oral cancer

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|

Study: Immunotherapy better than chemotherapy for subtype of head and neck cancer

Date: November 30th, 2018
Source: Scienmag

A randomized clinical trial involving 97 medical centers in 20 countries, including Moores Cancer Center at UC San Diego Health, found that treating patients who have chemotherapy-resistant head and neck cancer with the immunotherapy drug pembrolizumab is more effective and less toxic than standard chemotherapy, reports an international team of researchers in the November 30 online issue of The Lancet.

Previous research had shown that pembrolizumab (Keytruda) was safe and effective for treating patients with recurrent or metastatic head and neck squamous cell carcinoma whose disease had progressed while on or after receiving standard chemotherapy. Data from this clinical trial called KEYNOTE-040, a phase III study sponsored by Merck & Co., the manufacturer of the drug, takes the research a step further by comparing the immunotherapy drug head-to-head to three go-to chemotherapy drugs currently used as standard treatment: methotrexate, docetaxel and cetuximab.

“We compared pembrolizumab against standard of care to see if it fulfilled the promise of early data for patients who are unlikely to do well on standard therapy,” said Ezra Cohen, MD, professor of medicine at University of California San Diego School of Medicine and corresponding author on the study.

“In this trial, patients who received pembrolizumab alone had a higher response rate compared to those receiving standard chemotherapy while those responses lasted, on average, one-and-a-half years. Furthermore, the median survival at one year was markedly better. I feel it is safe to say that these types of therapies should be the new standard therapy for people with cancer that recurs and is resistant to therapy.”

Pembrolizumab is an antibody that inhibits the abnormal interaction between the molecule PD-1 on immune cells and the molecule PD-L1 on tumor cells, allowing the immune cells to activate and attack tumors. Similar results were recently published for another anti-PD-1 drug, nivolumab (Opdivo). Both drugs should be considered by treating physicians for patients with this disease, said Cohen.

The study also pointed to potential biomarkers that can guide oncologists to determine which patients are most likely to respond to these anti-PD-1 drugs.

“It’s fairly clear that patients whose tumors express PD-L1 are most likely to benefit from this type of immunotherapy drug,” said Cohen, associate director for translational science at Moores Cancer Center and an internationally recognized physician-scientist who specializes in novel cancer therapies. “In this trial, overall survival was driven by PD-L1 expression. Only patients whose tumors expressed PD-L1 had a response to pembrolizumab and those responses tended to be durable.”

Over a 17-month period, 247 patients were randomized to receive pembrolizumab and 248 patients were randomly selected by their physicians to receive one of the three standard therapies. The median overall survival for patients receiving immunotherapy was 8.4 months and 6.9 months for patients treated with standard care. Patients received treatment until their cancer progressed, they developed unacceptable toxicity, they withdrew or their physician removed them.

The median duration of response was 18.4 months in the pembrolizumab group, compared with five months in the standard therapy group.

Twelve months after initiating the trial, 37 percent of patients receiving pembrolizumab were alive compared to 26.5 percent of patients on standard therapy.

###

Co-authors include: Denis Soulières, Centre Hospitalier de l’Université de Montréal; Christophe Le Tourneau, Institut Curie, INSERM U900 Research Unit, Versailles-Saint-Quentinen-Yvelines University; José Dinis, Instituto Português de Oncologia do Porto Francisco Gentil; Lisa Licitra, Fondazione IRCCS Istituto Nazionale dei Tumori; Myung-Ju Ahn, Samsung Medical Centre; Ainara Soria, Hospital Universitario Ramón y Cajal; Jean-Pascal Machiels, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain; Nicolas Mach, Hôpitaux Universitaires de Genève; Ranee Mehra, Fox Chase Cancer Center; Barbara Burtness, Yale University School of Medicine and Yale Cancer Center; Pingye Zhang, Jonathan Cheng, Ramona F Swaby, Merck & Co; and Kevin J Harrington, The Institute of Cancer Research, The Royal Marsden NHS Foundation Trust, National Institute of Health Research Biomedical Research Centre.

This research was funded by Merck Sharp & Dohme, a subsidiary of Merck & Co. The funder contributed to study design, data collection, data analysis, data interpretation, and the writing of The Lancet paper. The funder maintained the study database. All authors had full access to all the data in the study and had final responsibility for the decision to submit for publication.

Disclosure: Cohen reports grant support to the institution from Merck Sharp & Dohme for clinical research related to the submitted work and serving an advisory role for AstraZeneca, Bristol-Myers Squibb, Eisai, Merck, Human Longevity and Pfizer, all outside the submitted work.

