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

Source: www.iflscience.com
Author: Rosie McCall

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

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

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

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

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

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

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

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

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

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

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November, 2018|Oral Cancer News|

A Look at Therapy Toxicities & Biology in Head & Neck Cancers

Source: journals.lww.com
Author: Valerie Neff Newitt

A measure of intrigue and discovery pertaining to head and neck cancer, spiked with compassion for patients struggling against treatment toxicities, helps quench the intellectual thirst of Yvonne Mowery, MD, PhD, Butler Harris Assistant Professor of Radiation Oncology at Duke University Medical Center, Durham, N.C.

Splitting time between the clinic and laboratory, Mowery is actively engaged in patient care as well as preclinical, translational, and clinical research. “I hope to get a better understanding of the biology of head and neck cancer and determine pathways that we can target to reduce metastatic spread of the disease and improve responsiveness to available treatments,” she told Oncology Times.

Long before reaching her current status as an award-winning investigator, Mowery grew up in Richmond, Va., in the midst of a “completely non-scientific” family. “I was an oddball,” she joked, while recalling her parents’ patience with her backyard composting experiments that became so foul-smelling that the health department was contacted. As a kid, her idea of a great present was an encyclopedia of science, and the thing that caught her eye at the toy store was a junior chemistry set.

Science was clearly her path when she headed to the University of Virginia. In her sophomore year, Mowery began working in a genetics lab. That’s where the lure of fruit flies took hold. “I looked at the development of their reproductive system and found that very interesting,” she recalled.

Nearing the completion of her undergraduate education, Mowery debated between attending medical school or graduate school. The eventual winner? Both. “I investigated physician-scientist training programs and arrived at Duke in 2004 to do a combined MD/PhD.” Today, Mowery spends 1 day a week in clinic where she sees patients, then moves to the lab for the remainder of the week to find strategies to improve patient care and develop therapies to deliver better outcomes for patients, both present and future.

Clinical Challenges
“I treat cancers primarily of the head and neck—such as oral cavity, larynx, tonsils, base of tongue, sinuses—with radiation therapy. I think of head and neck cancers as being in a ‘very high-stakes real estate’ area,” she said, “because they are often close to saliva glands, vocal cords, etc. This requires intricate planning for radiation treatment. Visualization of the tumor through fiberoptic laryngoscopy allows me to see a tumor responding to radiation and chemotherapy during the weeks of treatment; it is gratifying to watch it happen with your own eyes.”

Mowery said toxicity associated with treatment of this area of the body can be severe, partially due to the fact that it is typically “…one of the longer courses of radiation that we do—about 7 weeks, 5 days a week,” she explained. “Patients typically require pain medicine to eat and drink a soft diet, lose their sense of taste, and experience very dry mouth, sometimes requiring a feeding tube for nutrition. In addition, the skin on their neck often falls off.” Comparing it to severe sunburn, Mowery said skin typically blisters and peels off, leaving behind a neck that is “red, angry, and very uncomfortable. It just comes with the territory.”

In addition to these side effects, Mowery said there is also an unusual biological aspect to head and neck cancers which figures largely in her work. “Something very interesting scientifically drew me to these cancers,” she informed. “There are two main causes of cancer in this area: tobacco use and human papillomavirus (HPV). Outcomes for patients with HPV-positive oropharynx cancers are excellent; even when the cancer is locally advanced about 80-90 percent of patients are cured. But the tobacco-induced cancers, by contrast, do much worse (about 60% or less survival rate for locally advanced disease). Even if the tumor size is the same and the number of involved lymph nodes are the same, the biology is completely different for the HPV-related and the HPV-unrelated disease.”

In fact, the staging system was changed at the beginning of this year so that HPV-related cancers and HPV-negative cancers are staged differently. “HPV-positive cancers that used to be staged at IVA may now be staged at I or II, but they remain at stage IVA if the cancer is HPV-negative,” Mowery detailed.

Asked why tobacco-related cancer behaves so badly, Mowery answered, “We do not have a good understanding of that; it is something I am studying. We do know, however, that HPV-negative tumors exhibit a loss of function of the p53 gene, [which] is really the king of all tumor suppressors. In HPV-related tumors, p53 is usually genetically still intact but its activity is affected by HPV.”

She also commented that people still actively smoking during treatment tend to do much worse, likely due in part to having lower oxygen levels in the tumor, which in turn causes the radiation to work less effectively. “If we can figure out ways to make HPV-negative tumors behave more like HPV-positive tumors, outcomes would improve.”

From Clinic to Research
These realities on the clinical side have informed and inspired some of Mowery’s research efforts. One of her projects aims at reducing the toxicity of treatment while maintaining good outcomes in patients.

“A clinical trial that I am about to start will use PET/CT, a type of metabolic imaging, as an early litmus test to evaluate how patients are responding during treatment. If we find they are responding well, we will de-intensify and back off on the chemotherapy and radiation dose while still trying to achieve good outcomes,” Mowery explained.

