Surveillance of ctDNA in HPV-positive head and neck cancers may predict recurrence

Source: www.targetedonc.com
Author: Nichole Tucker

The detection of circulating tumor DNA (ctDNA) in human papillomavirus (HPV) with an experimental blood test has been associated with high positive predictive value (PPV) and negative predictive value (NPV) for identifying disease recurrence in HPV-positive oropharyngeal cancer, according to a press release from the University of North Carolina (UNC) Lineberger Comprehensive Cancer Center.1

“The major utility of this test is it’s going to improve our ability to monitor patients after they complete treatment,” said Bhisham Chera, MD, associate professor in the UNC School of Medicine Department of Radiation Oncology. “Currently, our methods to assess whether the cancer has recurred are invasive, expensive and not always accurate.”

In a prospective biomarker clinical trial published in the Journal of Clinical Oncology, investigators obtained 1006 blood samples for their analysis, 999 of which were evaluable for plasma circulating tumor human papillomavirus DNA (ctHPVDNA). The goal was to determine if surveillance of ctHPVDNA can facilitate earlier detection of recurrence compared with normal clinical follow-up.2

Patients were followed for a median of 23.7 months (range, 6.1-54.7 months), and out of 115 patients, 13% developed disease recurrence (n = 15). Of these recurrences, 1 was local only, 1 was regional only, 10 were distant only, 1 was local and distant, and the remaining 2 were regional and distant. Following treatment, 87 patients had undetectable ctHPVDNA, and none developed recurrence (95% CI, 96%-100%). The development of a positive ctHPVDNA occurred in 28 patients during post-treatment surveillance.

The median time to abnormal ctHPVDNA signal was 12.3 months after complete chemoradiotherapy (CRT; range, 2.6-29.1 months). Sixteen patients had 2 consecutive positive ctHPVDNA results, and 15 of those patients developed biopsy-proven recurrence. The 2 ctHPVDNA blood tests that were consecutively positive had a PPV of 54% (95% CI, 0.339-0.725). A 3.9-month median lead time between ctHPVDNA positivity and biopsy-proven recurrence was observed (range, 0.37-12.9). the actuarial 2-year response-free survival (RFS) rate was 30% in patients who had an abnormal blood test during post-treatment surveillance compared with 100% among the remaining participants (P <.001).

In the study, CRT included cetuximab 250 mg/m2, carboplatin AUC 1.5, and paclitaxel 45 mg/m2. Patients received intravenous chemotherapy during intensity-modulated radiotherapy treatment, which was given weekly. There were 6 doses of chemotherapy in total.

The secondary end points of the study were local control rate, regional control rate, local-regional control rate, distant metastasis-free survival, OS, head and neck quality of life assessments, and speech and swallowing function.

Patients aged 18 years and older were eligible to enroll if they had T0-3, N0 to N2c, M0 squamous head and neck cancer, HPV and p16 positivity, radiologically confirmed hematogenous metastasis within 12 weeks before treatment, and ECOG performance status of 0 to 1, and adequate bone marrow, renal, and hepatic function. Individuals with prior history of radiation to the head and neck, head and neck cancer, those with unresectable disease, severe comorbidity, or known human immunodeficiency virus, or those taking disease-modifying rheumatoid drugs were excluded from the study.

Based on this research the investigators reported a 99% accuracy in confirming whether or not patients remained recurrence-free with their screening method, compared with other methods. For patients who had 2 HPV-positive blood tests, the accuracy was said to be 94%.1

“With this new technology, it offers a noninvasive way to accurately monitor patients for cancer recurrence,” Chera said. “In the long run, blood-based surveillance could be more effective, and possibly help us to detect cancer sooner.”

References
1. Study finds blood test accurately tracks HPV-linked head and neck cancer [news release]. Chapel Hill, North Carolina: University of North Carolina Lineberger Comprehensive Cancer Center; February 4, 2020. https://bit.ly/2tzlw7x. Accessed February 6, 2020.
2. Chera BS, Kumar S, Shen C, et al. Plasma circulating tumor HPV DNA for the surveillance of cancer recurrence in HPV-associated oropharyngeal cancer. J Clin Oncol. doi: 10.1200/JCO.19.01598.

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February, 2020|Oral Cancer News|

Botanical drug is shown to help patients with head and neck cancers

Source: newsroom.ucla.edu
Author: Duane Bates, UCLA Research Brief

Findings
In a UCLA-led phase I clinical trial, a new plant-based drug called APG-157 showed signs of helping patients fight oral and oropharyngeal cancers. These cancers are located in the head and the neck.

APG-157 is made up of multiple compounds produced by plants, including curcumin. UCLA Jonsson Comprehensive Cancer Center researchers found that treatment with this botanical drug resulted in high concentrations of curcumin and its byproducts circulating in the blood and absorbed by tumor tissues within three hours after being taken orally.

