Saliva testing may allow early detection of human papillomavirus–driven head and neck cancers

Source: medicalxpress.com
Author: Elsevier

Cancer causing high-risk human papillomaviruses (HR-HPV) are responsible for the rising incidence of HR-HPV–driven head and neck cancers (HNC), particularly oropharyngeal cancers (OPC, or throat cancers). Investigators have determined that HR-HPV DNA can be detected in saliva in most patients with HPV-driven OPC at the time of diagnosis. This work highlights a potentially life-saving screening program based on salivary HR-HPV DNA testing for early cancer detection and patient monitoring. Their findings appear in The Journal of Molecular Diagnostics.

“Despite the upsurge in HPV-driven HNC, there are no early detection methods or screening strategies for this cancer type, unlike cervical cancer, which is caused by the same virus. Biomarkers enabling early detection, monitoring and disease prognostication are warranted to combat the rising incidence of HPV-driven OPC,” observed lead investigator Chamindie Punyadeera, Ph.D., head, Saliva & Liquid Biopsy Translational Laboratory, School of Biomedical Science, Faculty of Health, Queensland University of Technology (QUT), and Translational Research Institute, Brisbane, QLD, Australia.

Dr. Punyadeera and her colleagues investigated the efficacy of salivary HPV detection as a biomarker of HPV-HNC and survival patterns in patients with OPC to evaluate the utility of salivary HR-HPV as a prognostic biomarker for OPC.

Saliva testing was performed on 491 patients at the time of first diagnosis of HNC and 10 patients with recurring HNC. Forty-three percent were positive for salivary HR-HPV DNA. HPV16, a high-risk strain of the virus, was detected in 92% of the HPV-positive saliva samples. The vast majority of HPV-HNC had arisen from the oropharynx, especially from the palatine tonsils and the base of the tongue, confirming that the oropharynx is the hotspot for these cancers. Seventy-two percent of OPC patients were positive for HR-HPV DNA in their saliva, and tumor p16 overexpression was observed in 89.3%. These findings support the utility of saliva testing as a biomarker for facilitating early detection and screening of HR-HPV DNA.

Two hundred and fifteen patients with OPC were followed for up to five years. Salivary HR-HPV–positive patients had a clear survival advantage over their salivary HR-HPV–negative counterparts. The median event-free survivals were 205 months for HR-HPV–positive patients, compared to 82 months for HR-HPV–negative patients. Although the number of patients with recurrent cancer in the study was small, findings indicate that salivary HR-HPV tends to be positive in the majority of patients at the locoregional point of occurrence.

“When the noninvasive nature and convenience of the collection are considered, salivary HR-HPV testing is an ideal mode of screening asymptomatic individuals and the long-term monitoring of HPV-driven HNC patients. Our findings indicate that in the near future, salivary HR-HPV testing will become part of routine clinical management for HPV-driven OPC patients,” noted Dr. Punyadeera.

“Liquid biopsy in HNC has the potential to be truly transformative,” explained co-investigator Sarju Vasani, MD, Royal Brisbane and Women’s Hospital; and the Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia. “It has the potential to personalize treatment selection and aid in assessing disease prognosis. It can help us select patients for adjuvant treatment and will alert us to recurrence before imaging or clinical examination has detected any specific abnormality. It is only a matter of time before these biomarkers translate from research settings to clinical practice.”

In some countries, including the United States, HNC and particularly OPC, have surpassed cervical cancers as the most common HPV-driven cancer. Patients are usually diagnosed at an advanced stage. In the early stages, these cancers are difficult to locate with imaging studies or physical examination. The oropharynx is difficult to access, and detection is further complicated if these smaller lesions are hidden in the crevices of the tonsils. These cancers can metastasize at an early stage, even when the primary cancer is still undetectable in size.

2021-09-22T09:38:25-07:00September, 2021|Oral Cancer News|

World’s largest trial Of “Game-Changer” early cancer test begins in UK

Source: www.iflscience.com
Author: Maddy Chapman

Yesterday, England’s National Health Service (NHS) launched the world’s largest trial of a blood test that can detect more than 50 types of cancer before symptoms appear.

The trial aims to recruit 140,000 volunteers from different ethnic backgrounds, aged between 50 and 77, and living in eight areas across England. The test itself, the Galleri test, is a simple blood test that checks for the earliest signs of cancer. Ideally, it can be used to identify cancers at their earliest stages – stage one or two.

When it comes to detecting cancer, the earlier the better. A diagnosis at stage one can increase chances of survival by five to 10 times, compared to a diagnosis at stage four. The new test, developed by healthcare company GRAIL, is particularly effective at identifying cancers that are difficult to diagnose early – head and neck, bowel, lung, pancreatic, and throat cancers, for example.

“This quick and simple blood test could mark the beginning of a revolution in cancer detection and treatment here and around the world,” NHS chief executive Amanda Pritchard said in a statement.

