Natick company develops test to detect head and neck cancer that could lead to earlier diagnosis

Source: www.bostonherald.com
Author: Alexi Cohan

A saliva-based diagnostic test that can detect HPV-related head and neck cancer has the potential to catch the disease earlier and even serve as a standard screening method, which the medical community currently lacks.

Oropharyngeal squamous cell carcinoma, a cancer caused by human papillomavirus that develops in the mouth and throat, is expected to cause more than 10,000 deaths this year, according to the American Cancer Society. Cases have been increasing significantly in men in recent years.

But there is no screening method for this cancer right now, said Charlotte Kuperwasser, chief of clinical operations at Natick-based diagnostics company Naveris. She said most men who contract it will notice a lump in their throat and go to the doctor. But by that time, the cancer could be quite advanced.

The new saliva test developed by Naveris has been shown to detect HPV-associated head and neck cancer with high accuracy, which is a first-of-its-kind study result and could offer a patient-friendly way to catch the cancer early.

“Saliva is actually a very easy source, very non-invasive. It doesn’t require a medical professional to collect, it could even be done at home so there’s a lot of advantages to saliva,” Kupperwasser told the Herald.

Researchers at Washington University School of Medicine in St. Louis used the test to successfully analyze saliva for HPV genomes that are specific for DNA released from cancerous tumors. The study results highlighted the potential to use the test to catch the cancer early.

“Then, you can actually intervene and make a difference and prevent these cancers from showing up,” Kupperwasser said.

The saliva test builds off a Naveris blood test that detects HPV-associated head and neck cancer earlier than is possible with cancer imaging. That technology is already being used by hundreds of doctors.

Finding a way to detect HPV-related cancer early can’t come soon enough. Kupperwasser said by 2035, HPV cancers are expected to become the third leading cancer type among white men.

“The incidence is going up dramatically and the prevalence is getting to be so high,” Kupperwasser said.

Human papillomavirus is the most common sexually transmitted virus and infection in the United States. More than one of five U.S. adults are infected with a high-risk strain of HPV that can potentially develop into cancer.

But many people might not have any symptoms of HPV, which can take decades to turn into cancer.

Kupperwasser said a similar situation unfolded with cervical cancer in the United States. Cases were going up and a screening mandate was put into place, helping significantly.

She said the same thing could happen with the saliva test if it were used as a standard screening method.

The saliva test could be available to patients within 18 months, but it remains in clinical trials, said Kupperwasser.

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How a microscopic fungus could lead to a breakthrough in oral cancer research

Source: www.newswise.com
Author: Case Western Reserve University

Microscopic fungus may have more to do with oral cancer and aging than first thought, according to new research from Case Western Reserve University.

Researchers from the School of Dental Medicine, Case Comprehensive Cancer Center and School of Medicine are hoping a new study could lead to a medical breakthrough in understanding certain types of oral cancer.

Pushpa Pandiyan, an associate professor of biological sciences at the dental school, led a team of local researchers studying the function of specific T cells, known as Tregs, during the development of oral cancer in aging mucosa, the moist inner lining of some organs and body cavities, such as the nose, mouth and lungs.

“We think this is the beginning of something important and monumental,” she said.

Their findings recently appeared in Frontiers in Oncology.

Pandiyan and the researchers examined the role of dectin-1—a cell’s pattern-recognition and immune receptor—and its ability to trigger an inflammatory response that resists fungal infection. Dectin-1 is among the fungi receptors that expresses on a host cell.

Typically, human white blood cells have regulatory (Tregs) and myeloid derived suppressor cells, which curb the immune responses of cancer-fighting immune cells. Problems occur, Pandiyan said, when these cells accumulate during tumor growth.

“What we’re finding now is that the dectin-1 receptor, usually responsible for anti-fungal immunity, is now responsible for accumulation of these cells at excessive levels in tumors,” she said.

Researchers point out that the culprit is likely the result of immune cells somehow overreacting to fungal microbiota. Although dectin in normal levels serves as a protective measure, Pushpa said excessive amounts can promote tumor growth “because of its ability to recruit immunosuppressive cells.”

“Accumulation of these cells were much worse during aging,” Pandiyan said, adding that the findings may relate to aging. “Our bodies produce more dectin-1 the older that we get. In other words, anti-tumor defense mechanisms are weakened with age.”

While the research was limited to studying aging oral mucosa, Pandiyan said the findings may have broader implications for additional cancer research.

“We don’t know about other cancers yet, but in oral cancers, if there is dectin-1, there’s a better chance that anti-tumor cells can be staved off,” she said.

The research was funded by the Case Comprehensive Cancer Center’s Specialized Program of Research Excellence (SPORE) pilot program.

Other researchers involved in the work include: Natarajan Bhaskaran, Sangeetha Jayaraman, Cheriese Quigley and Prerna Mamileti from the School of Dental Medicine; Mahmoud Ghannoum and Quinton Pan, from the School of Medicine; Aaron Weinberg, from the dental school and Case Comprehensive Cancer Center; and Jason Thuener from the Case Comprehensive Cancer Center.

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Suicide incidence and risk among patients with head and neck cancer in rural vs urban areas

Source: www.2minutemedicine.com
Author: Davy Lau and Alex Chan

Survivors of head and neck cancer (HNC) from rural American counties had double the rate of suicides compared to HNC survivors from metropolitan and urban counties.

Evidence Rating Level: 2 (Good)

Suicide has been in the top 10 leading causes of death in the United States since 2008. As well, the suicide rate is twice greater among cancer survivors, and 4 times as great with head and neck cancer (HNC) survivors. There is currently not much information on how living in an urban or rural setting may affect suicide rates for HNC survivors. This data is imperative due to the fact that cancer survival is lower in rural areas, and there is less access to cancer and mental health services rurally. The current study compared the incidence of suicide across metropolitan, urban, and rural counties for 134,510 HNC patients in the USA, from the years 2000 to 2016. Rural counties were defined as those with a population of less than 2500 people. The study found that In metropolitan counties, there were 59.2 suicides per 100,000 person-years; in urban counties, there were 64.0 per 100,000 person-years; and in rural counties, there were 126.7 per 100,000 person-years. Through cumulative incidence analyses, rural patients had the greatest incidence of suicide. Compared to those in rural counties, urban and metropolitan counties had around 50% the suicide risk (hazards ratio 0.51, 95% CI 0.28-0.92 and HR 0.48, 95% CI 0.28-0.82 respectively). Overall, this study underlies the need for increased access to mental health services, especially for HNC survivors.