APG-157 reduced the concentration of cytokines — proteins involved in inflammation — in the saliva when administered to cancer patients. The therapy also reduced the relative abundance of Bacteroides species, a group of gram-negative bacteria. Gram negative refers to a group of dangerous bacteria that have an outer layer which hides them from the immune system. The relative abundance of gram-negative bacteria compared to the presence of other types of bacteria is correlated with oral cancer.

APG-157 also resulted in the expression of genes that are associated with attracting immune system T cells to the tumor area. This therapy could have a beneficial effect when used in combination with immunotherapy drugs that help immune system T cells recognize and kill tumors.

The treatment did not have any adverse effects on the study’s participants.

Background
Cancers of the head and neck account for 4% of all cancers. About 650,000 new cases are reported each year around the world. People with advanced head and neck cancers have a low survival rate and current treatment options such as surgery, radiation and chemotherapy can have adverse effects. Therefore, more effective and less toxic therapies are needed to help improve the quality of life and outcome for those with these cancers.

APG-157 is a botanical drug developed under the FDA’s Botanical Drug Guidance, which includes requirements for production of plant-based therapies that are marketed as prescription medications. The drug is made up of botanical compounds including curcumin from the Curcuma longa plant, which is commonly referred to as turmeric and is a member of the ginger family.

Curcumin is one of the medicinally active or therapeutic molecules that has been tested as a possible treatment to help fight multiple cancers because it is an antioxidant that reduces swelling and inflammation. However, there is poor absorption into the bloodstream when curcumin is taken orally. In this study, UCLA researchers found that when APG-157 is taken through oral mucosal absorption, patients have high levels of curcumin circulating in their blood and absorbed by cancer tissues.

Method
UCLA researchers conducted the study of APG-157 comparing 12 people who had oral and oropharyngeal cancer with a control group of 13 people who did not have cancer. The reason both the people with cancer and without cancer were part of the study was to show that the drug was not toxic to either people with cancer or those without cancer.

The medication was given each hour for three hours and was delivered as a lozenge that slowly dissolved in the mouth. Blood and saliva samples were collected beforehand — each of the three hours the medication was administered — and 24 hours after the last dosage. The medication was given to 12 people (some who had cancer and some who did not) and a placebo was given to 13 people. Blood and electrocardiogram tests did not show increased toxicity in the people who took the active medication in comparison with the people who took the placebo, regardless of whether they had cancer or not.

For the cancer patients who took the medication, there was a decrease in Bacteroides and an increase in T cells in the tumor tissue as compared to cancer patients who took the placebo. Neither the subjects nor the investigators knew whether the drug or a placebo was given when reviewing the blood and saliva test results of the blinded study.

Impact
APG-157 is a botanical drug that has low toxicity. It works effectively to reduce inflammation that contributes to the growth of cancer cells. It also attracts T cells to the tumor micro-environment. When used in combination with immunotherapy drugs, APG-157 might have the ability to make the immune system more effective in attacking head and neck cancers. With potential to inhibit the growth of Bacteroides species, APG-157 could also improve cancer therapy through oral microbial changes.

Authors
Dr. Marilene Wang from UCLA was the corresponding author. Other UCLA authors include: Saroj Basak, Alexander Yoon, Marco Morselli, Chan Jeong, Anela Tosevska, Tien Dong, Hassan Nasser, Venu Lagishetty, Rong Guo, Dipti Sajed, Kym Faull, Jonathan Jacobs, Matteo Pellegrini, Daniel Sanghoon Shin and Eri Srivatsan. Authors from Uniformed Services University of the Health Sciences in Maryland and Aveta Biomics also participated in the study.

Journal
The research is published in CANCER, a journal published by the American Cancer Society.

Funding
Funding for the study was provided by Aveta Biomics.

Disclosures
Authors Parag Mehta, Sharmila Mudgal and Luis Avila are employed by Aveta Biomics. They had no role in the recruitment of people for this study or the collection and analyses of the samples. They, as with all the authors, did not have any information on the subjects, therapy or placebo given until completion of the study.

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February, 2020|Oral Cancer News|

Curcumin has anti-proliferative and pro-apoptotic effects on tongue cancer in vitro: a study with bioinformatics analysis and in vitro experiments

Source: www.dovepress.com
Authors: Chao Ma,1 Zongming Zhuang,1 Qisheng Su,2 Jianfeng He,1 Haoyu Li1

Purpose:
This study focused on the mechanism underlying the therapeutic effect of curcumin against tongue cancer (TC). Accepted for publication in Drug Design, Development and Therapy, Volume 14.