She noted that because HPV-positive and HPV-negative cancers are still treated exactly the same way when not on a clinical trial, investigators also hope to find out if treatment can be de-intensified for the HPV-positive patients who tend to have more successful outcomes by virtue of their cancer type, thus allowing them to avoid some of the severe side effects.

“Of course, even in HPV-positive cancers, not every patient is cured,” cautioned Mowery, “so we want to see if we can identify, early on, who is going to do well and who, in contrast, still needs that full 7-week intensive course of radiation therapy and chemotherapy.”

Another clinical trial ongoing at Duke in which Mowery is involved is testing a drug called BMX-001 given to patients through a subcutaneous injection during radiation. “We hope the drug will reduce the—the inflammation and irritation of the lining of the mouth and throat during radiation—and dry mouth,” she said.

Mowery is also busy in lab with intensive work in developing new mouse models of both HPV-related and HPV-unrelated squamous cell carcinoma of the head and neck. “My objective is to develop a platform in which I can develop radiation with immunotherapy, as well as with chemotherapy and various novel systemic agents, to try to improve outcomes particularly for HPV-negative disease,” noted Mowery, also the winner of a 2017 Conquer Cancer Young Investigator Award. “I want to discover if there are ways that we can make our bodies and our immune system realize that these cells are not ‘self’ and activate the immune system to attack and eliminate them.”

Tobacco-related cancer is induced in mice by giving them a carcinogen present in tobacco, “… causing them to become like a tobacco chewer or smoker,” Mowery explained. “Having that exposure causes mutations in cells in the lining of their mouth.”

Mowery further said her research is taking advantage of large sequencing projects in which various head and neck tumors have been sequenced. These data are publicly available and published primarily by The Cancer Genome Atlas organization. “I have been able to see which genes are most commonly mutated and then can genetically engineer mice to have those mutations. In other words, I can specifically knock out certain genes in the head and neck to model the cancer in mice.”

This is extremely important because it allows Mowery and team to interrogate the biology of the mutations, and determine which genetic changes and pathways lead to the cancer spreading from its site of origin to the lymph nodes or the lungs. “It helps us to develop therapies to block the cancer and keep it at bay, and to determine if there are better ways to sensitize the cancer to radiation and chemotherapy,” she detailed. “And we have an opportunity to test drugs that we hope will help with side effects of radiation. We must make sure that drugs protecting normal tissue are not also protecting the tumor. Having great animal models of human cancer is really important to making progress.”

As if her work in head and neck cancer were not enough, Mowery is continuing an earlier effort begun in the lab of her research mentor David G. Kirsch, MD, PhD, by acting as radiation oncology principal investigator for a multi-site, international prospective randomized clinical trial investigating the combination of the immune checkpoint inhibitor pembrolizumab (anti-PD-1 antibody) and radiation therapy for patients with high-risk soft tissue sarcoma of the extremities. The researchers are also examining the biology behind the effects of radiation combined with pembrolizumab in a co-clinical trial using primary mouse models of sarcoma.

“We saw promising results combining them in this model. Our hope is by using this combination during the early stage of disease we may be able to eliminate those cells that have escaped the primary tumor before they cause a problem.”

Who Has Time for Hobbies?
Asked about her life outside of the clinic and lab, Mowery admitted that little time is left for hobbies. “I used to play tennis, but now I just enjoy watching it,” she said through a chuckle. “I splurged on a Labor Day vacation to the U.S. Open in New York. In my off time, I mostly read and spend time with my family. I am married; my wife is a nurse at Duke working in bone marrow transplant. We have no children.”

But the couple does have the patter of little feet in their midst. “We have two small dogs, Heidi and Cassie, a Maltese and a Maltese Shih Tzu mix—both less than 10 lbs.,” Mowery offered. “We live in downtown Durham, N.C., which is a burgeoning area. It’s kind of cool, and a little bit grungy—but in a good way. I love going for walks and checking out new restaurants. And I love food,” she added brightly.

After a brief pause, Mowery turned her thoughts again to patients. “There is one other clinical trial we’ve recently opened in the head and neck space. We are looking at financial toxicity of patients,” she said. “We are very concerned about the bills patients incur for cancer care and how that affects their quality of life.

“Unfortunately, some people just can’t afford to fill their whole prescription. Some take their drugs every other day because they are worried about cost. Some patients just do not follow through on therapy. We need to get a better sense of how much of that is going on and if there are early warning signs we can detect allowing us to intervene.”

Mowery added that better communications between health care providers and patients are needed to help patients better understand costs they face and identify resources that can help them.

“We just opened this survey-based pilot trial in June. We hope to have data next year and be able to develop a follow-up plan to employ the strategies that we find,” said Mowery. “There are a lot of ways we can try to help our patients.”

