Management strategies for oral potentially malignant disorders

Author: Joel M. Laudenbach, DMD

Oral potentially malignant disorders (OPMDs) include oral leukoplakia (OL), oral erythroplakia, oral submucous fibrosis, oral lichen planus, proliferative verrucous leukoplakia, and actinic keratosis. Once an OPMD has been clinically diagnosed, execution of management strategy is critical. When formulating the strategy, healthcare providers should consider histopathology, lesion characteristics (ie, surface texture, unifocal, multifocal), lesion location in the mouth (ie, tongue, floor of mouth), patient risk factor assessment, and a detailed medical/cancer history.

In this newly published article, Nadeau and Kerr[1] detail various parameters surrounding evaluation and management of OPMDs. The authors make it clear that OPMDs are challenging, each with their own nuances regarding risk for malignant transformation. For example, when OL is unifocal, nonhomogeneous, nodular, or verrucous, there is a much higher chance of the OL becoming dysplastic (12.63-fold) or demonstrating a focus of carcinoma (8.9-fold) when compared with homogeneous types of OLs.[1]

Provider knowledge of these variables is critical when counseling patients about their diagnosis and management options and when selecting interventions along with follow-up care. Although progression to malignancy is difficult to predict with OPMDs, clinicians can account for multiple risk factors such as smoking/alcohol status, high-risk location in the oral cavity, and size of lesion (>200 mm2) to help formulate a tailored management plan for each patient. Consultation with an oral pathologist to discuss the histologic appearance in the context of specific patient history and lesion characteristics can provide additional perspective and/or recommendations.

Modifiable oral cavity cancer risks related to tobacco and heavy alcohol use should be communicated to patients with OPMDs so that they are able to make changes that may lead to regression/disappearance of certain lesions such as OL. Providers confronted with patients who use tobacco and/or heavy alcohol can integrate recommendations for cessation of tobacco[2] and alcohol[3] because they are both established, independent, causative agents for oral cavity cancer and OPMDs.

Available treatment strategies for OPMDs include surgical removal/ablation, photodynamic therapy, and surveillance. The authors make a clear point with supportive studies that traditional surgical excision of dysplastic OPMDs may decrease malignant transformation (MT) risk, yet it does not fully eliminate that risk and, in some instances, has not changed the MT risk when compared with surveillance alone. Appropriate surgical margin identification for OPMDs is clinically challenging. The authors note that smaller excisional margin sizes (1-2 mm) without marginal histologic assessment are common surgical management goals for OPMDs.[1]

Nadeau and Kerr carefully outline updated considerations for all OPMDs. Healthcare providers involved in screening, diagnosing, referring, and/or managing patients with OPMDs should be well versed in standards of care, including baseline biopsy goals, tobacco/alcohol cessation, currently available interventions, and surveillance care.

Clinicians should also develop a local team of practitioners who are experts in diagnosis and management of OPMDs to help patients obtain the best opportunity for positive outcomes. I encourage readers with interest to retrieve and review the full article by Nadeau and Kerr as a strategy to update your knowledge base and to continue to improve overall morbidity, mortality, and survival rates related to OPMDs.

1. Nadeau C, Kerr AR. Evaluation and management of oral potentially malignant disorders. Dent Clin North Am. 2018;62:1-27.

2. US Preventive Services Task Force. Final recommendation statement. Tobacco smoking cessation in adults, including pregnant women: behavioral and pharmacotherapy interventions. September 2015. Accessed March 1, 2018.

3. US Preventive Services Task Force. Final recommendation statement. Alcohol misuse: screening and behavioral counseling interventions in primary care. May 2013.
/RecommendationStatementFinal/alcohol-misuse-screening-and-behavioral-counseling-interventions-in-primary-care Accessed March 1, 2018.

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March, 2018|Oral Cancer News|

Author:Pam Harrison
Date: March 5, 2018

So called “liquid biopsies” — which can detect circulating tumor DNA (ctDNA) in blood samples — are not yet ready for prime time in the diagnosis or management of early-stage or advanced solid tumors, a new expert review concludes.

These assays are also not useful, outside of clinical trials, for monitoring patients for minimal residual disease following definitive treatment of cancer, nor for cancer screening, the expert review concludes.

The review was prepared jointly by the American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) and was published online March 5 in the Journal of Clinical Oncology.

“This is an area of great interest to both pathologists and oncologists, [and] it’s also an area where we see a lot of commercial advertisement and a lot of enthusiasm from the public,” Jason Merker, MD, PhD, cochair of the expert panel, who was representing the CAP, said in a statement.

“We thought it was a good time to look at the literature and take an evidence-based approach to various uses for ctDNA assays,” he added.