Methods:
Target genes of TC and curcumin were identified, respectively. Three datasets of TC from Gene Expression Omnibus were included, and then the differentially expressed genes were collected. After combing the data from The Cancer Genome Atlas, bioinformatics analyses were performed to investigate hub genes in terms of the functions and correlations. The proliferation and migration of TC cells were evaluated with CCK-8 assay and scratch wound healing assay, respectively. Cell apoptosis was evaluated by TUNEL assay, flow cytometry and Western blot. Cell cycle was determined by flow cytometry.

Results:
In this study, 15 hub genes were identified (TK1, TDRD3, TAGLN2, RNASEH2A, PDE2A, NCF2, MAP3K3, GPX3, GPD1L, GBP1, ENO1, CAT, ALDH6A1, AGPS and ACACB). They were mainly enriched in oxygen-related processes, such as oxidation-reduction process, reactive oxygen species metabolic process, hydrogen peroxide catabolic process, oxidoreductase activity and Peroxisome-related pathway. The expression levels of hub gene mRNAs were positively correlated with each other’s expression levels. None of the hub genes was correlated with prognosis (P > 0.05). Curcumin significantly inhibited CAL 27 cell proliferation and migration (P < 0.05), but significantly promoted cell apoptosis (P < 0.05). Conclusion: Curcumin has potential therapeutic effect on treating TC by suppressing cell proliferation and migration, as well as promoting apoptosis through modulating oxygen-related signaling pathways.

Notes:
1 Department of Ophthalmology, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China;
2 Department of Clinical Laboratory, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China

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February, 2020|Oral Cancer News|

Cancers Caused by HPV Respond Better to Treatment — a New Study Helps Explain Why

Source: Memorial Sloan Kettering Cancer Center
Date: January 20th, 2020
Author: Matthew Tontonoz

Human papillomavirus (HPV) causes several types of cancer, including cervical, anal, and head and neck cancers. People with these tumors are more easily cured with radiation and chemotherapy than people with tumors not caused by HPV. Scientists at Memorial Sloan Kettering now think they understand why.

“We’ve known that HPV-associated cancers respond much better to radiation therapy, but it hasn’t been clear why that is,” says Daniel Higginson, a physician-scientist at MSK. “Our research shows that it’s likely because the virus alters the cells’ normal DNA repair machinery.”

Radiation therapy damages DNA. Cancers caused by HPV are less able to repair this damage and so they die.

The difference in cure rates between HPV-caused and non-HPV-caused cancers is stark: 85% to 90% of patients with HPV-associated oropharyngeal cancer (which affects the middle part of the throat), for example, are cured by radiation and chemotherapy, compared with about 60% of people with non-HPV-caused oropharyngeal cancer.

“We don’t have many biomarkers that predict response to radiation therapy,” says Dr. Higginson. “But HPV is a very good one and is consistent across multiple malignancies.”

What the Virus Does

HPV promotes cancer by inserting pieces of its own DNA into a person’s cells. The DNA pieces trick the human cells into making two distinct proteins that cooperate to turn normal cells cancerous. These proteins (called E6 and E7) disrupt the cells’ machinery for stopping unwanted growth (specifically, two proteins called p53 and Rb).

When this machinery is disabled, the cells begin to divide without restraint. They also tend to accumulate mutations because DNA damage goes unrepaired. Eventually, the cells have enough additional mutations to turn cancerous.

Tricking the cells into dividing repeatedly is advantageous to the virus because this is how HPV reproduces itself; each time a host cell divides it makes more of the virus.

Previous research had pointed to faulty DNA repair as a possible reason why HPV-caused cancers are more sensitive to radiation. But there are several types of DNA repair — which one might be involved was an open question.

Homing in on DNA Repair

To get to the bottom of these questions, the researchers first looked for evidence of different types of DNA repair in more than 10,000 tumors across 32 cancer types in data sets from The Cancer Genome Atlas. They discovered that HPV-caused cancers have DNA changes more characteristic of a repair process called microhomology-mediated end joining (MMEJ). This form of DNA repair is a backup system that comes into play when other repair systems fail, but it is prone to making errors.

The researchers then turned to laboratory experiments. By introducing DNA breaks into HPV-infected cancer cells and measuring how these breaks were repaired, the MSK scientists confirmed that HPV (specifically the E7 protein) suppresses a form of DNA repair called canonical nonhomologous end joining. As a result, the cells become more dependent on MMEJ.

Why might HPV prefer this form of less-than-accurate repair? Some evidence suggests that MMEJ helps the virus integrate its DNA into the host cell’s DNA.

Dr. Higginson says that looking for biomarkers of MMEJ dependence in cancers may help doctors tailor treatments to those who may benefit from them the most. In addition, the findings provide a rationale for exploring ways to block MMEJ factors with drugs in HPV-caused cancers. These results were published October 7, 2019 in the journal Proceedings of the National Academy of Sciences.