Click to read the study in JAMA ENT

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Giving hope: research on rare head and neck cancer treatment options

Source: www.curetoday.com
Author: Antonia DePace

Findings from a phase 3 clinical trial demonstrated improved tumor shrinkage rates with the immune checkpoint inhibitor toripalimab and a first-line chemotherapy combination for nasopharyngeal carcinoma, a tumor that occurs in the nasopharynx (located behind the nose and above the back of the throat). The promising results may open the door to new clinical trials assessing triplet therapies with Food and Drug Administration (FDA)-approved drugs and provide hope for better treatment options for this patient population.

Results from the JUPITER-02 trial were presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting. In 2020, toripalimab received a breakthrough-therapy designation (approval to expedite drug development) for metastatic nasopharyngeal carcinoma. Of note, toripalimab is approved in China for several indications, but it is not FDA approved.

Currently, the worldwide standard of care for these patients is first-line chemotherapy with gemcitabine and cisplatin. “By adding immunotherapy to the combination, we hope to improve survival and increase the time from starting therapy to progression of the cancer,” said Dr. Glenn Hanna, director of the Center for Salivary and Rare Head and Neck Cancers at Dana-Farber Cancer Institute in Boston, in response to the trial results. “If the triplet (therapy) has better rates of tumor shrinkage and prolongs survival with a reasonable side effect profile, that’s a win.”

The possible addition of a novel regimen is exciting. “Treatment advances for late-stage nasopharyngeal carcinoma have lagged behind those of other cancers,” Dr. Julie R. Gralow, ASCO chief medical officer and executive vice president, said in a news release. “Findings from the JUPITER-02 study offer new hope for patients with advanced disease, changing how we care for them.”

The trial was performed in China, and researchers observed an improved median progression-free survival (the length of time during and after treatment of a disease that a patient lives with the disease without it getting worse) of 11.7 months with the treatment regimen of toripalimab plus gemcitabine and cisplatin compared with eight months in patients treated with chemotherapy alone.

“It does get a little tricky when they’re testing an agent that’s primarily manufactured and approved in another country, but we did see practice-changing results,” said Dr. Malini Patel, a medical oncologist in the lung cancer/thoracic oncology and head and neck oncology programs at Rutgers Cancer Institute of New Jersey. “I’m fairly confident that in the near future, we should be able to see this drug in the United States.”

Patel noted that new clinical trials are underway replicating a similar treatment regimen with already-approved checkpoint inhibitors. “(JUPITER-02) is the first study to show a response like this in the first- line, recurrent and metastatic setting, and there are other trials using agents that we use in the United States that are piggybacking off this design,” she explained.

Hanna noted a new trial by the nonprofit research organization NRG Oncology, which is examining the efficacy of gemcitabine and cisplatin in combination with Opdivo (nivolumab). The hope is to see similar, if not identical, results by using the FDA-approved immune checkpoint inhibitor Opdivo in place of the not-yet-approved toripalimab. “The concept is built on the success that’s been observed in Asia,” he said. “I think it will be an analogous study in our population. So, hopefully, we see similar results.”

Both Hanna and Patel acknowledged, however, the possibility of seeing different results due to the difference in populations. Nasopharyngeal carcinoma is considered endemic in Southern China, Southeast Asia and Northern Africa, whereas it’s rare in the United States, with less than 1 case per 100,000 people each year, according to the American Cancer Society.

Although the exact reason for the uneven geographic distribution is unknown, it is partly due to the association with Epstein-Barr virus (EBV) — the infection of nasopharyngeal epithelial cells — that differs between the populations. EBV is known to increase the risk of developing various diseases, including nasopharyngeal carcinoma. “There are some EBV-associated endemic nasopharyngeal carcinomas that we see in the United States, primarily from those who migrate from areas of high risk to areas of low risk, but we encounter more smoking-related, non-EBV-related nasopharyngeal carcinomas (in the United States),” Patel explained.

Patel added that this doesn’t change the importance of the trial results. “I don’t think it should underscore the results of the study,” she emphasized. “Our survival data (are) certainly immature, but we do see a trend for improvement in survival.”

In addition to these studies, other trials have examined the use of drugs such as Keytruda (pembrolizumab) and Opdivo as single agents for the treatment of nasopharyngeal carcinoma. Hanna also noted that exciting new therapies targeting the EBV virus are on the horizon, as are studies combining immunotherapy with vascular targeting drugs, but that agreement on an official second-line treatment option remains an open question.

“Right now, outside of a clinical trial, it’s a little bit heterogeneous in what doctors prescribe and use. We are in need of trials that focus on the population that (progressed after) chemotherapy and immunotherapy in the first-line setting,” he explained. “It’s a tough disease to treat.”

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Calls grow for treatment deintensification of HPV-positive OPC

Source: ww.pharmacytimes.com
Author: Bryan Fitzgerald, PharmD, BCOP
Health-System Edition, July 2021, Volume 10, Issue 4

Oropharyngeal cancer (OPC) is a type of head and neck cancer that affects structures in the back of the throat, including the base of the tongue, the posterior pharynx, the soft palate, and the tonsils.1 In the United States, rates of OPC are increasing each year, with an estimated 54,010 new cases in 2021.2 Well-established risk factors include alcohol abuse; exposure to tobacco, including chewing tobacco, cigarettes, and pipes; and infection with human papillomavirus (HPV).

With an estimated 43 million infections in 2018, HPV is the most common sexually transmitted infection in the United States.3 HPV infection is causally linked with cancers of the anogenital region, including anal, cervical, penile, vaginal, and vulvar cancers. When HPV is spread orally, infections can also lead to the development of OPC. In the United States, more than 70% of OPC cases are caused by HPV.4

HPV is a group of more than 100 viruses, including certain high-risk strains associated with the development of cancer. The HPV-16 strain is responsible for causing the majority of HPV-positive (HPV+) OPC cases, with HPV-18, HPV-33, and HPV-35 also contributing, albeit significantly less than HPV-16.1 In these high-risk HPV strains, the viral genome encodes several oncogenic proteins that inhibit tumor suppressor proteins, leading to chromosomal instability and malignancy in infected cells.

