Monthly Archives: June 2016

New study analyzes physical therapy for head and neck cancer survivors

Source: www.curetoday.com
Author: Andrew J. Roth

The aftermath of treatment for head and neck cancer can be particularly difficult, according to Ann Marie Flores. Flores, assistant professor, Department of Physical Therapy, Movement & Rehabilitation Science, Bouvé College of Health Sciences, Northeastern University, conducted a pre-pilot study looking at early physical therapy education for this patient population.

CURE interviewed Flores about her poster, which she presented at the 8th Biennial Cancer Survivorship Research Conference in Washington, DC.

Could you first give some background about this study? How did it come to be?
It was a spinoff of some studies that I began in breast cancer. I conducted a literature review of rehab needs of breast cancer survivors about 10 years ago and found that there was very little out there. Then, when I started a rehab oncology program at a previous institution, the patient population that were referred to the program tended to not be breast cancer patients, because they physically and functionally tend to do well in aggregate. Most of my patients referred were those with head and neck cancer. I went through the same process to look through literature critically to figure out what exists in terms of physical therapy and rehabilitation-based approaches. I’ve updated this over a long period of time and this poster is a systematic review of the quality of evidence. I combined this literature and data review with talking to a focus group of cancer survivors.

What did you find?
I asked the focus group if they needed more information and the answer was “Yes!” over and over again. The majority of comments I heard were exactly about physical therapy, self-care and efficacy—things we specialize in. They were also adamant about oral health and dental care, understanding salivary function, tongue motion, muscles and more. We also heard a lot about emotional and social support. So many of these survivors said they felt they were losing their mind because no one around them understood what they were going through after treatment.

It was very interesting to see the concordance of the systematic review results with our focus groups.

What is it about this population that you think creates such a need for information?
Head and neck cancer survivors make up about 4 percent of all cancer survivors. What many of these patients have are multimodality therapies, highly disfiguring surgeries, surgeries that contribute to high rates of disability. Many patients also get chemotherapy and radiation. These survivors can have impairments that can compromise key functions of life—breathing, eating and speaking.

Can these patients get the services they need? Where?
They should be able to, yes. I am a long-standing member of the American Physical Therapy Association and we have a task force that specializes in head and neck studies. We’ve published four studies looking at measuring physical therapy–related impairments that we can rehabilitate, such as shoulder dysfunction, trismus and lymphedema. With trismus, patients can’t open their mouths. Many patients with head and neck cancer have either had muscle tissue removed or have highly scarred jaw muscles. And with lymphedema, you can get that in any part of your body, including the head and neck. Many patients will have lymph fluid collect in the under part of their neck.

For a patient who has finished treatment and facing some of these issues, where should he/she go for support?
As a patient, I’d tell my doctor that I need a referral to a physical therapist. In fact, the next steps following on our research will be to pilot test our patient education materials to determine their clinical feasibility, acceptability, and impact on PT outcomes. We want to ensure that these materials are patient-centered and relevant across the survivorship trajectory.

HPV vaccination could be offered to schoolboys to decrease risk of cancer

Source: www.mirror.co.uk
Author: Andrew Gregory

A vaccination could soon be offered to every schoolboy to help tackle the rising rate of some cancers in men, a Government minister revealed on Thursday. Health chiefs are poised to drop their opposition to extending the jab to protect against the human papilloma virus (HPV), which is already given to all Year 8 girls. The likely move follows growing alarm over cancers of the mouth, throat, neck and head, as well as penile and anal cancer, amid growing evidence that they are caused by HPV.

The NHS (National Health Service) spends more than £300m a year treating head and neck cancers, while giving the vaccine to all boys would cost just £22m, supporters say.

Health Minister Jane Ellison has revealed that the independent Joint Committee on Vaccination and Immunization (JCVI) is investigating the change, with its verdict due early next year. Mrs Ellison – who has previously described giving the HPV jab to girls only as “a little odd” – said: “I understand the wish for it to be available to all adolescents regardless of gender.

“The JCVI is reconsidering its initial advice on this and modeling is under way to inform its consideration. We will look at that as a priority when we get it.

“I recognize the frustration that people have expressed and I have talked personally to Public Health England officials who are involved in the modelling work.”

The minister said money was already available to extend the vaccination program if the JCVI said yes, adding: “The Government have always acted on its recommendations.” The looming move comes after a Commons debate heard that men are six times more likely than women to have an oral HPV infection – yet they are not vaccinated.

Conservative MP Sir Paul Beresford , a part-time dentist himself, said up to 70% of throat cancers are caused by HPV, adding: “The statistics make for hideous reading.”