Cancers caused by HPV constitute about 4.5% of all solid tumors. A vaccine to prevent infection with the most dangerous HPV strains is available.

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February, 2020|Oral Cancer News|

National Vaccination Program Leads To Marked Reduction In HPV Infections

Source: Forbes
Date: January 28th, 2020
Author: Nina Shapiro

While widespread vaccination continues to be a source of contention in this country and others, one of the newer vaccines has begun to demonstrate remarkable positive impact, which will hopefully become harder and harder to dispute. The HPV vaccine, with trade name GardasilR, is recommended for both boys and girls, ideally sometime between ages 11 and 12 years, given in two doses at a six month interval. It can be given as early as age 9, and as late as age 26. Older adults, even up to age 45, can receive the vaccine, although it is more likely that these adults have already been exposed to the virus, and are less likely to be protected by the vaccine.

The vaccine prevents infection with the human papillomavirus (HPV), which can cause health problems ranging from nuisance-causing warts to cancer-causing lesions of the cervix, throat, and anorectal area. When HPV-related cancers hit Hollywood, with Michael Douglas publicly attributing his throat cancer to HPV, it became clear that this disease can no doubt affect both men and women. When Marcia Cross announced that her anal cancer was due to HPV infection, it raised yet another red flag that HPV can affect the lower gastrointestinal tract, not just the female reproductive tract. Indeed, HPV can affect any of us, at any age, from stem to stern. As I wrote in an earlier Forbes piece, the vaccine to prevent HPV can prevent not only sexually transmitted infections (STI’s) causing genital warts, but it can also prevent cancer.

A lesser known impact of active HPV infection is that the virus can be transmitted from pregnant mother to her fetus via amniotic fluid. The child can later (usually as a toddler) develop warts on the vocal cords, known as recurrent respiratory papillomatosis, or RRP. These warts lead to progressively worsening airway blockage, and even death. And while there are treatments for RRP, there is no cure; only prevention. In another Forbes article, I explain how reduction of HPV infections, thanks to vaccine programs, can reduce the incidence of RRP in the next generation.

A report released this week by Public Health England, published in Health Protection Report, reviewed surveillance data from outcomes of a national HPV vaccination program, which began in 2008. The vaccine is offered to 12-13 year-old males and females, and the report then looked at incidence of HPV infection of the reproductive tract in sexually active 16-24 year-old females. As is the case with many viruses, HPV has many subtypes, some of which are more likely to be associated with aggressive cancers (subtypes 16 and 18 as well as 31, 33, and 45) and others are more likely to be associated with RRP infections and genital warts (subtypes 6 and 11). Until 2012, the bivalent (HPV 16/18) vaccine (CervarixR) was administered as a three-dose regimen. In years since then, the quadrivalent (HPV 16/18/6/11) (GardasilR) has been the standard vaccine administered in the U.K. as well as the U.S. as a two-dose regimen. Cervical cancer is due to HPV 16 or HPV 18 in up to 80% of cancers.

The recent report out of the U.K. analyzed results of over 18,000 vulvovaginal culture specimens obtained from sexually active 16-24-year-old females, collected between 2010 and 2018. There was significant decline in HPV infection rates in all subtypes in all age groups. Those who had been vaccinated more recently showed more reduction in HPV 6/11 than those who did not receive coverage for these strains in the earlier years of vaccination. Most notable was that the prevalence of HPV 16/18 in the 16-18-year-old cohort declined from 8.2% in 2010 to 0.0% in 2018. In the older groups, there was less decline (from 14% to 0.7% in 19-21-year-olds and 16.4% to 2.6% in 22-24-year-olds), but all reductions were statistically significant.

There was no evidence of increase in the HPV subtypes which were not included in the vaccine. Some have raised concern that vaccinating against specific HPV subtypes would increase growth of subtypes not included in the vaccine, but this was not found to be the case. While there are several limitations to this report, including the fact that each individual sample was not identified as being from a vaccinated or non-vaccinated individual, this marked reduction of all HPV subtype growth in a population which demonstrated a vaccination rate of 86% for both males and females ages 12-13 years is promising. While not all cervical cancers, throat cancers, or anal cancers are directly caused by HPV infection, the high rates of HPV-related cancers due to known HPV subtypes underscores the potential widespread benefits of this vaccine in the decades ahead.

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January, 2020|Oral Cancer News|

What parents need to know about the HPV vaccine

Source: www.news-medical.net
Author: University of Chicago Medical Center, reviewed by Kate Anderton, B.Sc. (Editor)

The vaccine that prevents infection from human papillomavirus (HPV) is nothing short of a medical marvel. “It’s one of the most effective vaccines we have against any disease or infection. And it prevents cancer,” said Andrea Loberg, MD, clinical associate of obstetrics and gynecology.