HPV+ OPC is considered a genetically distinct form of OPC. Compared with HPV-negative (HPC–) OPC cases, HPV+ OPC is associated with a favorable prognosis with improved rates of response prognosis with improved rates of response to treatment and overall survival. Because of the difference in tumor biology, the National Comprehensive Cancer Network (NCCN) has adopted different staging criteria for HPV+ and HPV– disease and recommends that HPV status be used to stratify patients with OPC.1

The treatment landscape for localized OPC typically involves a multidisciplinary approach consisting of chemotherapy, radiation, and/or surgery. For fit patients with locally advanced OPC who are able to tolerate intensive therapy, concurrent radiation with systemic high-dose cisplatin chemotherapy is the preferred treatment regimen.1 Unfortunately, treatment of OPC is associated with a high risk of treatment-related morbidity, which may leave patients cured of their malignancy but with lifelong complications, such as dysgeusia, dysphagia, and xerostomia, but also systemic complications from cisplatin chemotherapy, including hearing loss and neurotoxicity.

Because patients with HPV+ OPC are generally younger with more favorable prognoses, clinicians have hypothesized that less intensive treatment could result in fewer long-term complications from treatment but with continued favorable cancer-related outcomes.5 This concept, called deintensification, has become popular in recent years. Several strategies for treatment deintensification have been proposed, including reducing the dose of radiation; substituting cisplatin for an alternative agent with less toxicity, such as cetuximab; and surgical resection. Several phase 3 comparison trials have been conducted, and other trials are ongoing.

Aptly named De-ESCALaTE (NCT01874171), this phase 3 trial randomized patients with 334 HPV+ OPC to receive radiation plus cetuximab or cisplatin.6

Unfortunately, the trial results did not favor substitution of cisplatin with cetuximab. At 2 years, the incidence of severe toxicities did not significantly differ between cetuximab and cisplatin (P = .98), nor did rates of overall toxicities (P = .49). Significant differences in 2-year overall survival rates and recurrence rates were seen. However, these results favored cisplatin (HR, 5.0; P = .001 for overall survival; HR, 3.4; P = .0007 for recurrence).6

RTOG-1016 (NCT01302834) was a second phase 3 trial published comparing cetuximab with cisplatin in HPV+ OPC patients.7 This trial analyzed 805 patients who were randomized to receive radiation plus cetuximab or cisplatin. Similar to the De-ESCALaTE trial, the RTOG-1016 trial results favored cisplatin over cetuximab, with 5-year overall survival rates of 84.6% versus 77.9%.8

Because of the De-ESCALaTE and RTOG-1016 results, experts advise against the substitution of cisplatin for chemoradiation regimens for patients with localized HPV+ OPC, and cisplatin plus radiation continues to be the preferred systemic treatment option per the NCCN guidelines.1,5 Because cisplatin continues to be standard of care for the treatment of localized OPC, the role of deintensification for patients with HPV+ OPC may lie in adjustments to surgical strategies or radiation therapy. Treatment deintensification should be pursued only through clinical trials, and experts encourage clinicians to conduct and analyze phase 2 trials before moving on to phase 3 studies.1,5

CONCLUSION
The treatment landscape of cancer is ever-changing. Specifically in localized HPV+ OPC, the difference in tumor biology presents a unique clinical area where reducing the intensity of treatment may be warranted, particularly with long- and short-term toxicities associated with cisplatin. Interestingly, phase 3 data have shown evidence of harm in removing cisplatin from chemoradiation regimens for HPV+ OPC; therefore, cisplatin-based chemoradiation remains the standard of care for these patients. Future trials may support treatment deintensification in ways other than removing cisplatin.

REFERENCES
1. NCCN. Clinical Practice Guidelines in Oncology. Head and neck cancers, version 3.2021. Accessed June 16, 2021. https://www.nccn.org/professionals/physician_gls/pdf/head-and-neck.pdf

2. Cancer stat facts: oral cavity and pharynx cancer. National Cancer Institute. Accessed June 16, 2021. https://seer.cancer.gov/statfacts/html/oralcav.html

3. Genital HPV infection – fact sheet. CDC. Updated January 19, 2021. Accessed June 17, 2021. https://www.cdc.gov/std/hpv/stdfact-hpv.htm
4. HPV and oropharyngeal cancer. CDC. Updated September 3, 2020. Accessed June 17, 2021. https://www.cdc.gov/cancer/hpv/basic_info/hpv_oropharyngeal.htm

5. Mehanna H, Rischin D, Wong SJ, et al. De-escalation after DE-ESCALATE and RTOG 1016: a head and neck cancer intergroup framework for future de-escalation studies. J Clin Oncol. 2020;38(22):2552-2557. doi:10.1200/JCO.20.00056

6. Mehanna H, Robinson M, Hartley A, et al; De-ESCALaTE HPV Trial Group. Radiotherapy plus cisplatin or cetuximab in low-risk human papillomavirus-positive oropharyngeal cancer (De-ESCALaTE HPV): an open-label randomised controlled phase 3 trial. Lancet. 2019;393(10166):51-60. doi:10.1016/S0140-6736(18)32752-1

7. Gillison ML, Trotti AM, Harris J, et al. Radiotherapy plus cetuximab or cisplatin in human papillomavirus-positive oropharyngeal cancer (NRG Oncology RTOG 1016): a randomised, multicentre, non-inferiority trial. Lancet. 2019;393(10166):40-50. doi:10.1016/S0140-6736(18)32779-X

8. Gardasil 9. Prescribing information. Pfizer; 2017. Accessed June 23, 2021. https://www.fda.gov/fi les/vaccines,%20blood%20&%20biologics/published/Package-Insert—Gardasil.pdf

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Shades of Big Tobacco: How (and why) Juul bought an entire issue of a scientific journal

Source: Salon
Date: July 20th, 2021
Author: Jon Skolnik

 

Facing the imminent threat of corporate death, the embattled e-cigarette maker Juul is pulling out all the stops in its fight to convince the Food and Drug Administration that its vaping products are more beneficial than harmful.