HPV is also linked to around 80% of anal cancer in men, almost half of penile cancers and is responsible for nine out of 10 cases of genital warts. A national vaccination program HPV was introduced for 12 and 13-year-old girls as long ago as 2008, to prevent cervical cancer.

But experts agree the program does not create sufficient “herd immunity”, prompting a recent decision to begin a trial to give the jab to some gay men. Around 40,000 men who have sex with men (MSM) will be vaccinated, targeting under-45s who attend sexual advice clinics.

A campaign group called HPV Action has called for all boys to be vaccinated as soon as possible – warning 367,000 are at risk of developing a preventable disease in later life, for every year of delay.

Rodeo rider partners with nonprofit group to fight smokeless tobacco use

Source: www.fox13now.com
Author: Rebecca Cade
 

SALT LAKE CITY — Oral cancer is becoming an epidemic in the U.S., and has been in the news in the last year with the loss of major league baseball hall-of-famer, Tony Gwynn, who died at 54 from smokeless tobacco use.

Rodeo has a historic tie to smokeless tobaccos, and Oral Cancer Foundation, has teamed up with Bareback Rider Cody Kiser to draw awareness to, and prevent, this growing epidemic where it thrives – the rodeo circuit.

Smokeless/spit tobacco is one of the historic causes of deadly oral cancers, and is more addictive than other forms of tobacco use.

The nonprofit is seeking to spread awareness of oral cancer and the dangers of starting terrible tobacco habits. While others are focused on getting users to quit, The Oral Cancer Foundation is reaching out to young people to not pick up the habit that they may see one of their rodeo “heroes” engage in.

Their message is simple, “Be Smart. Don’t Start.”

With the strong addictive powers of smokeless tobacco, the foundation and Kiser aim to engage fans early.

At the rodeos, Kiser will be solely wearing OCF logos and wording, while handing out buttons, wristbands and bandanas with the campaign messaging on them. The bareback rider hopes this will make him an alternative positive role-model for the adolescent age group whose minds are so easily molded.

“It’s something I’ve always been passionate about, so when I got into the partnership with OCF, it was no big deal to be able to say ‘I don’t smoke or chew, never have, and it’s easy not to,'” Kiser said.

Kiser added it all starts with kids.

“Most of these guys I ride with started smoking and chewing in sixth or seventh grade,” he said. “So, if we can get to those kids now, and tell them ‘you don’t have to do this to be cool or be a cowboy’ and show them what you can do without it.”

More information on the campaign can be found at www.oralcancer.org

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

Number of circulating tumor cells up after surgery in SCCHN

Source: www.doctorslounge.com
Author: staff

Most patients with squamous cell carcinoma of the head and neck (SCCHN) have an increase in the number of circulating tumor cells (CTCs) after surgical resection, according to a study published online June 5 in Head & Neck.

Kris R. Jatana, M.D., from the Nationwide Children’s Hospital in Columbus, Ohio, and colleagues identified cytokeratin-positive CTCs using a negative depletion technique. They compared the numbers of CTCs immediately before and after surgical resection using blood samples from 38 patients with SCCHN.

The researchers found that 79 percent of patients had CTCs before and after surgery. Overall, 7.89 percent of patients had no CTCs before surgery but did have CTCs after surgery. After surgery there was an increased number of CTCs/mL in 60.5 percent of patients, with a 6.63-fold mean increase (P = 0.02).

“The timing of blood sample collection for such solid cancers that undergo surgical intervention, such as SCCHN, can potentially impact the number of CTCs identified,” the authors write. “Although a prognostic blood test for CTCs could have important treatment and surveillance implications, the viability and clinical significance of potentially surgically released CTCs in SCCHN is still not known.”

Aspen Dental Practices Donate More Than $20,000 To The Oral Cancer Foundation For Oral Cancer Awareness Month

Source: www.pharmiweb.com.org
Author: Aspen Dental
 

SYRACUSE, N.Y., May 31, 2016 /PRNewswire/ — Aspen Dental–branded practices will donate $22,375 to The Oral Cancer Foundation (OCF) as part of a program that contributed $5 for each ViziLite® oral cancer screening conducted during April for Oral Cancer Awareness Month. In total, more than 4,000 patients were screened across more than 550 practices in 33 states.

Since 2010, Aspen Dental-branded practices have donated more than $105,000 to OCF.