Pre-teens and teens who are vaccinated against HPV can be spared some of the deadliest, most disfiguring and hard-to-treat cancers-;those of the cervix, vagina, vulva, penis, anus, mouth and throat. Over 90% of cancers caused by HPV can be prevented-;29,000 cases of cancer per year-;with the HPV vaccine.

Concerns about sexual promiscuity
To some parents, however, the HPV vaccine may be an uncomfortable reminder that their child will be moving into adulthood and may choose to express his or her sexuality. HPV is transmitted by oral, vaginal and anal sex and other intimate skin-to-skin contact, and it is extremely prevalent; about 80% of people will be exposed to the virus in their lifetime.

Condoms reduce but don’t eliminate the risk of HPV infections because the virus lives in both oral and genital tissues. Condoms do not cover the entire genital area of either gender. Nor are same-sex female partners protected from contracting the virus, which often causes no symptoms until precancerous lesions or cancer show up years later. “It’s hard for parents to think about our kids becoming sexually active, but we also want them to have fulfilling lives,” said Truehart, whose own two teenagers have received the HPV vaccine. “We want to make sure they are protected before they start having sex.”

The recommended age for receiving the HPV vaccine is 11 or 12, when children are also scheduled to receive the Tdap vaccine (tetanus, diphtheria and pertussis) and the meningitis vaccine. But the two-dose vaccine-;the second dose is given six to 12 months after the first-;can be given to children as young as nine. Teens older than 15 and men and women need three doses of the vaccine to develop an immunity against HPV.

“Pre-teens have a more robust response to the vaccine and generate enough antibodies to protect against HPV after two immunizations, whereas older kids and adults need three doses to get the same immune response,” said Truehart. Another reason not to delay getting the HPV vaccine: an older teen may not want to wait six months or more to be fully immunized against HPV once he or she is on the verge of becoming sexually active. “It’s important for kids to be immunized before they are exposed to HPV,” Truehart said.

Not just for girls
When the U.S. Food and Drug Administration approved the HPV vaccine in 2006, it was recommended for girls and women to protect against cervical cancer. Three years later, the vaccine was approved for boys and men, based on evidence that males are also susceptible to HPV-related cancers. “Cancers caused by HPV affect women and men in equal numbers,” said Loberg. “Each year, there are approximately 10,800 cases of cervical cancer diagnosed in women, and 9,600 cases of head and neck cancer diagnosed in men.” And while there is a screening test for cervical cancer to catch and treat it early, there are no such screening tests for any of the other HPV-related cancers. And because most HPV infections are asymptomatic, people may be unwittingly transmitting the infection to their sexual partners.

HPV also causes genital warts which, although not harmful in most people, can be embarrassing and unsightly. In some cases, however, genital warts can be extremely painful and may even require surgery to remove them. For people with autoimmune disorders or who take medications that compromise their immune system, genital warts can be very difficult to manage, said Loberg. Out of more than 150 strains of HPV, the vaccine targets the most prevalent and harmful ones: two strains that cause genital warts and seven strains that cause various types of cancer.

No serious side effects
Despite HPV being the most common sexually transmitted infection, HPV-related cancers are relatively uncommon because in about 90% of people exposed to HPV, their immune systems clear the virus from their bodies before it causes cancer or precancer. “But we don’t know which individuals will develop a persistent infection, so why take that gamble when cancer can be the consequence?” said Loberg.

When parents ask whether the HPV vaccine is safe, Loberg’s ready answer is that “it’s incredibly safe.” More than 270 million doses of the HPV vaccine have been distributed worldwide since 2006, and there have been no serious side effects. One study that examined data from more than 56 million doses of HPV vaccine administered in the U.S. found that some girls became dizzy or fainted 15 minutes after receiving the vaccine. “That is the only side effect that we see,” other than mild side effects typical of other vaccines, such as fever, headache, and pain and redness at the injection site, said Loberg.

Pediatricians and primary care providers should be recommending the HPV vaccine for children, but if not, parents should bring it up.

“There is absolutely no downside to getting the HPV vaccine, and the upside is preventing your child from getting a deadly or disfiguring cancer,” she said.

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January, 2020|Oral Cancer News|

Ask the Doctors: Dysphagia common in elderly

Source: journalstar.com
Author: askthedoctors@mednet.ucla.edu

Dear Doctor: Why do the elderly often have a hard time swallowing, and sometimes experience a feeling that food is stuck in their throats? I heard there’s a procedure to stretch the throat. Does it help?

Dear Reader: The condition you’re asking about is known as dysphagia, which refers to difficulty in swallowing. Patients may have trouble starting a swallow, or problems with the esophagus, which is the muscular tube that connects the throat with the stomach.