If that sounds like a stretch, it probably is. Last month, Juul settled a $40 million lawsuit that accused the company of luring in teens to use its flavored vape products, allowing Juul to avoid the potential PR nightmare of a widely covered jury trial. Juul has also spent tens of millions in federal lobbying efforts over the past several years, presumably in an effort to block comprehensive regulations on the sale of e-cigarettes.

But the most bizarre Juul news came two weeks ago, when the New York Times reported that the company had funded an entire issue of a scientific journal, in which every article presented evidence that vaping is a beneficial harm-reduction practice that can wean smokers off tobacco cigarettes.

Last month, the American Journal of Health and Behavior (AJHB), a 44-year-old academic journal that has published many nationally recognized scholars, released a special edition specifically devoted to the question of whether e-cigarettes are harmful or helpful. The 219-page issue is unusual not just by virtue of its niche subject matter — e-cigarettes are a relatively new phenomenon in the field of health behavior — but also because its publication was bankrolled entirely by one source: Juul Labs.

This fraught episode comes at an exceptionally tumultuous time for the vape maker. In early 2019, Juul, a company founded just four years earlier, was riding a wave of explosive success, boasting $1 billion in revenue. Sales had grown by 641% from 2016 to 2017 alone. A national survey in 2019 found that nearly 30% of U.S. high school students reported using e-cigarettes in the last month, with 60% of them naming Juul as their preferred brand.

In 2018, the tobacco giant Altria — previously known as Philip Morris — took a 35% stake in Juul, believing the acquisition might help recover some of the company’s losses from an overall decline in U.S. cigarette sales over the past several decades. Only a few months later, however, disaster struck. A mysterious respiratory ailment, clearly linked to vaping, sickened more than 1,000 people in the U.S., and by the fall of 2019, 34 vape users had died from lung injuries. Facing an array of potentially devastating lawsuits and pressure from the Food and Drug Administration (FDA), Juul voluntarily pulled its products from many store shelves and canceled its youth advertising campaigns, rapidly losing more than 30% of its market share.

Now Juul remains in something like corporate limbo, awaiting FDA approval to continue selling its vape products in the U.S. The agency will likely decide this year whether the alleged health benefits of Juul products outweigh their potentially addictive qualities. It’s not entirely surprising, then, that Juul wanted to subsidize an entire edition of a medical journal: Its survival as a corporation is on the line.

But is the Juul-sponsored journal ethical? That’s a murkier question than it might appear. The special issue of AJHB makes no attempt to conceal the fact that essentially all the studies it contains were funded and facilitated by Juul. As The American Prospect notes, a cursory glance at the journal’s “Conflict of Interest” statements reveals that 18 co-authors of articles in the special issue are Juul employees.

Five other co-authors work at PinneyAssociates, a firm that “provides consulting on harm reduction exclusively to JUUL Labs,” as its senior scientific adviser, Dr. Saul Shiffman, told Salon by e-mail. “We participate in JUUL’s work to publish their scientific research to inform the public dialogue about tobacco harm reduction,” he added. An additional three co-authors are involved in the Centre for Substance Use Research, another consulting firm that has a contract with Juul. Nearly every study in the issue features the brand name in its title, and all of them effectively conclude that Juul’s products are a safe form of harm reduction.

As one paper in the journal, a study based on population modeling, puts it, “after considering both potentially beneficial and potentially harmful transitions and based on the available evidence to date — the (continued) availability of ENDS [i.e., vape products such as Juul’s] in the US is likely to have a positive impact on population mortality.”

The edition’s closing perspective, written by Dr. Karl O. Fagerström, a Swedish psychologist who specializes in smoking cessation and “tobacco harm reduction,” waxes a bit more philosophical. “Because it is unlikely that humankind will give up drugs, nicotine included,” he writes, “the findings from the studies presented in this issue suggest that ENDS, and JUUL in particular, can be an acceptable substitute for more harmful cigarette alternatives.” (It is duly noted that Fagerström has served as a paid consultant to Philip Morris International and British American Tobacco.)

Outside the world of corporate-sponsored research, the existing scientific literature is mixed, at best, on the question of whether products like Juul offer effective means of smoking cessation. One study from the University of California, San Francisco, found last year that Juul’s products deliver “more nicotine to the blood per puff than cigarettes or previous-generation e-cigarettes (e-cigs) and [impair] blood vessel function comparable to cigarette smoke.”

Another study published this year in Pediatrics, the official journal of the American Academy of Pediatrics, found that e-cigarette smokers are three times more likely to switch to tobacco cigarettes later on. Other studies have found that e-cigarettes elevate the risk of heart disease, high cholesterol and depression.

To get a better sense of how this strange edition of a previously respected journal came into being, Salon contacted dozens of people listed as associate editors or senior associate editors at AJHB — none of whom are paid for their work there. Virtually none of them knew about the Juul-sponsored edition prior to its release.

“There was certainly no email sent out to any of the editors that this was going to happen,” Dr. Richard Olmstead, a research psychologist at UCLA’s Semel Institute for Neuroscience and Human Behavior, and an associate editor of AJHB, told Salon. “I think there would have been quite a bit of pushback had there been some forewarning about it.”

Dr. Carl Fertman, a professor emeritus at the University of Pittsburgh’s School of Education and an associate editor at the journal, described the special issue as a “complete surprise.”

“There was no transparency,” he said in an interview with Salon. “I don’t want to be associated with this journal. It’s upsetting.”

“I think it’s fairly unusual that a single company would sponsor a special issue,” another associate editor told Salon, asking not to be identified by name. “I was surprised to see they called out a specific company in every article.” This person added that was “different” from anything they’d seen before in “any scientific behavioral journal.”

A number of editors, however, acknowledged that there’s nothing new about seeing corporations sponsor scientific research they believe will be favorable to their bottom line.

For decades, the tobacco industry worked diligently to steer the scientific consensus away from the conclusion — now universally accepted — that cigarette smoking causes lung cancer, emphysema and other serious or life-threatening health problems. Central to that strategy was ginning up fake controversy by pushing junk science that appeared to contradict the overwhelming weight of scientific and medical evidence. Tobacco companies poured money into shadowy front groups that supported dubious science, paid consultants to prepare “expert” testimony to Congress and regulatory bodies and suppressed internal research findings that made clear that the companies themselves understood their products were killing people.