December, 2018|Oral Cancer News|

HPV vaccine gains support of ADA

Source: Multi Briefs
Date: October 24th, 2018
Author: Tammy Adams

The American Cancer Society estimates there will be more than 50,000 new cases of oral cancer in 2018. And between 70 to 80 percent of these cases will be attributed to the human papillomavirus virus (HPV), a virus that has types associated with oropharyngeal cancer.

These staggering numbers call for action; action the American Dental Society is willing to take. Why? Because the HPV vaccine could prevent the vast majority of these new cases, but compared to other vaccines in the U.S., it is underutilized.

According to a resolution passed recently by the ADA House of Delegates, the ADA urges dentists to support the use and administration of the human papillomavirus virus vaccine, recognizing it as a way to help prevent infection of the types of HPV associated with oropharyngeal cancer.

Resolution 53H-2018 cites recommendations from the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices. It states that the vaccination is a “safe and effective intervention to decrease the burden of oral and oropharyngeal HPV infection.”

The policy is the result of a multifaceted ADA council proposal that includes input from the Council on Scientific Affairs, the Council on Advocacy for Access and Prevention and the Council on Dental Practice. A workgroup committed to the HPV issue and led by ADA volunteer members developed an evidence-based background report to help write the policy.

Dr. Paul Eleazer, past chair of the ADA Council on Scientific Affairs, said that he is encouraged to see the ADA “get behind” this growing crisis, referring to the rising number of HPV-associated cancers being reported. “There is incontrovertible evidence that this virus is responsible for the sharp uptick in oropharyngeal cancers, especially in younger patients and young adults,” said Dr. Eleazer.

In 2017, the ADA Council on Scientific Affairs and Center for Evidence-Based Dentistry published “Evidence-based Clinical Practice Guideline for the Evaluation of Potentially Malignant Disorders in the Oral Cavity” to inform dental professionals about the potential use of adjuncts as triage tools for the evaluation of lesions, including potentially malignant disorders, in the oral cavity. To view this guideline, visit ADA.org/OralCancer.

To read the full resolution related to the HPV vaccine, members can log in to the Member Center on ADA.org and click on “Committee C—Dental Education, Science and Related Matters” under Reports and Resolutions. It is Resolution 53.

October, 2018|Oral Cancer News|

Long-term implant failure in patients treated for oral cancer by external radiotherapy: a retrospective monocentric study

Source: Journal of Oral Medicine and oral Surgery, JOMOS
Date: October 10th, 2018
Authors: Aline Desoutter, Sophie Deneuve, Sophie-Charlotte Condamin and Anne-Gaëlle Chaux-Bodard

Abstract

Introduction: The placement of dental implants in irradiated bone has allowed functional rehabilitation for many oral cancer patients. Nonetheless, there is only few data about implant failure in irradiated tissues and their consequences. This retrospective study aims to highlight the rate and circumstances of implant failure.

Material and method: Patients treated with external radiotherapy for oral carcinoma and who received dental implants were included. Patients reconstructed with free bone flaps were excluded.

Results: Eighteen patients were included. Forty implants were placed between 2004 and 2007, 8 failed, of whom one osteoradionecrosis was observed. Time interval between radiotherapy and implantation was 44.6 (6–182) months. Mean dose was 51.8 (50–66) Gy.

Discussion: In the series, the implant failure rate is 20%, which corroborates the literature’s data. Failures occur more often for doses over 50 Gy. The placement of dental implant in irradiated bone leads to soft tissue complications but also increases the risk of osteoradionecrosis. The recent reimbursement of dental implants in oral cancer patients by the National Social Health system will probably increase the indications. Multidisciplinary staffs should be aware of benefit/risk ratio for each patient.

Introduction

Dental implants in patients treated for upper aerodigestive tract (UADT) cancers have facilitated the functional and aesthetic rehabilitation of patients whose postoperative anatomy did not allow for the placement of conventional prostheses. Several studies have been conducted and the success rates have varied from 62.5% to over 90% [1]. These success rates would be similar to those found in a healthy patient’s mandible, which is reported to be 92.6% [2]. However, there is little information regarding the types of failures that occur with these implants, as well as the consequences and circumstances surrounding their occurrence, especially when the radiation dose at the implant site is >40 Gy. Indeed, most of the published studies are case studies in which there is great heterogeneity in the initial tumor sites and in the radiation doses received at the implant site. It is therefore difficult to precisely determine the failure risk in patients who have received large radiation doses in the oral area. The expected complications are mainly peri-implantitis, loss of implants, and even osteoradionecrosis (ORN) [3]. The aim of this study was to highlight long-term implant failures in patients who were treated with radiotherapy for oral cancer and to observe the circumstances and consequences of these failures.

