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ASCO 2020: New optimized precision radiotherapy can reduce swallowing difficulties for head and neck cancer patients

Source: www.icr.ac.uk
Author: staff

A new optimized intensity-modulated radiation therapy (IMRT) pioneered at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, London, has been shown to spare head and neck cancer patients’ adverse life-long side effects post treatment.

The initial results from the Dysphagia-Aspiration Related Structures (DARS) trial, funded by Cancer Research UK and the National Institute for Health Research, were presented at the American Society for Clinical Oncology (ASCO) virtual conference this week.

The randomized study found patients with head and neck cancer experienced less adverse side effects with the new precision radiotherapy technique optimized to reduce the risk of swallowing difficulties, known as dysphagia.

Half of newly diagnosed patients with oropharyngeal and hypopharyngeal cancers (tumors of the throat) recruited to the trial received standard IMRT radiotherapy and the other half received IMRT optimized to reduce the radiation dose to the structures related to swallowing and breathing. The trial recruited 112 patients across 23 UK cancer centres.

Difficulties eating and drinking
Patients with head and neck cancer have a 90 percent survival rate but can be left with life changing side effects including swallowing problems, making it difficult to eat and drink. The self-reported measure of swallowing ability as perceived by patients themselves was better in the optimised IMRT group.

Twelve months after treatment, 40 percent of patients given the optimized form of precision radiotherapy reported their swallowing was as good as ever in comparison to just 15 percent on the standard treatment.

The DARS trial was managed by the ICR Clinical Trials and Statistics Unit and supported by strong collaborations between participating hospitals and a multidisciplinary team of doctors, speech and language therapists (SLT), radiographers, research nurses and physicists.

Professor Chris Nutting, Head of the Head and Neck Unit at The Royal Marsden and Joint Head of the Division of Radiotherapy and Imaging at the ICR, said:

“The optimized IMRT treatment will be a game changer for treating head and neck patients in the future. The DARS trial has proved the new technique can spare the swallowing muscles for patients without lessening the success of their treatment.”

Profound impact on quality of life
Dr Justin Roe, Consultant SLT and Joint Head of the Department of Speech, Voice and Swallowing at The Royal Marsden, said:

“Despite improvements in radiotherapy treatments in recent years, people can be left with varying degrees of swallowing difficulty. In some cases, this can have a profound impact on quality of life with people unable to eat and drink safely and comfortably. This has a particular impact during mealtimes and in social situations. It can also have a significant impact on hydration, nutrition and in the most severe cases, can lead to pneumonia. It is very encouraging to see how much improvement there has been in people who received the dysphagia-optimised IMRT.”

Martin Ledwick, Cancer Research UK’s head nurse, said:

“It’s difficult for many of us to imagine not being able to swallow, but this is often the devastating reality for head and neck cancer patients post treatment. The findings of this trial are very exciting and offer hope that this new radiotherapy technique has the potential to make a big improvement to quality of life for these patients after cancer.”

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May, 2020|Oral Cancer News|
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Sentinel node biopsy proves mettle in H&N cancer

Source: www.medpagetoday.com
Author: Ed Susman, Contributing Writer, MedPage Today

Sentinel node biopsy achieved “oncological equivalence” with neck dissection in patients with operable T1-T2N0 oral and oropharyngeal cancer, researchers reported.

In a head-to-head trial, the 2-year neck-relapse free survival (RFS) was 90.7% in the sentinel node (SN) biopsy group versus 89.4% in the neck dissection group, according to Renaud Garrel, MD, PhD, of Montpellier University Hospital Center in France.

That 1.1% difference fell well within the pre-specified 10% difference to determine if there was non-inferiority of SN biopsy to neck dissection, which is considered the standard of care for treatment of early stage head and neck cancers (P=0.008 for equivalence), he reported at the American Society of Clinical Oncology virtual meeting.

At 5 years, 89.4% of the SN biopsy group achieved neck-RFS versus 89.6% in the neck dissection group, he said in a pre-recorded oral presentation on the Senti-MER study.

Overall, there were 14 neck recurrences in 139 patients in the neck dissection group and 13 neck recurrences in 120 patients in the SN biopsy group. Also, overall survival was 82.2% in the SN biopsy group and 81.8% in the neck dissection group.