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November, 2018|Oral Cancer News|

Forms of tobacco that give you cancer

Source: www.medicalnewstoday.com
Author: Zawn Villines, reviewed by Philip Gregory, PharmD, MS

Nicotine is the primary substance in cigarettes that causes addiction, but most experts agree that it does not directly cause cancer.

Most research points to cigarette smoke, not nicotine, as being the primary contributor to cancer among smokers. However, although most experts agree that nicotine does not directly cause cancer, some research suggests that nicotine may lead to a type of DNA damage that increases the risk of cancer.

Research from 2015 reported in the Indian Journal of Medical and Paediatric Oncology suggests that nicotine may increase the risk of cancer because it might damage DNA, initiate cancer and cause it to progress faster, and interact with cancer-causing chemicals.

Research into the role of nicotine in cancer is ongoing. Many studies, however, do not differentiate between nicotine, tobacco, or smoking when they discuss cancer risk. This makes it difficult to determine which of them causes cancer.

Even if nicotine does cause or lead to cancer, the risks of developing cancer through the use of nicotine-only products are much lower than the risks from smoking.

Methods of consuming nicotine and their safety

Nicotine is addictive and is the primary reason most people smoke. However, almost every other nicotine-based product is safer than smoking. No nicotine replacement product is completely safe for all people, but some of the less harmful alternatives include:

Nicotine replacement therapy
A person with a heart condition should speak to a doctor before undergoing NRT.
Nicotine replacement therapy (NRT) refers to a group of treatments designed to help smokers quit. NRT is available in several forms, each of which delivers nicotine without smoke, tobacco, or other carcinogenic (cancer-causing) chemicals:

The following types of NRT are available over the counter:

  • a patch, which delivers nicotine through the skin
  • chewing gum, which allows a user to chew and swallow nicotine
  • a lozenge, which slowly dissolves and releases nicotine into the mouth

Two additional forms of NRT are available with a prescription:

  • an inhaler, which allows users to take in nicotine in a similar way to inhaling it from a cigarette
  • a nasal spray, which delivers nicotine through the nose

NRT poses some risks. In addition to nicotine’s potential link to cancer, it is also a stimulant. This may make it unsuitable for some people with heart disease or certain heart disease risk factors to use.

However, most people who have a heart condition can use NRT. However, there is a small group of people who should not use NRT, such as those with severe arrhythmia, severe angina, or people who have recently had a heart attack. People should talk to their doctor for individual advice if they are in any doubt about using NRT.

Some people also use NRT as a means of consuming nicotine regularly, instead of for cutting down or quitting, and the long-term effects of NRT are not clear.

A 2010 study in the American Journal of Public Health concludes that the benefits of NRT far outweigh the risks. Researchers specifically state that increasing NRT use could save 40,000 lives per year by preventing heart disease and lung cancer.

Electronic cigarettes
Electronic cigarettes, or e-cigarettes, sometimes called vaporizers or vapes, all work by vaporizing nicotine. The amount of nicotine in each electronic cigarette varies; some even allow users to decide the amount of nicotine they use.

E-cigarettes have been the subject of dozens of safety studies in recent years, often producing conflicting results. A 2013 study found that amounts of nicotine vary with these products and that some may provide dangerously high, or even fatal, levels of nicotine.

Other research, including another 2013 study comparing several e-cigarette brands, found that they may contain toxic chemicals. When e-cigarettes do contain these chemicals, they are generally fewer in number and quantity than in traditional cigarettes.

Despite these risks, most studies agree that e-cigarettes are significantly safer than tobacco or smoking. A 2014 systematic review in the journal Therapeutic Advances in Drug Safety argues that smokers who switch to vaping can expect significant health benefits.

Smokeless tobacco
Researchers have linked chewing tobacco with an increased risk of cancer.
Smokeless tobaccos are chewed or put in the nose. They contain nicotine, as well as a range of other carcinogenic chemicals. According to the American Cancer Society, smokeless tobaccos are safer than cigarettes, but still have links to cancer.

Some types of smokeless tobacco include:

Snus or Swedish tobacco
Snus, sometimes called Swedish tobacco, is a moist powder form of tobacco. The user can suck on or chew the tobacco. Unlike chewing tobacco, people swallow it instead of spitting it out. According to the American Cancer Society, Snus may contain less nicotine than other types of moist tobacco types. However, because it is tobacco, it contains a variety of chemicals that may be carcinogenic.

A World Health Organization (WHO) analysis of previous research argues that snus is unlikely to cause oral or gastric cancer. As a result of this research, the WHO suggest that snus may be an important method of harm reduction.

However, not all research supports this claim. A 2013 case study reported on snus users in Iran who presented with oral cancer. The authors of that study argue that snus and other forms of smokeless tobacco significantly increase the risk of oral cancer. However, this risk appears to vary by region.

Overall the potential risks of snus are unclear.

Chewing tobacco
Chewing tobacco, sometimes called dip, allows a user to chew on or suck tobacco. Some people hold it between their cheeks and gum while tissues in the mouth absorb the nicotine. People then spit it out.