Material and methods

The clinical records of oral cancer patients treated between 2004 and 2007 by radiotherapy (exclusively or not) and who received implants were reviewed. In the interest of maintaining the homogeneity of the study sample, patients treated with a microanastomosis fibula flap were excluded.

The following information was extracted from the case records: tumor location, tumor stage, and type of treatment received, the duration between radiotherapy and implantation, the type of implants placed, the surgical and operative protocol, the patient’s medical history (excluding oncology) as well as any implant or peri-implant clinical events and their time of occurrence. Failure was defined as loss of implant osseointegration resulting in implant loss or removal. Surgical and implant loading failures were considered. Statistical analysis was performed using XLSTAT® software (Microsoft).

Results

Eighteen patients, consisting of 14 males (77%) and four females (13%) were eventually included. The mean age at the time of implant placement was 57.5 years (range: 42–78 years).

The initial tumor locations, the initial tumor stage, and the treatments received are presented in Table I.

Table I : Population studied: sites, tumor stages, and treatments received.
Table II : Implant failures as a function of the radiation dose received, initial tumor site, and failure onset delay.

Discussion

Cervicofacial radiation is one of the primary causes of implant loss [1,4] regardless of whether it is administered early or late [5]. Several failure factors specific to implant placement in irradiated areas have been identified; these include the duration after radiotherapy and the radiation dose received.

For successful implantation, the minimum time after radiotherapy before implantation should be 6–12 months [6]. A delay of >12 months would improve implant success rates [7]. In the current study, a minimum period of 6 months was selected after the multidisciplinary consultation with the surgical oncologists and radiotherapists. After excluding the two patients who were treated several years ago, missed their follow-up, and then reappeared for prosthetic rehabilitation, the average implantation time after radiotherapy in our study was 20.37 months (range: 6–49 months). One study [8] showed that the failures are less severe in patients receiving implants a later stage of oncological treatment (17.1% failure rate for intraoperative implants versus 4.6% for those placed postoperatively). Of course, the idea of early rehabilitation encourages the surgical team to perform implantation along with tumor removal, before additional treatments are administered. Although this technique has the advantage of decreasing treatment duration, it is not always feasible because of the constraints of tumor management.

The radiation dose received at the implant site is also a major cause of implant failure, with doses <50 Gy being more favorable [9,10]. Animal studies and literature reviews show that the implant failure rate is directly correlated with the radiation dose received [9,10]. In the study, implant sites that received estimated doses >55 Gy had failure (mean: 59.33 Gy). In fact, all implant failures occurred in patients who received treatment for cancer involving the anterior aspect of the floor of the mouth. The therapeutic target was therefore very close to the implant site, and the dose administered at the implant site was close to the therapeutic dose delivered.

The biggest challenge consists in evaluating the radiation dose received at the implantation site. In most studies, the initial tumor sites involved all the UADTs, including the oropharynx, with low radiation doses of about 30 Gy at the symphyseal and parasymphyseal level. It therefore seems more appropriate to limit the evaluation of failure rates to patients treated for cancer of the oral cavity, as the radiation doses at the implant site are therefore more homogeneous. In published studies, only a few authors [11] highlight the antecedents or lack thereof of radiation, with irradiated tissue implants having osseointegration rates of 83% at 5 years.

Long-term implant survival rates reported by the previous clinical studies are nonhomogeneous, with values of 72.8% at 10 years [9], 24% at 5 years [10], or 72% at 8 years [11]; however, these values support the results of our present study. Thus, Wagner [12] reports a 5-year osseointegration rate of 97.5% and at 10 years of 72.8%, whereas other authors report success rates of 48.3% [3]. Another study reports complications in 41.5% patients [13].

Seven out of eight failures encountered in the series began with peri-implantitis. Werkmeister [14] observed a soft-tissue complication rate of 28.6% in irradiated areas versus 8.3% in nonirradiated areas. These complications can be explained in part by the small amount of keratinized gingiva, along with the predisposing factors of radiotherapy-related sensitization and dry mouth. The occurrence of peri-implantitis should be carefully monitored to avoid ORN [15].

An increased loss of marginal bone was reported by many authors, with 2–9 mm variations for a period of 3 years after implant surgery [16]. According to Tanaka [17], early failures are more frequent. In the studies, all failures occurred >1 year after implant placement.