Hisham Mehanna, MBChB, PhD, of the University of Birmingham and the Warwickshire Head and Neck Clinic in England, commented that “Elective neck dissection is the standard, especially for oral cancer. Sentinel node biopsy is an accepted technique as there have been large series that show benefit, but there has never been a head-to-head study with the standard of care.”

Mehanna, who was not involved in the study, said that several questions remain: “Is sentinel node biopsy as effective as elective neck dissection, is it less morbid, and importantly, is it more cost-effective or as cost-effective, because sentinel node biopsy is resource intensive,” he said.

“The study determined that sentinel node biopsy is non-inferior to elective neck dissection; it has equivalent recurrence-free survival; equivalent locoregional recurrence free survival; equivalent disease-specific recurrence free survival; and equivalent 2- and 5-year survival,” Mehanna added. “It was also less morbid at the 2-, 4- and 6-month assessment point, but showed the same morbidity at 12 months. It also showed better function and less physiotherapy up to the 12-month assessment point and then it was the same as elective neck dissection.”

He called the study a ” significant achievement. We have been talking about it for a long time. So sentinel node biopsy should be considered a standard of care. It should be offered as an option alongside, or instead of, neck dissection.” Mehanna added that “really data on cost-effectiveness will be important if this is going to be adopted widely because sentinel node biopsy is resource intensive and, in my mind, it is much easier just to do an elective neck dissection. Cost-effectiveness will remain an issue.”

Garrel reported that cost-effectiveness is being assessed in an ancillary study.

For Senti-MER, 307 patients at 10 institutions were enrolled. After exclusions, 140 patients had SN biopsy and 139 had neck dissection. Patients were diagnosed with operable cT1-cT2NO oral or oropharyngeal squamous cell carcinomas, and had no history of head and neck surgery, neck surgery, or radiation therapy. Patients had to be able to receive transoral radiotracer injection for lymphoscintigraphy.

Garrel and colleagues found that morbidity was reduced among the patients undergoing SN biopsy. The median hospital stay was 1 day less in the SN biopsy group (P=0.001), while the mean hospital stay also was reduced (P=0.013).

He noted that physical problems in the arm were less common among the SN biopsy patients at the 2-, 4-, and 6-month assessment points, but the differences disappeared at 1 year. Similarly, SN biopsy patients required less physiotherapy at 2, 4 and 6 months, but the differences were not significant at 1 year.

“Senti-MER is a high level of evidence study,” Garrel said. “It establishes that sentinel node [biopsy] is the standard of care among patients with T1-T2NO oral and oropharyngeal cancer.”

Disclosures:
Garrel disclosed relevant relationships with Norgine.
Mehanna disclosed relative relationships with AstraZeneca, Merck, MSD, Sanofi, GlaxoSmithKline, Silence Therapeutics.

Primary Source:
American Society of Clinical Oncology
Source Reference: Garrel R, et al “Equivalence randomized trial comparing treatment based on sentinel node biopsy versus neck dissection in operable T1-T2N0 oral and oropharyngeal cancer” ASCO 2020; Abstract 6501.

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May, 2020|Oral Cancer News|
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Less intense treatment safe for HPV+ throat cancer

Source: www.miragenews.com
Author: public release, University of Pittsburgh School of Medicine

A less intense treatment for human papillomavirus positive (HPV+) throat cancer—using robotic surgery followed by low-dose radiation—could provide as much benefit as standard higher-dose radiation and chemotherapy while preserving a patient’s throat function, and with potentially less toxicities, according to researchers at UPMC Hillman Cancer Center and Yale Cancer Center.

The results of their randomized phase two clinical trial will be presented virtually this week at the American Society of Clinical Oncology (ASCO) annual meeting during the Head and Neck Oral Abstract Session (Abstract 6500).

“These results present a promising deintensification approach that has proven to be safe in patients with intermediate risk, locally advanced oropharynx cancer,” said Robert Ferris, M.D., Ph.D., director, UPMC Hillman Cancer Center and a surgical oncologist specializing in head and neck cancer, who was lead investigator of the trial. The results are not yet published in a peer-reviewed journal.

About 60% of oropharynx cancer, in which cancer cells form in the back of the throat, base of the tongue and tonsils, is associated with HPV infection. The incidence has been increasing in recent years, especially in individuals under the age of 45.