“Like all new things in medicine, the use of ctDNA assays in routine cancer care requires evidence of clinical utility. At present, there is insufficient evidence of clinical validity and utility for the majority of ctDNA assays in advanced cancer, including those that interrogate a panel of genes,” said Daniel F. Hayes, MD, coauthor of the review, who was representing ASCO.

“What is promising is that this area of research is rapidly evolving, so there should be enough evidence soon to formulate evidence-based guidance for a variety of clinical scenarios,” Hayes suggested.

Review Based on Literature Review

For the review, panel members identified 77 relevant articles in the literature. They limited their analysis to variants in ctDNA for solid tumors and to sequence or copy number variants in DNA.


They assessed overall evidence of the ability of a test to reliably detect the variant or variants of interest (analytic validity); whether a test accurately detects the presence or absence of a pathologic state or predicts outcomes for patients (clinical validity); and whether the use of the test improves patient outcomes compared with not using it (clinical utility).

The authors focused largely on the use of ctDNA assays in the setting of metastatic cancer, because that is the area for which there is most evidence. Much less research supports the use of liquid biopsy in other settings.

Advanced Cancer

“Fundamentally, there are two paradigms to demonstrate clinical utility and the adoption of ctDNA as a clinically useful test,” the panel members write.

The most reliable strategy is to conduct a prospective clinical trial designed to evaluate how well the test performs as a stand-alone diagnostic test. However, no such trial has yet been carried out, they write.

The second approach is to assess whether the ctDNA test in question delivers the same information that physicians would seek through tissue genomic evaluation.

“[D]emonstrating that a ctDNA assay has high agreement with tumor tissue genotyping may provide sufficient evidence of utility for ctDNA assays in driving patient treatment decisions,” the panel members explain.

They go on to document how far short ctDNA assays fall with respect to meeting this high level of agreement.

First, only one polymerase chain reactin–based ctDNA test has been approved by the US Food and Drug Administration and the European Medicines Agency. That test is the COBAS assay for the detection of EGFR genetic variants in non–small cell lung cancer (NSCLC).

Another assay is available in Europe for the detection of the KRAS mutation in colorectal cancer (CRC).

“These assays have demonstrated clinical validity but the clinical utility in this setting is based on retrospective analyses,” the panel members point out.

Even in light of these approvals, the panel members note that physicians should continue to rely on tissue sample analysis if nothing is detected on ctDNA testing.

They also point out that ctDNA levels may drop while a tumor is still responding to treatment, and as a result, the sensitivity of the test may be compromised.

As for tumor types other than NSCLC and CRC, there is limited evidence to support the clinical validity of ctDNA analysis, the panel members conclude.

The clinical utility of assays developed for the detection of other potentially targetable variants, such as BRAF in melanoma, is not yet established, they add.

Further confounding the diagnostic potential of ctDNA testing is the fact that advanced cancers may be “genetically heterogeneous.”

Although ctDNA tests may be able to pick up subclonal variants in cancer, these variants may not predict how well patients will respond to treatments that theoretically target the variant.

“[S]ubclonality may undermine the clinical utility of ctDNA assays,” the panel members state.


Monitoring Response to Therapy

Ideally, liquid biopsies could help physicians monitor patients’ response to treatment, as some tumor-associated proteins now enable them to do.

This, too, remains a challenge, because quantifying changes in ctDNA over time is not as simple as determining whether or not a variant is present. Nor has the best unit by which to measure DNA burden been established.

“Correlations between changes in ctDNA levels and tumor responses or outcomes have been demonstrated in small proof-of-principle studies in a variety of cancer types,” the panel members acknowledge.

“However, currently there is a lack of rigorous evidence on clinical validity, let alone clinical utility, because few large, prospective validation studies have been performed on ctDNA-based monitoring,” they conclude.


Use to Monitor Residual Disease

Researchers expressed hope that after curative treatment of a solid tumor, ctDNA assays could be used to monitor patients for minimal residual disease, much as is done in hematogic malignancies using assays to detect leukemic cells in blood following completion of chemotherapy.

However, there is not enough evidence to support the ability of ctDNA tests to detect low levels of minimal residual disease in a manner similar to assays used in the management of diseases such as leukemia, the panel members conclude.

Moreover, “[t]he false-negative rate of ctDNA analysis in…patients who relapse without ctDNA being detected and the false-positive rate [in] patients who do not relapse despite the ctDNA assay being positive have not been established sufficiently for any assay,” they caution.

There is also no evidence that treatment based on detection of ctDNA improves patient outcomes, a major metric of clinical validity.

Screening for Cancer

In an ideal world, ctDNA tests could be used in the early detection of cancer in patients who have no signs of disease.

However, the feasibility of using ctDNA tests to screen asymptomatic individuals has not been demonstrated.

“[D]iagnosing the presence of cancer in a patient without cancer, and determining tissue of origin, have not been established,” the authors point out.