In the present series, a case of loss of osseointegration resulted in extensive ORN at a rate of 2.5%. Treatment of ORN required a subsequent free vascularized bone transfer reconstruction. This patient had been treated for a mouth floor lesion in the past and had received a postoperative radiation dose of 64 Gy (See Patient 3, Tab. I). This implant failed 1 year previously, and a reimplantation was proposed because of the impossibility of prosthetic rehabilitation without bone anchorage. Thus, there were two interventions on adjacent parasymphyseal mandibular bone sites. The patient had reverted to smoking regularly despite tobacco counseling. The risk of triggering ORN following implant placement was estimated to be 1.6%–5% [9,16,18,19]. Some authors advocate the use of hyperbaric oxygen therapy before and after implantation to stimulate or optimize healing and decrease ORN risk [20,21]. Others believe that the risk/benefit/cost ratio is not sufficiently favorable. More recently, the use of low-intensity pulsed ultrasound to increase healing capacity has been advocated [22]. Animal studies are currently underway [23].

Conclusion

It is widely accepted that the use of implant techniques in cancer patients is sometimes essential to ensure functional prosthetic rehabilitation. This retrospective study, which was conducted on patients who had specifically received oral radiotherapy, confirmed that it was a reliable therapeutic treatment for radiation doses of 45–50 Gy. However, the small number of patients in this study prevents the extrapolation of results to larger populations, considering the significant morbidity and lower success rate than patients who were not irradiated. Thus, the inherent risk of a past history of radiotherapy must be taken into account. The use of software like Dentalmaps® [24] allows a better evaluation of the doses received at potential implantation sites. This software is based on the automatic segmentation and delineation of the dental zones, making it possible to estimate the dose received at different points of the dental arch to the nearest 2-Gy fraction. However, the software is expensive, the work is laborious, and this device cannot be routinely used. Considering that health organizations are responsible for the cost management of implants in patients with cancer of UADT, there will be a definite increase in the indications for implantation [25]. It is up to the members present at the multidisciplinary consultation meetings to evaluate the benefit/risk ratio on a case-by-case basis.

October, 2018|Oral Cancer News|

OCF’s Tobacco Cessation Spokesperson and Bradley Cooper’s Stunt Double Rides in Pendleton

You won’t find Cody Kiser at this year’s NFR, but you will find him working as a stuntman in the 2014 blockerbuster hit “American Sniper” starring Bradley Cooper.

The biographical war drama was directed by Clint Eastwood, and told the story of U.S. Navy Seal Chris Kyle.

Kiser, who rode Saturn Rocket for a 75.5-point score Friday at the Pendleton Round-Up, stepped in for Bradley during the scene that shows Kyle riding broncs during his rodeo days before he joined the Navy.

“That was the coolest thing I have ever done,” Kiser said. “I got to hang out for a day with Clint Eastwood and Bradley Cooper. Clint told me I looked a lot like Bradley. They said they wished they had me for the whole movie.”

A friend of Kiser’s who does stunt work in California put Kiser in touch with the people from the movie.

“They needed a bareback rider who had a certain look,” he said. “They had me and a saddle bronc rider, but he couldn’t ride bareback very well, so the job was mine.”

Kiser, 27, said he was living in Texas near where Kyle was shot in 2013, and that he had a friend working at the Rough Creek Ranch-Lodge in Erath County, Texas, where Kyle was shot.

“It’s such a small world,” he said.

Kiser earned a nice paycheck for his work, but said playing Kyle, even in a stunt role, was an honor.

“To be a part of that was unreal,” he said.

September, 2018|OCF In The News|

Penn-led study raises hopes for vaccine to treat head and neck cancer

Date: 09/21/18
Source: The Inquire, philly.com
Author: Marie McCullough

The patient’s head and neck cancer came roaring back, spreading to his lymph nodes and skin, which developed bleeding tumors. Yet despite a grim prognosis, that man is alive and cancer-free more than two years later.

In a study led by the University of Pennsylvania and published Friday, researchers hypothesize that his remarkable remission is due to a promising combination: an experimental cancer vaccine that activated his disease-fighting T cells, plus Opdivo, one of the revolutionary “checkpoint inhibitor” drugs that cut a brake on the immune system.

“Of course, I’m biased,” said Charu Aggarwal, the Penn oncologist who led the study. “In my career, I haven’t seen a vaccine as impactful as this.”

However, the remission may have been due to Opdivo alone; the study lacks data to rule out that possibility.

Robert Ferris, director of the University of Pittsburgh Medical Center’s Hillman Cancer Center and head of the pivotal study leading to approval of Opdivo, called the Penn-led study “an important intermediate step exploring a strategy that we hope will work.”

Conventional vaccines prevent diseases by priming the immune system to recognize the distinctive “antigens” on invading microbes. Therapeutic cancer vaccines, like the one in this study, are intended to work after cancer develops by provoking a heightened immune response.