“Approximately 48,250 people in the U.S. will be diagnosed with an oral or oropharyngeal cancer this year; and of those only about 57% will be alive in five years,” said Natalie Riggs, Director of Special Projects for The Oral Cancer Foundation. In 2016 we estimate that 9500 individuals will lose their lives to oral cancers and we are grateful for the support from Aspen Dental practices in helping us raise awareness and aiding in our efforts to fight this disease.”

Oral cancer is frequently preceded by visible pre-malignant lesions and can be diagnosed at a much earlier stage (I or II) with ViziLite® Plus, a specially designed light technology.  When caught early and treated, the survival rate is 80 to 90 percent.

“We’re working to educate our patients about the risk factors, warning signs and symptoms associated with oral cancer so that we can help them catch the disease before it progresses,” said Dr. Murali Lakireddy, a general dentist who owns Aspen Dental offices in Ohio. “Many of our patients do not think about oral cancer when they go to the dentist, but in fact, oral cancer screenings are just as much a part of your routine dental visit as a deep clean from the hygienist.”

To learn more about oral cancer screenings, visit the OFC website at http://www.oralcancerfoundation.org/dental/how_do_you_know.html.

About Aspen Dental Practices
Dentists and staff at Aspen Dental practices believe everyone has the right to quality, affordable oral health care. As one of the largest and fastest-growing networks of independent dental care providers in the U.S., local Aspen Dental practices – more than 550 of them across 33 states – offer patients a safe, welcoming and judgment-free environment to address their dental challenges. Every Aspen Dental-branded practice offers a full range of dental and denture services – including comprehensive exams, cleanings, extractions, fillings, periodontal treatment, whitening, oral surgery, crown and bridge work – allowing patients to have the peace of mind that they are taken care of and protected, so they can focus on getting the healthy mouth they deserve. In 2015, Aspen Dental-branded practices recorded more than 3.7 million patient visits and welcomed nearly 785,000 new patients.

Nivolumab Demonstrated Survival Benefit, Good Tolerance in Refractory HNSCC

Source: www.asco.org
Author: Tim Donald, ELS
 

In the phase III comparative CheckMate 141 trial, nivolumab demonstrated a “significant improval in survival” in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), compared with therapy of the investigator’s choice, according to Robert L. Ferris, MD, PhD, FACS, of the University of Pittsburgh Cancer Institute (Abstract 6009). There were fewer treatment-related adverse events with the PD-1 inhibitor than with investigator’s choice therapy, Dr. Ferris said, and nivolumab stabilized patient-reported quality-of-life outcome measures, whereas the investigator’s choice therapy led to meaningful declines in function and worsening of symptoms.

AM16.6009-Ferris2Dr. Robert L. Ferris

“Nivolumab is a new standard-of-care option for patients with refractory or metastatic HNSCC after platinum-based therapy,” Dr. Ferris said.

Dr. Ferris presented the trial results at the “Harnessing the Immune System in Head and Neck Cancer: Evolving Standards in Metastatic Disease” Clinical Science Symposium on June 6. He noted that in this trial of patients whose disease had progressed after platinum-based therapy, nivolumab doubled the 1-year overall survival (OS) rate, with 36.0% OS for the immunotherapeutic drug compared with 16.6% for the investigator’s choice therapy. These top-line results were presented at the 2016 American Association of Cancer Research meeting1; Dr. Ferris presented data the additional endpoints of quality of life, correlative biomarkers, and safety.

There is an extremely poor prognosis for patients with platinum-refractory recurrent or metastatic HNSCC, with median OS of 6 months or fewer. Previous research, by Dr. Ferris and others, has shown that HNSCC can express T-cell suppressive ligands, such as PD-L1, thereby evading host immune response. PD-L1 is frequently expressed on HNSCC cells, both HPV-positive and -negative.

The phase III CheckMate 141 study enrolled patients with HNSCC aged 18 and older with ECOG status 0 or 1, and with disease progression within 6 months after the most recent dose of platinum-based therapy. Patients were enrolled regardless of PD-L1 status and irrespective of number of previous lines of therapy. Immunohistochemistry testing for p16 was performed to determine HPV status. Patients were randomly assigned 2:1 to nivolumab (3 mg/kg intravenous [IV] every 2 weeks) or investigator’s choice of single-agent therapy with methotrexate (40 mg/m² IV weekly), docetaxel (30 mg/m² IV weekly), or cetuximab (400 mg/m² IV once, then 250 mg/m² weekly).

