Monthly Archives: February 2018

New cancer test isn’t ready for prime time

Author: H Gilbert Welch
Date: February 14, 2018
Source: http://www.cnn.com/2018/02/13/opinions/liquid-biopsy-opinion-welch/index.html

(CNN)- A simple blood test to detect cancer early. How great is that?

There has been enthusiasm about the so-called “liquid biopsy” for years. In mid-January, however, doctors learned more — both about this vision and its problems.

A widely reported study in the journal Science described a liquid biopsy test — CancerSEEK — which combined measuring eight tumor biomarkers with testing for pieces of DNA with cancer associated mutations in 16 genes.

It’s not one test; it’s a battery of tests. And while collecting the blood may be simple, the subsequent analysis is extraordinarily complex.

The task at hand is particularly challenging. We all have pieces of DNA in our blood. Distinguishing the tumor DNA from the background DNA requires finding the mutations specifically associated with cancer.

Adding to the complexity, healthy individuals can have mutations. To avoid labeling innocuous mutations as cancerous requires a bunch of statistical fine-tuning.

In other words, there are a lot of steps in a liquid biopsy and much potential for things to go awry.

To their credit, the CancerSEEK investigators were very forthright that the study conditions were ideal for the test to accurately detect cancer. The liquid biopsy simply had to discriminate between patients with known cancer (the majority of whom had symptoms) and healthy individuals. And the statistical fine-tuning was tailored to the study participants — with the knowledge of who had, and who did not have, cancer.

Although the test was able to detect most of the late-stage cancers, it detected less than half of the stage 1 cancers.

But doctors don’t screen to find advanced cancer, we screen to find early cancer. And we don’t screen people with symptoms of cancer, we screen people who don’t have symptoms of cancer.

There’s no doubt that there would be more detection errors in the less controlled environment of the real world.

Just how often was made clear in a recent JAMA-Oncology study. Forty patients with metastatic prostate cancer received liquid biopsies to tailor therapy in real time to the genetics of their spreading tumors. That’s the vision for precision medicine.

But the investigators added a little twist. They wanted to know whether it mattered which lab the liquid biopsies were sent to. So they sent each patient’s blood for two different commercial liquid biopsies: Guardant360 and PlasmaSELECT. Both tests were designed to detect mutations in the same genes.

Yet in over half of the 40 patients, the tests gave different answers about which mutations were present. Different liquid biopsy tests give different answers in a majority of patients? That’s not precision, that’s awful.

Sure, the analyses of liquid biopsies will improve. But if this much confusion exists about what mutations are present in the blood of patients with metastatic cancer (who have a lot of tumor DNA), imagine the uncertainty that will exist for asymptomatic individuals not known to have cancer — the very people who would be screened.

And then there is the question of what to do with a positive result. This is very different than detecting a concerning lung nodule on a screening chest CT scan or a concerning breast mass on a screening mammogram. In these cases, it’s clear what to do to get a definitive answer: surgically biopsy the nodule or the mass. But with a liquid biopsy, the anatomic location of a cancer can be a mystery. It may not even be clear what organ the cancer is in.

Imagine what this might mean for a patient: A doctor says, “It looks like you have cancer, but we are not sure where.”

Even if there is certainty that the cancer is in, say, the liver, doctors may not know where in the organ. What to do then? Randomly biopsy different parts of the liver?

This is doubly concerning when screening average-risk individuals, because most positive results are expected to be false alarms. We typically learn that a screening test is falsely positive because a surgical biopsy is normal. But absent the knowledge of where to biopsy, how can we ever be sure a positive liquid biopsy is wrong?

Doctors won’t know where to look, but we will keep looking. Liquid biopsies are a recipe for more health anxiety, more procedures, more complications and more overdiagnoses. Not to mention, more out-of-pocket costs for our patients.

Of course, we should continue to study liquid biopsies. The detection of circulating tumor DNA may ultimately prove useful in selected settings, such as tailoring therapy for aggressive cancers that are rapidly mutating. But the real enthusiasm is for screening average-risk individuals.

One reason is obvious: there is a lot of money to be made. A Goldman Sachs video estimated the potential liquid biopsy market to be $14 billion annually, adding “and we’re just at the beginning.” That kind of money doesn’t come from testing the few patients with aggressive cancer, that comes from screening millions of people.

And there is a less obvious reason: it is easier for a new test to pass regulatory muster than it is for a new drug. While the FDA has a longstanding mandate to protect us from snake oil treatments, this often doesn’t extend to snake oil testing.