There is also a risk that such tests might be positive for cancers in cases in which none exists and thus lead to overdiagnosis. Currently, overdiagnosis is a major problem with, for example, mammography in breast cancer and prostate-specific antigen screening for prostate cancer, the panel members observe.

Dr Merker has served as a consultant to or in an advisory role for Bio-Rad Laboratories, Rainbow Genomics, and Genoux and has received patents or royalties or has other intellectual property in the measurement and monitoring of cell clonality. Dr Hayes owns stock or has other ownership interests in OncImmune and InBiomotion and has served as a consultant or as an advisor to Cepheid. He has also received research funding, mostly for his institution, from AstraZeneca, Puma Biotechnology, Pfizer, Eli Lilly, Merrimack Pharmaceuticals, Parexel, and Menarini Silicon Biosystems (aka Veridex/Johnson & Johnson). He also holds a number of patents and receives royalties for some of them.



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March, 2018|Oral Cancer News|

Experts reveal why men are four times more likely to get cancer from oral sex than women

Author: Sofia Petkar

Men are four times more likely than women to be diagnosed with oral cancer, as studies suggest a lower immune system could be behind this. Research has found men who perform oral sex on their female partners have a higher than average chance of developing an oral cancer triggered by the human papilloma virus (HPV).

While sexual norms and fewer inhibitions have played a role in this alarming trend, scientists now say the male immune system is the real problem. Research has found that compared with women, men are more likely to be infected with HPV and its “high-risk” cancerous strains. Men are also less able to get rid of the infection through the body’s natural defences, harbouring the virus for longer periods of time.

Ashish A. Deshmukh, a University of Florida HPV researcher, said: “There is good evidence that men acquire oral infections more readily than women, even if they have similar sex practices.

“And more than the acquisition, it’s the persistence of the virus.

“The clearance rate is not that fast in men.”

Traditionally, smoking and heavy alcohol usage were seen as the big risk factors for oral cancer. However, studies have shown that non-HPV tumours linked to these bad habits has declined significantly in recent years. In stark contrast, HPV-related tumours have increased more than 300 per cent over the last 20 years, with the virus now found in 70 per cent of all new oral cancers.

In 2013, Michael Douglas hit the headlines when he blamed his throat cancer on oral sex. The 72-year-old actor said he believed his cancer was triggered by the HPV virus, which he says he contracted after performing oral sex.

While many ridiculed his theory, experts say there is growing evidence to support his claims. The human papillomavirus (HPV) is a very common sexually transmitted disease which affects at least half of people who are sexually active. The STD is the most widespread worldwide and four out of five of the population will contract some form of the virus at least once in their life.

The types of HPV found in the mouth are almost entirely sexually transmitted, so oral sex is seen as the primary route of contracting them. In most cases, the body’s immune system will fight off the virus and there won’t be any need for further tests, in fact, some people may not even know they contracted it at all.

The HPV infection affects the skin and mucosa (any moist membrane, such as the lining of the mouth and throat, the cervix and the anus).

Dentists have warned that dating apps such as Tinder are putting more people at risk of catching HPV passed on by oral sex. The British Dental Association said: “Data used to model sexual behaviour are out of date, and factors such as the recent introduction of dating apps may have led to significant changes in behaviour over the last few years, which have not been taken into account.”

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March, 2018|Oral Cancer News|

Australia may become the first country to eliminate one form of cancer

Author: Brad Jones
Date: March 8, 2018

The International Papillomavirus Society has announced that Australia could become the first country to eliminate cervical cancer entirely.

According to a new study, Australia’s efforts to distribute a human papillomavirus (HPV) vaccine for free in schools have been a resounding success. The sexually transmitted infection causes 99.9 percent of cases of cervical cancer.

In 2007, the Australian federal government began offering the vaccine to girls aged 12-13, and in 2013 it was made available to boys, too. Girls and boys outside of that age bracket but under nineteen are also entitled to two free doses of the vaccine.

Between 2005 and 2015, the percentage of Australian women aged between 18 and 24 who had HPV dropped from 22.7 percent to just 1.1 percent. Immunization rates have increased further since 2015, contributing to what’s being described as a “herd protection” effect.

Coupled with a more advanced screening test that was introduced by the Australian government in December 2017, there are hopes that no new cases of cervical cancer will be reported within ten or twenty years.


In the US, the HPV vaccine is not free. It can cost as much as $450 for the full regimen, according to the Association of Reproductive Health Professionals, although financial assistance is often available. In 2016, 78.6% of 15-year-old Australian girls, and 72.9% of 15-year-old Australian boys were vaccinated – but only 50% of American girls between 13 and 17, and 38% of American boys between 13 and 17 had received the vaccination, as per data published by the Henry J. Kaiser Family Foundation.