OS was compared between arms and by PD-L1 expression and HPV (p16) status. Nivolumab demonstrated a survival benefit in the overall study population, regardless of PD-L1 expression or p16 status, Dr. Ferris said. The magnitude of the OS benefit of nivolumab was greater in patients expressing PD-L1 at 1% or more (HR 0.55, 95% CI [0.36, 0.83]) compared with those expressing PD-L1 at less than 1% (HR 0.89, 95% CI [0.54, 1.45]). However, increasing levels of PD-L1 expression ( ≥ 5%, ≥ 10%) did not result in further OS benefit.

The OS benefit was greater with nivolumab than investigator’s choice therapy in both patients who were p16 positive (HR 0.56, 95% CI [0.32, 0.99]) and p16 negative (HR 0.73, 95% CI [0.42, 1.25]). When OS was analyzed for both PD-L1 expression and p16 status, the hazard ratios favored nivolumab for all subgroups.

Treatment-related adverse events of any grade were lower in the nivolumab arm (58.9%) than the investigator’s choice therapy arm (77.5%). Serious (grade 3 or 4) treatment-related adverse events were also lower in the nivolumab arm (13.1%) than in the investigator’s choice therapy arm (35.1%). Patient-reported outcome measures for quality of life were assessed based on two EORTC scales. Treatment with nivolumab stabilized the outcome measures of physical function, social function, absence of sensory problems, and absence of trouble with social contact, whereas the investigator’s choice therapy led to meaningful declines in function and worsening of symptoms.

AM16.6009-Uppaluri_0Dr. Ravindra Uppaluri

Discussant Ravindra Uppaluri, MD, PhD, of Washington University School of Medicine, said that the CheckMate 141 trial “continues to highlight the use of PD-L1 status as a stratifier.” The trial results “offer hope for patients with refractory or metastatic HNSCC,” he said. “Obviously better biomarkers are needed, and, ultimately, a composite immune profile may be required.”

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

June, 2016|Oral Cancer News|

Heading back to the office following head and neck cancer

Source: blogs.biomedcentral.com
Author: Daniel Caley

In Cancers of the Head & Neck launching today publishes the first study looking at disability and employment outcomes in patients with head and neck cancer related to the human papillomavirus (HPV). Dr Shrujal Baxi, Section Editor for survivorship and patient related outcomes and author of this study, explains more about their work in this Q&A:

The rates of patients diagnosed with HPV-related head and neck cancer is rising annually. By 2020, there will be more cases of HPV-related head and neck cancer than HPV-related cervical cancer in the United States. Numerous studies have shown that most patients with this diagnosis are likely to be cured of their disease, placing an increased emphasis on quality of life and non-cancer outcomes in this population of survivors. The majority of patients diagnosed with HPV-related head and neck cancer are working-age adults and employment is a serious issue both financially and psychologically.

How can treatment for head and neck cancer impact employment?
Treatment for head and neck cancer often involves a combination of chemotherapy and radiation given over a six to seven week period, often known as concurrent chemoradiation or combined modality chemoradiation. This process is considered toxic and can impact a patient’s ability to function normally including speaking, chewing, breathing and swallowing. Many patients require numerous supportive medications to get through treatment including narcotics for pain and anti-nausea medications. Patients can lose on average 10-15% of their weight within a few months and can suffer from severe fatigue and post-treatment depression.

Who was in your study?
We included 102 participants with HPV-related head and neck cancer treated with chemoradiation at our institution who were employed full-time for pay at the time of diagnosis.

How did the treatment impact employment?
97% of patients had to change their employment responsibilities in some way from reducing work, taking a break and then returning at a later date, or stopping altogether and not returning. There were 73 patients that stopped but eventually returned to work after treatment, and they required a median of 14.5 weeks to return. This is longer than the 12 weeks currently allowed according to the Family Medical Leave Act (FMLA).

Eight patients stopped working altogether and never went back. Eight patients stopped working during treatment and never returned to work. Aside from younger age predicting extra time off before returning to work, we did not find a patient, treatment or disease factor that accounted for needing extra time off.

What happened to these patients?
The majority of patients who returned to work continued. At nearly two years from completion of treatment, 85% of the original 102 patients were working for pay. Overall, survivors were doing very well in terms of quality of life with the majority not having any major limitations secondary to their treatment.

There were a group of survivors who were dissatisfied with their ability to work. Some were working but not satisfied with their abilities, while others were looking for work. Compared to those who were satisfied with their abilities, those that were unsatisfied were more likely to have more functional problems and more head and neck specific late toxicities from their treatment.

What does this mean for patients and providers?
I think that this study provides some guidance for patients and providers as they prepare for chemoradiation to treat HPV-related head and neck cancer. It is hopeful that most patients will return to work, but realistic expectations of ability to work will help in treatment planning. Employment is another reason why managing late toxicities remains an important aspect of optimal care for head and neck cancer survivors.