However, the American Cancer Society note that while users consume roughly the same amount of nicotine as people who smoke cigarettes, they also take in lots of dangerous chemicals.

The Society state that there are strong correlations between chewing tobacco and the development of oral cancer, pancreatic cancer, and esophageal cancer, as well as gum disease and other mouth health problems.


Quitting or cutting down on nicotine

Smokeless nicotine products that do not contain tobacco may offer a useful harm reduction strategy for many smokers, and also a way of reducing the side effects of quitting nicotine.

Smokeless nicotine products, such as NRT, provide the most significant benefit. Users should steadily reduce the amount of nicotine they use, or increase the time between each use until they are no longer regularly consuming nicotine and are not experiencing withdrawal or side effect symptoms.

Smokers who are unable or do not want to quit should still consider alternative forms of consuming nicotine. Though not wholly safe, e-cigarettes and vaping offer an experience similar to smoking, but with less exposure to harmful chemicals and an overall reduction in the risk of cancer.

Takeaway

Nicotine is a drug, and no drug can be completely safe — particularly at higher levels of consumption. People with heart disease or heart disease risk factors may be more vulnerable to the adverse effects of nicotine.

It is smoking and the many chemicals it exposes a person to, not nicotine itself, which presents the highest risk. Switching to a nicotine-only product does not remove all likelihood, but it greatly reduces the risk of cancer. People interested in trying these products can consider NRT or vaping, but not smokeless tobacco, as safer alternatives.

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November, 2018|Oral Cancer News|

No De-escalation of Therapy for HPV+ Throat Cancer

Source: www.medscape.com
Author: Alexander M. Castellino, PhD

Another trial has shown that de-escalating therapy does not work in patients with good prognosis human papillomavirus-positive (HPV+) oropharyngeal squamous cell carcinoma or throat cancers.

Results from the De-ESCALaTE HPV study show that using the targeted drug cetuximab with radiotherapy does not improve side effects and, more importantly, has worse survival compared with the standard of care — chemotherapy with cisplatin and radiotherapy.

The finding echoes the results from the US National Cancer Institute’s Radiation Therapy Oncology Group (RTOG) 1016 trial, the top-line results of which were released earlier this year, and details of which were presented this week at the American Society of Radiation Oncology (ASTRO) 2018 meeting.

“Do not change your clinical practice of using cisplatin with radiotherapy in these patients,” cautioned Hisham Mehanna, MBChB, PhD, chair of head and neck surgery at the University of Birmingham, United Kingdom, and lead investigator of the De-ESCALaTe study. He presented the results during a presidential session here at the European Society for Medical Oncology (ESMO) 2018 Congress (abstract LBA9).

“Cetuximab did not cause less toxicity and resulted in worse overall survival and more cancer recurrence than cisplatin. This was a surprise — we thought it would lead to the same survival rates but better toxicity. Patients with throat cancer who are HPV+ should be given cisplatin, and not cetuximab, where possible,” Mehanna said in a statement.

Hope for Fewer Side Effects
Cetuximab with radiation is already approved by the US Food and Drug Administration for use in head and neck cancer, including oropharyngeal cancer, and is an accepted standard of care, especially for patients who cannot tolerate cisplatin.

The hope behind de-escalation of therapy was that this regimen would offer similar efficacy but have fewer side effects than the standard regimen of cisplatin plus radiation.

“The side effects of treatment for patients with head and neck cancers are devastating. They experience loss of speech, loss of taste, and have trouble swallowing,” explained ESMO expert Jean-Pascal Machiels, MD, PhD, head of the department of medical oncology at the Cliniques Universitaires Saint-Luc, Brussels, Belgium.

“With HPV increasing rapidly in the Western world, HPV+ head and neck cancers are typically seen in younger patients who respond well to treatment and live for three to four decades. These patients would like to live without the toxicities associated with treatment,” he added.

“Based on a large study in 2006, many patients have been receiving cetuximab with radiotherapy on the assumption that it was as effective as chemotherapy with radiotherapy and caused fewer side effects,” Mehanna commented. That study showed that for patients with squamous cell carcinoma of the head and neck, treatment with cetuximab and high-dose radiotherapy improved locoregional control and reduced mortality. At the same time, side effects were no worse (N Engl J Med. 2006;354:567-578).

 

OCF NOTE: The foundation’s donors were funders of the RTOG 1016 clinical trial over several years.

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HPV vaccine gains support of ADA

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

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

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

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

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

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

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

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

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

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October, 2018|Oral Cancer News|

Lowering Radiation Dose Could Improve QoL, Cut Costs in Oral Ca

Source: MedPage Today, Medpage.com
Date: October 25th, 2018
Author: Elizabeth Hlavinka

SAN ANTONIO — Radiation de-intensification was tied to a quicker rebound in a number of quality of life (QoL) measures and reduced costs for patients with HPV-associated oropharyngeal cancer, a pair of studies found.

