head and neck cancer

ASCO Urges Aggressive Efforts to Increase HPV Vaccination

Source: www.medscape.com
Author: Zosia Chustecka
 

Human papillomavirus (HPV) vaccines have now been available for 10 years, but despite many medical professional bodies strongly recommending the vaccine, uptake in the United States remains low.

Data from a national survey show that about 36% of girls and 14% of boys have received the full schedule of HPV vaccines needed to provide protection (Vaccine. 2013;31:1673-1679).

Now the American Society of Clinical Oncology (ASCO) has become involved, and in a position statement issued today the organization calls for aggressive efforts to increase uptake of the HPV vaccines to “protect young people from life-threatening cancers.”

“With safe and effective vaccines readily available, no young person today should have to face the devastating diagnosis of a preventable cancer like cervical cancer. But unless we rapidly increase vaccination rates for boys and girls, many of them will,” ASCO President Julie M. Vose, MD, said in a statement.

“As oncologists, we see the terrible effects of these cancers first hand, and we have to contribute to improving today’s alarmingly low vaccination rates,” she added.

The new policy statement is published online April 11 in the Journal of Clinical Oncology.

The statement notes that HPV vaccination has been previously recommended by many US medical societies, including the American Cancer Society, the American College of Obstetrics and Gynecology Committee, the American Dental Association, the American Head and Neck Society, the American Nurses Association, the American Pharmacists Association, the Association of Immunization Managers, the Society for Adolescent Medicine, and the Society of Gynecologic Oncology.

In addition, a joint letter was sent out to all physicians urging them to give a strong recommendation from the American Academy of Family Physicians, the American Academy of Pediatrics, the American College of Obstetricians and Gynecologists, the American College of Physicians, the Centers for Disease Control and Prevention, and the Immunization Action Coalition.

Now oncologists are specifically being asked by their professional body, ASCO, to join in with the push toward greater uptake of the HPV vaccines.

“ASCO believes oncologists can play a vital role in increasing the uptake of HPV vaccines,” the new policy statement says. “Although most oncologists will not be direct providers of these preventive measures, this does not abrogate us from contributing to this process. Our unassailable role in the mission to lessen the burden of cancer…places us in a position of influence. We should use interactions with our patients, primary care colleagues, and health care systems to raise awareness of HPV-related cancers and the role of vaccination in preventing them.”

Oncology providers have a responsibility to serve as community educators.

“Oncology providers have a responsibility to serve as community educators, disseminating evidence-based information to combat misconceptions concerning the safety and effectiveness of the HPV vaccine,” it continues.

“ASCO encourages oncologists to advocate for and actively promote policy change to increase vaccination uptake,” the statement concludes.

Issues With the Statement

However, there are a few issues with the statement, says a prominent researcher in the field of HPV and cervical cancer, Diane Harper MD, professor and chair of the department of Family and Geriatric Medicine, University of Louisville, Kentucky. Dr Harper, who was approached for comment, was involved in early clinical trials with both HPV vaccines (Gardasil, Merck & Co, and Cervarix, GlaxoSmithKline), and has emphasized the need for ongoing screening with Pap tests to prevent cervical cancer.

This is also one of the issues she raises about the ASCO statement, which does not mention screening. “All messages about HPV vaccination must be couched in terms of continued lifetime screening for cervical cancer,” Dr Harper told Medscape Medical News.

The ASCO statement highlights the potential that HPV vaccination has for preventing cancer. (Both vaccines protect against HPV types 16 and 18, and Gardasil offers additional protection against several other types). The statement notes that HPV is the cause of nearly all cervical cancer cases and that HPV genotypes 16 and 18 are responsible for 70% of cervical cancers. In the United States, HPV is responsible for 60% of oropharyngeal cancers, 90% of which are caused by HPV 16. HPV is also the cause of 91% of anal cancers, 75% of vaginal cancers, 69% of vulvar cancers, and 63% of penile cancers, again with HPV 16 as the predominant oncogenic genotype.

However, the statement also notes that “because of the long latency and the prolonged preinvasive phase after infection with HPV, many years of follow-up are needed for the ongoing trials to demonstrate a significant reduction in HPV-related cancers.”

Therefore, intermediate outcomes are being used as surrogate endpoints, it continues. HPV vaccines have been shown to prevent new cancer-causing HPV genotype-specific infections and resultant diseases, such as grades 2 and 3 cervical intraepithelial neoplasias (CIN), vaginal, vulvar, and anal intraepithelial neoplasias (as precursor lesions to cancer).

There is “almost certainty that cancers caused by oncogenic HPV genotypes will be dramatically reduced,” according to the statement.

Dr Harper told Medscape Medical News that the studies conducted to date have shown that “Cervarix has a 93% efficacy against CIN 3 regardless of HPV type; Gardasil has a 47% efficacy against CIN 3 regardless of HPV type, and Gardasil 9 is equivalent to Gardasil in the prevention of CIN 3 disease regardless of HPV type. None of these vaccines can prevent all CIN 3 or potentially all cancers.”

“Hence, the most important take home point is that screening is absolutely necessary as a prevention tool for preventing cancer by early detection of disease that when found, is curable,” Dr Harper emphasized.

Also, Dr Harper noted that the studies ended at prevention of CIN 2/3 disease as a clinical outcome. CIN 3 on average progresses to cancer in 20% of women within 5 years, and to 40% of women in 30 years. But, she points out, “there are no long-term follow-up studies that show that cancers will be averted.”