Type 2 diabetes drug could be beneficial for head and neck cancer patients

Source: www.eurekalert.org
Author: press release

Researchers at the University of Cincinnati (UC) College of Medicine have found that adding increasing doses of an approved Type 2 diabetes drug, metformin, to a chemotherapy and radiation treatment regimen in head and neck cancer patients is not well tolerated if escalated too quickly, but allowing slower escalation could be beneficial.

These findings are being presented via poster June 4 at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting: Collective Wisdom, being held June 3-7 in Chicago.

Trisha Wise-Draper, MD, PhD, assistant professor in the Division of Hematology Oncology at the UC College of Medicine, a member of both the Cincinnati Cancer Center and UC Cancer Institute and principal investigator on this study, says retrospective studies have shown improved outcomes in tumors treated with chemotherapy and radiation if they were also on metformin for diabetes.

“In head and neck squamous cell carcinoma, which develops in the mucous membranes of the mouth, nose and throat, diabetic patients taking a medication called metformin had better overall survival compared to those not on metformin when also treated with chemotherapy and radiation,” she says. “Additionally, pancreatic cancer patients treated with chemotherapy and metformin required higher doses of metformin–1,000 milligrams twice a day–to experience positive results.

“In basic science studies, metformin has been shown to stop mTOR, a molecular pathway present and active in this type of head and neck cancer, and pretreatment with metformin resulted in a decrease in the occurrence of oral cavity tumors in animal models. In this study, we wanted to see if the combination of escalating doses of metformin with the chemotherapy agent cisplatin and radiation for head and neck cancer tumors in non-diabetic patients would be effective.”

Wise-Draper says that metformin, which is an approved Type 2 diabetes medication, was provided by their investigational pharmacy. Metformin was administered orally in escalating doses for 7 to 14 days prior to starting the cisplatin and radiation and continued throughout standard treatment. Blood samples were collected before and after metformin treatment as well as during chemotherapy. Flow cytometry, a technique used to count cells, was used to detect the percent of circulating immune activated cells, and clinical laboratory tests including glucose, B12 and C-peptide (an amino acid that is important for controlling insulin) were performed.

“This is part of an ongoing clinical trial,” says Wise-Draper. “We found that eight patients with advanced head and neck cancer have been enrolled so far; we plan to have 30 total. Due to the relatively quick escalation of metformin, the patients’ tolerance was poor with higher doses of metformin when initiated 7 days prior to their chemotherapy and radiation therapy regimen.

“Therefore, the protocol was modified to allow slower escalation over 14 days. The most common toxicities observed included nausea (71 percent of patients) and vomiting (43 percent of patients), increase in creatinine (57 percent of patients), decreased white blood cell count (43 percent of patients) and pain when swallowing (43 percent of patients) with only nausea being directly attributed to metformin and the rest attributed to cisplatin and radiation.”

She adds that there wasn’t a substantial change in T cell or glucose levels with administration of metformin in the small sample of patients but that there were increased C-peptide levels in response to metformin administration.

“These results show that the combination of metformin and cisplatin and radiation was poorly tolerated when metformin was escalated quickly. However, there has been no significant increase in side effects thus far with the addition of metformin,” Wise-Draper says. “The trial is continuing with escalation of metformin over a longer period of time to provide more data; we will also try to increase our sample size.”

Note:
This research is being funded by the UC Cancer Institute. Wise-Draper cites no conflict of interest.

HPV is changing the face of head and neck cancers

Source: www.healio.com
Author: Christine Cona
 

A drastic increase in the number of HPV-associated oropharynx cancers, particularly those of the tonsil and base of tongue, has captured the attention of head and neck oncologists worldwide.

In February, at the Multidisciplinary Head and Neck Cancer Symposium in Chandler, Ariz., Maura Gillison, MD, PhD, professor and Jeg Coughlin Chair of Cancer Research at The Ohio State University in Columbus, presented data that showed that the proportion of all head and neck squamous cell cancers that were of the oropharynx — which are most commonly HPV-positive cancers — increased from 18% in 1973 to 32% in 2005.

9ea467bbf8646a69da2a432f8fcc5452Maura Gillison, MD, PhD, Jeg Coughlin Chair of Cancer Research at The Ohio State University, said screening for HPV in the head and neck is years behind cervical screening for HPV.

 

In addition, studies from the United States, Europe, Denmark and Australia indicate that HPV-positive patients have a more than twofold increased cancer survival than HPV-negative patients, according to Gillison.

