calling for sustainable and innovative approaches to oral cancer treatment, and expressing concern over the potential impact of the OHIP.

BDA Scotland said it wanted a strategic focus on early detection, prevention and joining-up services, with measures including sufficient resources for alcohol treatment and smoking cessation programmes, and a catch-up programme to offer 140,000 older school-aged boys access to the vaccination programme for the cancer-causing Human Papillomavirus (HPV).

David Cross, vice-chair of the BDA’s Scottish Council said: “Dentists are on the front line of a battle against some of the fastest rising cancers in Scotland. Early detection is key, but now risks becoming a casualty of a cost-cutting exercise.

“People in otherwise good health are succumbing to this disease. Telling our ‘lower risk’ patients to come back in two years will only handicap efforts to meet a growing threat, while putting further pressure on NHS cancer services.

“Oral cancer now claims three times as many lives in Scotland as car accidents. Rather than chasing quick savings we need to see concrete plans and real investment to help turn the tables on this devastating but preventable disease.”

The BDA is working with the BMA and Community Pharmacy Scotland on the plan and is developing partnerships and links with other organisations such as ASH (Action on Smoking and Health) Scotland.

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|

Researchers evaluate efficacy of salivary biomarkers for early detection of oral cancer

Source: www.news-medical.net
Author: staff, reviewed by Kate Anderton, B.Sc.

Over 90% of malign tumors in the head and neck are originated from carcinomas of squamous cells that appear in superficial areas of the oral cavity. Their detection with salivary biomarkers can contribute to their early treatment, before they transform into tumors. Researchers of the Oral Microbiology Research Group of the CEU Cardenal Herrera University (CEU UCH) in Valencia, Spain, have conducted a systematic review and a meta-analysis of the salivary markers that show the highest efficacy for the early detection of oral cancer in different clinical trials. The results have just been published in the Journal of Oral Pathology and Medicine, the official magazine of the International Association of Oral Pathogens in the field of Dentistry, Oral Surgery and Medicine.

According to Verónica Veses, head researcher of the Group and professor at the Biomedical Sciences Department of the CEU UCH, “detection of this type of squamous cell cancer in the surface of the mouth essentially depends of the visual examination on behalf of oral health professionals. This is why it is important to find new diagnostic methods to help with accurate early detection. Specially if we take into account that oral cancer is the most common of the tumors in the head and neck, and which is increasingly prevalent among the young population due to the consumption of tobacco and alcohol”.

Three types of biomarkers
The research team headed by Dr. Veses has conducted a systematic review and a meta-analysis of the clinical trials that have thus far evaluated the efficacy of the three types of salivary biomarkers that are the most promising for the early detection of this type of oral cancer. These salivary markers are two types of cytokines, proteins involved in cellular proliferation and differentiation; two markers that are present in the ribonucleic acid that transfers the genetic code, the messenger RNA or mRNA (DUSP‐1 and S100P); and two more in the micro-RNA (miRNA) of the saliva, but which require further research.

Research team
The results are part of the final degree project of UCH CEU Dentistry student Fariah Gaba, under the guidance of professors Verónica Veses and Chirag Sheth, members of the Oral Microbiology Research Group of this university. Fariah Gaba, who has obtained the Extraordinary Degree Prize for her Dentistry studies, is currently working as a dentist in Holland and began her research efforts working on one of the UCH CEU’s research and teaching projects of the Oral Microbiology Group.

Source:
http://ruvid.org/ri-world/researchers-detect-the-most-efficient-salivary-biomarkers-for-detecting-oral-cancer/

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|

Cultural barriers still stand in the way of HPV vaccine uptake

Source: arstechnica.com
Author: Cathleen O’Grady

Every year, nearly 34,000 cases of cancer in the US can be attributed to HPV, the human papillomavirus . The CDC estimates that vaccination could prevent around 93 percent of those cancers. Yet HPV vaccination rates are abysmal: only half of the teenagers in the US were fully vaccinated in 2017.

Cultural barriers play a role in that low rate. Vaccinating pre-teens against a sexually transmitted infection has had parents concerned that that this would encourage their kids to have sex sooner, with more partners, or without protection or birth control. And vaccine rates vary across different social and cultural groups: for instance, rural teenagers are less likely to be vaccinated than urban ones.

Two recent studies explore different facets of the cultural barriers standing in the way of better HPV vaccine uptake. The first, a paper published last month in the Canadian Medical Association Journal, looks at the data on whether the vaccine encourages riskier sexual behavior and finds no evidence that it does. And the second, an early draft of a paper presented at an American Association for Cancer Research meeting this week, reports the results of a culturally-targeted intervention aiming to increase vaccine uptake among low-income Chinese Americans.

The kids are alright
Although the vaccine is now recommended for both boys and girls, the initial drive was to get teenage girls vaccinated, given the link between HPV and cervical cancer. That’s why girls are the focus of the recent study on risky sexual behavior: the researchers used data from high school girls in Canada, where a huge survey on adolescent health is administered every few years.

A team of researchers was able to use this data to compare results from the survey before and after a large-scale HPV vaccine program was implemented across high schools in Canada in 2008. The researchers compared data from 2003, before the program began, to data from 2008 and 2013. Altogether, nearly 300,000 girls’ survey responses were analyzed.

The researchers found that, on every measure they looked at, risky sexual behaviors either decreased or stayed the same. The number of girls who had ever had sex decreased from 21.3 percent in 2003 to 18.3 percent in 2013. The girls who’d had sex before age 14 decreased from 14.3 percent to 10.2 percent, and girls who’d ever been pregnant went from 5.9 percent to 3.4 percent. The use of condoms increased, as did the use of birth control pills.