Following robotic surgery, patients with HPV-associated throat cancer would typically undergo high dose radiation and chemotherapy. While robotic surgery allows for more precise and optimal preservation of the organs and surrounding tissue, there is still concern with the toxicities from the chemotherapy and consequences of tissue damage from radiation therapy, particularly in a younger population.

“Most throat cancers caused by HPV have good outcomes, and the cancer doesn’t return or spread to other parts of the body after treatment,” said Ferris, who also is professor, Department of Otolaryngology, of Immunology, and of Radiation Oncology, University of Pittsburgh School of Medicine.

“In this trial, we studied the pathologic features of the tumors obtained at surgery to determine patients’ risk of recurrence—low, intermediate or high—to then administer the right amount of postoperative treatment for each risk group.”

Patients at low risk were observed. Patients at intermediate risk were randomized to two arms of radiation alone, at standard or lower doses of radiation. Patients at high risk were assigned to usual high-dose radiation therapy plus chemotherapy.

For patients at low and intermediate risk, the two-year, progression-free survival rate was approximately 95%, and reducing radiation or chemotherapy intensity did not increase the risk of recurrence.

“The tissue samples and imaging studies collected in the course of this trial are a rich resource for studying the biology of intermediate- and high-risk disease, in work that is ongoing,” said ECOG-ACRIN Head and Neck Committee Chair Barbara Burtness, M.D., professor of medicine, and co-leader, Developmental Therapeutics Program, Yale Cancer Center and Yale School of Medicine.

Note:
The ECOG-ACRIN Cancer Research Group designed and conducted the trial with funding from the National Cancer Institute, part of the National Institutes of Health.

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May, 2020|Oral Cancer News|
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Vaping e-cigarettes could increase the risk of oral disease, study finds

Source: technology.inquirer.net
Author: staff

New American research has found that individuals who use e-cigarettes could be at risk of developing oral diseases in the future, which could range from gum disease to cancer.

Carried out by researchers at The Ohio State University, the new study looked at a group of 123 people with no signs of oral disease. The group included 25 smokers, 25 non-smokers, 20 e-cigarette users, 25 former tobacco smokers who used e-cigarettes and 28 people who smoked both tobacco cigarettes and e-cigarettes.

The team collected plaque samples taken from under the gums of the participants to analyze the bacteria in this part of the mouth; bacteria here is the last line of defense against disease as it is the least likely to be disrupted by environmental changes in the mouth, such as food, toothpaste and tobacco.

The researchers then carried out DNA deep sequencing of the bacteria’s genomes to identify what types of microbes were living in participants’ mouths and what their functions were.

The findings, published in the journal Science Advances, showed that although the e-cigarette users didn’t have signs of active disease, their oral bacteria composition was similar to that of people with severe periodontitis, a severe gum infection that can lead to health problems such as tooth loss, and, if left untreated, is a risk factor for serious conditions such as heart and lung disease.

The effect of e-cigarette smoking was also seen with or without nicotine, which the researchers say suggests that it is the heated and pressurized liquids in e-cigarette cartridges that are making vapers’ mouths a welcoming environment for a dangerous combination of microbes.

Even long-term current and former cigarette smokers had worse oral profiles linked to using e-cigarettes after just three to 12 months of vaping.

“Vaping is such a big assault on the oral environment, and the change happens dramatically and over a short period of time,” said Purnima Kumar, senior author of the study.

“If you stop smoking and start vaping instead, you don’t move back toward a healthy bacterial profile but shift up to the vaping profile,” Kumar explains. “Knowing the vaping profile is pathogen-rich, you’re not doing yourself any favors by using vaping to quit smoking.”

The researchers say this is the first human study on the effects of e-cigarette exposure in the mouth, and like previous research into e-cigarettes, also questions their safety.

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May, 2020|Oral Cancer News|
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Deintensification of Treatment in HPV-Associated Cancers Holds Promise, But With Caveats

Source: Targeted Oncology
Date: May 17th, 2020
Author: Tony Berberabe

 

De-escalating therapy has the potential to dramatically reshape the treatment of patients with HPV-associated oropharyngeal cancers, but only if a number of key trials come back with positive long-term data with 3 cycles of cisplatin at 100 mg/m2 times 3, given every 3 weeks, Sue Yom, MD, PhD, a professor in the Departments of Radiation Oncology and Otolaryngology-Head and Neck Surgery atthe University of California, San Francisco, said in an interview with Targeted Therapies in Oncology (TTO).