With the rising incidence of HPV-related oropharynx cancers, it will soon be the predominant type of cancer in the oral or head and neck region, according to Andy Trotti, MD, director of radiation oncology clinical research, H. Lee Moffitt Cancer Center & Research Institute, in Tampa, Fla.

“We should be focusing on HPV-related oropharyngeal cancer because it will dominate the field of head and neck cancers for many years,” he said during an interview with HemOnc Today. “It is certainly an important population for which to continue to conduct research.”

Because HPV-associated oropharyngeal cancer is emerging as a distinct biological entity, the recent rise in incidence will significantly affect treatment, and prevention and screening techniques, essentially reshaping current clinical practice.

Social change driving incidence

In the analysis performed by Gillison and colleagues, trends demonstrated that change in the rates of head and neck cancers was largely due to birth cohort effects, meaning that one of the greatest determinants of risk was the year in which patients were born.

The increased incidence of HPV-related oropharyngeal squamous cell carcinoma started to occur in birth cohorts born after 1935, indicating that people who were aged in their teens and twenties in the 1960s were demonstrating increased incidence, Gillison said.

“Two important and probably related events happened in the 1960s. In 1964, the surgeon general published a report citing smoking as a risk factor for lung cancer, and public health policy began promoting smoking cessation along with encouragement not to start smoking,” she told HemOnc Today.

If you were 40 years old between 2000 and 2005, your risk for having HPV-related cancer is more than someone who was between the age of 40 and 45 years in 1970, according to Gillison. Social changes that occurred among people born after 1935, for example, a reduction in the number of smokers, is consistent with the increasing proportion of oropharyngeal cancers that were HPV-related.

“The rates for HPV-related cancers began to increase and the rates for HPV-unrelated cancers started to decline, consistent with the known decline in tobacco use in the U.S. population,” she said.

Now, most cases of head and neck squamous cell carcinoma in non-smokers are HPV-related; however, oral HPV infection is common and is a cause of oropharyngeal cancer in both smokers and non-smokers, research shows.

In addition to a decrease in tobacco use reducing HPV-unrelated oral cavity cancers, the number of sexual partners may have increased during this time and have helped to increase HPV-related oropharyngeal cancers, according to Gillison.

Determining the cause of the elevated incidence is only a small piece of the puzzle. Screening, establishing who is at risk, and weighing vaccination and treatment options are all relevant issues that must be addressed.

Screening is problematic

A critical area for examination and research is the issue of screening for oral cancers. In contrast to cervical cancer, there is no accepted screening that has been shown to reduce incidence or death from oropharyngeal cancer, according to Gillison.

Not many studies have examined the issue of screening for HPV-unrelated oral cancers, and the few that have, tend to include design flaws.

Gillison said there is a hope that dentists would examine the oral cavity and palpate the lymph nodes in the neck as a front-line screen for oral cancer; however, in her experience, and from her perspective as a scientist, this has never been shown to provide benefit for oral cancer as a whole.

Another caveat with regard to HPV detection is that head and neck HPV screening is about 20 years behind the cervical field.

“Clinicians screening for HPV in the field of gynecology were incredibly fortunate because Pap smear screening was already an accepted cervical cancer screening method before HPV was even identified,” she said. “There was already a treatment algorithm: If there were cytologic abnormalities, patients were referred to the gynecologist, who in turn did a colposcopy and biopsy.”

A similar infrastructure does not exist for oropharyngeal cancer. People with HPV16 oral infection are at a 15-fold higher risk for oropharynx cancer and a 50-fold increased risk for HPV-positive head and neck cancer, yet there is no algorithm for treatment and management of these at-risk individuals, Gillison said.

In 2007, WHO said there was sufficient evidence to conclude that HPV16 was the cause of oropharynx cancer, but with no clinical algorithm already established, progress in this area is much further behind.

Another problematic aspect of HPV-related oropharyngeal cancer screening is that the site where the cancer arises is not accessible to a brush sampling, according to Gillison.

“To try to find this incredibly small lesion in the submucosal area that you cannot see and cannot get access to with a brush, highlights that we need to develop new techniques, new technologies and new approaches,” she said.

The near future consists of establishing the actual rates of infection in the oral cavity and oropharynx, and then screening for early diagnosis, according to Erich Madison Sturgis, MD, MPH, associate professor in the department of head and neck surgery and the department of epidemiology at The University of Texas M.D. Anderson Cancer Center.