Despite decades of research, this approach remains experimental. The only approved product, the prostate cancer vaccine Provenge, was barely effective; the maker filed for bankruptcy in 2015.

A major obstacle to treatment vaccines is the fact that cancer arises from the body’s own cells. Although cancer cells produce antigens as they mutate, using these telltale proteins as targets for the immune system has proved to be very difficult.

Even so, at least four pharmaceutical groups are developing therapeutic vaccines that target human papillomavirus, HPV, the sexually transmitted virus that causes cervical cancer, head and neck cancer, and some rare genital cancers.

These diseases can be warded off with the preventive HPV vaccine that is recommended for all adolescents, but it didn’t exist until 12 years ago. Much to the dismay of public health authorities, vaccination rates remain low. And while screening can detect and treat cervical precancers, there are no early detection methods for head and neck cancers; experts call the surging incidence of these malignancies an “epidemic.”

The vaccine in the new study, called MEDI0457, was originally developed by Inovio with technology pioneered at Penn. In 2015, MedImmune, which is part of AstraZeneca, acquired exclusive rights to the drug.

MEDI0457 contains a DNA ring called a plasmid that programs the patient’s cells to produce two HPV antigens. The vaccine is injected into the patient’s muscle and enters cells with the help of a small electrical pulse applied to the skin. When the cells make the antigens, this triggers the immune system to activate disease-fighting white blood cells, so-called “killer” T cells.

For the study, published Friday in Clinical Cancer Research, 22 patients with head and neck cancer received conventional treatment — either surgery or chemotherapy and radiation — that eliminated all signs of cancer. This was supplemented by four doses of the experimental vaccine, which caused no serious side effects.

Eighteen patients, or 80 percent, showed elevated T cell activity that lasted at least three months after the final vaccine dose. While that is an encouraging sign, the study was too preliminary to detect clinical effectiveness such as tumor shrinkage or improved survival.

In the one patient who relapsed, cancer recurred seven months after vaccine treatment and spread to his lymph nodes and skin. He was given Opdivo and, eight weeks later, the cancer was gone.

Aggarwal and her co-authors note that such remarkable remissions do occasionally occur with checkpoint inhibitors. But they speculate that the vaccine revved up the patient’s T cells, then Opdivo removed the immune brake, enabling the T cells to attack the cancer.

“The response suggests the vaccine may in some manner prime the immune system, potentially boosting the effects of subsequent [checkpoint inhibitor] therapy,” Aggarwal said.

Rajarsi Mandal, director of the head and neck cancer immunotherapy research program at Johns Hopkins University, took a more conservative view: “They demonstrated vaccine specific T cell proliferation very nicely. But there is not a lot of data to suggest the vaccine is inducing any clinical response in these patients. Overall, it’s very interesting, but future studies are needed to demonstrate definitive clinical responses to the vaccine.”

Still, the combination approach is sufficiently promising that MedImmune is now funding a Penn-led clinical trial of MEDI0457 and MedImmune’s own experimental checkpoint inhibitor.

Ferris, meanwhile, said he is part of a trial of a competing experimental vaccine for HPV-related cancers, plus the approved checkpoint inhibitor Keytruda.

“The preventive HPV vaccine works really well,” he said. “But if you’re too old to get it, there is hope that you can stimulate the immune system to fight the cancer. This [new study] suggests the next logical step.”

September, 2018|Oral Cancer News|

Study: Cetuximab, radiation inferior to standard HPV throat cancer treatment

Source: upi.com
Author: Allen Cone

Treating HPV-positive throat cancer with cetuximab and radiation had worse overall and progression-free survival results compared with the current method of treatment with radiation and cisplatin, the National Institutes of Health revealed Tuesday.

The trial, which was funded by the National Cancer Institute, was intended to test whether the combination would be less toxic than cisplatin but be just as effective for human papillomavirus-positive oropharyngeal cancer. The trial, which began in 2011, enrolled 849 patients at least 18 years old with the cancer to receive cetuximab or cisplatin with radiation. The trial is expected to finish in 2020.

Cetuximab, which is manufactured under the brand name Erbitux by Eli Lilly, and cisplatin, which as sold as Platinol by Pfizer, are used in chemotherapy.

The U.S. Food and Drug Administration had approved cetuximab with radiation for patients with head and neck cancer, including oropharyngeal cancer.

HPV, which is transmitted through intimate skin-to-skin contact, is the leading cause of oropharynx cancers, which are the throat at the back of the mouth, including the soft palate, the base of the tongue and the tonsils. Most people at risk are white, non-smoking males age 35 to 55 — including a 4-to-1 male ratio over females — according to The Oral Cancer Foundation.