“The modeling exercises indicate that we have to wait at least 40 years before we will have a detectable decrease in cervical cancers from vaccination, assuming that at least 70% of the population being surveyed is vaccinated,” she added.

In its statement, ASCO cites the success of widespread vaccination against hepatitis B virus in reducing the incidence of liver cirrhosis and liver cancer as “an exemplary health model that supports more widespread HPV vaccination.”

But Dr Harper argues that “the prevention of liver cancer was an unexpected highlight of HBV vaccination. The primary purpose was to relieve the symptoms of chronic HBV sufferers. The continual re-infection with HBV seems to allow a natural infection to act as a booster in this population, which may not be the same for HPV.”

There also remains a question of how long the protection offered by HPV vaccination will last.

The ASCO statement says, “Both vaccines have a known duration of protection of at least 5 years, with ongoing study of the full duration of their effect,” and it notes that “additional research is needed to evaluate duration of protection to determine if booster doses are required.”

Dr Harper said, “Estimates of long-term effectiveness are based on antibody titers, yet there is no surrogate of protection defined by antibody titers.”

She added: “I agree that observational studies will inform the public health authorities about when a booster will be needed and whether it is needed sooner if only 2 doses are received vs later if 3 doses​ are received.”

Last, but not least, there is the issue of safety.

The ASCO statement notes that both Gardasil and Cervarix “reported excellent short- and long-term safety results in clinical trials. The most common adverse effects were mild and included injection site pain (approximately nine in 10 people) and swelling (approximately one in three), fever (approximately one in eight), headache, and fatigue (approximately one in two). These symptoms were transient and resolved spontaneously. The incidence of serious adverse effects was low and was similar to those who received placebo (aluminum-containing placebo or hepatitis A vaccine).”

However, worldwide there continue to be reports of adolescents who report chronic side effects and pain syndromes after being vaccinated against HPV. Some of these have been documented in the medical literature, with physicians reporting instances of previously healthy athletic girls becoming incapacitated with pain, fatigue, and autonomic dysfunction, and some remaining permanently disabled.

The US Food and Drug Administration and the Centers for Disease Control and Prevention have repeatedly said that HPV vaccines have an excellent safety record and that no causal associations have been found with atypical or unusual pain syndromes or autonomic dysfunction. The European authorities have investigated two chronic syndromes reported with HPV vaccination, and have said that there is no evidence to show causation.

However, Danish researchers who were among the first to report these syndromes criticized the investigation and are conducting their own study. There have also been lawsuits filed in several countries, and a class action lawsuit is now planned in Japan against the government and the vaccine manufacturers.

In an interview with Medscape Medical News, lead author on the ASCO statement, Howard H. Bailey, MD, from the University of Wisconsin Carbone Cancer Center, Madison, said that the concerns over safety should not be dismissed and should be studied further.

These issues need to be studied further, even if the authorities say that the vaccines are safe, he emphasized. These reports of girls becoming very ill, having pain syndrome and weakness, should not be diminished, he said, adding: “We can’t just ignore these reports…if there is risk involved, then that needs to be sorted out better.”

However, there is always a possibility that the syndromes and side effects that have been reported “have nothing to do with the vaccine,” Dr Bailey commented, citing the case of now-discredited theory linking autism to the pediatric vaccine for measles, mumps, and rubella.

There may be other explanations for the symptoms that are reported, or it could be that the symptoms/syndrome would have developed in the individual, anyway, but the vaccination precipitated it sooner, he suggested.

Dr Bailey noted that across the United States physicians are very sensitive to the fact that rates of pediatric vaccination have gone down because of the link that had been made to autism, subsequently shown to be false. Even though science eventually showed no link between the vaccine and autism, public confidence in the vaccine was damaged.

“When a person’s life has been devastated by an illness, that is very important, but if it turns out that the illness is not related to the vaccine, and in the meantime, the concerns over safety have stopped thousands of young people from being vaccinated….”well, eventually this will mean that there are more people who die from cancer, he said.

“I would be very reluctant right now to shut down the goals of vaccination over what has been reported, because the bottom line is that we have a tremendous problem with the rising incidence of HPV related cancers including in men as well as women when it comes to oropharyngeal cancers here in the States,” he added.

“The data, at least in my opinion, are so strong that HPV vaccination if it’s done in a [systematic] way will reduce the incidence of these cancers…I don’t want to stop whatever progress we are making when there is at best disagreement over whether these things are associated,” he said, although he also added that “maybe if it was my daughter, I would feel differently.”

Dr Bailey also addressed some of the other issues that had been raised about the ASCO statement, and said he agreed about the importance of screening.

“Even if vaccination does all the things we expect it to do, there is no doubt that cervical cancer screening needs to continue, and that’s a pretty standard recommendation across all of the groups,” he said. “We do not mean to diminish the importance of continued screening,” he said, but he added that screening lies in the domain of other physicians, such as primary care and gynecology, whereas this statement was targeted specifically at oncologists. “To take a step back, we are taking the view of cancer physicians, who take care of women, who are unfortunately too often dying of cervical cancer, and…we wanted to remind people that HPV vaccination can prevent this…as well as other associated cancers,” he said.