In 1998, a torrent of secret internal documents from a number of tobacco giants was released to the public as part of the Tobacco Master Settlement Agreement. By the early 2000s, the veil was just about lifted. Ruling on a landmark Justice Department suit back in 2006, U.S. District Judge Gladys E. Kessler found that several big-name tobacco companies, including Philip Morris, had systematically defrauded the American public with a decades-long effort to launder pro-tobacco “science” through academic and government channels.

To be clear, Juul is not a tobacco company. It makes and sells e-cigarettes, aka “vapes,” which contain no tobacco and are meant to simulate the experience of smoking cigarettes. They deliver high doses of nicotine to the brain through water vapor, often flavored in various ways. Whether vaping is “safe” remains an unsettled question, but it’s not the same thing as smoking.

Still, the fact Altria holds a significant interest in Juul creates an uncomfortable parallel, even if the two companies’ products would seem to be in competition. Juul’s decision to bankroll an entire edition of a medical journal struck many people as reminiscent of the Big Tobacco playbook.

Following AJHB’s publication of the special edition, a number of editors resigned from the journal, according to New York Times reporting later confirmed by Salon. Most editors declined to comment on the scientific merit of the papers published in the special edition. But there are reasons to be dubious about how the journal’s peer-review process worked in this case.

Before studies are published in any scientific journal, they are typically subject to peer review, in which experts in the relevant field read the papers and offer comments. As AHJB states in its ethical guidelines: “To decrease bias during the editorial process, we employ the classic double-blind peer review process. … The Editor-in-Chief transmits reviewer evaluations and comments to the corresponding author, usually within 4 weeks.”

AJHB editor-in-chief Dr. Elbert Glover, however, apparently told reviewers that the issue was about e-cigarettes in general — and then offered them cash rewards to complete their reviews within a week, according the the Philadelphia Inquirer. Many editors told Salon that in itself was unusual. Only after reviewers reportedly began to ask questions about “fishy” aspects of the studies did Glover reveal that the entire issue was funded by Juul. One reviewer told the Inquirer that the design of one particular study seemed so biased that she recommended it be rejected outright. “I thought, ‘No way it wasn’t funded by Juul,'” she said.

In an email exchange with Salon, Glover acknowledged that he had been privately approached by Juul, who personally paid him $57,500 to publish the edition. (Glover is the sole owner of the publication.) He maintained, however, that the peer review process was conducted in good faith.

“Reviewers were not initially notified regarding the funder of the special issue as it has been journal policy to not identify the funder of special issues during the review process,” Glover wrote to Salon. “However, during the review process, one reviewer requested the identity of the funder. As a result of the reviewer’s response, I decided to share the identity of the funder with all the reviewers of the special issue.”

Asked whether he believed it was appropriate to publish a corporate-sponsored special issue without consulting the other listed editors, Glover responded that it had not occurred to him, saying he “was more concerned about the science and did not consider who funded this issue.”

“I should have been more perceptive to their issue,” he said. “In retrospect, it was probably an error but I still do not understand the ability to ignore science and allow negative bias to enter into the decision.

“My philosophy is to allow the scientific merit to determine publication, not personal bias. Just because the tobacco industry lied, manipulated data and currently promote a product that causes death, does not mean that I have to compromise my values.”

But it’s precisely because of the tobacco industry’s dark history of lies and manipulative spin that Glover should have come clean about Juul’s sponsorship from the beginning, say experts on the other side of the issue.

“The problem is that the tobacco industry has a decades long history of spinning science to meet its regulatory, legal and PR needs,” wrote Dr. Stanton Glantz, former director of the Center for Tobacco Control Research and Education, in a blog post responding to AJHB’s special issue.

As one meta-analysis of research data found in 1998, “the only factor associated with concluding that passive smoking is not harmful was whether an author was affiliated with the tobacco industry.”

A number of AJHB editors told Salon that any study funded by an interested party, especially a large corporation, should be met with heightened scrutiny. One said it was “a red flag when the authors are part of the organization that sponsored the research,” adding: “It doesn’t mean that one can dismiss all of the findings, but it needs to be carefully scrutinized.”

It remains unclear which way the wind is blowing for Juul. In September 2019, the FDA issued a formal warning to the company, making clear that “before marketing tobacco products for reduced risk, companies must demonstrate with scientific evidence that their specific product does in fact pose less risk or is less harmful.”

“JUUL has ignored the law,” the department added, “and very concerningly, has made some of these statements in school to our nation’s youth.”

Months later, it was reported that Juul had begun beefing up its scientific staff, hiring a number of former FDA officials and recruiting researchers in hopes of clearing potential regulatory hurdles. Last July, Juul submitted a Premarket Tobacco Product Application (PMTA) to the FDA, providing “detailed scientific data from over 110 studies totaling over 125,000 pages evaluating the product’s impact on both current users of tobacco products and nonusers, including those who are underage.”

The Juul-sponsored special issue of AJHB is one aspect one part of the company’s PMTA, a Juul spokesperson told Salon in a statement.

“The research in the special issue derives from an extensive research program designed to provide the US Food and Drug Administration’s Center for Tobacco Products with information, scientific data, and analysis to determine whether JUUL products are appropriate for the protection of public health,” the statement read. “This determination, through the submission of Premarket Tobacco Product Applications (PMTAs), is based on a rigorous, science-based process. Indeed, FDA has received not only the findings and reports reflected in the published papers, but also the subject-level data and other supporting information required through the PMTA process.”

In April of this year, six major health organizations — including the American Academy of Pediatrics, the American Cancer Society, the American Heart Association and the American Lung Association — wrote a letter to the FDA urging the agency to reject Juul’s Premarket Tobacco Product Application.

“The devastating combination of appealing flavors that appeal to youth, targeted marketing strategies, and technological innovations that deliver a powerful hit of nicotine, has caused enormous damage to public health, primarily through youth uptake,” they wrote. “Because of this, no JUUL products currently on the market can meet the public health standard, and therefore, none should be authorized by CTP or be allowed to stay on the market.”