The situation is much worse in the developing world, where papillomavirus incidence rate remains high. “Two-thirds of the world’s population of women don’t get access to what Australian women do,” said Joe Tooma, the chief executive of the Australian Cervical Cancer Foundation. “Unless we do something, it will still be one of the major cancer killers in developing countries.”

Administering the HPV vaccine in schools has also proven to be effective in a trial that took place in Bhutan. Offering this kind of free access to the vaccine in other developing countries may seem like an expensive measure, but as the Australian example shows, it could ease the burden of cervical cancer down the line.


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March, 2018|Oral Cancer News|

Non-smokers with oral precancerous lesions at increased risk of cancer

Author: press release

Precancerous lesions in the mouths of non-smokers are more likely to progress to cancer than those in smokers, new research from the University of British Columbia has found.

Although tobacco use is still one of the strongest risk factors associated with mouth cancers, UBC dentistry PhD candidate Leigha Rock found that oral precancerous lesions in non-smokers are more than twice as likely to progress to cancer. Furthermore, lesions in non-smokers progressed to cancer faster than smoking-associated lesions. The study was published this week in Oral Oncology.

“This is the first published study where the main focus was to examine the difference in risk of progression to oral cancer between non-smokers and smokers with oral precancerous lesions,” said Rock, lead author of the study. “While other studies have also reported a higher rate of transformation among non-smokers, we looked at multiple risk factors including genetic markers.”

Rock and colleagues looked at case history of 445 patients with oral epithelial dysplasia (OED), a type of precancerous oral lesion, enrolled in the B.C. Oral Cancer Prediction Longitudinal study. One-third of the patients were non-smokers.

“As smoking rates decline, we are seeing an increase in the proportion of these types of lesions in non-smokers,” said Rock.

Among the scientists’ findings were that lesions on the floor of the mouth in non-smokers were 38 times more likely to progress to cancer than in smokers. The study is also the first to report on quicker progression to cancer in non-smokers: both three-year and five-year rates of progression were seven per cent and 6.5 per cent higher than smokers, respectively.

The researchers suggest that the marked difference in outcomes is due to a difference in the root causes of the lesions. In smokers, the OED is likely the result of environmental factors, whereas in non-smokers, genetic susceptibility or mutations are likely to blame.

“Our findings show that molecular genomic markers can identify high risk lesions, regardless of risky habits like smoking, and should be an important consideration in patient management,” said Rock.

The study’s results stress the importance of taking oral lesions seriously, especially when they occur in non-smokers: “If you see a lesion in a smoker, be worried. If you see a lesion in a non-smoker, be very worried. Don’t assume it can’t be cancer because they’re a non-smoker; our research indicates non-smokers may be at higher risk.”

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March, 2018|Oral Cancer News|

HPV is causing an oral cancer epidemic in men by outwitting natural defenses

Author: Marie McCullough, staff writer

Five years ago, when actor Michael Douglas candidly revealed that his throat cancer was linked to having oral sex, two things happened.

He made headlines that mortified his family. And he helped publicize the fact that a pervasive, sexually transmitted virus called HPV was unleashing an epidemic of oral cancer among men.

Since then, scientists have made headway in figuring out why HPV, the human papillomavirus, has this glaring gender bias. Men are four times more likely than women to be diagnosed with oral cancer, a hard-to-detect, hard-to-treat disease that has overtaken cervical cancer as the most common HPV-related malignancy in the United States.

To be sure, changes in sexual norms over the last few generations have played a role in this alarming trend. But research increasingly shows the real problem is something men have practically no control over: their immune response.

Compared with women, men are more likely to get infected with HPV — including “high-risk” cancer-causing strains. They also are less able to wipe out infection on their own, and more likely to get reinfected. The reasons are unclear.

“There is good evidence that men acquire oral infections more readily than women, even if they have similar sex practices,” said Ashish A. Deshmukh, a University of Florida HPV researcher. “And more than the acquisition, it’s the persistence of the virus. The clearance rate is not that fast in men.”

Michael Becker of Yardley has stepped up as the face of this immunological inequity. The 49-year-old former biotech executive is health-conscious, clean-living, happily married for 26 years – and battling terminal oropharyngeal cancer, the medical term for malignancies in parts of the mouth and throat.

He’s also battling the misconceptions and ignorance that keep too many parents from protecting their pubescent children — especially boys — against HPV-driven cancers. Two shots. That’s all it takes for the leading vaccine, Gardasil, to prevent most cervical cancers, less common genital malignancies, and the disease that is killing Becker.

“I can’t tell you how many emails I got from parents after the CBS segment,” he said, referring to a national television interview last month. “They said, ‘What do you mean this vaccine is for boys?’ and ‘What do you mean oral cancer incidence has eclipsed cervical cancer?’ ”

An inescapable virus
HPV is a family of more than 100 virus types that can live in the flat, thin cells on the surface of the skin, cervix, vagina, anus, vulva, penis, mouth, and throat. The virus is spread through contact with infected skin, mucous membranes, and bodily fluids. Some types can be passed during intercourse or — as Douglas pointed out — oral sex. While virtually all sexually active people will get infected at some point, the virus is usually wiped out by the immune system without so much as a symptom.