The origins of the disorder fall into several basic categories. There are neurological causes, such as stroke, Parkinson’s disease, multiple sclerosis, dementia and head injury. Certain muscular conditions can affect the proper functioning of the esophagus. So does obstruction, which can result from a narrowing of the esophagus, or from inflammation. These can be caused by head and neck cancers, radiation therapy, tuberculosis and chronic acid reflux.

Although dysphagia can affect people of all ages, you’re correct that it’s seen more often in older adults. This is commonly due to age-related changes in the body, such as loss of muscle tone, mass and strength, and changes to nerve function. Still, dysphagia is not considered to be a normal sign of aging.

Understanding dysphagia starts with the mechanics of swallowing. We tend to think of it as the “gulp” that empties the mouth. But that’s just the first step of a complex process.

A successful swallow moves the contents of your mouth through the throat, and all the way down to the stomach. This happens when a ring of muscles known as the upper esophageal sphincter and located at the lower end of the throat, open. Next, coordinated contractions along the length of the esophagus send the food to a second ring of muscles known as the lower esophageal sphincter. This leads to the stomach. At the same time, muscles and specialized structures within the throat prevent anything from getting into the nose, voice box and windpipe.

Symptoms of dysphagia can include pain while swallowing, struggling or being unable to swallow, feeling as though food is stuck in the esophagus, coughing or gagging when trying to swallow, regurgitation or frequent heartburn. Some people may experience drooling or develop a hoarse voice. Diagnosis of the condition includes a physical exam and any of a variety of tests that may include X-rays, muscle tests and swallowing studies.

Treatment depends on the specific cause of the condition. Patients may be asked to change their diet, use certain exercises and techniques that help with swallowing coordination or manage acid reflux with medication.

The procedure you asked about, known as esophageal dilation, is useful when dysphagia results from a narrowing of the esophagus. It involves the use of an endoscope and either plastic dilators or a special balloon to slowly and gradually stretch the esophagus. Complications, which are rare, include bleeding and tears or holes in the esophagus. In most cases, the patient is able to resume normal eating and drinking the following day.

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January, 2020|Oral Cancer News|

Study explores correlation between Medicaid expansion and disease stage and time to treatment initiation in head and neck cancer

Source: www.docwirenews.com
Author: Kaitlyn D’Onofrio

A new study examined the relationship between Medicaid expansions as part of the Affordable Care Act (ACA) with stage at diagnosis and time to treatment initiation (TTI) for head and neck squamous cell carcinoma (HNSCC) patients.

“Medicaid expansions as part of the Patient Protection and Affordable Care Act (ACA) are associated with decreases in the percentage of uninsured patients who have received a new diagnosis of cancer. Little is known about the association of Medicaid expansions with stage at diagnosis and time to treatment initiation (TTI) for patients with head and neck squamous cell carcinoma (HNSCC),” the study authors explained.

The study authors performed a retrospective cohort study at Commission on Cancer-accredited facilities. A total of 90,789 HNSCC patients aged between 18 and 64 years who received a cancer diagnosis between Jan. 1, 2010, and Dec. 31, 2016, were identified using the National Cancer Database. The primary outcomes were health insurance coverage, stage at diagnosis, and TTI. The researchers figured out the absolute percentage change in health insurance coverage, crude and adjusted difference in differences (DD) in absolute percentage change in coverage, stage at diagnosis and TTI before (2010-2013) and after (2014-2016) the ACA took effect for Medicaid expansion and nonexpansion states.

Of the 90,789 HNSCC patients (mean [SD] age, 54.7 [7.0] years) included in the analysis, the majority (n = 70,907, 78.1%) were male, and most (n = 72,911, 80.3%) were non-Hispanic white. More than half (n = 52,142, 57.4%) were aged between 55 and 64 years, and about three-fifths (n = 54,940, 60.5%) lived in a Medicaid expansion state. Following the implementation of the ACA, the percentage of HNSCC patients with Medicaid, compared to nonexpansion states, increased more in expansion states (adjusted DD, 4.6 percentage points; 95% confidence interval [CI], 3.7–5.4 percentage points). In expansion states, compared to nonexpansion states, there was a greater increase in the percentage of patients with localized disease (defined as American Joint Committee on Cancer stage I-II) at diagnosis in the overall cohort (adjusted DD, 2.3 percentage points; 95% CI, 1.1–3.5 percentage points) as well as a subset of patients with nonoropharyngeal HNSCC (adjusted DD, 3.4 percentage points; 95% CI, 1.5–5.2 percentage points). In the entire study cohort, there was no significant different in mean TTI between expansion and nonexpansion states (adjusted DD, –12.7 percentage points; 95% CI, –27.4 to 4.2 percentage points), but improvements were observed in the nonoropharyngeal HNSCC subset (adjusted DD, –26.5 percentage points; 95% CI, 49.6 to –3.4 percentage points).