The FDA is expected to rule on Juul’s application by Sept. 9.

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Taste, smell dysfunction may persist after HNSCC treatment for longer than survivors anticipate

Source: www.oncologynurseadvisor.com
Author: Bette Weinstein Kaplan

Many people who survive squamous cell cancers of the head and neck (HNSCC) experience difficulty eating and drinking. The problem goes beyond the survivors’ active disease state and into recovery, where it continues to negatively affect their quality of life. HNSCC is the seventh most common cancer worldwide. These cancers are usually found in the oral cavity, pharynx, and larynx. Although often attributed to alcohol and tobacco use in the past, many malignancies seen today result from exposure to the human papillomavirus (HPV).

Treatment plans for HNSCC include combination regimens such as chemoradiation or single therapy such as surgery or radiation by itself. Taste dysfunction is one of the most common adverse effects patients report after treatment, and it has a significant impact on patients’ quality of life.

M. Yanina Pepino, PhD, professor of Food Science and Human Nutrition at the University of Illinois Urbana-Champaign, and her colleagues recently conducted a study on the long-term effects of HNSCC treatment. Their goal was to determine when and if senses of taste and smell fully recover after treatment is completed. Most sensory evaluation studies reported the difficulty in taste and smell should be expected to resolve within several months after cessation of treatment; however, many survivors report continued taste dysfunction more than 6 months after treatment completion.

For this study, Dr Pepino and her group recruited 40 survivors of HNSCC who had been treated with radiation therapy between 6 months and 10 years prior to recruitment. A control group of 20 healthy persons who were equivalent in age, sex, race, smoking history, and body mass index to the study group also were recruited.

Taste stimuli were solutions with strawberry extract (sweet) and lemon extract (sour), sodium chloride in a vegetable broth (salty), coffee (bitter), and deionized water as a blank. Taste quality and intensity was measured using whole mouth and regional methods. For the whole mouth method, participants were asked to swish the taste sample around in their mouths for approximately 5 seconds before spitting it out. Participants performed this without a nose clip and with one, to exclude the stimulation of smell. For the regional evaluation, a team member soaked a cotton swab with stimulus and applied it encircling the tip of the patient’s tongue.

Study results demonstrated subtle differences in taste perception over the long term in the HNSCC survivors compared with the control group. The whole mouth tests suggested that taste function was normal in the study group. However, some taste deficits became evident with the regional tests. The survivors had difficulty perceiving low concentrations of stimuli for bitter, sweet, and salty tastes in the front of the tongue. This lasted for several months after treatment was completed.

The researchers suggest that a deficit in taste on the tip of the tongue but normal in the whole mouth indicates localized damage to the chorda tympani or the taste buds in the fungiform papillae. Any part of the area tested can be damaged by chemotherapy or surgery, as well as radiation therapy.

“The concurrent presentation of smell and taste stimuli in the mouth resulted in mutual enhancements of perceived taste and smell intensity,” noted the researchers. Thus, when the participants did not use the nose clip, they perceived the sucrose solutions to be sweeter, and citric acid solutions to be more sour. The senses of smell and taste are often synergistic.

This study also evaluated sense of smell. The University of Pennsylvania Smell Identification Test (UPSIT) was used to measure smell. UPSIT utilizes 40 small boxes containing microencapsulated common odors. Participants would scratch off the box to release the odor, sniff the box, and identify the descriptor that matched the perceived smell. This enabled the researchers to evaluate survivors’ sense of smell separately from their sense of taste, demonstrating that in some patients smell was slightly impaired by the cancer and/or its treatment.

These results suggest persistent and subtle damage occurs, which may explain why survivors complain of sensory loss long after completing radiation therapy, concluded the researchers.

Reference

Alfaro R, Crowder S, Sarma KP, Arthur AE, Pepino MY. Taste and smell function in head and neck cancer survivors. Chem Senses. 2021;46:bjab026. doi:10.1093/chemse/bjab026

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Blood test that finds 50 types of cancer is accurate enough to be rolled out

Source: www.theguardian.com
Author: Nadeem Badshah

A simple blood test that can detect more than 50 types of cancer before any clinical signs or symptoms of the disease emerge in a person is accurate enough to be rolled out as a screening test, according to scientists.

The test, which is also being piloted by NHS England in the autumn, is aimed at people at higher risk of the disease including patients aged 50 or older. It is able to identify many types of the disease that are difficult to diagnose in the early stages such as head and neck, ovarian, pancreatic, oesophageal and some blood cancers.

Scientists said their findings, published in the journal Annals of Oncology, show that the test accurately detects cancer often before any signs or symptoms appear, while having a very low false positive rate.

The test, developed by US-based company Grail, looks for chemical changes in fragments of genetic code – cell-free DNA (cfDNA) – that leak from tumours into the bloodstream.

The Guardian first reported on the test last year and how it had been developed using a machine learning algorithm – a type of artificial intelligence. It works by examining the DNA that is shed by tumours and found circulating in the blood. More specifically, it focuses on chemical changes to this DNA, known as methylation patterns.

Now the latest study has revealed the test has an impressively high level of accuracy. Scientists analysed the performance of the test in 2,823 people with the disease and 1,254 people without.

It correctly identified when cancer was present in 51.5% of cases, across all stages of the disease, and wrongly detected cancer in only 0.5% of cases.

In solid tumours that do not have any screening options – such as oesophageal, liver and pancreatic cancers – the ability to generate a positive test result was twice as high (65.6%) as that for solid tumours that do have screening options such as breast, bowel, cervical and prostate cancers.

Meanwhile, the overall ability to generate a positive test result in cancers of the blood, such as lymphoma and myeloma, was 55.1%. The test correctly also identified the tissue in which the cancer was located in the body in 88.7% of cases.

Dr Eric Klein, chairman of the Glickman Urological and Kidney Institute at Cleveland Clinic in the US and first author on the research, said: “Finding cancer early, when treatment is more likely to be successful, is one of the most significant opportunities we have to reduce the burden of cancer.

“These data suggest that, if used alongside existing screening tests, the multi-cancer detection test could have a profound impact on how cancer is detected and, ultimately, on public health.”