“By finding cancer before signs and symptoms even appear, we have the best chance of treating it and we can give people the best possible chance of survival.”

The Galleri test works by identifying fragments of DNA that have been shed by tumors into the bloodstream. Participants in the trial, who must not have received a cancer diagnosis in the last three years, will therefore be asked to give an initial blood sample, before returning after 12 months, and then again after two years, to give repeat samples.

The trial is being run by Cancer Research UK and King’s College London Cancer Prevention Trials Unit in partnership with NHS England and GRAIL. It is a randomized control trial, meaning that half of the individuals involved will have their blood sample tested with the Galleri test and half will not. The samples of this latter group will be stored and may be screened in the future, allowing the scientists to find out whether the test does in fact help to identify cancers early. Neither group will know if they’re in the test group, unless early signs of cancer are detected, in which case the individual would be notified and referred for further tests.

Currently, the trial is operating through eight NHS Cancer Alliances spanning Cheshire and Merseyside, Cumbria, Greater Manchester, the North East, West Midlands, East Midlands, East of England, Kent and Medway, and South East London. Results are expected by 2023, and, if successful, it could be rolled out to a further 1 million people in England in 2024 and 2025.

According to the NHS, one in two people will develop some form of cancer in their lifetime. It is therefore hugely important that we develop screening methods capable of identifying these cancers as early as possible, to open up a broader range of treatment options and improve chances of survival.

Previous research in the US has found that the Galleri test identified more than 67 percent of 12 pre-specified stage one to three cancers, which account for approximately two-thirds of annual US cancer deaths. It also picked up around 41 percent of all cancers.

“The test could be a game-changer for early cancer detection and we are excited to be leading this important research,” said Professor Peter Sasieni, Director of The Cancer Research UK & King’s College London Cancer Prevention Trials Unit and one of the trial’s lead investigators.

2021-09-15T06:09:46-07:00September, 2021|Oral Cancer News|

Chemotherapy and radiation therapy issues: What audiologists need to know

Source: journals.lww.com
Author: A. Croutch, Carl AuD

With hearing loss, tinnitus, and imbalance as among the numerous side-effects of cancer treatment,1 audiologists play a critical role in monitoring patients receiving chemotherapy and radiation therapy. Sensorineural hearing loss (SNHL) attributed to chemotherapy and radiation therapy is usually permanent, making audiometric monitoring essential to detect its early occurrence.2

Cisplatin, carboplatin & radiation therapy
Chemotherapy is used to treat cancer, control the growth and spread of cancer cells, and ease cancer symptoms. Cisplatin and carboplatin are two common antineoplastic agents used to treat testicular, ovarian, breast, esophageal, lung, and head and neck cancers among others. Besides hearing loss, these can cause other side effects including kidney, gastrointestinal disorders, allergic reactions, decreased immunity to infections, and hemorrhaging. Cisplatin was first found to have cytotoxic properties in the 1960s, and in 1978 was the first platinum compound approved by the FDA for cancer treatment.3 On the other hand, carboplatin is less potent than cisplatin and does have fewer side effects, especially on kidney problems.3

Both drugs work by interfering with DNA repair mechanisms causing DNA damage and inducing apoptosis in cancer cells. Cancerous cells cannot limit cell division as do normal cells. Normal cells cease dividing when they encounter similar cells whereas cancerous cells do not. The effectiveness of chemotherapy is determined by its ability to damage the RNA or DNA that gives the cell instructions to copy itself. The cells will die if they are unable to divide. The more quickly they are dividing, the more effective is the chemotherapy.4

The incidence of hearing loss in post-chemotherapy patients is highly variable, ranging from 17% to 80% depending on the age, baseline hearing levels, and cisplatin dosage.5 Generally, those receiving a higher dose of cisplatin showed more hearing loss than those receiving a smaller dose.6,7

In addition to chemotherapy, a cancer patient may also be treated with radiation therapy (RT), which is the use of high-energy X-rays or other types of energy such as protons to kill cancer cells. RT also works by destroying the genetic material that regulates cell growth and division. The objective of RT is to kill fewer normal cells since it can damage both cancerous and normal cells. The incidence of SNHL ranges from 0-43% depending on the radiation dosage to the cochlea as well as age and baseline hearing levels.5 Radiation dosage reaching the cochlea may be higher when treating cancer of the nasopharynx, parotid salivary gland, and paranasal sinuses compared to other sites.7

RT can cause both SNHL and conductive hearing loss (CHL). SNHL may occur if the RT is directed near the cochlea, and CHL if it is near the Eustachian tube. Factors that may influence whether a hearing loss occurs include the strength and direction of the beam, location, size of the tumor, patient age, and pre-treatment hearing levels. The frequency of otitis media with effusion in head and neck cancer patients undergoing RT was found to be 39.3% with retracted tympanic membrane and 7.1% with air-fluid levels seen.8 Treatment of head and neck squamous cell carcinoma (HNSCC) patients using radiation can result in mixed (SNHL and CHL) hearing loss, which can be more severe in those with tumors near the ear as well as those treated with cisplatin.7