“The audience in North America has not been paying attention to this vaccination issue very much,” he continued, and “we wanted to remind oncologists and the public that at the heart of the issue is cancer prevention.

“We have this relatively easy way of preventing cancers over and above the ways that we already use,” he added.

“We wanted to remind people, especially in the oncology community, that there is this intervention out there that we think is highly, highly likely — if applied and used in a population format — will significantly reduce the number of women dying of cervical cancer, the number of men and women dying from oropharyngeal cancer, which is increasing in the US…and that was the main focus of the article,” Dr Bailey commented.

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

April, 2016|Oral Cancer News|

Merck Says FDA Accepts Its SBLA For Keytruda For Treatment Of Head & Neck Cancer

Source: www.finchannel.com
Author: Fin Channel News Editorial Staff
 
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The FINANCIAL — Merck, known as MSD outside the United States and Canada, on April 13 announced that the U.S. Food and Drug Administration (FDA) has accepted for review the supplemental Biologics License Application (sBLA) for KEYTRUDA (pembrolizumab), the company’s anti-PD-1 therapy, for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy.

The application is seeking approval for KEYTRUDA as a single agent at a dose of 200 mg administered intravenously every three weeks. The FDA granted Priority Review with a PDUFA, or target action, date of Aug. 9; the sBLA will be reviewed under the FDA’s Accelerated Approval program, according to Merck.

“Starting in the early days of our development program, we have explored the role of KEYTRUDA for patients with head and neck cancer, a difficult-to-treat and debilitating disease with very few treatment options,” said Roger Dansey, M.D., senior vice president and therapeutic area head, oncology late-stage development, Merck Research Laboratories. “We are encouraged by the data emerging from our program in this type of cancer, and welcome today’s news as this is an important step toward making KEYTRUDA available to these patients.”

Merck currently has the largest immuno-oncology clinical development program in head and neck cancer and is advancing multiple registration-enabling studies with KEYTRUDA as a single agent and in combination with chemotherapy.

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

April, 2016|Oral Cancer News|

Suicide: A Major Threat to Head and Neck Cancer Survivorship

Source: www.jco.ascopubs.com
Authors: Nosayaba Osazuwa-Peters, Eric Adjei Boakye, and Ronald J. Walker
, Mark A. Varvares
 

TO THE EDITOR: The article by Ringash that was recently published in Journal of Clinical Oncology provided a compelling narrative of both the improvements made in head and neck cancer survivorship, as well as the challenges created by longer-term treatment and associated toxicities. There are currently at least 280,000 head and neck cancer survivors in the United States. As the article by Ringash stated, the upturn in head and neck cancer survivorship in the last three decades has coincided with the emergence of human papilloma virus-positive oropharyngeal cancer, as well as a decrease in tobacco use in the general population. These make it a challenge to isolate survival gains as a function of improved therapy from the natural prognostic value of a diagnosis of human papilloma virus-positive oropharyngeal cancer. Whatever the case, the fact that more than one-quarter million Americans are currently alive after a diagnosis of head and neck cancer means there needs to be a more deliberate effort in longer-term management of treatment-related toxicities, some of which are lifelong.

We agree with Ringash’s conclusion that new models of care need to be developed in response to the significant quality-of-life issues faced by patients with head and neck cancer. The Institute of Medicine publication From Cancer Patient to Cancer Survivor: Lost in Transition, also cited by Ringash, called for a clear individualized survivorship plan for cancer patients. There is a serious need for this model to be implemented universally in head and neck cancer management. Although we agree with Ringash that patients with head and neck cancer face competing mortality risks from second primary cancers and other noncancers, what we found lacking was recognition of an important competing cause of mortality in head and neck cancer survivors: suicide.

Suicide associated with head and neck cancer is not just a competing cause of death; it is also a quality-of-life issue. Many authors agree that head and neck cancer is among the top cancer sites associated with suicide. One national study of 1.3 million cancer patients even found that head and neck cancer carried the highest risk of suicide among cancer survivors. As a quality-of-life issue as well as a competing cause of death, the elevated risk of head and neck cancer-related suicide, although it peaks during the first few years after diagnosis, remains virtually throughout the course of the cancer survivor’s life. Additionally, some other well-known quality-of-life issues associated with head and neck cancer (eg, pain, disability, esthetic compromise and body image issues, psychosocial function, anxiety, emotional distress, and depression) are all associated with suicide. Therefore, it is difficult to have a discussion of quality-of-life interventions in head and neck cancer without addressing the issue of suicide.

Thus, we believe that suicide in patients with head and neck cancer should be addressed as a major threat to cancer survivorship. Cardiovascular disease, for example, is a known competing cause of death among patients with head and neck cancer, and is listed in Figure 4 of Ringash’s article. Cardiovascular disease may be managed for a long time; however, when a cancer patient decides that he/she is “better off dead,” a finality, or terminality, is invoked. This is quite unique to suicide compared with other competing causes of death.

Thus, in the urgent call for “new strategies and models of care to better address quality-of-life issues and meet the needs of survivors of head and neck cancer,” we believe it is pertinent that suicide is recognized as an important threat to head and neck cancer survivorship.

DOI: 10.1200/JCO.2015.65.4673; published online ahead of print at www.jco.org on January 19, 2016

To read or download the full article, please visit: http://jco.ascopubs.org/content/34/10/1151.full.pdf+html

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.
March, 2016|Oral Cancer News|

The Oral Cancer Foundation’s Founder, Brian R. Hill, honored by the Global Oral Cancer Forum – International oral cancer community honor his accomplishments in the field.