But not always.

In the cervix, persistent infection with high-risk HPV types can lead to precancerous changes that, left alone, slowly turn malignant. Fortunately, the Pap smear enables the detection and removal of abnormal cells before cancer develops. What’s more, age-related changes in cervical cells reduce the risk that HPV will take hold there as women get older.

No such screening test exists for oropharyngeal sites – the tongue, soft palate, tonsils, the throat behind the nasal cavity – and symptoms usually don’t appear until cancer is advanced. Becker, for example, had metastatic disease by the time he noticed a lump under his jaw line in late 2015.

Traditionally, smoking and heavy alcohol use are the big risk factors for oral cancer, but the non-HPV tumors linked to these bad habits have been declining in recent years. HPV-related tumors, in contrast, have increased more than 300 percent over the last 20 years. The virus is now found in 70 percent of all new oral cancers.

About 13,200 new HPV oral cancers are diagnosed in U.S. men each year, compared with 3,200 in women, according to federal data. Treatment — surgery, chemotherapy, radiation — can have disfiguring, disabling side effects. About half of late-stage patients die within five years.

Natural defenses go awry
Oral HPV infection rates are skewed by gender, just like the resulting cancers. The latest national estimates of this disparity, published in October, come from Deshmukh and his University of Florida colleagues. They used a federal health survey that collected DNA specimens to estimate that 7.3 percent of men and 1.4 percent of women have oral infections with high-risk HPV types. That translates to 7 million men and 1.4 million women.

The chance of oral infection increases for women as well as men who have simultaneous genital HPV infections or a history of many sex partners, but male infection rates still far surpass female rates.

Patti Gravitt, an HPV researcher at George Washington University, believes these estimates are a bit oversimplified because women counted as uninfected may actually have undetectably low virus levels, or HPV may be hiding in a dormant state in their cells.

Still, Gravitt said the study is in line with others that suggest “men are more susceptible to HPV viral infection than women.”

In women, an HPV infection usually sets off the body’s defense mechanisms. The immune system makes antibodies that kill off the invader, then immune cells remain on guard, ready to attack if the virus reappears.

But in men, something goes awry. The HIM study — for HPV in Men — documented this by collecting genital, anal, and oral samples from 4,100 unvaccinated men in Florida, Mexico and Brazil between 2005 and 2009. The samples were tested for the presence of two high-risk HPV types and two that cause genital warts.

Among 384 men who developed infections during a 24-month period, only 8 percent produced antibodies. But this response rate varied depending on the site of infection; none of the small number of orally infected men produced antibodies.

Rather than putting the immune system on guard and protecting men from the virus, infection sharply increased the chance of getting infected again with the exact same HPV type. And many men who got reinfected were celibate at the time.

How could this be? Anna R. Giuliano, the researcher at the Moffitt Cancer Center in Tampa, Fla., who led the HIM study, said recurring infections may be due to reactivation of dormant virus, or to auto-inoculation – the man spreads infection from one part of his body to another. Or to something else entirely.

While the scientific understanding of this puzzle is evolving, one implication is clear. “HPV vaccination is the only reliable method to ensure immune protection against new HPV infections and subsequent disease in males,” Giuliano and her co-authors declared in a recent paper.

Becker hammers that message – when he is not being hammered by chemotherapy – using his self-published memoir and his blog. This week’s blog gave a shout-out to Sunday’s first-ever International HPV Awareness Day, declared by Giuliano and other members of the International Papillomavirus Society.

Becker realizes that the novelty of the vaccine, the complexity of HPV, and its link to sex are obstacles to immunization. But he focuses on the life-saving aspect.

“Parents are being asked to vaccinate their 11-year-old child and they can’t imagine 30 or 40 years down the line, it will prevent cancer,” Becker said. “If you don’t know it’s connected to six cancers, you’re not going to care. So it really should be cast as an anti-cancer vaccine.”

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March, 2018|Oral Cancer News|

Immunotherapy: beyond melanoma and lung cancer treatment

Author: David Crow
Date: March 4, 2018
In the late 1800s, William Coley, a surgeon in New York, developed what scientists now think was the first cancer immunotherapy.

Coley noticed one of his patients, Fred Stein, had started recovering from cancer after catching a serious infection. The observation made him wonder whether the bacteria had somehow stimulated the patient’s immune system and recruited the body’s natural “resisting powers” in the fight against Mr. Stein’s tumours.

The surgeon began treating inoperable cancer patients with bacterial injections — known as “Coley’s toxins” — and recorded some success, but his poorly documented findings were dismissed by contemporaries who favoured radiation and chemotherapy.