The researchers are careful to point out that they don’t think the HPV vaccine caused the increase in safe sex among the teenagers. That shift was already underway, they write, pointing to data showing “a downward trend in risky sexual behaviors since before 2003.” But it does suggest that the introduction of the vaccine in 2008 wasn’t associated with an increase in risky sexual behaviors.

Survey data like this has its problems, especially when the questions involve sex. It’s likely that the girls aren’t telling all, even when the survey is anonymous. But because all three years of the survey are likely to suffer from the same problem, the comparison is still apples with apples. And it’s possible that in a parallel universe without the vaccine, the risky behaviors could have plummeted even further; there’s simply no way to tell.

The researchers plan to explore whether risky behavior looks different in girls who had been vaccinated compared to those who hadn’t. To do this, they will introduce a new question in the survey, which asks girls about their HPV vaccination status. But in the meantime, these results fit in well with a growing body of literature: a study in the US that compared girls who were and weren’t vaccinated found no differences in pregnancy or STD rates between the two groups, while a different Canadian study found similar results.

Some research has even found that girls who’ve had the vaccine have safer sex than those who haven’t. That could be because HPV vaccine programs often go hand-in-hand with sex education, and teasing apart those influences is extremely difficult. But it seems unlikely that a significant change in risky behavior is lurking hidden in the data.

Different tactics for different groups
The obvious benefits of the vaccine make it important for us to understand why its uptake isn’t higher. The rate is even lower among certain groups, says Grace X. Ma, director of the Center for Asian Health in Philadelphia. While Asian American teenagers have rates similar to the average, “there are certain subgroups, such as Chinese Americans whose parents are low-income and have limited English proficiency, for whom uptake is much lower.” According to Ma, different sources placed the rate at between 10 and 30 percent at the time she started her research.

Ma designed a program to reach these parents through doctors, using materials written in their own languages and delivered through a source they were inclined to trust. In a small pilot study, Ma engaged pediatricians working in low-income Asian communities in Philadelphia and New York. By the end of the study, 110 parents had been reached by the materials, while a control group of 70 hadn’t. More than 70 percent of the teenagers of those 110 parents “had at least one dose of the HPV vaccine, compared with 10 percent of adolescents whose parents did not receive the intervention,” Ma reports.

Without a lot more information, it’s difficult to know what was driving this difference: it could be the cultural specificity of the materials, it could simply be access to the information in a language the parents understand, or a longer and more focused conversation with the doctor might drive the change.

But research in this vein, exploring the effects of different kinds of interventions, could give important clues to how vaccine uptake could be improved in a wider range of population groups. The potential barriers could range from cultural attitudes about sex to language issues to financial access to medical care. But clearly, simple access to the vaccine isn’t enough to encourage widespread adoption.

Source: Canadian Medical Association Journal, 2018. DOI: 10.1503/cmaj.180628 (About DOIs).

November, 2018|Oral Cancer News|

Scientists untangle the evolutionary history of the world’s most common STI

Source: www.iflscience.com
Author: Rosie McCall

Scientists have analyzed the genomes of viruses to reveal the surprisingly complex evolutionary past of the human papillomavirus (HPV), exposing the salacious details of our ancestors’ sexual history in the process.

HPV comes in several flavors but HPV16 is the most common subtype worldwide – and it is the one most frequently identified in cervical cancer. Together HPV16 and HPV18 are responsible for 70 percent of all cases, accord to stats from the World Health Organization (WHO).

The problem is, it isn’t exactly clear how HPV strains contribute to cervical cancer (and other types, including cancer of the anus, the throat, the base of the tongue, and the tonsils). Or why the virus naturally clears in some people but not others. Researchers hope that studying the evolution of the virus will expose biological insights and point at mechanisms that might explain how cervical cancer develops.

To try to untangle HPV16’s thorny evolutionary past, scientists led by the Chinese University of Hong Kong isolated and examined oral, perianal, and genital samples in 10 adult female squirrel monkeys (Saimiri sciureus) and eight adult rhesus monkeys (Macaca mulatta), half of whom were male and half of whom were female.

They found that the virus strains with most in common came from the same part of the body – meaning the oral samples from the squirrel monkeys and rhesus monkeys had more in common than oral and genital samples from the same species, for example. This, the authors say, implies the viruses adapted to a specific body part (or niche) where they co-evolved with their host for millions of years before passing to humans.

For the next part of the study, published in the journal PLOS Pathogens, the researchers compared 212 complete HPV16 virus genomes and 3,582 partial sequences to find out when exactly the HPV16 variants A, B, C, and D diverged from one another.

Schematic illustration of HPV16 codivergence with archaic hominins. Chen et al./PLOS Pathogens

Previous studies have shown that one (the HPV16 A variant) was a lover’s gift from our hominid relatives, the Neanderthals, transmitted to modern humans after a few too many nights of interspecies shagging. Now, it looks like this particular variant split from the virus’ “family tree”, setting off its own trajectory, just as modern humans and archaic hominins (Neanderthals and Denisovans) parted ways, evolutionarily speaking, 618,000 or so years ago.

While the HPV16 A variant co-evolved with its Neanderthal and Denisovan hosts, HPV16 B and HPV16 C variants co-evolved with modern humans. The different strains remained in their respective hosts for hundreds of thousands of years, the study authors say. Then, 100,000 years ago or thereabouts, a small band of Homo sapiens ventured outside of Africa and into Eurasia where they met – and intermingled – with other hominin species, contracting certain HPV16 A variants in the process.

The consequences of this can still be seen today and can help explain why certain variants are more commonly seen in certain groups, the HPV16 A variant in Europeans and Asians, for instance. Hopefully, the authors say, this new information will improve our understanding of why some variants of HPV16 may be inherently more carcinogenic than others.

November, 2018|Oral Cancer News|