Source: www.prnewswire.com
Author: The Oral Cancer Foundation
 

Bryan R. Hill receiving the award at the Global Oral Cancer Forum. (PRNewsFoto/Oral Cancer Foundation)

NEWPORT BEACH, Calif., March 10, 2016 /PRNewswire-USNewswire/ — At the recent Global Oral Cancer Forum (GOCF), Brian R. Hill, Executive Director and Founder of the Oral Cancer Foundation (OCF), was honored for his work as an advocate and innovative thinker in the oral cancer arena. The GOCF organizers and community awarded Hill the 2016 Global Oral Cancer Forum Commitment, Courage and Innovation Leadership Award for his dedication and contributions to the field of oral cancer over the last 18 years. Upon accepting the award, Hill received a standing ovation from those in attendance, which included global oral cancer thought leaders, researchers, treatment physicians, other non-profit organizations and representatives from various government agencies, including the National Institutes of Health / National Cancer Institute, and the World Health Organization (WHO).

When asked about being honored Hill said, “In the beginning and for many years I was alone at OCF and it was just the seed of an idea. Those grassroots efforts matured into a robust network of important relationships with a common goal. Today OCF is so much more than just me and my singular efforts. Through the benevolence of the many OCF supporters, particularly in the RDH, dental/medical professional communities and survivor groups, OCF has grown into a powerful national force for proactive change of the late discovery paradigm, access to quality information, disease and patient advocacy, funding of research, and patient support.” Hill acknowledges that he had the mentorship of some of the brightest minds of the non-profit world to build his understanding of appropriate governorship of an entity such as OCF, as well as support from core researchers and treatment professionals in the oral cancer arena. “To paraphrase someone far more famous, if I was able to see farther than others had going before me, it was because I stood on the shoulders of many highly accomplished others who helped me achieve my goals,” says Hill.

Hill, a stage four oral cancer survivor, became a student of the disease after his own diagnosis left him looking for answers. Since founding OCF and overseeing the path and initiatives of the foundation for more than a decade and a half, Hill often finds the advocacy role suits him well. He has championed anti-tobacco legislation within the political system, and is an advocate at various government entities such as the CDC regarding vaccination of boys against the virus known to be the primary cause of most oropharyngeal cancers.  He also sits on two National Institutes of Health (NIH) oversight committees—one at the National Cancer Institute (NCI), which oversees clinical trials in immunotherapies in head and neck cancers, the other at the National Institute of Dental and Craniofacial Research (NIDCR) reviewing trials looking at long-term outcomes and complications of treatment in head and neck cancers. In addition, Hill still one-on-one counsels patients, participates in OCF’s online Patient Support Forum, and is often the voice for a community that has lost its own, through many diverse media interviews and lectures.

While OCF has received many awards for its advocacy work and contributions to the battle against oral cancer, including recognition from the NIH/NIDCR, WHO, Great Non-Profits, various universities and professional medical and dental societies, and even Internet guru Mashable.com for innovations in applying technology to serve its health oriented goals, receiving recognition from this forums organizers and some of the  leading authorities on oral cancer in the international community is particularly meaningful. Those in attendance are recognized as experts in the field and understand the challenges and importance of the work OCF has undertaken. Sponsored by the Henry Schein Cares Foundation, the benevolent arm of the powerful Henry Schein Inc., known for its long-term commitment to improve issues related to oral care, The Global Oral Cancer Forum’s vision is to build partnerships that will promote the changes required for a substantial impact on the incidence, morbidity, and mortality of oral cancer worldwide. The importance of the Schein organization’s leadership in creating this venue cannot be overstated.

Top oral cancer experts and advocates from around the world, representing countries as far away as Japan, China, and India as well as from the Americas, convened over the weekend to attend the inaugural forum. Attendees included clinicians, scientists, epidemiologists, activists, public health experts, as well as OCF Directors and other NPO organization heads who are working hard to find impactful avenues to reduce the global oral cancer burden. Attendees met to exchange ideas and learn from one another about what is and isn’t working in the global realm of this disease. Delegates from thirty-three countries presented new research findings and discussed their unique challenges and approaches to understanding and addressing one of the leading burdens of the cancer world.

Globally, the incidence rate for oral cancer is growing and has reached what many experts are calling epidemic proportions. This year approximately half a million patients will be newly diagnosed with an oral or oropharyngeal cancer. Among the topics discussed by GOCF panelists were the rise in disease incidence and the regional disparities and factors affecting global populations. Communities throughout much of South East Asia report a high percentage of the population chewing betel and areca nut, a significant risk factor for the development of oral cancer. Meanwhile in the U.S. and other developed countries the prevalence of the HPV virus is the leading contributor to the rising rates of oropharyngeal cancers. Identifying these differences is vital to the development of effective prevention, public policy, and treatment strategies. Advancement of a universal understanding of what the problems are and what initiatives are working around the globe, reveals commonalities, and within them the group will find its beginning joint efforts to effect change.