The enthusiasm for finding things that might benefit people in the future ignores the fact that doing so can cause people to have problems now. In short, a bad test can do as much damage as a bad drug. Worrisome liquid biopsies will start a cascade of subsequent, not-so-simple tests and procedures. People will be hurt in the process.

February, 2018|Oral Cancer News|

Should kids be required to get the HPV vaccine?

Source: www.forbes.com
Author: Bruce Y. Lee

If a bill recently introduced in Florida passes, the human papillomavirus (HPV) vaccine would be mandatory for adolescents attending public school in the state. Currently, the vaccine is mandatory for boys and girls in Rhode Island and just girls in Virgina and Washington, DC. (AP Photo/John Amis, File)

Florida isn’t kidding about low human papillomavirus (HPV) vaccination rates. If you are a kid enrolled in a Florida public school, come July 1, 2018, you may be required to get the HPV vaccine. That is if you are old enough and if a bill now being debated in the Florida state legislature ends up passing.

If it gets through, Senate Bill 1558 would then become known as the “Women’s Cancer Prevention Act”, which is a much easier name to remember and also reflects some major benefits of the HPV vaccine. As the National Cancer Institute explains, HPV vaccine can help prevent not only cervical cancer but also many vaginal and vulvar cancers. In fact, two types of HPV (16 and 18) cause around 70% of cervical cancers. But just because you don’t have a vagina, cervix, and vulva doesn’t mean that you are in the clear. HPV is responsible for about 95% of anal cancers, 70% of oropharyngeal (the middle part of the throat) cancers, and 35% of penile cancers. Thus, the “Women’s Cancer Prevention Act” is really a “Cancer Prevention Act.”

Regardless, Florida State Senator José Javier Rodríguez (D-Miami) filed this bill on January 4 in an effort to boost Florida’s not so great HPV vaccination rates. According to the just-released Blue Cross Blue Shield Association (BCBSA) Health of America Report, only 29.0% of adolescents in Florida got the first dose of the HPV vaccine and only 7.3% got all doses in the series as of 2016. Those numbers are lower than the national average (34.4% got the first dose) but not the worst in the country.

New Jersey was the worst (not in general as a state but in terms of HPV vaccination rates). Based on the BCBSA report, as of 2016, only 20.6% of adolescents in New Jersey had gotten the HPV vaccine by age 13 and only 3.4% had completed the series. The Health of America report was the result of an analysis of medical claims data from 2010 through 2016 of over 1.3 million BCBSA commercially-insured adolescents across the country. The analysis considered vaccination to be on time if performed between the adolescent’s 10th and 13th birthdays, corresponding with the Centers for Disease Control and Prevention (CDC) recommendations of 11 to 12 year olds getting the vaccine.

Of course, the analysis did not include all adolescents in America. As BCBSA Chief Medical Officer Trent Haywood, MD, JD, explained, “the analysis represented the commercial population and didn’t include Medicaid populations. Also, to be included in the analysis, an adolescent had to be continuously enrolled with BCBS.” But studying such a large population is a pretty good shot at trying to figure what’s going on with shots and adolescents nationwide.

The report also showed that girls were better than boys (again, not in general, but in terms of HPV vaccination rates). In 2016, 37% of girls had received the first dose of the HPV vaccines by age 13 compared to 32%.

The best state of the bunch? Rhode Island with 57% of adolescents having received their first dose by age 13. Not coincidentally Rhode Island is the only state requiring HPV vaccine for both male and female students, starting with the first dose by 7th grade. Virginia and Washington, DC, have requirements just for females.

The good news is that nationwide vaccination rates steadily rose from 22% getting the first dose by age 13 in 2013 to 34% in 2016. But why are vaccination rates still well below 50% in most states? A BCBSA-commissioned survey of over 700 parents of adolescents aged 10-13 revealed the following top three reasons for parents not vaccinating their child against HPV:

  • Being concerned about adverse side effects (59.4%)
  • Not thinking their child is at risk (23.6%)
  • Not knowing their child needed an HPV vaccination (15.7%)

Is requiring the HPV vaccine the solution? One argument against making the HPV vaccine mandatory is that people should be allowed freedom of choice. When Rhode Island first introduced its requirement, protests resulted various groups such as parents, a 2,400-member plus Facebook group, and the American Civil Liberties Union.

However, the counter-argument is that freedom of choice does not always hold when in the words of Spock, “the needs of the many outweigh the needs of the few.” You aren’t free to run up and down the aisle of an airplane naked and screaming because the needs of other on the plane outweigh the needs of you. Similarly, the HPV vaccine could help slow and even stop the transmission of HPV throughout the population, which can result in cancers that not only affect the cancer victims but also society by adding to health care costs.