With lower doses of radiotherapy (RT), QoL measures including speech, pain, and socialization still generally worsened after treatment, but returned to baseline within 3 to 6 months, reported Kevin Pearlstein, MD, of the University of North Carolina in Chapel Hill.

And more aggressive de-intensification led to a 22% cost reduction for treatment overall ($45,884 versus $57,845 with standard care), with 33% lower costs for RT itself and 50% lower costs for post-treatment care (P=0.01), according to findings presented by Mark Waddle, MD, of the Mayo Clinic in Jacksonville, Florida.

The studies were presented here at the American Society for Radiation Oncology (ASTRO) meeting during a session on improving outcomes while minimizing toxicity in oropharyngeal cancer.

In the research from Pearlstein’s group, patients reported global QoL scores of 81 at baseline (using the 100-point EORTC QLQ-C30 questionnaire, where higher scores connote better health), which dipped to 69 at 3 months post-treatment, then rose to 75 at 6 months. Global QoL scores increased to 82 and 84 by months 12 and 24, respectively.

Common long-term side effects such as sticky saliva, taste, and ability to swallow did not return to baseline within months 3 to 6, but continued to improve between months 12 and 24. Pearlstein noted that swallowing took longer to return to baseline, typically between 1 to 3 years.

“This highlights the possibility that there can be improvement in these symptoms with longer-term follow-up,” he said.

Although oropharynx cancers associated with HPV generally have a more favorable prognosis compared with those that are not, the treatment is similar for both. As a result, these lower-risk patients still typically experience symptoms of dysphagia, dry mouth, and taste changes for upwards of 1 year after treatment, Pearlstein said.

While standard treatments typically include 70 Gy RT along with 100 mg/m2cisplatin, this study investigated whether patients given 60 Gy RT along with weekly 30 mg/m2 doses of cisplatin would result in improved QoL. Cisplatin-intolerant patients were treated with cetuximab, and patients who could not tolerate either did not receive chemotherapy.

The authors also conducted a multivariate analysis that controlled for type of chemotherapy, gender, and age. Those with with worse baseline symptoms of dry mouth, taste, and sticky saliva were more likely to return to baseline function at 12 months (ORs of 1.06, 1.09, and 1.02, respectively). Similar associations for sticky saliva and swallowing were found among patients who underwent unilateral neck RT.

“One obvious limitation is that we don’t have a direct comparison with standard intensity chemotherapy/radiotherapy,” Pearlstein said. “However, when we view these findings in the context of what we already know for patients with head and neck cancer, we do feel our findings suggest that patients who receive de-intensified chemotherapy/radiotherapy may benefit from faster return to baseline quality of life, continue improvement in symptoms over time, and less long-term morbidity.”

To conduct the study, the researchers collected data from two de-intensification phase II trials that took place from 2012 to 2017. A total of 126 patients were included, a majority of which were ages 60 and over (53%) and were non-smokers (63%). Patients were followed for an average of 25 months.

Cost of Treatment

De-intensification of radiation may also benefit these patients by decreasing total treatment costs, according to an analysis of a prospective phase II study.

“Several studies have or are investigating de-escalation of treatment to reduce toxicity while maintaining outcomes,” Waddle said during his presentation. “However, those studies haven’t investigated the cost of care that may be associated with de-escalation of treatment.”

He reported that the median cost was $17,309 for RT among those who received de-escalated doses compared with $28,161 with standard treatment (P<0.0001). The per-patient costs were $797 versus $933 per month, respectively, in the first 6 months after treatment and $518 versus $611 in the 16 to 24 months after treatment.

Among the post-treatment savings, gastrointestinal-related costs were 79% lower (P<0.01), hospitalization costs were 40% lower, and emergency department visit costs were 90% lower.

This study obtained data from the MC1273 trial, in which 68 patients received aggressive de-escalated doses of RT (30-36 Gy), and then compared the costs to 84 patients treated with standard of care (60-66 Gy). The average patient age was 58.5 years and the majority of them were white men.

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October, 2018|Oral Cancer News|

HPV blood test shows promise for tracking head and neck cancer after treatment

Source: www.eurekalert.org
Author: from UNC Lineberger Comprehensive Cancer Center

A new blood test developed by University of North Carolina Lineberger Comprehensive Cancer Center researchers shows promise for tracking HPV-linked head and neck cancer patients to ensure they remain cancer-free after treatment.

Researchers will present preliminary findings at the 60th Annual Meeting of the American Society for Radiation Oncology in San Antonio on Tuesday, Oct. 23. Their study evaluated a blood test for HPV-linked oropharyngeal squamous cell carcinoma, which is a cancer of the back of the throat. The findings demonstrated the test could be an effective and less costly alternative for monitoring for cancer recurrence after radiation treatment.