Looking forward there is clearly much work to be done. The good news is that there are significant strides being made in research and treatment; but balancing those positives, there are also significant shortcomings in current governmental policies, prevention, and public awareness and understanding. Hill said, “While I and OCF are very proud to have been chosen by the organizers, and the global oral cancer community to receive this award, it only serves to motivate us to strive to accomplish more. We have built relationships here that will translate into new avenues of endeavor for OCF in the future.” Jamie O’Day, OCF’s Director of Operations, also attended the conference and spent her time networking with her counterparts from around the world. Many new ideas were garnered from these discussions that will be applied in future OCF initiatives and support OCF’s mission to reduce the suffering caused by this disease both nationally and globally.

About the Oral Cancer Foundation:
The Oral Cancer Foundation, founded by oral cancer survivor Brian R. Hill, is an IRS registered non-profit 501(c)(3) public service charity that provides vetted information, patient support, sponsorship of research, as well as disease and risk factor reduction advocacy related to oral cancer. Oral cancer is the largest group of those cancers that fall into the head and neck cancer category. Common names for it include such things as mouth cancer, tongue cancer, tonsil cancer, head and neck cancer, and throat cancer. The Oral Cancer Foundation maintains the websites: www.oralcancer.org , www.oralcancernews.org , www.oralcancersupport.org , which receive millions of hits per month. Supporting the foundation’s goals is a scientific advisory board composed of leading cancer authorities from varied medical and dental specialties, and from prominent educational, treatment, and research institutions in the United States. The foundation also manages the Bruce Paltrow Oral Cancer Fund, a collaboration between the Paltrow family represented by Ms. Blythe Danner (Paltrow), Gwyneth Paltrow, Jake Paltrow and the Oral Cancer Foundation.

Media Contact: Jamie O’Day / The Oral Cancer Foundation (949) 723-4400 jamie@oralcancerfoundation.org

Immunotherapy Continues to Advance in Head and Neck Cancer

Source: www.onclive.com
Author: Megan Garlapow, PhD
 

Concomitant administration of motolimod with cetuximab (Erbitux) increases the innate and adaptive immune response in the blood and the tumor microenvironment in head and neck squamous cell carcinoma (HNSCC), overcoming negative prognostic biomarkers of cetuximab therapy alone, according to the biomarker data from a recent phase Ib clinical trial that was presented at the 2016 Head and Neck Cancer Symposium. The trial was recently amended to add nivolumab to the combination of cetuximab and motolimod.

Robert-FerrisDr. Robert Ferris, MD PhD

 

“We know that PD-1 and PD-L1 are overexpressed in head and neck cancer, and so it was somewhat irresistible to combine our baseline treatment of cetuximab and motolimod with the PD-L1 inhibition pathway. EGFR itself drives PD-L1, so combining cetuximab with anti-PD-1 inhibitor makes sense. So, we’ve amended this trial. We’re now accruing to treatment with cetuximab, motolimod, and the anti–PD-L1 nivolumab in this trial,” said lead author Robert Ferris, MD, PhD, professor, Departments of Otolaryngology, Radiation Oncology, and Immunology, Cancer Immunology Program, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.

According to the authors of the phase Ib data presented at the symposium, the rationale for combining cetuximab with motolimod (VTX2337) as neoadjuvant therapy was that cetuximab induces cellular immunity that correlates with neoadjuvant clinical response. The phase I dose-escalation and safety of the combination had been established (NCT 01334177).

This study of neoadjuvant cetuximab and motolimod had accrued 14 patients with HNSCC that was stage II-IV, resectable, and located in the oropharynx, oral cavity, hypopharynx, or larynx. These patients were biopsied, treated with cetuximab and motolimod for 4 weeks, and then underwent surgery. The endpoints of the trial were the modulation of immune biomarkers.

Interferon-inducible cytokine IP-10 increased after the patients were administered neoadjuvant cetuximab and motolimod (P = .0001). After the neoadjuvant treatment, the peripheral blood lymphocytes had an increased frequency of EGFR-specific CD8 T cells. After the neoadjuvant treatment, regulatory T cells had decreased suppressive receptors and transforming growth factor-β, which induces Foxp3. Also, after the neoadjuvant treatment, circulating MDSCs had decreased PD-L1 (P <.07) and macrophages had increased CD16 expression (P <.07).

After the neoadjuvant treatment with cetuximab and motolimod, genotyping of T-cell receptors showed increased clonality in peripheral blood lymphocytes (P = .003 by Wilcox signed rank test) and tumor-infiltrating lymphocytes (P = .081 by Wilcox signed rank test). Most patients are more oligoclonal than healthy individuals, and some are very clonal with highly prominent expanded clones. Genotyping of T-cell receptors found that clonality was increased by the combination of cetuximab and motolimod compared with treatment with cetuximab alone.

Recent studies have indicated that the PD-1/PD-L1 pathway is upregulated in the HNSCC microenvironment, and that EGFR blockade prevents interferon-γ-mediated upregulation of PD-L1. Thus, this study has been amended to add nivolumab to the adjuvant treatment with cetuximab and motolimod. The endpoints are still the modulation of immune biomarkers.

The aim is to target the tumor microenvironment, such that tumor immune escape is reversed and T cells eliminate HNSCC. Antitumor T cells are reprogrammed to reverse inhibitory signals. Combining the toll-like receptor agonist, motolimod, with cetuximab and with PD-1 pathway inhibitors, such as nivolumab, may enhance the priming and activity of T cells.