Here is a Today show segment on the HPV vaccine:

Also, when a child doesn’t get vaccinated, it is usually because of the parent’s choice and not the child’s. Could making the vaccine mandatory in fact be protecting the child?

Another argument used by some is that the HPV vaccine has adverse effects. There are websites claiming that HPV vaccine can cause “crippling side effects” and “death.” But many of these scarier claims are not supported by rigorous scientific evidence. (Note: there are also websites that say that the Earth is flat, Elvis was an alien, and the government controls the weather). While nothing is completely safe (e.g., even a chocolate chip cookie in the right situation could do some real damage) and all vaccines do have their risks, the risks of the HPV vaccine are comparatively very low and far outweighed by the potential benefits as indicated by the CDC.

As I wrote before for Forbes, some have argued that the HPV vaccine is a “gateway to sex” and thus making it mandatory would increase the number of teenagers having sex and encourage promiscuity. However, this goes counter to the recent trend of teenagers delaying when they first have sex and suggests that teenagers would not have sex if it weren’t for that darn HPV vaccine. A related argument is that the HPV vaccine would give teens a false sense of security that they are protected against all sexually transmitted infections, leading them to not practice safe sex. However, raising awareness of what the HPV vaccine actually does could help overcome this concern.

All of this does not necessarily mean that making HPV vaccination mandatory is the solution. However, what then is the solution to a majority of adolescents still not getting vaccinated (at least by age 13 and when sexual activity for some begin)? As Haywood described, this is a situation in which many are “not taking full advantage of preventive measures. A big issue is lack of awareness of the HPV vaccine and its benefits.” HPV vaccine awareness campaigns may help push up vaccination rates, but by how much?

The wonderfully straight-forward and transparent world of politics will help determine whether Senate Bill 1558 becomes a law in Florida. A similar bill failed to pass in 2011. But things have changed since 2011, in good ways and bad.

February, 2018|Oral Cancer News|

Should dentists ask their patients about their sexual health to fight cancer?

Source: www.ibtimes.co.uk
Author: Kashmira Gander

A visit to the dentist often involves a quick check-up, a spot of gum cleaning and, if you’re unlucky, a filling. But should dentists also ask their patients about their sex lives in order to prevent oral cancer caused by human papillomavirus (HPV)?

A recent report published in the Journal of the American Dental Association highlighted it was important for dentists to actively check their patients mouths for signs that HPV has caused cancer. The most common sexually transmitted infections (STI), HPV is transmitted through vaginal, anal, and oral sex.

The study involved four focus groups with a total of 33 dentists. It showed that many dentists did not know how to approach the subject of cancer caused by HPV.

Those with HPV can show no symptoms and most people with the virus do not suffer health problems, according to the US Centre for Disease Control. “Others may only find out once they’ve developed more serious problems from HPV, such as cancers,” the website warned.

Up to 93% of oral cancer cases are preventable, according to Cancer Research UK. Over 12,000 cases of head and neck cancer were dignosed according to the latest statistics from 2015, while over 2,300 people died that year.

Mouth cancer can occur anywhere in the head and neck area, including the tongue, lips, salivary glands and even the throat, Dr Eddie Coyle’s, clinical director at Bupa Dental Care, told IBTimes UK.

“There are a number of symptoms that patients should look out for, which include sores and swelling in or around your mouth that doesn’t heal or bleed; persistent mouth ulcers; persistent lumps in the lymph glands in the neck or in the mouth; tongue pain; changes in your voice or speech; unexplained weight loss: a sore throat and difficulty in chewing or swallowing.”

However, Dr Coyle stressed that while it was important to be aware of mouth cancer, similar symptoms are often a sign of less serious conditions. “Therefore, we would only recommend they visit a dentist or doctor only if these have lasted for longer than two weeks,” Dr Coyle added.

The study sparked headlines suggesting that dentists may ask patients about their sexual history.

However, lead author Ellen Daley of the University of South Florida, told Newsweek that a person aware they have HPV can cause unnecessary anxiety as it may never cause cancer. Clinicians should instead focus on prevention, including advising patients to get vaccinated against HPV.

In line with this advice, the British Dental Association is leading calls for the UK government to extend its HPV vaccination programme for girls to boys.

“Dentists are on the front line in the battle against oral cancer, and are often the first to spot the tell-tale signs,” BDA Chair Mick Armstrong told IBTimes UK.