Stages & grades of cancer
Cancer has four stages: Stage 0 is when the cancer has not spread from its original location (in situ), Stage 1 is when a small cancer has not spread, Stage 2 is when it has grown but not spread, Stage 3 is when it may have spread to near-by tissues possibly the lymph nodes, and Stage 4 is when it has metastasized and spread to at least another body organ. Cancer is also divided into three grades, with the lower grades indicating a slower-growing malignancy and a high grade, a faster-growing one.9

Nasopharyngeal cancer (NPC) is frequently seen in head and neck clinics and offices. Tumors originating in the nasopharynx may be benign or malignant. The majority of nasopharyngeal cancers are nasopharyngeal carcinoma. A carcinoma is a cancer that originates in the epithelial cells, which line the internal and external surfaces of the body. A patient about to undergo chemotherapy and radiation therapy should be seen for a baseline audiogram prior to the initiation of any treatment. An in-depth history of any occupational or recreational noise exposure is essential.

Audiometric test battery
Both chemotherapy and noise exposure can result in high-frequency SNHL. Distinguishing between the two can be difficult, which is why obtaining a baseline audiogram and careful case history is essential. One tip-off may be the high-frequency notch seen between 3000 and 6000 Hz often present in cases of noise trauma.

Speech-in-noise testing should be done since understanding speech in background noise is a common complaint from most adults. Using the Quick Speech-in-Noise (Q-Sin) test may aid in the treatment of these patients.1 Extended high-frequency pure-tone audiometry (EHF-PT) and distortion-product otoacoustic emissions (DP-OAEs) are useful tests in monitoring these patients. Ototoxic effects frequently occur initially at frequencies above 8 kHz. EHF-PT are tested from 8-20 kHz and can often detect hearing loss in these ranges before it affects the speech frequencies. This will enable the oncologist to monitor the treatment and if possible, conserve the patient’s hearing. DP-OAEs are measured from 0.5-8 kHz. They can determine if the outer hair cells are intact since they are usually damaged prior to inner hair cells (IHC) and can result in a more severe hearing loss compared with outer hair cell damage. This may provide useful information to the oncologist. It is also an objective test and can be used regardless of the patient’s age or state of health.2

Criteria for change
In addition to baseline testing, follow-up testing should occur after each treatment, when the course of treatment is completed, and on an annual basis or sooner if indicated. A significant change is considered per the ASHA 1994 guidelines13:

>= 20 dB change at one frequency
>= 10 dB change at two consecutive frequencies
No response at three consecutive frequencies where responses were previously obtained

Ototoxicity can be grouped by using at least 13 different classification systems based on changes from a baseline audiogram to those that focus on the functional impact of the hearing loss. These scales do not consider high-frequency audiometry.13

Despite these grading scales, most clinicians do not use them on a routine basis. How ototoxicity is defined is a significant part of the inconsistencies between pre- and post-clinical data across patient groups.13

Two commonly used ototoxic grading systems in use are the Common Terminology Criteria for Adverse Events version 4 (CTCAEv4) and the American Speech-Language-Hearing Association (ASHA) system. Each of these systems has certain shortcomings.13

To devise a more comprehensive system, Theunissen et al., purposed the TUNE grading system, which details the shortcomings of both the CTCAEv4 and the ASHA systems14 and propose seven different grade levels:

  • Grade 0: No hearing loss
  • Grade 1a: Threshold shift >= 10 dB at 8, 10, and 12.5 kHz OR subjective complaints in the absence of a threshold shift
  • Grade 1b: Threshold shift >= 10 dB at 1, 2, and 4 kHz
  • Grade 2a: Threshold shift >= 20 dB at 8, 10, and 12.5 kHz
  • Grade 2b: Threshold shift >= 20 dB at 1, 2, and 4 kHz
  • Grade 3: Hearing level >= 35 dB at 1, 2, and 4 kHz
  • Grade 4: Hearing level >= 70 dB at 1, 2, and 4 kHz

They feel this system can better assess the effects of hearing loss in daily life and can distinguish between mild, moderate, and severe degrees of ototoxicity compared to the current systems in use.14

Significant changes in DP-OAE findings were a reduction in the signal-to-noise ratio at f2 frequencies below 1 kHz of > 14 dB and a reduction of 7 dB of f2 frequencies above 1 kHz. These criteria were used by Yu, et.al.,2 but no standard criteria are available for defining changes in the DP-OAEs.15

The potential for hearing loss from chemotherapy and radiation therapy is dependent upon the patient’s baseline hearing levels and the strength and frequency of the treatments. Dosage is often determined by the patient’s body surface area indicated by m2. It is calculated by taking the square root of the product of the weight in kilograms times the height in centimeters divided by 3600. The average body surface area for adult men is 1.9 m2 and for women is 1.6 m2.16 Typical doses vary from 25-100 mg/m2. The frequency of treatments is also patient-specific. Chemotherapy is given in cycles—-typically one week of chemotherapy followed by three weeks of rest.