“Targeting the tumor microenvironment requires understanding as well as reversal of immune escape mechanisms in the cellular compartment. Reprogramming antitumor T cells to reverse inhibitory signals can be done by directly disrupting those inhibitory signals, the so-called checkpoint receptor field, and can be done potentially by combining proinflammatory signals, such as toll-like receptor agonists, to chemo-attract cells into the microenvironment and to create good inflammation to overcome suppressive factors,” said Ferris.

Recent findings have shown tremendous promise for nivolumab in head and neck cancer. Bristol-Myers Squibb (BMS) announced in January 2016 that nivolumab improved overall survival versus investigator’s choice of therapy for patients with platinum-refractory squamous cell carcinoma of the head and neck in the phase III CheckMate-141 trial. Findings from the study are being discussed with the FDA and other health authorities, according to BMS.

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.
February, 2016|Oral Cancer News|

Study: HPV vaccine reduces HPV incidence in teenage girls

Source: www.upi.com
Author: Stephen Feller
 
Study-HPV-vaccine-reduces-HPV-incidence-in-teenage-girlsJust over half of girls have received the HPV vaccination, but a new CDC study shows it has significantly reduced prevalence of the cancer-causing STI among females who have received the vaccine when compared with those who have not. Photo by Adam Gregor/Shutterstock

 

WASHINGTON, Feb. 22 (UPI) — The prevalence of human papillomavirus infection among teenage and young adult women is down nearly two-thirds since the U.S. Centers for Disease Control and Prevention started recommending vaccine in 2006, according to a new study.

The study is the first to show a drop in prevalence among women in their 20s, and continues to show decreases seen in smaller studies during the last few years, but researchers say the effect could be much stronger.

The vaccine is recommended by the CDC and other organizations for girls and boys starting at age 11, experts say, in order to protect children from HPV before they become sexually active and can become infected.

Concerns that the vaccine would influence teens’ sexual practices have also been unfounded, as research has shown the vaccine does not make children more likely to engage in risky sexual behavior, based on a the lack of an increase in other STI incidence among vaccinated girls.

“It’s just like putting on your seatbelt before turning on the car,” Dr. Alix Casler, medical director of pediatrics for Orlando Health, told UPI. She suggests separating the adolescents’ eventual discovery of sex from the effort to prevent life-threatening diseases.

Recommendations for the HPV vaccine — Cervarix, Gardasil and Gardasil 9 — have been expanded to boys, because of the wide range of cancers for which HPV increases risk, including cervical, anal, head and neck cancer, though a 2015 study showed vaccination rates remain relatively low, with just 57 percent of eligible girls and 35 percent of boys vaccinated.

“We are continuing to see decreases in the HPV types that are targeted by the vaccine,” Dr. Lauri Markowitz, a medical epidemiologist at the CDC, told CBS News. “We have seen declines in genital warts [caused by HPV] already. The next thing we expect to see is a decline in pre-cancers, then later on declines in cancer.”

For the study, published in the journal Pediatrics, used survey information collected as part of the National Health and Nutrition Examination Survey between 2003 and 2006 and between 2009 and 2012 on females between the ages of 14 and 34.

The researchers compared prevalence of HPV between the pre-vaccine group before 2006 and post-vaccine group after the vaccine was introduced, finding HPV prevalence declined by 64 percent, from 11.5 percent to 4.3 percent, in girls between age 14 and 19, and by 34 percent, from 18.5 percent to 12.1 percent, among women age 20 to 24.

Among women aged 14 to 24, the prevalence of HPV among vaccinated women, at 2.1 percent, was also significantly lower than the 16.9 percent of unvaccinated women with the STI.

The research is based on the 4vHPV vaccine, which protects against the four most common forms, though the 9vHPV vaccine was approved by the FDA for use to prevent more forms of HPV.

Casler said data in the next several years is likely to show continuing decreases in HPV prevalence as more adolescents receive the vaccine, however some pediatricians are hesitant because of personal bias. Many parents also are nervous the vaccine will act as a message to teens that sex is OK, making some parents want to delay vaccination until their adolescents are sexually active — by which time it may be too late.

“The infection is sexually transmitted, but that doesn’t need to be part of the conversation,” Dr. Joseph A. Bocchini, a pediatric infectious disease specialist at Louisiana State University, told the New York Times. “If a parent is concerned, physicians should be prepared to talk about it. But we don’t really discuss how people become infected with every vaccine-preventable disease.”

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

February, 2016|Oral Cancer News|

Nivolumab Could Change Head and Neck Cancer Treatment Paradigm

Source: www.Targetedonc.com
Author: Laura Panjwani
 

“To have an anti–PD-1 agent be proven to improve survival in head and neck cancer in a randomized phase III trial, and the potential for a new FDA approval in the near future is a game changer.” – Robert Ferris, MD, PhD

With the phase III CheckMate-141 trial being stopped early due to the anti–PD-1 agent nivolumab having met its primary endpoint of overall survival improvement in head and neck cancer, Robert Ferris, MD, PhD, couldn’t be more elated.

“This is what I’ve devoted my career to, and it is gratifying to see that really come to pass,” said Ferris, professor and chief, Division of Head and Neck Surgery, vice chair for Clinical Operations, associate director for Translational Research, and coleader of the Cancer Immunology Program at the University of Pittsburgh Cancer Institute, in an exclusive interview with Targeted Oncology.