The NIH released the trial results after an interim analysis showed that cetuximab with radiation wasn’t as effective.

In a median follow-up of 4.5 years, the test combination was found to be “significantly inferior” to the cisplatin method.

“Clinical trials designed to test less toxic treatment strategies for patients without compromising clinical benefit are a very important area of interest for NCI and the cancer research community,” said Dr. Shakun Malik, of NCI’s Division of Cancer Treatment and Diagnosis.

Toxic side effects were different, with adverse events of renal toxicity, hearing loss and bone marrow suppression more common in patients in the cisplatin group and body rash more frequent in the cetuximab method.

For patients who cannot tolerate cisplatin, cetuximab with radiation is an accepted standard of care.

“The goal of this trial was to find an alternative to cisplatin that would be as effective at controlling the cancer, but with fewer side effects,” lead investigator Dr. Andy Trotti, of the Moffitt Cancer Center in Tampa, Fla., said in a press release. “We were surprised by the loss of tumor control with cetuximab.”

August, 2018|Oral Cancer News|

HPV: The gender-neutral killer in need of prevention among men

Source: CNN
Author: Dominic Rech

In July 2014, Phil Rech, then 59, was diagnosed with tonsil cancer.

“I had got a lump in my neck. I had the tonsils out, and within the next few days, I was having radical neck dissection,” he said. “Then I had six weeks of intensive, targeted radiotherapy. The burning effect towards the end of the treatment became very painful.”

The therapy involved a radiotherapy mask, molded to the shape of his face, that went over his head as radiotherapy was beamed in, targeting the cancer.

The discovery of his cancer not only startled him, it startled everyone who knew him.
Phil is my dad, and to our family, he had always been healthy: He doesn’t smoke, he rarely drinks alcohol, and he generally stays fairly fit.

But that’s not how cancer works.

At the time of the diagnosis, Phil didn’t question how or what could have caused his cancer, as he focused on getting better.

Like many men in the UK and around the world, he wasn’t aware of a group of viruses that were a threat, human papillomavirus or HPV, which were eventually connected to his cancer.

“To discover it was linked to HPV was a massive shock,” he said. “There was a lot of speculation over what could have caused it. To discover it was that, was certainly a surprise. I didn’t really know it was a threat to me.”

A cancerous virus

HPV is a group of 150 related viruses that can be transmitted through any form of sexual contact, whether kissing or intercourse. In most cases, the human body will get rid of it naturally, but certain high-risk types can develop into things like genital warts and cancers, including cervical, anal and throat.

But there is a vaccine, and how it works is pretty simple. It’s a mimic of the virus particle; when administered into someone’s muscle, it creates many more antibodies than a natural infection would, according to John Doorbar, professor of viral pathogenesis at Cambridge University.

According to the US Centers for Disease Control and Prevention, “almost every person who is sexually active will get HPV at some time in their life if they don’t get the HPV vaccine.”

The vaccine needs to be given before a person is exposed to HPV. Its effectiveness in terms of preventing infections is well-known — 100% in some studies — but who gets it is a question of debate around the globe, particularly in the UK.

In the UK, girls ages 12 to 13 are routinely offered the first HPV vaccination. They can get the vaccine for free via the National Health Service from ages 12 to 18. This is encouraged to help combat cervical cancer, which a recent report suggests it has done globally.

In England, between 2010 and 2016, infections with HPV 16 and 18 (two types of the virus responsible for most cervical cancer cases) fell 86% among women 16 to 21 who were eligible for the vaccine during this period, Public Health England found.

But what about men?

Until now, some experts in the UK have argued that men would ultimately be protected against the virus through “herd immunity”: As long as girls are well-protected, the male population should be shielded, too.

But according to the Royal Society of Public Health, which supports providing the vaccine to boys, uptake of the vaccine for girls is insufficiently high to ensure herd immunity in several areas of the UK. Men are still at risk of acquiring HPV from sexual contact with women from countries without a vaccination program, the society said.

In April, NHS England and Public Health England, on recommendation from the UK’s Joint Committee on Vaccination and Immunisation, decided to introduce the vaccine to men 45 or younger who have sex with other men, often called MSM, after concluding that this group does not benefit from herd immunity.

Historically, heterosexual men and young boys have not been offered it through the NHS but can pay to receive it privately. Pharmacies including Boots, Lloyds and Superdrug in the UK charge about 150 pounds ($196) per dose, with people typically needing two or three doses.