Mr. Coley died in 1936 and his theories were all but forgotten: it would take almost 80 years for oncologists to take cancer immunotherapy seriously.

Today, immunotherapies are among the world’s best selling drugs and they have dramatically improved the survival prospects for some of the sickest patients, especially those with melanoma and lung cancer.

“Immunotherapy is here to stay,” says Jill O’Donnell-Tormey, chief executive of the Cancer Research Institute. “It’s not just a blip, it’s not overhyped — I think it is going to become the standard of care for many cancer types.”

The most common immunotherapy drugs are known as checkpoint inhibitors, which work by removing brakes in the immune system so the body can attack cancer.

Their discovery was made possible by the research of James Allison, now a professor at the MD Anderson Cancer Center in Texas, who spent the 1990s and early 2000s working on immunotherapy even as many other scientists dismissed it as an intriguing but futile sideshow.

60 percentage of advanced melanoma patients who survive three years when they take a combination of two checkpoint inhibitors Checkpoint inhibitors have proven remarkably effective in people with advanced melanoma, a disease once known as the “cancer that gave cancer a bad name” because it had such a terrible prognosis, with most patients dying within three to 18 months.

Today, almost 60 per cent of advanced melanoma patients survive three years if they take a combination of two checkpoint inhibitors, both made by Bristol-Myers Squibb, the US pharmaceutical group that bought Yervoy, the drug based on Dr Allison’s findings, in 2009.

A rival drug made by Merck, known as Keytruda, can significantly boost survival in lung cancer patients when added to a type of chemotherapy, according to early findings from a trial that is due to be published shortly. Other companies, including Roche and AstraZeneca, make competing versions.

It was not until 2013 that checkpoint inhibitors gained widespread acclaim among oncologists, but the drugs were soon being hailed as the biggest breakthrough in cancer treatment since the advent of chemotherapy.

The hype served to cloud some uneasy truths.

When checkpoint inhibitors work, they are remarkably effective, helping patients live for months or years longer than expected with less severe side-effects than other drugs. However, with the exception of the remarkable impact in melanoma and, to a lesser extent, lung cancer, most patients do not respond.

Although immunotherapies have now been approved in a long list of cancers from bladder and gastric to liver, the response rates in these illnesses is lower, with as many as 4 out of 5 patients deriving no benefit at all.

When the second generation of checkpoints, known as PDL1 inhibitors, were approved in 2014, researchers and pharma executives confidently predicted they would quickly push response rates higher by combining them with newer experimental immunotherapies.

So far no one has come up with the magic combination, despite running hundreds of trials.

Giovanni Caforio, chief executive of Bristol-Myers Squibb, hails “unprecedented progress” with immunotherapies, but concedes the next step, which he describes as finding “intelligent combinations”, has not moved as quickly.

“I think that it is not growing at the same speed, but I wouldn’t call it stalling,” he says. “I think it’s moving at a speed that is probably more typical of the speed of [traditional] cancer research.”

Sean Bohen, chief medical officer of AstraZeneca, says the quick advent of checkpoint inhibitors was all the more remarkable because immunotherapy “had been a disappointment for decades”. Yet he cautions progress might become slower because the “science is going to harder places”.

That is not necessarily a bad thing, says Dr. Bohen, because it encourages companies and researchers to work in a more methodical way rather than making speculative guesses: “I believe it’s a healthier way to do drug development”.

The challenge now is finding new drugs that can be added to checkpoints and boost the immune response to cancer without putting patients at risk or causing intolerable side effects.

One hope is a so-called IDO inhibitor, which suppresses an enzyme that tumours use to hide from the immune system. Both Merck and Bristol-Myers are testing their checkpoints in combination with this type of medicine in a partnership with Incyte, a US biotech group that is developing the most advanced IDO inhibitor. The first trials are due to complete in May.

Regardless of whether drugmakers and scientists find the right combination any time soon, the remarkable progress in recent years means the field is unlikely to languish as it did after Mr. Coley’s early discoveries.


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March, 2018|Oral Cancer News|

Hall-Of-Fame Bills Quarterback Jim Kelly Says Oral Cancer Is Back

Author: Elana Glowatz
Date: March 1, 2018
Hall-of-Fame quarterback Jim Kelly, who led the Buffalo Bills to four Super Bowls, announced March 1 that he is fighting oral cancer for the third time.

“As our family has faced many trials and triumphs throughout the years, you have blessed us with your prayers. We are asking for those prayers once again,” Kelly said in a statement. “The oral cancer we hoped would be gone forever has returned.”

Oral cancer falls within the realm of head and neck cancers and can include malignancies on the lips, the tongue, the back of the mouth or throat, the tonsils and the tissue around the jaw, among other locations. According to the Oral Cancer Foundation, signs of cancer in those areas could include trouble swallowing, chewing or speaking, numbness or an earache.