“To have an anti–PD-1 agent be proven to improve survival in head and neck cancer in a randomized phase III trial, and the potential for a new FDA approval in the near future is a game changer. There is now hope for a lot of patients and physicians who have been frustrated by this difficult-to-treat disease. This opens up a whole new class of therapies for this population.”

Ferris, who acted as cochair/coprimary investigator for the trial alongside Maura Gillison, MD, PhD, Ohio State University, said the trial pitted nivolumab against the investigator’s choice of cetuximab (Erbitux), methotrexate, or docetaxel in patients with platinum-refractory squamous cell carcinoma of the head and neck (SCCHN).

Eligible patients who are still enrolled in the study are now able to continue their current treatment regimen, or switch over to nivolumab. Ferris says the prospect of having a new drug available for SCCHN is exciting, especially considering the last FDA approval for the disease type came in 2006.

“It was 2006 when cetuximab was approved and that was a relatively modest advance, although it was the first targeted therapy. We have a population without any other therapeutic options and a very rapid progression,” he said.

“Anti–PD-1 agents have had promising data in melanoma and squamous non–small cell lung cancer (NSCLC). Squamous NSCLC genomically resembles HPV-negative head and neck cancer in its behavior regarding carcinogen exposure. Therefore, we felt it might respond well to anti–PD-1 agents, too. We designed the study to hopefully create something new and effective for an essentially hopeless palliative group of patients.”

The phase III data have not yet been released from the trial, though early discontinuation has generated significant excitement in the field. The trial was scheduled to run until October 2016, has generated significant excitement in the field, says Ferris, who is a primary author on the abstract submitted for presentation at the ASCO Annual Meeting.

Ferris says the study was designed reflect the idea that there are different standards of care for SCCHN throughout the world, which is why cetuximab, methotrexate, or docetaxel were chosen for the control arms.

“We still don’t have public data for what all of the standard of care selections were, but we do know that cetuximab tends to be used more in North America. Meanwhile, the other 2 agents are more likely to be used in Europe and other countries because cetuximab is not approved there,” he said.

“The benefits are really very modest with those single-agent treatments and they are toxic. There is very much a need for a new treatment. We are very interested in the toxicity profile of nivolumab, as it has proven to be well tolerated in other cancers.”

Ferris adds that the excitement generated in the field stems from the revelation of efficacy for pembrolizumab (Keytruda) at the 2015 ASCO Annual Meeting, saying the data from both pembrolizumab and nivolumab “appear to be very similar.”

“There was a suspicion that nivolumab would be promising in head and neck cancer, as well. There is a great deal of buzz from medical oncology leaders all over the country regarding this. People have really been waiting with bated breath for something for our patients. This is a real win for the community and for a population of patients with a devastating disease in a very important area of the body,” he said.

“This disease can disrupt speaking, drinking, swallowing, and has catastrophic consequences. I expect enthusiasm and support from the community regarding this.”

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

February, 2016|Oral Cancer News|

Expanded age indication cleared for Gardasil 9 in males

Source: www.FormularyJournal.ModernMedicine.com
Author: Erin Bastick
 

FDA approved an expanded age indication for Human Papillomavirus 9-valent Vaccine, Recombinant (Gardasil 9, Merck) in males.

Seven HPV types in Gardasil 9 (HPV 16, 18, 31, 33, 45, 52, and 58) cause approximately 90% to 95% of HPV-related anal cancers, 90% of cervical cancers, and 80% of high-grade cervical lesions worldwide.These 7 types also cause the majority of HPV-related vulvar and vaginal cancers. Gardasil 9 includes the greatest number of HPV (Human Papillomavirus) types of any available HPV vaccine.

Gardasil 9 was previously approved for use in girls and young women aged 9 to 26 years for the prevention of cervical, vulvar, vaginal, and anal cancers caused by HPV 16, 18, 31, 33, 45, 52, and 58, precancerous or dysplastic lesions caused by HPV 6, 11, 16, 18, 31, 22, 45, 52, and 58, and genital warts caused by HPV types 6 and 11. As for use in male patients, the vaccine was previously approved for use in boys aged 9 to 15 years for the prevention of anal cancer caused by HPV types 16, 18, 31, 33, 45, 52, and 58, precancerous or dysplastic lesions caused by HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58.

With the newest approval, Gardasil 9 is now also indicated for use in males aged 16 to 26 years for the prevention of these diseases. According to the CDC, HPV vaccination rates are unacceptably low compared to rates for other adolescent vaccines, and vaccination coverage in males is especially low in males. The approval of the expanded age indication in male patients was based on results from a clinical trial program for Gardasil 9 that was designed to build upon the safety and efficacy established in clinical trials with Gardasil [Human Papillomavirus Quadrivalent (types 6, 11, 16, and 18) Vaccine, Recombinant].

“Any health plans that have not yet made a decision regarding coverage for Gardasil 9 for males 16-26 can do so now that that the vaccine is indicated in this population,” according to a company statement from Merck. “Most managed care plans have already made decisions to cover the cost of Gardasil 9, including for males 16 through 26 years of age, making the number of plans covering Gardasil 9 similar to the number covering the cost of Gardasil. The approval of Gardasil 9 for males 16 through 26 years of age is a milestone in the planned transition from Gardasil to Gardasil 9, as both products are now approved for the same populations.”