The study appeared in JAMA Otolaryngology-Head & Neck Surgery.

“Medicaid expansions were associated with a significantly greater increase in the percentage of Medicaid-insured patients with HNSCC, an increase in localized diseases at diagnosis for the overall cohort, and improved TTI for patients with nonoropharyngeal HNSCC. Selective state-level uptake of Medicaid expansion may exacerbate existing regional disparities in access to care and outcomes among patients with HNSCC,” concluded the study authors. “As data mature, additional research addressing the associations of Medicaid expansions with disparities and survival after diagnosis is warranted.”

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January, 2020|Oral Cancer News|

How Marijuana Accelerates Growth of HPV-related Head and Neck Cancer Identified

University of California San Diego School of Medicine researchers have identified the molecular mechanism activated by the presence of tetrahydrocannabinol (THC) — the ingredient that causes people to feel the euphoria or “high” associated with cannabis — in the bloodstream that accelerates cancer growth in patients with human papillomavirus (HPV)-positive head and neck squamous cell carcinoma.

“HPV-related head and neck cancer is one of the fastest growing cancers in the United States. While at the same time, exposure to marijuana is accelerating. This is a huge public health problem,” said Joseph A. Califano III, MD, senior author and professor and vice chief of the Division of Otolaryngology in the Department of Surgery at UC San Diego School of Medicine.

Head and neck squamous cell carcinoma is the sixth most common cancer worldwide. These cancers begin in the cells that line the mucous membranes inside the mouth, nose and throat. Approximately 30 percent of cases of this disease are related to HPV infection, and it is these cases, in particular that are on the rise. Califano suggested increased marijuana use may be a driving factor.

Previous studies have linked daily marijuana exposure to an increased prevalence of HPV-related throat cancer. However, a mechanism linking cannabis exposure to increased growth of the cancer was unknown.

Reporting in the January 13, 2020 online edition of Clinical Cancer Research, a journal of the American Association for Cancer Research, researchers outline how the presence of THC in the bloodstream activates the p38 MAPK pathway, which controls programed cell death called apoptosis. When activated, p38 MAPK prevents apoptosis from occurring, thus allowing cancer cells to grow uncontrollably.

Working with Chao Liu, MD, visiting scientist at UC San Diego and a physician at China’s Central South University, and other colleagues, Califano and team used animal and human cell lines to show that THC turns p38 MAPK on and were able to stop the growth of HPV-positive head and neck cancer by turning off the pathway.

The team then analyzed blood samples from patients with HPV-related throat cancer who had their genomes comprehensively mapped to define activated gene pathways. Similar to the cell lines, the blood samples showed p38 MAPK activation and loss of apoptosis in tumors from patients with THC in their blood.

The authors said studies and public opinion suggestions that THC and other cannabis products have cancer-fighting properties need additional, more critical evaluation. Past studies showing anticancer effects of THC and other cannabinoids often used levels of THC higher than those found with recreational use, but doses used recreationally clearly activate a cancer-causing pathway, said Califano.

“We now have convincing scientific evidence that daily marijuana use can drive tumor growth in HPV-related head and neck cancer,” said Califano. “Marijuana and other cannabis products are often considered benign, but it is important to note that all drugs that have benefits can also have drawbacks. This is a cautionary tale.”

According to the Centers for Disease Control and Prevention (CDC), HPV infections are responsible for approximately 35,000 new cancer diagnoses each year in the United States. Infection is so common that nearly all men and women will get at least one type of HPV at some point in their lives. Most clear up on their own, without the person ever knowing they’ve had it.

Several vaccines are available that can prevent the majority of HPV-related cancers. The vaccines work best when they are given before a person is exposed to the virus. The CDC recommends vaccinating boys and girls age 11 to 12 years old but it can be administered as early as age 9.

According to the National Institute on Drug Abuse, 15 percent of youth 12 to 17 years old and 47 percent of adults age 26 and older have used or tried marijuana.

Together, a low HPV vaccination rate and an increase in marijuana use among youth has the makings of a storm, said Califano, physician-in-chief and director of the Head and Neck Cancer Center at Moores Cancer Center at UC San Diego Health.

Moores Cancer Center is one of only 51 National Cancer Institute-designated Comprehensive Cancer Centers in the country and the only such center in San Diego County.

Treatment options for patients with early- or late-stage head and neck cancers include minimally invasive surgery, reconstruction and rehabilitation, proton therapy and other radiation therapy, innovative clinical trials and targeted therapy, including immunotherapy.

The Head and Neck Cancer Center provides comprehensive care that includes counseling, education and support groups, nutrition, dental rehabilitation, speech and language therapy and social workers to help patients through every step of the process beginning with diagnosis to support lifelong wellness.