But on July 18, the vaccination committee recommended extending the HPV immunization program to boys after it reviewed the evidence for vaccinating boys since 2013. A recommendation last year concluded it was still not cost-effective to vaccinate this group, but experts and campaigners appealed for the committee to look again — and their stance changed.

“It is clear that a programme to vaccinate adolescent males would provide those vaccinated with direct protection against HPV infection, and associated disease including anogenital warts, anal, penile and oropharyngeal cancers,” the statement says. The committee confirmed that evidence has strengthened on the association of HPV with non-cervical cancers, which affect men as well as women, and that vaccination is efficacious in preventing these other HPV-related cancers.

In response to the recommendation, the same day, the Scottish government announced that it would implement a vaccination program to boys as soon as it practically could, Public Health Minister Joe FitzPatrick said. Wales also opted to roll out the vaccine to boys.

The question remaining is whether England will follow suit.

There is some disparity over the number of other countries vaccinating boys against HPV. Shirley Cramer, chief executive of the Royal Society of Public Health, said 20 countries vaccinate boys, while the HPV Action partnership says that about 15 roll it out to boys as well as girls.

The vaccine has been approved for males in the United States for almost 10 years. Italy and Australia are also pioneering gender-neutral vaccination plans.

Lagging behind and increasing rates

In 2017, after being in remission for three years, Phil’s cancer surfaced again — this time, in the brain and the lungs.

“I started to feel some funny fluttery feelings in my chest,” he said. “It was only my oncologist, who revealed to me that I had six small lesions on my lungs. An MRI scan also showed three on my brain.

“That’s the nature of cancer. It’s a crafty disease,” he said.

A 2017 study found that one in nine American men is infected with the oral form of HPV. Nationwide, rates for oral HPV infections are 11.5% of men and 3.2% of women: 11 million men, compared with 3.2 million women, the researchers estimated.

Among HPV-related cancers, a type of head and neck cancer called oropharyngeal squamous cell carcinoma was far more likely to strike men in the US, the same study found, with its incidence surpassing cervical cancer among women. Men who have had multiple sex partners, men who reported having sex with men and men with genital HPV infections were found to have the highest rates of oral HPV.

But in the UK, the discussion around vaccinating boys has been ongoing. In less than 10 years, admissions for primary cancerous tumors of the head and neck increased by almost 10,000, according to the NHS, from 29,198 in 2008-09 to 37,417 in 2016-17.

A recent review by the nonprofit medical research group Cochrane acknowledged that HPV was not only linked to cervical cancers, it increases risk of vulval cancers, penile cancers and some head and neck cancers. But the review also said that these cancers were rarer and that ascertaining the effects of vaccination on them may require the evaluation of non-randomized, population-level evidence over many years.

Beyond the price tag

“The problem is cost-effectiveness, and that is why the government hadn’t made a decision to vaccinate boys in this country,” said Jo Morrison, co-ordinating editor for the Cochrane Gynae, Neuro and Orphan Cancer Group.

However, she added, “doctors and other informed people are looking to get their boys vaccinated.”

Giampiero Favato is one of them. “Twenty years from now, we will laugh about this discussion,” said the health economics specialist at Kingston University. “It is obvious we should vaccinate boys. HPV is a gender-neutral killer. When my son is 12, I will pay for the vaccination if necessary.”

He is skeptical of “herd immunity” and giving the vaccine only to girls: “The current models are not capable of replicating the sexual behavior and preference in the normal population. Most of the models are based on the assumption that sex is only happening between fully heterosexual couples and their partnerships.”

This of course would mean more money for the NHS, but Favato says “price is not the issue,” and the private cost of the vaccine is unlikely be anywhere near that for the NHS, which is likely to get it at a competitive rate. “In Italy, the vaccination costs about $30 to $32 per vial.”

But Helen Bedford, professor of children’s health at the UCL Great Ormond Street Institute of Child Health, added that cost-effectiveness still needs to be taken into account and that the method of calculating this is what ultimately needs to change.

“In view of the long interval between infection with HPV and development of disease, [the Joint Committee on Vaccination and Immunisation] are supportive of changing the methods for calculating cost effectiveness to consider HPV vaccine for boys,” she said. “A review of cost-effectiveness modeling is soon to be concluded, and this is one of the issues that is being considered as part of that review.”

Phil said that if he could have had the vaccine readily available when he was younger, he would have taken it.

He continues to fight his cancer today, but cases like his are increasing amid the discourse on HPV vaccination rollouts in the UK.

“I would urge all boys to be vaccinated as a matter of course,” he said. “We have long vaccinated against the likes of polio, measles, mumps and rubella. HPV is just as serious and life-threatening as any of these.”