Sure, there were some minor variations over the years, small alterations made on a case-by-case basis. “But long story short, that’s fundamentally what was happening: 70 Gy with 3 cycles of high-dose cisplatin,” Yom said. The story began to change a little over a decade ago, with the introduction of a variable that could potentially change the course of therapy for a large percentage of patients with head and neck cancers. Today, the operative word remains potentially.

In 2008, Maura L. Gillison, MD, PhD, of Johns Hopkins University, and colleagues found that whether head and neck squamous cell carcinoma tumors were associated with the human papillomavirus (HPV) turned out to be a major prognostic indicator.1

“When that finally came to be reported, there was a very, very striking result,” said Barbara Burtness, MD, a professor of medicine (medical oncology), Disease-Aligned Research Team leader of the Head and Neck Cancers Program, and coleader of Developmental Therapeutics at Yale Cancer Center in New Haven, Connecticut Patients with HPV-associated stage III or IV head and neck squamous cell carcinoma of the oropharynx or larynx had a 2-year overall survival (OS) rate of 95% versus 62% for patients with HPV-negative tumors.

Two years later, Gillison collaborated with K. Kian Ang, MD, PhD, of The University of Texas MD Anderson Cancer Center in Houston and published the results of a study in oropharyngeal cancer (NCT00047008), which again found that HPV made a difference in terms of survival.2

Patients with HPV-positive tumors had better OS and progression-free survival (PFS) than patients who were HPV negative (P<.001 for both comparisons). Ang and colleagues reported that the 3-year OS rate was 82.4% (95% CI, 77.2%-87.6%) in patients who were HPV positive compared with 57.1% (95% CI, 48.1%-66.1%) in those who were HPV negative. Similarly, the 3-year PFS rate favored the HPV-positive group, at 73.7% (95% CI, 67.7%-79.8%) versus 43.4% (95% CI, 34.4%-52.4%) for the HPV-negative group (TABLE 1).2

The 3-year absolute benefit of HPV-positive status for OS was 25% (95% CI, 11%-40%), and the absolute benefit for PFS was 30% (95% CI, 15%-45%).

The results were similar with stratification according to p16 expression status. The 3-year rates of OS were 83.6% (95%CI,78.7%-88.6%) in the subgroup that was positive for p16 expression and 51.3% (95% CI, 41.5%-61.0%) in the subgroup that was negative (P<.001). Three-year PFS rates were 74.4% (95% CI, 68.5%-80.2%) and 38.4% (95% CI, 28.9%-47.9%), respectively (P<.001) (TABLE 2).

The study also found that the number of pack-years an individual smoked had a substantialnegative impact on prognosis.

These findings raised serious questions because the current standard of care, unchanged from that described by Yom, can have a profound effect on the life of a patient who survives the cancer. “The after- effects of that dose of radiation are quite real, and they include chronic pain, chronic swallowing difficulties, dry mouth, and dental complications,” Burtness said.

“We are concerned that these patients may be at higher risk for death from the late effects of the treatment.”

Moreover, patients with HPV-associated cancers tended to be younger at diagnosis than those with non-HPV cancers. Patients who develop the cancer in their 50s might have decades of life left—plenty of time for the long-term adverse effects (AEs) of aggressive treatment to show up.

The issue is pressing because HPV-associated cancers represent about 7 in 10 cases of oropharyngeal cancer.3 The most recent statistics from the Centers for Diseases Control & Prevention suggests that 3500 new cases of HPV-associated oropharyngeal cancers are diagnosed in women versus 15,500 diagnosed in men (FIGURE 1).4

Cherie-Ann O. Nathan, MD, chairman of the Department of Otolaryngology–Head and Neck Surgeryat Louisiana State University Health Shreveport, said the new findings underscored the need for more research. “We need to start to look at de-escalating for that low-risk group,” she said.

De-escalation Strategies

Deciding that different strategies might be warranted and choosingwhich approaches make the most sense are 2 different considerations, and both come with difficult questions. Burtness said it can be a challenge just to figure out how to tackle the question.

I think, first of all, it’s challenging to do deintensification trials because they require very large sample sizes, and you want to be sure you’re not deintensifying [treatment in] somebody who would be cured by the full treatment and wouldn’t be cured by the reduced regimen,” Burtness said.