“The goal of this study was to evaluate whether this test can be used to track patients who are completely asymptomatic, and thought to have no active cancer,” said UNC Lineberger’s Gaorav P. Gupta, MD, PhD, assistant professor in the UNC School of Medicine Department of Radiation Oncology. “We already knew that our test was very sensitive and specific, but we did not know the degree to which it would be useful in early detection of disease recurrence in patients who are otherwise thought to be disease-free.”

HPV, or the human papillomavirus, is the most common cause of sexually transmitted infection in the United States, according to the U.S. Centers for Disease Control and Prevention. Infection with certain strains of HPV can cause cervical cancer in women, genital cancers in both men and women, and cancer of the oropharynx, which is the back of the throat, including the base of the tongue and tonsils. The CDC estimates that approximately 70 percent of oropharyngeal cancer cases diagnosed in the United States are probably caused by HPV, which accounts for nearly 13,000 cases per year.

Gupta and his colleagues developed a blood test that can detect fragments of HPV’s genetic material that have been released into the blood by dying cancer cells.

“We realized it is important to distinguish HPV DNA that’s being released by dying tumor cells from the natural HPV DNA that is present during a viral infection,” Gupta said. “Our method accomplishes this feat, thus making it a more sensitive and specific test for cancer.”

For their study, the researchers followed 89 patients with HPV-associated oropharyngeal squamous cell carcinoma who received chemotherapy and radiation treatment. They administered the blood test before and during treatment, and then during follow-up visits. The patients received scans three months after treatment, and then came back for clinical exams every two to four months during the first two years, and then every six months in years three through five. Patients received X-rays or CT scans every six months, and again if they had positive HPV results.

“We are detecting subclinical disease with this blood test, and the imaging patients received confirmed those findings,” said UNC Lineberger’s Bhishamjit S. Chera, MD, associate professor in the UNC School of Medicine Department of Radiation Oncology and the study’s co-corresponding author. Chera presented the findings from the study at the ASTRO meeting.

Of the 70 patients whose blood tests were negative three months after treatment, none developed recurrence. Nineteen patients had positive blood tests, and eight of those patients developed recurrence. Physicians are continuing to monitor the remaining eleven who had positive blood tests but no evidence of recurrence.

“The most striking finding of our study is that of the patients who did not have any signal using our blood test, none of them developed disease recurrence,” Chera said. “That raises the question: Do we need to be scanning these patients? Scans come with a lot of cost, and because of the cost, we’re not able to do it as frequently. Patients end up having a lot of anxiety from one scan to the next, wondering if their cancer has come back. This blood test could spare patients the need for additional imaging and potentially alleviate some anxiety.”

The researchers say the next steps will involve investigating whether the test can be used prospectively to monitor patients and to make decisions that could avoid unnecessary imaging, thereby reducing costs. They also see additional applications for the blood test, including monitoring for other HPV-linked cancers, including cervical cancer.

“We are confident this blood test will be translatable to other cancers driven by HPV, and as a monitoring tool for cancer diagnosis,” Chera said. “We strongly believe that this test may also have a role in screening, not just for oropharyngeal cancer, but also cervical or anal cancers, possibly in a general population setting, or at least in patients who may be at higher risk of developing these conditions.”

In addition to Chera and Gupta, other authors include Sunil Kumar, PhD; Colette Shen, MD, PhD; Robert Amdur, MD; Roi Dagan, MD; Jared Weiss, MD; Juneko Grilley-Olson, MD; Adam Zanation, MD; Trevor Hackman, MD; Jeff Blumberg, MD; Samip Patel, MD; Brian Thorp, MD; Mark Weissler, MD; Nathan Sheets, MD; and William Mendenhall, MD.

The study was supported by the University Cancer Research Fund, Burroughs Wellcome Fund, the University of North Carolina School of Medicine Department of Radiation Oncology, UNC Lineberger and the University of Florida School of Medicine Department of Radiation Oncology.

Intellectual property related to the test and held by the University of North Carolina at Chapel Hill has been licensed to Naveris, a company in which Chera and Gupta hold equity stakes.

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October, 2018|Oral Cancer News|

University of Cincinnati researcher studies cancer-detecting mouthwash with help from ACS grant

Source: healthnews.uc.edu
Author: staff

Scott Langevin, PhD, assistant professor in the Department of Environmental Health and a member of both the Cincinnati Cancer Center (CCC) and UC Cancer Institute, was recently awarded $782,000 from the American Cancer Society to continue his research, which will hopefully assist in use of a certain oral rinse to catch recurrence of these types of cancers in their earliest stages.

He originally received a National Cancer Institute K22 award to begin this study.

“In 2017, mouth and throat cancer, otherwise known as oral and pharyngeal cancer, accounted for an estimated 49,670 new cancer diagnoses and 9,700 cancer-related deaths in the US, and the outcomes for patients with this cancer is relatively poor. About half of these patients will have cancer recurrence within 2 years of treatment,” Langevin says. “Earlier detection of recurrent tumors is associated with better clinical outcomes, so there is a clear need for new tests that can help facilitate early detection.”