Treatment Options
SNHL may be treated with hearing aids, and CHL by medicine, myringotomy, or PE tube placement. If any hearing loss is found, treatment options should be discussed with the patient. In cases of SNHL that will benefit from amplification, the patient may wish to postpone it until after the cancer treatment has been completed. Some may wish to obtain hearing aids right away to better participate and understand their treatment options. In patients with CHL, a referral to HNS is usually indicated. At Kaiser Permanente, for example, patients with a unilateral CHL without an NPC diagnosis are referred to HNS as that may be an indication of NPC.

Overall, audiologists need to monitor hearing loss in cancer patients undergoing chemotherapy and radiation therapy and provide treatment and counseling when hearing loss has become inevitable.

References:
1. Baguley D, Prayuenyong P. Looking beyond the audiogram in ototoxicity associated with platinum-based chemotherapy. Cancer Chemother Pharmacol. 2020; 82(2): 245-250.

2. Yu K, Choi, C. et.al. Comparison of the effectiveness of monitoring cisplatin-induced ototoxicity with extended high-frequency pure-tone audiometry or distortion-product otoacoustic emission. Korean J of Audiology. 2014;18(2):58-68.

Source:
The Hearing Journal: September 2021 – Volume 74 – Issue 9 – p 44-45

2021-09-09T06:48:49-07:00September, 2021|Oral Cancer News|

UArizona clinical trail expanding after early results with personalized cancer vaccine

Source: www.kold.com
Author: Karly Tinsley

Despite the pandemic, groundbreaking research has not stopped at the University of Arizona. Researchers with the UArizona Health Sciences are working to help treat cancer by using personalized vaccines. It works in combination with the immuno-therapy drug Pembrolizumab.

According to the UArizona, Julie E. Bauman, MD, MPH, deputy director of the University of Arizona Cancer Center and a professor of medicine and chief of the Division of Hematology and Oncology at the UArizona College of Medicine – Tucson, presented preliminary data on the first 10 patients with head and neck cancer, seven of which were treated at Banner – University Medicine, the clinical partner for the UArizona Cancer Center. Five of the 10 patients experienced a clinical response to the personalized cancer vaccine, and two patients had a complete response after the treatment (no detectable disease present).

Molly Cassidy is one of the 10 who went through the trial.

“I was a young healthy woman, so it was a big shock to get diagnosed,” said Cassidy.

She was first diagnosed with oral cancer after complaining of an ear ache. Dentists initially found a tumor in her tongue that was later identified as cancer. She then went through treatment for the tumor, but her cancer came back aggressively.

“I had tumors throughout my neck, in my lungs, I was really really ill,” said Cassidy.

At this time she was seeing Dr. Bauman, who said they both understood her chances of survival were slim at that point.

“I was writing my will,” said Cassidy.

“She asked me to prepare her. It was not viewed as curable and she began to do end of life work,” said Dr. Bauman.

That’s when Dr. Bauman offered her the option of joining her clinical trial. It’s a treatment tailored specifically to the patient. Their cancer cells are used to develop a personalized vaccine that teaches their immune system how to recognize and destroy their cancer.

According to UArizona, to identify the patient-specific mutations of the cancer, mutated DNA from the patient’s tumor is simultaneously sequenced with healthy DNA from the patient’s blood. Computers compare the two DNA samples to identify the unique cancer mutations.

The results are used to develop a set of genetic instructions that are loaded onto a single molecule of messenger RNA (mRNA) and made into a vaccine. These instructions teach immune cells such as T-cells – white blood cells that help protect against infection – how to identify and attack the mutated cancer cells.

“It’s a medicine that is individualized, personalized, and is not one size fits all,” said Dr. Bauman.

Cassidy began the series of 9 shots of her specific vaccine and for the first time things were improving.

“We were cautiously hopeful,” said Dr. Bauman.

It makes her one of two patients in the trial who’ve responded completely, with cancer no longer detectable on a CT scan.

“To see that reversed was striking, stunning, extremely unusual,” said Dr. Bauman.

The trial is now being expanded to more patients due to the early results, as Dr. Bauman is now working with 40 patients with head and neck cancer. Giving those like Cassidy a second chance to picture life after a cancer diagnosis.

“To have such a great response has given me so much of my life back,” said Cassidy.

Her treatment is for two years in the trial, and so far Cassidy remains in complete response.

Dr. Bauman said a personalized vaccine also strives to be less toxic on the body, by not awakening cells that typically attack the organs with regular immunotherapy.