Note from OCF: We are one of the first supporters and donors to the HPV Action Partnership that originally supported research and early perception of the concept of boys being vaccinated for herd immunization. This has been a long term endeavor and a labor of love.  Men get oral cancers more than woman do and we want to inform that the HPV Vaccine goes beyond protecting from cervical cancers; it also protects from anal, penile and oropharyngeal cancer.

 

July, 2018|OCF In The News|

Smoking hits new low; about 14 percent of US adults light up

Source: https://flipboard.com
Author: Mike Strobbe, AP Medical Writer

NEW YORK (AP) — Smoking in the U.S. has hit another all-time low.

About 14 percent of U.S adults were smokers last year, down from about 16 percent the year before, government figures show.

There hadn’t been much change the previous two years, but it’s been clear there’s been a general decline and the new figures show it’s continuing, said K. Michael Cummings of the tobacco research program at Medical University of South Carolina.

“Everything is pointed in the right direction,” including falling cigarette sales and other indicators, Cummings said.

The new figures released Tuesday mean there are still more than 30 million adult smokers in the U.S., he added.

Teens are also shunning cigarettes. Survey results out last week showed smoking among high school students was down to 9 percent, also a new low.

In the early 1960s, roughly 42 percent of U.S. adults smoked. It was common nearly everywhere — in office buildings, restaurants, airplanes and even hospitals. The decline has coincided with a greater understanding that smoking is a cause of cancer, heart disease and other health problems.

Anti-smoking campaigns, cigarette taxes and smoking bans are combining to bring down adult smoking rates, experts say.

The launch of electronic cigarettes and their growing popularity has also likely played a role. E-cigarettes heat liquid nicotine into a vapor without the harmful by-products generated from burning tobacco. That makes them a potentially useful tool to help smokers quit, but some public health experts worry it also creates a new way for people to get addicted to nicotine.

There was no new information for adult use of e-cigarettes and vaping products, but 2016 figures put that at 3 percent of adults.

Vaping is more common among teens than adults. About 13 percent of high school students use e-cigarettes or other vaping devices.

The findings on adult smokers come from a national health survey by the Centers for Disease Control and Prevention. About 27,000 adults were interviewed last year.

June, 2018|Oral Cancer News|

Nivolumab Plus Stereotactic Body Radiotherapy Fails To Improve Outcomes in Head and Neck Cancer

Source: https://www.cancertherapyadvisor.com

 

CHICAGO—Although the addition of stereotactic body radiation therapy (SBRT) to nivolumab did not increase toxicity, it did not lead to any improvement in response rates or survival outcomes among patients with metastatic head and neck squamous cell carcinoma (HNSCC), according to an oral presentation at the American Society of Clinical Oncology 2018 Annual Meeting on Friday, June 1.

Researchers sought to determine whether or not SBRT to a single lesion plus nivolumab would improve abscopal responses (tumor regression in non-irradiated lesions) and other outcomes among this patient population.

In this phase 2 interventional study (ClinicalTrials.gov Identifier: NCT02684253), researchers randomly assigned 53 patients with metastatic HNSCC to receive nivolumab alone every 2 weeks or with SBRT between the first and second doses of nivolumab. The 2 study arms did not have any significant differences in terms of age, EBV/HPV viral status, primary site, or median lines of previous chemotherapy. The median follow-up was 12.8 months.

Results showed that the overall response rate (ORR) was 26.9% (95% CI, 13.7-46.1) compared with 22.2% (95% CI, 10.6-40.8) in the nivolumab alone arm and nivolumab plus SBRT arm, respectively (P = .94). Patients receiving nivolumab alone did not have an evaluable median duration of response (DOR) compared with 9.3 months (95% CI, 55.2-not reached [NR]) among patients in the SBRT arm.

The 1-year overall survival rate was 64% (95% CI, 47-88) in the nivolumab alone arm compared with 53% (95% CI, 36-79) in the nivolumab plus SBRT arm (P = .79); median progression-free survival (PFS) was 1.9 months (95% CI, 1.78-NR) compared with 2.4 months (95% CI; 1.0-11.4) with nivolumab plus SBRT (P = .8).

Treatment-related grade 3 and worse adverse effects were reported in 15% of patients who received nivolumab alone and in 11% of patients who received SBRT plus nivolumab (P = .96).

The authors concluded that “While safe, the addition of SBRT to nivolumab in M1 HNSCC failed to improve ORR, PFS, or OS. This is the first randomized evaluation of the abscopal response in any tumor histology.”

June, 2018|Oral Cancer News|