Langevin says that researchers in his lab previously identified a biomarker panel made up of 22 regions of DNA; based on the amount of a certain molecule attached to these regions—a process called DNA methylation—scientists could identify the presence of mouth and throat cancer with a high level of accuracy by using noninvasive oral rinse (mouthwash) samples.

“With this project, we hope to evaluate the potential of this oral rinse methylation panel as a clinical tool for early detection of cancer recurrence following diagnosis and treatment,” he says. “This will hopefully help us develop a new test that can reduce the impact of these cancers.”

Langevin adds that his team will take a deep look into methylation within the tumors themselves to enhance understanding of the prevalence and extent of these alterations in mouth and throat cancers.

“Facilitated by my clinical co-investigators, Dr. Trisha Wise-Draper and Dr. Alice Tang, we will identify and recruit a cohort of patients who have been diagnosed with mouth and throat cancers and will regularly collect oral rinse samples, roughly every 3 months for 2 years, following their initial diagnosis and treatment,” he says. “Our team will catalog the methylation patterns across the 22 regions that make up our biomarker panel and document how they impact gene expression by applying DNA and RNA sequencing techniques on matched tumor and normal tissue from mouth and throat cancer patients.”

Langevin says his team will assess the potential use of the oral rinse methylation panel as a tool for early detection of cancer recurrence during the first 2 years of post-treatment patient follow-up.

“This has clear clinical relevance and could serve as a beneficial tool for early detection and subsequent early intervention of these very serious cancers, potentially improving outcomes for patients,” he says.

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October, 2018|Oral Cancer News|

Patients with HPV-positive oropharynx cancer should receive chemoradiation

Source: medicalxpress.com
Author: provided by European Society for Medical Oncology

Patients with human papilloma virus (HPV)-positive throat cancer should receive chemoradiotherapy rather than cetuximab with radiotherapy, according to late-breaking research reported at the ESMO 2018 Congress in Munich.

“Many patients have been receiving cetuximab with radiotherapy on the assumption that it was as effective as chemotherapy with radiotherapy and caused less side effects but there has been no head-to-head comparison of the two treatments,” said study author Prof Hisham Mehanna, Chair, Head and Neck Surgery, Institute of Cancer and Genomic Sciences, University of Birmingham, UK.

Throat cancer is rapidly becoming more common in Western countries. For example in the UK, incidence was unchanged in 1970 to 1995, then doubled in 1996 to 2006, and doubled again in 2006 to 2010.The rise has been attributed to HPV, a sexually transmitted infection. Most throat cancer was previously caused by smoking and alcohol and affected 65-70 year-old working class men. Today HPV is the main cause and patients are around 55, middle class, working, and have young children.

HPV-positive throat cancer responds well to a combination of cisplatin chemotherapy and radiotherapy, and patients can survive for 30-40 years, but the treatment causes lifelong side effects including dry mouth, difficulty swallowing, and loss of taste. Patients deemed unable to tolerate chemotherapy, for example because of poor kidney function or older age, receive cetuximab, an epidermal growth factor receptor (EGFR) inhibitor, and radiotherapy.

This study compared side effects and survival with the two treatments in 334 patients with HPV-positive throat cancer enrolled from 32 centres in the UK, Ireland, and the Netherlands. Patients were randomly allocated to radiotherapy and either cisplatin or cetuximab. Eight in ten patients were male and the average age was 57 years.

During the two-year study there were ten recurrences and six deaths with cisplatin compared to 29 recurrences and 20 deaths with cetuximab. Patients on cisplatin had a significantly higher two-year overall survival rate (97.5%) than those on cetuximab (89.4%; p=0.001, hazard ratio [HR] 4.99, 95% confidence interval [CI] 1.70-14.67). Cancer was over three times more likely to recur in two years with cetuximab compared to cisplatin, with recurrence rates of 16.1% versus 6.0%, respectively (p=0.0007, HR 3.39, 95% CI 1.61-7.19).

There were no differences between groups in the overall number of side effects, or of acute or late severe (grade 3-5) toxic events including dry mouth and difficulty swallowing. There were significantly more serious adverse events such as renal and haematological problems with cisplatin than with cetuximab.

Mehanna said: “Cetuximab did not cause less toxicity and resulted in worse overall survival and more cancer recurrence than cisplatin. This was a surprise—we thought it would lead to the same survival rates but better toxicity. Patients with throat cancer who are HPV positive should be given cisplatin, and not cetuximab, where possible.”

Commenting on the study for ESMO, Dr. Branislav Bystricky, Head, Medical and Radiation Oncology Department, University Hospital Trencin, Slovakia, said: “It was believed that cetuximab causes less side effects and was therefore a good option for HPV-positive throat cancer patients who are young and expected to survive for several decades, as well as those less able to tolerate chemotherapy. This study shows that the best treatment choice for patients with HPV-positive throat cancer is cisplatin and radiotherapy. This combination gives ‘double’ the benefit since it is more effective in terms of survival and does not worsen all grade toxicity compared to cetuximab with radiotherapy.”