2020-11-21T10:33:28-07:00November, 2020|Oral Cancer News|

New blood test can detect wide range of cancers, now available to at risk individuals in clinical study at Dana-Farber

Source: www.dana-farber.org
Author: news release

In a study involving thousands of participants, a new blood test detected more than 50 types of cancer as well as their location within the body with a high degree of accuracy, according to an international team of researchers led by Dana-Farber Cancer Institute and the Mayo Clinic.

The results, published online today by the Annals of Oncology, indicate that the test – which identified some particularly dangerous cancers that lack standard approaches to screening – can play a key role in early detection of cancer. Early detection can often be critical to successful treatment.

Developed by GRAIL, Inc., of Menlo Park, Calif., the test uses next-generation sequencing to analyze the arrangement of chemical units called methyl groups on the DNA of cancer cells. Adhering to specific sections of DNA, methyl groups help control whether genes are active or inactive. In cancer cells, the placement of methyl groups, or methylation pattern, is often markedly different from that of normal cells – to the extent that abnormal methylation patterns are even more characteristic of cancer cells than genetic mutations are. When tumor cells die, their DNA, with methyl groups firmly attached, empties into the blood, where it can be analyzed by the new test.

“Our previous work indicated that methylation-based tests outperform traditional DNA-sequencing approaches to detecting multiple forms of cancer in blood samples,” said Dana-Farber’s Geoffrey Oxnard, MD, co-lead author of the study with Minetta Liu, MD, of the Mayo Clinic. “The results of this study suggest that such assays could be a feasible way of screening people for a wide variety of cancers.”

In the study, investigators used the test to analyze cell-free DNA (DNA from normal and cancerous cells that had entered the bloodstream upon the cells’ death) in 6,689 blood samples, including 2,482 from people diagnosed with cancer and 4,207 from people without cancer. The samples from patients with cancer represented more than 50 cancer types, including breast, colorectal, esophageal, gallbladder, bladder, gastric, ovarian, head and neck, lung, lymphoid leukemia, multiple myeloma, and pancreatic cancer.

The overall specificity of the test was 99.3%, meaning that only 0.7% of the results incorrectly indicated that cancer was present. The sensitivity of the assay for 12 cancers that account for nearly two-thirds of U.S. cancer deaths was 67.3%, meaning the test could find the cancer two-thirds of the time but a third of the time the test returned a negative result. Within this group, the sensitivity was 39% for patients with stage I cancer, 69% for those with stage II, 83% for those with stage III, and 92% for those with stage IV. The stage I-III sensitivity across all 50 cancer types was 43.9%. When cancer was detected, the test correctly identified the organ or tissue where the cancer originated in more than 90% of cases – critical information for determining how the disease is diagnosed and managed.

“Our results show that this approach to testing cell-free DNA in blood can detect a broad range of cancer types at virtually any stage of the disease, with specificity and sensitivity approaching the level needed for population-level screening,” Oxnard observed. “The test can be an important part of clinical trials for early cancer detection.”

The study was funded by GRAIL, Inc. As part of further validation research, Dana-Farber has joined a multi-center clinical trial of the test. The PATHFINDER study intends to enroll about 6,200 participants across the U.S. Participants in the study will have the results of the test communicated to them.

Dana-Farber researchers are aiming to enroll hundreds of individuals, mainly cancer survivors and other people who are at elevated cancer risk. Enrollment is limited to individuals who receive care through the Partners HealthCare system.

New blood test capable of detecting multiple types of cancer

Source: www.sciencedaily.com
Author: Materials provided by Dana-Farber Cancer Institute.

A new blood test in development has shown ability to screen for numerous types of cancer with a high degree of accuracy, a trial of the test shows. Dana-Farber Cancer Institute investigators will present the results of the multi-center trial during a session today at the European Society for Medical Oncology (ESMO) 2019 Congress.

The test, developed by GRAIL, Inc., uses next-generation sequencing technology to probe DNA for tiny chemical tags (methylation) that influence whether genes are active or inactive. When applied to nearly 3,600 blood samples — some from patients with cancer, some from people who had not been diagnosed with cancer at the time of the blood draw — the test successfully picked up a cancer signal from the cancer patient samples, and correctly identified the tissue from where the cancer began (the tissue of origin). The test’s specificity — its ability to return a positive result only when cancer is actually present — was high, as was its ability to pinpoint the organ or tissue of origin, researchers found.

The new test looks for DNA, which cancer cells shed into the bloodstream when they die. In contrast to “liquid biopsies,” which detect genetic mutations or other cancer-related alterations in DNA, the technology focuses on modifications to DNA known as methyl groups. Methyl groups are chemical units that can be attached to DNA, in a process called methylation, to control which genes are “on” and which are “off.” Abnormal patterns of methylation turn out to be, in many cases, more indicative of cancer — and cancer type — than mutations are. The new test zeroes in on portions of the genome where abnormal methylation patterns are found in cancer cells.

“Our previous work indicated that methylation-based assays outperform traditional DNA-sequencing approaches to detecting multiple forms of cancer in blood samples,” said the study’s lead author, Geoffrey Oxnard, MD, of Dana-Farber. “The results of the new study demonstrate that such assays are a feasible way of screening people for cancer.”