“I am not extremely hopeful because the oropharyngeal anatomy makes screening complicated, and these cancers likely begin in small areas within the tonsils and the base of the tongue,” Sturgis told HemOnc Today. “I am hopeful, however, that preventive vaccines will eventually, at a population level, start to prevent these cancers by helping people avoid initial infection by immunity through vaccination earlier in life.”

Much of the currently known information surrounding the issue of HPV-related oral cancers is new, so researchers continue to conduct research in various relevant areas. One key question to answer is who may be at higher risk for HPV-related oropharynx cancers.

Who is at risk?

As mentioned earlier, the number of oral sex partners seems to play a role in the risk for contracting the HPV virus.

In one study published in The New England Journal of Medicine in 2007, findings demonstrated that a high lifetime number of oral sex partners (at least six partners) was associated with an increased risk for oropharyngeal cancer (OR=3.4; 95% CI, 1.3-8.8).

In addition to a higher number of oral sex partners, other still unknown factors may be contributing to risk. This is an area that needs further research, according to Barbara Burtness, MD, chief of head and neck oncology, and professor of medical oncology at Fox Chase Cancer Center in Philadelphia.

The effect of smoking status is another area that needs further research. According to Burtness, smokers with HPV-associated oropharynx cancer have less favorable outcomes.

When discussing the prognosis of HPV-associated cancers, Sturgis said low risk is defined as low or no tobacco exposure and positive HPV status, and intermediate risk is defined as significant tobacco exposure but an HPV-positive tumor, and the highest risk group appears to be the HPV-negative group.

Although HPV-negative cancers are overwhelmingly tobacco-related cancers and tend to have multiple mutations, it appears that HPV-positive cancers, particularly those in patients with low tobacco and alcohol exposure, tend to lack mutations and to have a better prognosis, and this may ultimately help to guide treatment practices, according to Sturgis. Yet, there is still much to learn about HPV-related oropharyngeal cancers on various fronts.

Vaccination a hopeful ally

In HPV-related head and neck cancer, particularly oropharynx cancers, more than 90% of patients who have an HPV-type DNA identified, have type 16, according to Sturgis.

The two current HPV vaccines, Gardasil (Merck) and Cervarix (GlaxoSmithKline), which are approved for cervical cancers, include HPV types 16 and 18; therefore, in theory, they should be protective against the development of infections in the oropharynx and protective at preventing these HPV-associated cancers from occurring.

The presumption is that if there was a population-wide vaccination against HPV, there would be less person-to-person transmission, and this would lead to fewer oropharynx cancers, according to Burtness, who said this theory still needs further research.

There is excitement at the possibility that therapeutic vaccines could be developed, and various groups are investigating this, Burtness added.

“There is reason to think that the vaccines may be helpful; however, when HPV infects the tonsillar tissues, it exerts control in the host cells by making two proteins: E6 and E7; so another potentially exciting therapeutic avenue would be to target those specific viral proteins,” she told HemOnc Today.

Anxiety about protection from the HPV virus is palpable, according to Sturgis. He described the worry that many patients experience about contracting and transmitting HPV infection.

“Many patients are concerned they will put their spouses and/or children at risk in ways such as kissing them; and we need to tone down those worries until we have better data,” he said.

Screening and vaccination are fundamental aspects of current ongoing research, but of equal importance is determining what clinicians should do to treat a population of patients with HPV-related oropharyngeal cancers.

HPV status may influence treatment

With rates of HPV-related cancers escalating, determining the appropriate treatment for these patients is crucial.

During the past 10 years, findings from retrospective studies have shown that patients with HPV-related cancers have a much better prognosis than patients who test negative for HPV. Findings from several retrospective analyses from clinical trials conducted during the past 2 years have come to the same conclusion, according to Gillison: HPV-positive patients have half the risk for death compared with patients negative for HPV.

Therefore, there may be several alternative treatment options, including the possibility of reducing the dose of radiation given to patients after chemotherapy, thereby reducing toxicity.

Comparing HPV-negative and HPV-positive patients may not be enough to determine proper treatment, researchers said. Data between different cohorts of HPV-positive patients also needs to be examined. Smoking, for example, may play a role in patient outcome.

In a prospective Radiation Therapy Oncology Group clinical trial (RTOG 0129), presented by Gillison at the 2009 ASCO Annual Meeting and recently published in The New England Journal of Medicine (see page 53), researchers conducted a subanalysis of the effect of smoking on outcome in uniformly staged and treated HPV-positive and HPV-negative patients while accounting for a number of potential confounders. HPV-positive patients who were never smokers had a 3-year OS of 93% compared with heavy smoking HPV-negative patients who had an OS of 46%.