The foundation estimates that almost 10,000 people die from oral cancers every year.

Kelly played 11 seasons in the NFL, all with Buffalo, and is most well-known for leading the team to four consecutive conference championships between 1991 and 1994, although the Bills subsequently lost the Super Bowl each time.

The Bills have since retired Kelly’s number 12 jersey and he was inducted into the Pro Football Hall of Fame.

The quarterback was first diagnosed with the cancer in 2013 and had part of his upper jaw removed, according to Sports Illustrated. He received radiation and chemotherapy the following year when more cancer was found.

“Jim is a tough and courageous man and we know he will fight this battle with strength and determination,” the Buffalo Bills organization said in a statement, responding to Kelly’s announcement. “The Buffalo Bills will support the Kelly family during this trying time and we ask our fans to pray for the family as Jim begins the treatment process and the road to recovery.”


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March, 2018|Oral Cancer News|

HHC study supports web-based care plans for head, neck cancer patients

Author: John Stearns

A joint study by the Hartford HealthCare (HHC) Cancer Institute and the Memorial Sloan Kettering (MSK) Cancer Center has demonstrated benefits of a web-based care plan for patients with head and neck cancer as a tool to better cope with side effects of treatment.

A web-based tool to help patients with head and neck cancer better deal with effects of their cancer treatment has proved beneficial to patients and doctors, according to a HHC doctor involved in developing the tool and studying its effectiveness.

“The compelling reason to do this work is because head and neck cancer has changed,” said Dr. Andrew Salner, medical director of the Hartford HealthCare Cancer Institute at Hartford Hospital, HHC’s lead doctor on the joint study with MSK.

Head and neck cancer, once mostly associated with heavy drinkers and smokers who had other chronic diseases, is showing up more in younger and healthier patients, he said. That’s because of the prevalence of human papillomavirus (HPV), now the leading cause of the cancers that often target the tonsils and back of the tongue.

HPV is the most commonly sexually transmitted infection in the U.S. HPV is equally divided among males and females, the latter who’ve been getting vaccinated against HPV to prevent cervical cancer, but oral cancers are happening more prevalently and are appearing in males and females, Salner said. As such, boys and girls are now recommended for the vaccine before they become sexually active to hopefully prevent future disease, he said.

Immunization rates were 38 percent for boys and 50 percent for girls in 2016, Salner said.

Most people with HPV will not develop cancer, according to HHC, but for those who do, treatment outcomes are good, but the effects of head and neck cancer treatment can cause difficulty with taste and swallowing, dental problems, jawbone injury, underactive thyroid and other issues, Salner said.

The study of 43 head and neck cancer patients in Hartford and New York tracked the benefit of a web-based care plan tailored to their specific cancer, treatment and side effects. Historically, so-called survivorship care plans were fairly generic in addressing issues patients might or might not encounter, Salner said.

“This study was unique because it personalized the side effects for the tumor site and the treatment for each patient,” Salner said. It offers specific effects to watch for, some of which may not show up for years after treatment, ways to help prevent problems, cope with treatment side effects and timelines for follow-up medical screenings.

“The patients really appreciated all components of the care plan,” which also included a 60- to 90-minute meeting to review with medical staff.

HHC and MSK are talking with the National Cancer Institute to do a much wider study of the care plan, Salner said. He also wants to examine how to scale up the plan for larger populations and integrate it into patients’ medical records.

Salner and Dr. David Pfister, chief of head and neck oncology services at the MSK Cancer Center, will discuss the study and link between HPV and head and neck cancer in a talk this afternoon, from 4 to 5, at the Hartford Hospital Wellness Center at Blue Back Square, West Hartford.

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February, 2018|Oral Cancer News|

In Memoriam: Jimmie C. Holland, MD

The Oral Cancer Foundation is deeply saddened by the passing of OCF Science Advisory Board member, Dr. Jimmie C. Holland. When our organization was in it’s infancy, Dr. Holland was an early supporter of OCF.  She was one of the first in the profession to focus attention on the mental well being of cancer patients. With OCF being a foundation that is heavily geared to funding the advancement of research, and being very hard science and research oriented,  her compassion for the mental health of cancer patients was a key component in humanizing our efforts, and ensuring that we stayed people centric.  We are tremendously grateful for her advanced work in Psycho-oncology, the good it has done for so many in the oral cancer community, and the guidance she offered us. She will be missed by many.

Author: William Breitbart
Date: Feb. 23, 2018

Jimmie C. Holland, MD, internationally recognized as the founder of the field of Psycho-oncology, died suddenly on 24 December 2017 at the age of 89. Dr. Holland, who was affectionately known by her first name, “Jimmie,” had a profound global influence on the fields of Psycho-oncology, Psychosomatic Medicine, and Oncology.