In the study, investigators analyzed cell-free DNA (DNA that had once been confined to cells but had entered the bloodstream upon the cells’ death) in 3,583 blood samples, including 1,530 from patients diagnosed with cancer and 2,053 from people without cancer. The patient samples comprised more than 20 types of cancer, including hormone receptor-negative breast, colorectal, esophageal, gallbladder, gastric, head and neck, lung, lymphoid leukemia, multiple myeloma, ovarian, and pancreatic cancer.

The overall specificity was 99.4%, meaning only 0.6% of the results incorrectly indicated that cancer was present. The sensitivity of the assay for detecting a pre-specified high mortality cancers (the percent of blood samples from these patients that tested positive for cancer) was 76%. Within this group, the sensitivity was 32% for patients with stage I cancer; 76% for those with stage II; 85% for stage III; and 93% for stage IV. Sensitivity across all cancer types was 55%, with similar increases in detection by stage. For the 97% of samples that returned a tissue of origin result, the test correctly identified the organ or tissue of origin in 89% of cases.

Detecting even a modest percent of common cancers early could translate into many patients who may be able to receive more effective treatment if the test were in wide use, Oxnard remarked.

Note:
Materials provided by Dana-Farber Cancer Institute. Content may be edited for style and length.

2019-09-29T06:38:28-07:00September, 2019|Oral Cancer News|

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

E-cigarettes ‘could give you mouth cancer by damaging your DNA’

Source: metro.co.uk
Author: Zoe Drewett

Researchers say vaping could lead to an increased risk of developing mouth cancer. A study carried out by the American Chemical Society found evidence to suggest using e-cigarettes raises the level of DNA-damaging compounds in the mouth. If cells in the body are unable to repair the DNA damage after vaping, the risk of cancer can increase, the study claims.

The long-term effects of e-cigarettes are not yet known but researchers say they should be investigated further (Picture: PA)

The researchers admit the long-term health effects of using electronic cigarettes are still unknown. Researcher Dr Romel Dator said: ‘We want to characterize the chemicals that vapers are exposed to, as well as any DNA damage they may cause.’

Since they were introduced in 2004, e-cigarettes have been marketed as a safer alternative to smoking. But the team carrying out the study claim genetic material in the oral cells of people who vape could be altered by toxic chemicals. E-cigarettes work by heating a liquid – which usually contains nicotine – into an aerosol that the user inhales. It is often flavoured to taste like fruit, chocolate or bubblegum.

‘It’s clear that more carcinogens arise from the combustion of tobacco in regular cigarettes than from the vapor of e-cigarettes,’ Silvia Balbo, the project’s lead investigator said. ‘However, we don’t really know the impact of inhaling the combination of compounds produced by this device. ‘Just because the threats are different doesn’t mean that e-cigarettes are completely safe.’ The latest study, due to be presented at a meeting of the American Chemical Society this week, analysed the saliva and mouth cells of five e-cigarette users before and after a 15-minute vaping session.

Researchers found levels of the toxic chemicals formaldehyde, acrolein and methylglyoxal had increased after vaping. Now they plan to follow up on the preliminary study with a larger one involving more e-cigarette users. They also want to see how the level of toxic chemicals differs between e-cigarette users and regular cigarette smokers.

According to a 2016 report by the US Surgeon General, 13.5% of middle school students, 37.7% of high school students and 35.8% of 18 to 24-year-olds have used e-cigarettes, compared with 16.4% of adults aged 25 and over. Ms Balbo, a professor at the Masonic Cancer Center at the University of Minnesota, said:

‘Comparing e-cigarettes and tobacco cigarettes is really like comparing apples and oranges.  The exposures are completely different. ‘We still don’t know exactly what these e-cigarette devices are doing and what kinds of effects they may have on health, but our findings suggest that a closer look is warranted.’

 

How oral bacteria could lead to breakthroughs in cancer, weight loss, and overall health

Source: www.mensjournal.com
Author: Marjorie Korn

As if you don’t have enough reasons to feel guilty for avoiding the dentist, it turns out a healthy mouth is linked to a lot more. than the absence of cavities and plaque. Researchers say our mouths are home to an ecosystem of billions of bacteria with influence far beyond our teeth and gums—influence they are just starting to unravel.

“We know that oral bacteria affect almost every aspect of our health—metabolism, cardiovascular system, neurological health, and more,” says Yiping Han, a microbiologist at Columbia University Dental and Medical Schools in New York City.

Scientists like Han are grappling with questions that will change our understanding of how the body works. Not only are they studying the ways bacteria in our mouths interact with one another but they’re also investigating why mouth bacteria show up in other parts of the body, such as the lining of the heart, around tumors, and even in the brain.