Dr Marco Gerlinger, from the Institute of Cancer Research in London and consultant medical oncologist at the Royal Marsden NHS foundation trust, said: “This new study shows impressive results for a simple blood test that can detect multiple cancer types.

“False positives are low which is important as this will avoid misdiagnoses. For some of the most common tumour types such as bowel or lung cancer, the test even picked up cancers that were very small, at a stage where many of them could potentially be cured.

“The study was done in patients whose cancer was already diagnosed based on other tests and this screening technology still needs to be tested in actual screening trials before routine use.

“But it already allows a glance at early cancer detection in the future which will almost certainly be built around liquid biopsy tests, which detect cancer DNA in the bloodstream.”

Meanwhile, the results of the NHS pilot of the test, which will include 140,000 participants, are expected by 2023.

Prof Peter Johnson, national NHS clinical director for cancer, said: “This latest study provides further evidence that blood tests like this could help the NHS meet its ambitious target of finding three-quarters of cancers at an early stage, when they have the highest chance of cure.

“The data is encouraging and we are working with Grail on studies to see how this test will perform in clinics across the NHS, which will be starting very soon.”

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Marine Corps corporal gets 3D-printed teeth with jaw reconstruction

Source: www.upi.com
Author: Ed Adamczyk

A Marine Corps member is the first recipient of the Defense Department’s first jaw reconstruction using 3D-printed teeth, the Pentagon said on Friday. A tumor prompted the removal of most of Cpl. Jaden Murry’s jaw in a November 2020 surgery. Murry is a member of Logistics Battalion 7, Marine Corps Air Ground Combat Center at Twentynine Palms, Calif.

The jaw was reconstructed using a portion of his fibula, or lower leg bone, but his lower teeth were made using a digital model, which was then printed into a physical replacement bridge and inserted in the new jaw. The surgery was conducted by a multi-department team of surgical specialists at the Naval Medical Center in San Diego.

“All of the providers worked as a team to keep his recovery on track,” Lt. Cmdr. Daniel Hammer, maxillofacial surgical oncologist and reconstructive surgeon, said in a press release.

“We were able to safely remove his tracheostomy tube [inserted in a patient’s neck when there are concerns about postoperative breathing] within a week of the surgery, and it was then we knew he was making strides in the right direction.”

Murry is recovering in the Naval Center’s Wounded Warrior Battalion, and on a diet of soft foods. A final prosthetic set of teeth will be available to him in about two months.

“Since his surgery, [OMFS specialists and I] see Jaden twice weekly for check-ups, and we’re guiding his healing process,” Hammer said in December. “To see him swallowing, speaking, walking and not using a tracheostomy tube one week post-surgery was a huge victory, both for [Murry] and for us.”

The success is also a part of a program developed by the U.S. Armed Forces Institute of Regenerative Medicine whose researchers work to use the body’s natural healing powers, in this case through the fibula transfer to the jaw, to improve head and face reconstruction.

Murry said that he is eager to resume his Marine Corps duties.

“I really look forward to getting back to a healthy mindset and working out, running and bodybuilding,” he said, adding that he will seek pizza when he again can eat solid food.

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A challenge to chew on: eating and drinking after cancer treatment

Source: www.curetoday.com
Author: Dara Chadwick, Heal

Exercise has always been part of Scott Wieskamp’s life. But after cancer treatment, the longtime runner and marathoner added a new element to his training regimen — exercises to strengthen and maintain his swallowing muscles.

“Every day while I’m driving to work, I open my mouth like I’m yawning to stretch all my facial muscles as much as I can,” says Wieskamp, 62, who lives just outside Lincoln, Nebraska. “I take my tongue and put it under the back of my lower teeth and push as hard as I can to exercise my tongue muscles. There’s about half a dozen things I do for a few minutes every day.”

Four years ago, Wieskamp was treated for oral cancer caused by the human papillomavirus. The aggressive treatment, which included 39 radiation sessions and several doses of the chemotherapy drug cisplatin, knocked out the cancer. But it also left Wieskamp unable to eat, and he lost 15 pounds in a matter of weeks.

“As you get radiation in the neck and throat area, it becomes painful to swallow,” he says. “I quit doing all that. I quit eating, quit swallowing — I couldn’t even drink.”

Because he was unable to get adequate nutrition, his doctors inserted a feeding tube so Wieskamp wouldn’t have to swallow. The tube stayed in place throughout his two months of treatment and for about a month after, he says.

Although his nutrition improved, Wieskamp says he was left with another problem: His muscles “forgot” how to swallow.

“I had to go to a speech-language pathologist to help me learn how to swallow again,” he says. “It was scary, painful and frustrating.”

Wieskamp’s swallowing challenges aren’t uncommon. After treatment, survivors of cancer may experience not only difficulty swallowing but also dry mouth and changes in taste, smell, digestion or bowel habits. Any of these changes can make eating and drinking a struggle, which then makes it difficult to get adequate nourishment.

When you’re not getting the nutrients you need, it’s hard for the body to regain strength and rebuild cells, according to Rachel Wong, an oncology dietitian at the Georgetown Lombardi Comprehensive Cancer Center at MedStar Georgetown University Hospital in Washington, D.C.

“Patients can experience delayed healing and recovery caused by poor nutrition post treatment” she says. “A rapid decline in weight from inadequate nutrition often results in both fat and muscle loss, causing significant fatigue and weakness, which can greatly impact one’s ability to accomplish tasks and resume a normal way of living.”

“It can be possible that patients find delayed healing and delayed recovery because of poor nutrition post treatment,” she further explains. “If you’ve lost a lot of weight and you’ve lost muscle, you may sleep a lot during the day.”

Eating challenges can also make it tough for survivors of cancer to enjoy time with family and friends, Wieskamp says. After treatment, he didn’t look forward to social occasions like he used to. “People say, ‘Hey, let’s meet for coffee’ or ‘Let’s have family over and we’ll have a meal,’” he says. “Our lives revolve around food.”

IMPACTS FROM CANCER TREATMENT
Some types of cancer require treatments that are more likely to affect how people eat and drink. According to Dr. David G. Pfister, medical oncologist and chief of the Head and Neck Oncology Service at Memorial Sloan Kettering Cancer Center in New York City, treatments for cancers of the head and neck pose particular challenges because they can affect swallowing, taste and smell.