Bystricky noted that the results were in agreement with interim findings of the US National Cancer Institute’s RTOG 1016 trial, which is scheduled to report this month. He said: “We now have two studies showing that these patients should not be given cetuximab. Future research should examine whether genotyping for the KRAS-variant can select a group of patients that will benefit from cetuximab treatment with radiotherapy.”

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October, 2018|Oral Cancer News|

A case for second opinions in cancer care

Source: healthblog.uofmhealth.org
Author: Beth Uznis Johnson

Jim Sitko expected minor surgery to remove a small lesion that his dentist discovered under his tongue during a routine checkup in July 2017.

An oral surgeon near his home in Clarkston, Michigan, took several samples to biopsy, a procedure that left Sitko’s tongue badly damaged. Resulting pain left the patient barely able to swallow for more than a week.

And the pathology report revealed devastating news: squamous cell carcinoma of the tongue.

Treatment, Sitko was told, would include major surgery to remove a portion of his tongue and rebuild it with veins and tissue from other parts of his body. Rehabilitation would be extensive and might also require radiation therapy once the patient healed.

Because he had received successful treatment for prostate cancer six years earlier at the University of Michigan Rogel Cancer Center, Sitko opted to return and meet with surgeon Steven Chinn, M.D., MPH.

Sitko’s mouth was still healing from his initial surgery, so Chinn relied on the outside pathology report to prep for the complicated surgery ahead. He ordered additional pathology testing by Rogel Cancer Center head and neck specialists — an essential step to confirm an advanced cancer diagnosis.

Meanwhile, the thought of having tongue cancer overwhelmed Sitko.

“The complications aside from taking care of the cancer were unbelievable,” the 70-year-old says. “I might have a breathing tube and feeding tube. I took a retreat to my condo in northern Michigan to review 25 pages of paperwork for two clinical trials, but I did not quality.”

Sitko and his wife, Jane, a master gardener, had been planning a 50th anniversary celebration in Vancouver and Victoria, British Columbia, world-renowned for its gardens. Because of his tongue cancer diagnosis, the couple canceled their plans.

But everything changed for the better one month later when Sitko and Chinn were preparing for surgery.

A second opinion and ‘tears of joy’
During the first of five preoperative meetings, Chinn was able to examine Sitko’s mouth, which had healed remarkably well for a person with tongue cancer.

Chinn called for Sitko’s prior pathology labs from the outside hospital for a careful review and comparison with the new results from the U-M pathology lab.

“My years of training taught me be thorough and make sure you are working with the best information possible,” says Chin, an assistant professor of otolaryngology at Michigan Medicine. “As part of my standard of care, I make sure all pathology is reviewed by head and neck specialists here at U-M.

“This is what makes our head and neck oncology program one of the best in the world.”

Sitko and Jane had again retreated to their northern Michigan condo. They were just unpacking their bags when a phone call with good news from Chinn came.

“He told me with cautious optimism that he saw no cancer in the pathology report but needed to verify with new samples taken at U-M,” Sitko says. “We agreed I’d go in on my scheduled surgery date. I would be in the surgical suite for an hour or 12 hours, depending on what they found.”

To begin, Chinn took three additional section samples for biopsy. Pathology results found no cancer.

Chinn took two more samples. No cancer.

He then used laser treatment to remove abnormal, non-cancerous cells from Sitko’s tongue. Surgery was over.

“We were in tears of joy,” Sitko says. “I am certainly indebted to U-M and specifically Dr. Chinn and the manner he handled my case. He could have done the complete surgery and I never would have known I didn’t have cancer.”

Life after a cancer scare
In hindsight, Sitko sees that his original tongue surgery did far more damage to his tongue than necessary.

It still surprises him that he was able to stop to eat dinner and have a beer after his surgery by Chinn. He experienced none of the discomfort.

Over the past year, he and Jane have resumed their normal retirement activities, including golfing, biking, hiking and snow skiing. They also rescheduled their wedding anniversary trip.

“We decided to kick off with a trip out East, where we spent our honeymoon,” Sitko says. “We went to Bar Harbor, Acadia National Park, Nova Scotia and New Brunswick. We drove 2,900 miles in 11 days, going from hotel to hotel.

“It was like revisiting our honeymoon 50 years later.”

Because of the abnormal non-cancerous cells found on his tongue, Sitko continues to see Chinn for follow-up and monitoring. There have been so signs of cancer.

A careful, specialized approach has guided treatment throughout.

“Having a team that’s only focus is head and neck cancer is critical to making the right diagnosis and management in a complex disease,” Chinn says. “In this case, when there was a discrepancy between the outside report and our review, I felt it prudent to do additional biopsies to make sure the initial one wasn’t a sample error and that we were, in fact, missing an advanced stage cancer.”

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October, 2018|Oral Cancer News|