Dr. Holland was the Attending Psychiatrist and Wayne E. Chapman Chair at Memorial Sloan-Kettering Cancer Center (MSK) and Professor of Psychiatry, Weill Medical College of Cornell University in New York. In 1977, she was appointed Chief of the Psychiatry Service in the Department of Neurology at MSK. The Psychiatry Service at MSK was the first such clinical, research, and training service established in any cancer center in the world. In 1996, Dr. Holland was named the inaugural Chairwoman of the Department of Psychiatry and Behavioral Sciences at MSK Cancer Center, also the first such department created in any cancer center in the world. Over 25 years ago, Dr. Holland founded and co-edited the international Psycho-Oncology journal.

Dr. Holland edited the first major textbooks of Psycho-oncology, and in 1989 edited the Handbook of Psychooncology: Psychological care of the patient with cancer. This landmark textbook was notable for several reasons; it established a “new” field, a subspecialty of both Psychosomatics and oncology. I remember being a young faculty member in Dr. Holland’s service and the very real sense that we were creating something that had not existed before. I remember her asking me to write multiple chapters, including several in which I had very little expertise. I expressed my concern, “I’m not an expert on the psychiatric complications of head and neck cancer!” She calmly reassured me, “Well, Bill, no one is. So when you finish researching and writing the chapter I suppose then you’ll be the world’s expert!”

Psycho-oncology was born and named with the publication of this textbook and with Dr. Holland’s founding of the International Psycho-oncology Society (IPOS) in 1984, then the American Psychosocial Oncology Society in 1986. Subsequently, Dr. Holland edited, with a group of co-editors, what became known as the “Bible” of Psycho-oncology; Psycho-oncology was published in 1998, and represented the most comprehensive, multidisciplinary, and international encyclopedia of a field entering its adolescence. 2010 saw the publication of the second edition followed by the third edition in 2015. Every card-carrying “psycho-oncologist” (in 57 countries with national psycho-oncology societies) had to have the latest edition in their library to demonstrate their link to Jimmie Holland. Dr. Holland also co-wrote two well received books for the public: The Human Side of Cancer and Lighter as We Go: Virtues, Character Strengths, and Aging, the latter reflecting her interests in Geriatric Oncology as she approached her 90th birthday.

Dr. Holland was born in the small farming community of Nevada, Texas in 1928. She credits the local family physician in that community for her interest in medicine and caring for those who were suffering. She was one of only three women in her class at Baylor College of Medicine. In 1956, Dr. Holland married the renowned oncology pioneer James Holland, MD, who was then Chief of Medical Oncology at Roswell Park in Buffalo, NY. She would chide James, complaining that cancer patients were asked every conceivable question about their physical functioning but never, “How do you feel emotionally?” Dr. Holland pioneered the inclusion of psychological and emotional well-being patient-reported outcomes in quality of life measures and as a component of clinical outcomes in clinical trials.

Dr. Holland has received too many awards to list, however some notable ones include: The Medal of Honor for Clinical Research from the American Cancer Society, The Marie Curie Award from the Government of France, and the Margaret L. Kripke Legend Award for contributions to the advancement of women in cancer medicine and cancer science from the MD Anderson Cancer Center. She served as President of the Academy of Psychosomatic Medicine (APM) in 1996 and was the recipient of the APM’s Hackett Lifetime Achievement Award in 1994. She was also the inaugural recipient of the Arthur Sutherland Award for Lifetime Achievement from IPOS.

Over a 40-year career at MSK Cancer Center, Dr. Holland created and nurtured the field of Psycho-oncology, established its clinical practice, advanced its clinical research agenda, and through her pioneering efforts, launched the careers of the leaders of a national and worldwide field who mourn her passing and continue to work in what has become a shared mission to emphasize the care in cancer care.

After stepping down as Chairman of the MSK Department of Psychiatry and Behavioral Sciences in 2003, she kept working full time, seeing patients, conducting research, training and supervising fellows, and traveling the world lecturing and teaching. She also helped bring Psycho-oncology to Africa through her work with the African Organization for Cancer Research & Training in Cancer (AORTIC).

Born in a humble farming community with a one room school house, Dr. Holland created a life that led her to New York and the capitals of the world, honored by so many organizations and societies. She was teaching and seeing patients up until two days before her death. I think we’ll all remember her for various reasons. I certainly have many memories from a 34 year career working beside her. But on that list was her generosity and loving attitude towards her family, her patients, her colleagues, trainees, and everyone who crossed her path. Those who worked alongside her in medicine have made her mission our mission. We will continue this mission’s work, always remembering and honoring Dr. Jimmie Holland. Her death is a profound loss for all of Psychiatry, Psychosomatic Medicine, Psycho-oncology, and Oncology. We’ve lost a pioneer, a remarkable woman, a once-in-a-generation influencer.

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February, 2018|Oral Cancer News|