Califano and team are now looking at whether cannabidiol, or CBD, has a similar effect to THC. CBD is another major chemical compound found in marijuana, but does not produce the “high” and is now commonly used in various over-the-counter products, such as lotions, ointments and edibles.

In addition, the team is investigating whether p38 MAPK can be targeted with drugs to stop HPV-related head and neck cancer from growing.

Co-authors include: Chao Liu, Sayed Sadat, Koji Ebisumoto, Akihiro Sakai, Bharat Panuganti, Shuling Ren, Yusuke Goto, Sunny Haft, Takahito Fukusumi, Mizuo Ando, Yuki Saito, Pablo Tamayo, Huwate Yeerna, William Kim, Jacqueline Hubbard, Andrew Sharabi and J. Silvio Gutkind from UC San Diego; and Theresa Guo from Johns Hopkins Medical Institutions.

Funding for this research came, in part, from the National Institute of Dental and Craniofacial Research and National Institute of Health (R01 DE023347, U01CA217885, R01HG009285, R01CA121941 and P30CA023100).

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January, 2020|Oral Cancer News|

Healthy diet may avert nutritional problems in head, neck cancer patients

Source: medicalxpress.com
Author: University of Illinois at Urbana-Champaign

At least 90 percent of head and neck cancer patients develop symptoms that affect their ability or desire to eat, because of either the tumor itself or the surgery or radiation used to treat it. These problems, called nutrition impact symptoms, have wide-ranging negative effects on patients’ physical and mental health and quality of life.

However, patients who eat foods high in antioxidants and other micronutrients prior to diagnosis may reduce their risks of developing chronic nutrition impact symptoms up to one year after being diagnosed with head or neck cancer, according to a recent study led by researchers at the University of Illinois.

The scientists analyzed the dietary patterns of 336 adults with newly diagnosed head and neck cancers and these patients’ problems with eating, swallowing and inflammation of the digestive tract. This painful inflammatory condition, called mucositis, is a common side effect of radiation treatment and chemotherapy.

The mitigating effects of a healthy diet were particularly significant in people who had never smoked and in patients who were underweight or normal weight at diagnosis, who often experience the greatest eating and digestive problems during treatment, said Sylvia L. Crowder, the paper’s first author.

Crowder is a research fellow in the Cancer Scholars for Translational and Applied Research program, a collaborative initiative of the U. of I. and Carle Foundation Hospital in Urbana, Illinois.

“While previous work has established that the presence of nutrition impact symptoms is associated with decreased food intake and weight loss, no studies have examined how pre-treatment dietary intake may influence the presence of these symptoms later in the course of the disease,” Crowder said.

In the early 2000s, researchers hypothesized that consuming antioxidant supplements might protect patients’ normal cells from damage during radiotherapy, enabling them to better tolerate treatment and higher dosages.

Accordingly, prior research by Anna E. Arthur, a professor of food science and human nutrition at the U. of I. and the current study’s corresponding author, indicated that eating a diet of whole foods abundant in antioxidants and phytochemicals improved recurrence and survival rates in head and neck cancer patients.

Like Arthur’s prior research, the new study was conducted with patients of the University of Michigan Head and Neck Specialized Program of Excellence.

Data on patients’ tumor sites, stages and treatment were obtained from their medical records. More than half of these patients had stage 4 tumors at diagnosis.

Prior to starting cancer treatment and again one year post-diagnosis, the patients completed a questionnaire on their diet, tobacco and alcohol use, and quality of life. Patients reported whether they experienced any of seven nutrition impact symptoms—such as pain or difficulty chewing, tasting or swallowing foods and liquids—and rated on a five-point scale how bothersome each symptom was.

In analyzing the patients’ eating habits, the scientists found that they followed either of two major dietary patterns—the Western pattern, which included high amounts of red and processed meats, fried foods and sugar; or the prudent pattern, which included healthier fare such as fruits and vegetables, fish and whole grains.

Patients who ate healthier at diagnosis reported fewer problems with chewing, swallowing and mucositis one year after treatment, the scientists found.

“While the origin and development of nutrition impact symptoms are complex and varied, they generally share one common mechanism—cell damage due to inflammation,” said Arthur, who is also an oncology dietitian with the Carle Cancer Center. “The prudent dietary pattern has the potential to reduce inflammation and affect the biological processes involved in the pathogenesis of these symptoms.”

The scientists hypothesized that some patients may begin eating healthier after being diagnosed with cancer, potentially counteracting the pro-inflammatory effects of their previous dietary habits.

Reverse causation was possible too, they hypothesized—patients’ lack of symptoms may have enabled them to consume a broader range of foods, including healthier whole foods, before their cancer was discovered.

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January, 2020|Oral Cancer News|