The idea that our bodies host a world of bacteria may sound familiar. For the past decade, we’ve seen a surge of scientific research on the gut microbiome, which describes the bacteria that live in the gastrointestinal tract. Gut bacteria seem to have a hand in a surprising number of functions, from the predictable (like digestion and nutrient uptake) to the more surprising (obesity and depression). So it makes sense that the next place for a breakthrough would be upstream—the mouth.

Scientists have identified 700-plus strains of bacteria swiped from cheeks around the world, which makes the mouth the second-largest microbiome in the body (just behind the GI tract). And they’re trying to figure out the roles of these strains. Sussing out what combination of bacteria makes a person healthy or sick would be a major step in staving off diseases.

For instance, certain bacteria are the culprits behind a bunch of maladies that send you to the dentist, like plaque, gum disease, and bad breath. Those kinds of discoveries get dentists excited. That said, what’s really interesting is that oral bacteria pop up all over the body and are linked to a host of other medical issues.

This newfound knowledge is made possible by advancements in DNA and RNA decoding, and microscopic imaging. Scientists upload new information to oral microbiome repositories at the Forsyth Institute in Cambridge, Massachusetts; Ohio State University; and Los Alamos National Laboratory in New Mexico.

This knowledge sharing has helped to unravel some long-standing medical mysteries. For instance, doctors have, for decades, puzzled over why people with cardiovascular issues, like endocarditis (an infection of the lining of the heart) or clogged arteries, also have gum disease. Turns out that the inflamed gums allow oral bacteria to get into the bloodstream, where they can wreak havoc on the heart and vessels.

That’s not the only way that bacteria in the mouth end up elsewhere. Swallowing a teaspoon of saliva disperses 5 million bacteria into your digestive tract, says Colleen Cavanaugh, a biology researcher at Harvard University. (Preliminary findings suggest that oral sex can be a conduit, too, Han says.)

“It’s a mobile microbiome,” Han says. “There are some bacteria that, when they’re in the mouth, they’re mostly harmless, but when they go to other sites in the body, they become pathogens,” Han says.

Take Fusobacterium nucleatum, or Fn for short. In your mouth, it causes dental plaque. But it’s a menace if it encounters a colon cancer tumor. Han’s lab has found that Fn acts as an accelerant, prompting a tumor to grow faster, protecting it from chemotherapy drugs, and encouraging it to metastasize to the liver (which is particularly dangerous). Fn has also been found in the joint fluid in people with rheumatoid arthritis, an inflammatory disease. And it’s even been detected in brain abscesses, meaning it has the ability to jump the blood-brain barrier, which is quite a feat— very few substances that float in the blood can get to the brain and spinal cord.

Does Fn cause colon cancer? No. But down the road, knowing that a patient’s tumor is being bodyguarded by Fn may change the way he’s cared for.

And new research suggests that the oral bacteria can also have a direct impact on how cancer plays out. A study published in Scientific Reports found that people who are diagnosed with oral or throat cancers—which are notoriously difficult to treat and have high rates of mortality—had similar oral microbiome compositions.

There are a couple of explanations for why people with the same disease would share similar bacteria. It could be that bad habits like drinking, smoking, and poor oral hygiene create the perfect conditions for certain bacteria to grow (and others to die off). Genetics probably play a role, in that a person’s mouth is predisposed to having more of some bacteria, less of others. Most likely, it’s a little bit of both. Regardless, knowing how the microbiome changes composition when it’s sick may help doctors prevent and treat disease.

Scientists are interested not only in the bacteria they find but also in what they don’t. A six-year study from the University of Copenhagen finds that not enough of bacteria called Lactobacillus can be a predictor of weight gain. We’re not at the place that simply peppering a person’s mouth with some Lactobacillus would get people to drop pounds. But that could be where things are headed.

Bacteria also interact with one another. It’s an ecosystem, after all. Decoding these relationships could be the beginning of a new way to treat oral issues, says Ted Jin. He’s the founder of Qii, which makes a canned tea drink designed to encourage balanced mouth bacteria. The beverage is more anti-plaque than anti-cancer, but it’s part of a larger effort by Jin and his team of researchers to understand the intricacies of the mouth biome in order to make better oral-care products down the road.

What experts are learning about the state of our maws isn’t entirely rosy. For one, there’s a hypothesis that the mouths of people in the U.S. aren’t as diverse as they should be. Crappy, overly processed diets with too much sugar and not enough fresh produce are not great for a healthy oral ecosystem. Nor is our fascination with all things antibacterial, which is why experts are beginning to discourage patients from using harsh mouthwashes that kill good and bad bacteria indiscriminately. (The Food and Drug Administration banned certain ingredients in antibacterial hand soap in 2016, in part because they were killing off good bacterial strains and promoting “superbugs.”)

These differences may also help explain why there are areas of the world with less-advanced oral hygiene practices, but where people generally have teeth and gums that are just fine. And in addition to geography and diet, there’s certainly a genetic component to all of this, so if your kid’s got a mouthful of cavities, you’re at least partially to blame.