The study found that smoking was independently associated with OS and PFS. Patients had a 1% increased risk for death and cancer relapse for each additional pack-year of smoking. This risk was evident in both HPV-positive and HPV-negative patients. Gillison said smoking data must be paid attention to, and she encouraged cooperative group research on the topic.

Most of the findings demonstrate improved outcomes for patients with HPV-positive oropharyngeal cancers vs. patients with HPV-negative oropharyngeal cancers, according to the experts interviewed by HemOnc Today.

Dose de-intensification for less toxicity

To date, there is no evidence that HPV-related cancers should be managed differently than HPV-unrelated cancers, but it is a hot topic among clinicians in the field, according to Burtness.

The superior outcomes for HPV-associated oropharynx cancer have suggested the possibility of treatment de-intensification. The use of effective induction chemotherapy may permit definitive treatment with a lower total radiation dose. In theory, this would reduce the severity of late toxic effects of radiation, such as swallowing dysfunction. Such a trial is being conducted by the Eastern Cooperative Oncology Group. Burtness said this is currently pure research question.

“There is still much research that needs to be done before clinicians can safely reduce the dose of radiation administered to HPV-positive patients,” Burtness said.

Currently, she and colleagues in the ECOG are conducting a study of patients with HPV-associated stage III or IV oropharynx cancers to examine the possibility of tailoring therapy to these patients. Patients are assigned to one of two groups: low-dose intensity-modulated radiotherapy 5 days per week for 5 weeks (27 fractions) plus IV cetuximab (Erbitux, ImClone) once weekly for 6 weeks, or standard-dose intensity-modulated radiotherapy 5 days per week for 6 weeks (33 fractions) plus IV cetuximab once weekly for 7 weeks.

If patients have a very good clinical response to chemotherapy, which is likely to happen with HPV-associated cancers, they are eligible to receive a reduced dose of radiation, and hopefully, they would experience less adverse effects, Burtness said.

“Patients who are treated with the full course of radiation for head and neck cancer are now getting 70 Gy, and they are often left with dry mouth, and speech and swallowing difficulty,” she said. “We are hopeful that if these particular cancers are treatment responsive to chemotherapy, we may be able to spare the patient the last 14 Gy of radiation.”

Immunotherapy a viable treatment

Another possible treatment technique that may benefit patients with HPV-related cancers is immunotherapy. One form of immunotherapy uses lymphocytes collected from the patient, and training the cells in the laboratory to recognize in this case a virus that is associated with a tumor and consequently attack it. This approach potentially may be used to treat HPV-related oropharynx cancers, according to Carlos A. Ramos, MD, assistant professor at the Center for Cell and Gene Therapy at Baylor College of Medicine, Houston.

“With some infections that lead to cancer, even though the virus is present in the tumor cells, the proteins shown to the immune system are limited; therefore, they do not drive a very strong immune response,” Ramos told HemOnc Today. “Training the immune system cells, T lymphocytes, may make them respond better to antigens.”

Data from ongoing trials that are taking T lymphocytes from patients and educating them to recognize antigens in patients with the Epstein-Barr virus associated tumors have shown some activity against them, according to Ramos. This adoptive transfer appears to be safe and may have the same effect on the HPV virus associated tumors. Immunotherapy does not cause the usual toxicities associated with chemotherapy, he said.

“There are currently no trials showing whether we can prevent more recurrences with this approach, but the results of trials examining viruses such as Epstein-Barr are good so far, in both patients who have no evidence of disease and in those who still have disease,” he said.

Even patients with active disease who have not responded to other therapies have responded to this therapy, Ramos said. He and colleagues are working toward compiling preclinical data to study the possibility of using immunotherapy to treat patients with HPV-related cancers.

Journey is just beginning

Much of what is known about risk, screening, prevention and treatment of HPV-related oropharynx cancers is in the early stages of discovery and much is still theoretical, according to Sturgis.

“As far as we can tell, these infections are transmitted sexually; the hope is that as we have better vaccines for prevention of cervical dysplasia, the downstream effect will help prevent other HPV-related cancers, such as anal cancers and penile cancers and oropharyngeal cancers,” he said.

Several recent studies examining new therapies that may reduce the intensity of traditional treatments while maintaining survival rates would have a major effect on the field, according to Sturgis.

Gillison said the rise in the number of cases of HPV-related cancers is changing the patient population considered to be at risk, and more research is vital.

“The most important thing for clinicians to do is be aware that trials are being developed and strongly encourage their patients to participate,” she said.  Christen Cona

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

June, 2016|Oral Cancer News|