For example, surgery in certain areas of the head and neck can disrupt structures used in swallowing, such as the throat and tongue. In addition, oral mucositis — mouth pain, sores and infection — can develop after radiation and chemo- therapy. Some survivors experience damage or changes to their salivary glands, which can make the mouth exceptionally dry. This can also predispose them to dental problems.

Jean DiNapoli, 62, of Newburgh, New York, says trying to swallow after completing 30 rounds of radiation for oropharyngeal cancer (a type of cancer found in an area of the throat called the oropharynx) was like “swallowing glass.” She also experienced mouth sores and thrush, a yeast infection that develops in the mouth, along with significant dry mouth.

DiNapoli, who is now seven years post treatment, says she lost about 35 pounds immediately following radiation.

“I could have gotten a feeding tube, but I really didn’t want it,” she says. “I didn’t want my muscles to atrophy.”

Pfister says the decision to place a feeding tube is one that doctors make carefully. “Not that long ago, when significant swelling, pain and weight loss were expected, we would prophylactically put in a feeding tube to get patients over the hump, so to speak,” he says. But doctors found that people would soon start taking all their calories through the tube, leading to the exact problem DiNapoli feared — muscle atrophy.

“Your swallowing muscles are like any other muscle. If you don’t use it, you lose it,” Pfister says, adding that it’s critical to make swallowing therapy a routine part of treatment along with good pain control. “We evaluate every patient in an individualized way. (Although) there clearly are settings where we put in a feeding tube, we’re more selective.”

After her treatment ended, DiNapoli worked with a speech pathologist once a week for a couple of months to regain strength in her tongue muscles and improve her ability to swallow. “I did different exercises, such as swallowing with my tongue between my teeth,” she says. “I also had the help of a good nutritionist.”

MANAGING EATING CHALLENGES
Registered dietitian nutritionists trained in mitigating the impact of cancer treatments can help survivors find new ways not only to get nourishment but also to enjoy food again. Annette Goldberg, a senior nutritionist at Dana-Farber Cancer Institute in Boston, says choosing the tools to help individuals bring their symptoms under control can be a bit of a puzzle. It depends on factors such as their overall health prior to treatment, the type of cancer and treatment they had, and the social support system they have.

“Sometimes I’ll ask patients if they live alone, and they’ll wonder why I’m asking that question,” she says. “I want to make sure they have the proper support. If you’re not feeling well, you don’t want to do anything.” That includes cooking, she says.

Maureen Gardner, a clinical oncology nutritionist at Florida Cancer Specialists & Research Institute in Tampa, says survivors who’ve had cancers in the gastrointestinal (GI) tract or treatment for any cancer in areas near the GI tract — such as prostate, ovarian or uterine cancer — may experience ongoing effects on how food is digested and eliminated. Some survivors may experience weight gain, such as breast cancer survivors who are on long-term hormone therapies or those who have entered menopause. Other people may experience ongoing diarrhea or dumping syndrome — when food moves too quickly from the stomach to the small intestine — after being treated for GI cancers.

Gardner says dietary changes, both in what and how patients eat, can help manage eating challenges after cancer treatment ends. If you have dry mouth, try to:

• Focus on hydration. In addition to drinking water, Goldberg recommends keeping your mouth clean and avoiding toothpastes and mouthwashes that are too harsh.

• Boost saliva production. Tart foods can stimulate the salivary glands, Goldberg notes. Adding tart lemon juice to water or chewing a strong sugarless mint gum can help.

• Add soft, moist foods to your diet. Wong recommends adding extra sauces or broth or even cream to casserole-type dishes or when having drier foods like meat, potatoes and rice.

“Drinking fluids along with your meals can certainly help improve the moisture content in the mouth and make swallowing easier,” Wong says. “Just having a glass of water, juice or any type of liquid in between each bite can really help get the food down.”

DiNapoli says she drank lots of water to relieve her dry mouth. She also tried different lozenges, mouthwashes and gels. “I still use XyliMelts,” she says. “I put (one) in my mouth at night and it slowly dissolves.”

Some survivors experience changes in taste and smell that affect the way they experience food. “I lost my sense of taste right after radiation,” DiNapoli says. “Everything tasted like paste. But then my sense of taste came back so strong that spicy food was overly spicy. And my sense of smell is stronger.”

“I tell patients that your taste buds and smell will constantly change,” Wong says, encouraging people to keep a running list of things that work well and things that don’t. “In my experience, a list of what works gives you the motivation to keep trying new things.”

If you’ve had changes in taste and smell that affect how you experience food, try experimenting with seasonings. Adding spices such as basil, pepper or dill can make food more sweet, savory or salty and improve its flavor. Wong also recommends adding different types of sauces, such as ranch, barbecue, or sweet and sour to help bring out the flavor in foods and add some moisture.

If you’re experiencing ongoing GI symptoms such as diarrhea, Goldberg recommends talking to your doctor or nutritionist about supplements that might help, such as banana flakes. “It’s a product that’s made from dehydrated bananas, which contain several soluble fibers including pectin. The soluble fiber absorbs fluid to help firm the stool,” she says. “A combination of foods, maybe some supplements and working with your care team can help.”

IMPROVEMENTS WITH TIME
Although eating and drinking can be difficult during active treatment and the weeks immediately after, strengthening exercises and dietary changes can help most people overcome these challenges with time. Addressing issues right from the start can help the healing process, Wong says.

“Getting guidance from a dietitian can impact how patients recover after their treatment,” she says, adding that it’s important for doctors to talk with patients about challenges they might experience. She also recommends resources such as the American Institute for Cancer Research and the American Cancer Society for advice on managing eating challenges after treatment.

Support groups — both online and in person — can also help. DiNapoli and Wieskamp are members of an organization called Support for People with Oral and Head and Neck Cancer (SPOHNC). Both say SPOHNC has been incredibly helpful as they’ve healed.

“I would tell most people that I’m 100% normal, but I’m not 100% the same,” Wieskamp says. “My brain has had to learn that things that used to taste one way taste a little different today. But I’m only one person. You could probably interview 20 people and they may have 20 different answers.”

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