Another upshot to all of this will come in the form of precision medicine. In the future, you may be able to send off some spit and receive back a mouthwash tailored specifically for your oral microbiome, Jin says. If you have too much of a certain bacteria strain, you could swish with a formula that contains another, which would act like a microscopic smart bomb to get conditions like halitosis (bad breath) or gum disease under control.

You don’t have to wait for the mouthwash of the future to do right by your mouth. For starters, eat a Mediterranean diet, says Jason Tetro, a visiting scientist at the University of Guelph in Ontario and author of The Germ Code. “Staples of the diet, such as fish and vegetables, have omega fatty acids and phytochemicals,” Tetro says. “And in some cases, things like pomegranates have antimicrobials, which seek out and kill bad bacteria and help maintain a less acidic environment.”

His secret weapon against oral inflammation? The sesame paste tahini. It helps promote an alkaline environment in the mouth, Tetro says. So if your maw feels a little sore from fast food or booze, swish with a spoonful of tahini for some low-tech relief.

And low-tech is kind of the point. While researchers like Han are teasing out microscopic secrets, one petri dish at a time, what we’re learning seems to substantiate what we already know. Brushing and flossing is still a great way to keep your oral microbiome healthy. And no more excuses: time to schedule that dentist appointment.

Changes in cancer staging: what you should know

Source: health.clevelandclinic.org
Author: staff

When you learn you have cancer, you want to know what to expect: How will doctors treat your illness? How effective is treatment likely to be?

Much depends on the way doctors first classify, or “stage,” your cancer, using the official staging manual from the American Joint Committee on Cancer. Staging guidelines continue to evolve as knowledge about individual tumor growth and innovative technologies come into play.

An ever-evolving system
“Historically, we staged cancers according to tumor size, lymph node involvement and the presence of metastases,” says oncologist Dale Shepard, MD, PhD.

“The latest staging manual incorporates new findings on the importance of changes in molecular DNA and tumor genomic profiling. This will affect many patients going forward.”

Among those most impacted by changes in staging are people newly diagnosed with breast cancer; head and neck cancer caused by human papillomavirus (HPV); or sarcoma.

How staging works
“Staging allows us to stratify patients into groups based on anatomic and other criteria. It gives us a framework for understanding the extent of disease,” Dr. Shepard explains.

Cancers are staged clinically and pathologically:

  • The clinical stage is determined during the initial workup for cancer.
  • The pathologic stage is determined by studying a surgically removed tumor sample under the microscope.

Adds Tumor Registry Manager Kate Tullio, MPH, MS, “Staging helps physicians and other researchers to compare patients with the same types of cancer to each other in a consistent way — so that we might learn more about these cancers and how to effectively treat them.”

Staging allows doctors to determine the best course of treatment for different types of cancer and helps families to understand the prognosis, or likely outcome, of that treatment.

It also allows doctors to offer patients a chance to participate in clinical trials of new therapies targeting their form of cancer.

The impact of DNA changes on breast cancer
In the past, most breast cancer patients with lymph node involvement were automatically classified as stage II or higher, and were often given chemotherapy.

“Previously, physicians considered only tumor size, lymph node involvement and spread of the cancer to distant areas of the body when staging breast cancer,” says Ms. Tullio.

Today, staging has improved with the addition of advanced multi-gene panel testing and specific information on the biology of the tumor.

“This incorporates what we have found clinically: that some patients previously identified with stage II breast cancer did better than others,” says Dr. Shepard. “In essence, patients with HER2-positive disease were more like patients with stage I disease.”

HPV’s effect on head and neck cancers
The classification of head and neck tumors has changed because of advances in genomic profiling.

“We now have a separate system for classifying head and neck cancer caused by HPV infection because we realize that, clinically, it is a different disease,” says Dr. Shepard.

Ms. Tullio notes that patients with head and neck cancers caused by HPV have a better prognosis — living longer, on average, than head and neck cancer patients without HPV.

“Patients with HPV-positive mouth or throat cancers usually respond well to treatment and may need less aggressive therapy than those who are HPV-negative,” she says.

Also new, adds Dr. Shepard, are separate classification systems for soft-tissue cancers called sarcomas. Doctors have found that, based on the primary tumor’s location, sarcomas will behave and respond to treatment differently.

How will these changes affect you?
The impact of these staging changes will be far greater for patients with cancers diagnosed on or after Jan. 1, 2018.

“If your cancer is new, then changes in classification may affect early decisions about your initial care and likely prognosis,” says Dr. Shepard.

If you received a cancer diagnosis before that date, the stage of your tumor will not change, Ms. Tullio notes. However, new data in the manual may allow your doctors to better assess and treat you.

Adds Dr. Shepard, “Talk to your doctor if you have any questions about the new staging systems. It’s important to be sure all the right tests are ordered to accurately assess your cancer.”

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