The most common adverse reactions associated with the use of Gardasil 9 in males aged 16 to 26 years included injection-site pain, swelling, and erythema. Not all vulvar, vaginal and anal cancers are caused by HPV; Gardasil 9 only protects against those cancers caused by HPV 16, 18, 31, 33, 45, 52, and 58. Gardasil 9 is contraindicated in individuals with hypersensitivity, including severe allergic reactions to yeast, or after a previous dose of Gardasil 9 or Gardasil.

This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

December, 2015|Oral Cancer News|

Depressed Head and Neck Cancer Patients Have Lower Survival and Higher Recurrence Risk

Source: www.OncologyNurseAdvisor.com
Author: Kathy Boltz, PhD
 

Depression is a significant predictor of 5-year survival and recurrence in patients with head and neck cancer, according to a new study published in Pyschosomatic Medicine (doi: 10.1097/PSY.0000000000000256). These findings represent one of the largest studies to report on the impact of depression on cancer survival.

Although depression can have obvious detrimental effects on a person’s quality of life, its impact on cancer patients is more apparent, explained lead author Eileen Shinn, PhD, assistant professor of Behavioral Science at The University of Texas MD Anderson Cancer Center, in Houston. Increasing evidence shows modest associations between elevated symptoms of depression and greater risk for mortality among patients with lung, breast, ovarian, and kidney cancers.

The research team sought to clarify the influence of depression on survival, focusing their analysis on a single cancer type. By limiting the sample set and adjusting for factors known to affect outcome, such as age, tumor size, and previous chemotherapy, they were able to uncover a more profound impact of depression.

The researchers followed 130 patients at MD Anderson with newly diagnosed oropharyngeal squamous cell carcinoma (OSCC), a type of cancer in which the tumor originates at the back of the throat and base of the tongue.

At the beginning of their radiation therapy, Patients completed a validated questionnaire at the beginning of their radiation therapy to identify symptoms of clinical depression. Researchers monitored the participants, all of whom completed treatment, until their last clinic visit or death, a median period of 5 years.

“The results of this study were quite intriguing, showing depression was a significant factor predicting survival at 5 years, even after controlling for commonly accepted prognostic factors,” said senior author Adam Garden, MD, professor, Radiation Oncology. Furthermore, depression was the only factor shown to have a significant impact on survival.

Patients who scored as depressed on the questionnaire were 3.5 times less likely to have survived to the 5-year interval compared with those who did not score as depressed. The degree of depression was also found to be significant, as every unit increase on this scale indicated a 10% higher risk for reduced survival.

The results were replicated with a different psychological health survey and were not influenced by how soon following diagnosis the depression assessment was done.

OSCC is diagnosed in 10 000 to 15 000 Americans each year. Major risk factors known to be associated with OSCC include smoking and tobacco use, alcohol consumption, and human papillomavirus (HPV) infection. Incidence of OSCC has doubled in the last 20 years due to increasing HPV infection rates, noted Shinn.

Neither alcohol nor tobacco use, also surveyed in this group, had a significant impact on survival. HPV infection status, when available, also did not appear correlated.

Despite a high cure rate, normally 60% to 80%, recurrence rate of disease is unusually high in these patients (approximately 30%). The researchers also investigated a potential link between depression and disease recurrence.

“When we controlled for all variables, depression was linked with a nearly 4 times higher risk of recurrence,” said Shinn. In addition, never smokers had a 73% lower chance of recurrence, compared with current smokers. Those were the only two factors associated with cancer recurrence.

This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

December, 2015|Oral Cancer News|

Head, Neck Cancer Patients May Be at Higher Risk for Suicide: Study

Source: www.health.usnews.com
Author: Robert Preidt
 

THURSDAY, Nov. 12, 2015 (HealthDay News) — Head and neck cancer patients may be at raised risk for suicide, new research suggests.

However, the overall risk is still small, the findings showed.

The study included over 350,000 patients in the United States diagnosed with head and neck cancer between 1973 and 2011. Of those patients, 857 died by suicide.

The investigators found that the suicide rate among head and neck cancer patients was three times higher than in the general population. And suicide rates were higher among patients treated with radiation alone compared to surgery alone.

Suicide rates were highest among those with cancers of the lower part of the throat, including the larynx (“voice box”) and hypopharynx, at five times and 12 times higher, respectively, than in the general population.

“This may be linked to these anatomic sites’ intimate relationship with the ability to speak and/or swallow. Loss of these functions can dramatically lower patients’ quality of life,” Dr. Richard Chan Woo Park, of Rutgers New Jersey Medical School, and colleagues wrote.

“It is possible that the increased rates of tracheostomy [breathing tube] dependence and dysphagia [difficulty swallowing] and/or gastrostomy [feeding] tube dependence in these patients are . . . factors in the increased rate of suicide observed,” the authors added.

The study was published online Nov. 12 in the journal JAMA Otolaryngology–Head & Neck Surgery.

“While there is a considerable body of research that examines survival outcomes for patients with head and neck cancer, additional research and effort should also be devoted to the psychological toll that the cancer, treatments and resulting morbidity have on patients,” the researchers concluded.

Suicide is the 10th leading cause of death in the United States and cancer patients are at increased risk for suicide, the study authors pointed out in a journal news release.

More information

The American Cancer Society offers resources on coping with cancer.

Copyright © 2015 HealthDay. All rights reserved.

This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

November, 2015|Oral Cancer News|