“HPV is fuelling this preventable disease, a killer that can have a 90% survival rate – but only if it’s spotted early.

“Men aren’t currently protected from HPV through jabs offered at school, so patients shouldn’t be surprised if they are asked about their sexual health,” he said.

“These questions would be redundant if the government finally bit the bullet and brought boys into the vaccination programme.”

MORE

February, 2018|Oral Cancer News|

Living with cancer in the country: Many Wyoming residents must leave home to seek the care they need

Source: trib.com
Author: Katie King

Bob Overton is all too familiar with the 140-mile stretch of land between Thermopolis and Casper.

He and his wife, Sherry, made the two-hour trip in their white pickup dozens of times while Bob was undergoing treatment for lymphoma in 2015. Even with the help of Alan Jackson and Martina McBride’s music, the hours still lagged, with nothing to stare at except endless grassy plains.

“That trip is pretty monotonous, and it doesn’t get any better with time,” he recalled.

But the couple didn’t have a choice. Their hometown of Thermopolis, population 3,009, doesn’t offer the care Bob needed.

And the Overtons aren’t alone.

As the least populated state in the country, Wyoming appeals to those in search of space and wilderness. But the peace and quiet comes with drawbacks: Services that urban residents may take for granted, like advanced medical care, aren’t readily available for thousands of people living in small towns and rural areas.

Many of those battling cancer in Wyoming subsequently end up seeking treatment in Casper, according to Rocky Mountain Oncology’s Patient Navigator Sam Carrick. She said the center is the only medical facility in the state that offers radiation, chemotherapy and Positron emission tomography scans.

Other areas may offer one or two of those services, but many prefer the convenience of a one-stop shop, she said.

About 15 percent of their patients are from out-of-town, added Carrick, who is responsible for guiding all patients through the treatment process. She said it’s often devastating for people to learn that they can’t get the care they need at home.

“First you are hit over the head with a diagnosis that you didn’t want, and then you can’t get treatment at home, so you have to travel and be away from your family members or pets,” she said.

Some patients drive back-and-forth, but temporarily relocating often becomes necessary during the more intensive treatment phases.

And that was the case with Bob. The 75-year-old initially remained in Thermopolis, only traveling to Casper for intermittent doses of chemotherapy. But he said that wasn’t possible while he was undergoing radiation, which he needed daily for 30 days.

Sherry remembers breaking down into tears when she realized they had to leave home. Already faced with the possibly of losing her husband, not to mention mounting medical bills, the thought of relocating for a month was overwhelming.

“That was just more than I could handle … I just thought, ‘How are we going to do this?’” she said.

***
Battling cancer is difficult for anyone, but those living far away from treatment centers need extra help, said Wyoming Foundation for Cancer Care treasurer Kara Frizell. Finding the money for gas and hotel accommodations can quickly become a serious problem.

“It’s not something you can just come up with,” she explained.

Frizell said the Casper-based charity annually spends between $20,000 and $30,000 assisting patients with necessary travel expenses. The nonprofit also oversees a network of volunteers, called Angels, who help out-of-towners feel at home by delivering meals or dropping off gift baskets.

***
Robert Rasmussen also lives in Rawlins, but he hasn’t had much of a chance to grow attached to the town. He moved from Tuscon, Arizona, in search of peace and quiet. But about a year after moving, he was diagnosed with stage four throat cancer last fall. It quickly became apparent that traveling back and forth to Casper for treatment wasn’t a safe option.

Sitting in his bed in January at the Shepherd of the Valley Healthcare Community — where he’s recovering from surgery — the emaciated 50-year-old removed his oxygen mask and explained that intense radiation and chemotherapy treatments left him far too nauseous and exhausted to drive.

Rasmussen temporarily relocated to Casper in October and brought along his dog, Piggy. The Australian Shepherd is family, and he couldn’t bear to be without her.

“She’s the only thing that keeps me together,” he explained.

Although Rasmussen was worried hotels wouldn’t allow animals, Carrick arranged for both patient and pet to stay at the Sleep Inn in Evansville. The patient navigator also connected him with the cancer foundation to help with the bill.

The hotel staff has since fallen in love with Piggy, according to general manager Carmen Bartow. Employees walk her each day, sneak her treats from the breakfast buffet and even take her to visit her dad.

“She’s our mascot,” said Bartow.

The manager said the inn annually receives about 15 guests who are in town for cancer treatments, likely because of their close proximity to the oncology center. The hotel offers discounted rates for its sick visitors and employees try to help them out in any way possible.

“If we can’t help one another out then there is something wrong with us,” she said.

Rasmussen greatly appreciates everyone who made it possible for Piggy to stay in Casper.

His condition is serious, and distracting himself from the possibly of death isn’t easy, he explained. Surrounded by feeding tubes and beeping monitors, it’s impossible to forget his situation.

“I try to read or watch TV or just focus on something different, but when I’m just sitting here by myself, it’s hard,” he said.

But Rasmussen said he can manage with Piggy by his side for support.

Although his former home in Tuscon was closer to advanced medical care, Rassmussen said he prefers living in small towns because its safer and more peaceful.

“I don’t have any regrets [about moving],“ he said. “City life isn’t for everybody.”

February, 2018|Oral Cancer News|

Biofilms in tonsil crypts may explain HPV-related head and neck cancers

Source: www.genengnews.com
Author: staff

Human papilloma virus (HPV) encased in biofilms inside tonsil crypts (pictured) may explain why the roughly 5% of HPV-infected people who develop cancer of the mouth or throat are not protected by their immune systems. Tonsil crypts with HPV are shown in green; epithelial and biofilm layers are shown in red. [Katherine Rieth. M.D.]

How can human papilloma virus (HPV) be prevalent in otherwise healthy people not known to carry it? A just-published study concludes that the virus may be lurking in small pockets on the surface of their tonsils.

Researchers from University of Rochester Medical Center (URMC) found HPV encased in biofilms inside tonsil crypts, where HPV-related head and neck cancers often originate. HPV is shed from the tonsil during an active infection and gets trapped in the biofilm, where it may be protected from immune attack.

In the crypts, the virus likely lays in wait for an opportunity to reinstate infection or invade the tonsil tissue to develop cancer.

“The virus gains access to the basal layer of stratified squamous epithelium through structural breaks in the stratified epithelial superstructure,” the investigators reported in the study. “Tonsillar crypt reticulated epithelium itself has been shown to contain numerous small blood vessels and has a discontinuous basement membrane, which may facilitate this infection and reinfection process.”

The URMC researchers said their finding could help prevent oropharyngeal cancers that form on the tonsils and tongue—and may explain why the roughly 5% of HPV-infected people who develop cancer of the mouth or throat are not protected by their immune systems.

HPV 16 and 18, high-risk strains that are known to cause cervical cancer, also cause head and neck cancers. While verified tests can detect HPV in people before they develop cervical cancer, that’s not the case with head and neck cancers, which according to a 2016 study are expected to outnumber cervical cancer cases by 2020.

“Far-Reaching Implications”
“Given the lack of universal HPV immunization and the potential for the virus to evade the immune system, even in individuals with detectable HPV in their blood, our findings could have far-reaching implications for identifying people at risk of developing HPV-related head and neck cancers and ultimately preventing them,” Matthew Miller, M.D., associate professor of otolaryngology and neurosurgery at URMC, said in a statement.

Dr. Miller and six colleagues detailed their findings in “Prevalence of High-Risk Human Papillomavirus in Tonsil Tissue in Healthy Adults and Colocalization in Biofilm of Tonsillar Crypts,” published online January 25 in JAMA Otolaryngology-Head & Neck Surgery, and announced by URMC today. The study’s corresponding author is Katherine Reith, M.D., an otolaryngology resident at URMC.

The researchers carried out a retrospective, cross-sectional study using samples obtained from tonsils archived at a university hospital following elective nononcologic tonsillectomy from 2012 to 2015. The samples consisted of formalin-fixed, paraffin-embedded samples of tumor-free tonsil tissue from 102 adults who had elective tonsillectomies and were between ages 20 and 39. More than half the patients (55, or 53.9%) were female.

Five of the samples contained HPV and four contained HPV 16 and 18. In every case, HPV was found in tonsil crypts biofilms.

HPV status was assessed by polymerase chain reaction (PCR), and high-risk subtypes 16 and 18 were assessed with quantitative PCR assay. Samples that demonstrated presence of HPV were then analyzed by in situ hybridization to localize the viral capsid protein.

These samples were then stained with concanavalin A to establish biofilm presence and morphology and with 4′,6-diamidino-2-phenylindole (DAPI) to visualize location of the virus in relation to cell nuclei. Data was assembled for aggregate analysis to colocalize HPV in the biofilm of the tonsillar crypts, the URMC researchers reported.

The research team plans to develop topical antimicrobials designed to disrupt the biofilm and allow the immune system to clear the virus—part of their investigation of potential screening tools, such as an oral rinse, to detect HPV in the mouth and throat.

February, 2018|Oral Cancer News|