For the most fortunate patients, the OS rate with the current standard of care is in the range of 90% to 95%, setting a high bar for its replacement, Yom said. “It’s a huge ethical and practical situation where you’re actually having to estimate: ‘What would it take to prove that this less intense alternative was as good?’” Yom said.

“Patients do get better with time,” Yom said. “After a year or 2, they can live very normal lives.It’s actually a great treatment in some ways, and 1 question is if we should even be messing with it.”

Another strategy is to reduce the dose or field of radiation. In Yom’s much-anticipated trial, NRG-HN002 (NCT02254278), 306 patients with p16-positive, non–smoking-associated, locoregionally advanced oropharyngeal cancer were stratified by unilateral or bilateral radiation and randomized into 2 groups.4 One group received 60 Gy of intensity-modulated radiation therapy (IMRT) for 6 weeks plus cisplatin (IMRT + C) at 40 mg/m2 weekly. The other group received 60 Gy of modestly accelerated IMRT alone for 5 weeks. The goal was to compare the arms in terms of 2-year PFS rates without unacceptable swallowing difficulty at 1 year. The IMRT + C group met the desired benchmarks; the IMRT alone group did not.

Although the study was just a phase II trial, Yom said the results were encouraging and will lead to further study.

Another strategy is to perform surgery up front, Nathan said. If the margins are negative and there is not a significant number of metastatic lymph nodes or significant extranodal extension, chemotherapy might be avoided. She said transoral surgery has become much more effective and precise in the age of robotics. A common site of lymph node involvement is the retropharyngeal region, shown in FIGURE 2.5

“When robotic surgery became popular and we were able to get margins on these tumors at the base of [the] tongue and tonsils, people started saying [that] for the HPV-associated [tumors], you don’t need the typical wide margins of 5 mm; you could get away with 3 mm,” she said.“ So, the whole purpose of transoral surgery was that after removing the tumor, you could de-escalate.”

Other research has tested the replacement of cisplatin with cetuximab (Erbitux), though one study found that the latter resulted in inferior OS.6

With the exception of the cetuximab strategy, the novel approaches have shown promise. However, Nathan said, clinicians should realize that these are all still hypotheses; there is much that is not yet known.

“Unfortunately, people look at all [these] retrospective data and small institutional trials and make [treatment] decisions, not realizing that it’s still not standard of care,” Nathan said. “It’s fine to de-escalate, but always de-escalate if you can on a clinical trial.”

Ongoing Research

A number of important ongoing trials have the potential to add significant scientific rigor to the debate. Among them is Eastern Cooperative Oncology Group’s ECOG-E3311 trial (NCT01898494), which is examining transoral surgery followed by low- or standard-dose radiation therapy with or without chemotherapy. Initial findings are expected to be presented at the 2020 American Society of Clinical Oncology Annual Meeting and the trial is expected to be completed in 2023. The PATHOS trial (NCT02215265), which is evaluating transoral resection followed by reduced-intensity radiotherapy with or without cisplatin, is expected to be completed in 2026.

Yom and colleagues are working on NRGHN005 (NCT03952585), a phase II/III study in which patients will undergo deintensified radiation therapy with cisplatin or the PD-1 inhibitor nivolumab (Opdivo) versus standard-of-care chemoradiation. The investigators used an innovative design so that the study will produce scientifically rigorous results for the 70 Gy versus 60 Gy question at the phase III level, even if the nivolumab phase II investigation does not meet its targeted end points, Yom told TTO.

In the meantime, Burtness said, the data are beginning tosuggest, if not conclusively, which types of patients might be a good fit for deintensification. “The omission of chemotherapyin the postoperative setting after transoral resection is probably better for patients with smaller nodes, maybe only 1 or 2 nodes,” she said. “The use of more induction chemotherapy and a lesser dose of radiation is better, obviously,for patients who are going to tolerate chemotherapy well. The omission of systemic chemotherapy and the use of immunotherapy may eventually [lead to the development of] a biomarker signature.”

She cautioned that it is not clear that all HPV-associated cancers should be treated the same way. Certain other factors appear to affect the opportunity for deintensification. “Repeatedly, we’ve seen [that] patients with T4 cancers don’t do well with deintensification,” she said. “Patients who’ve smoked more than 10 pack-years won’t do well.”

Burtness added that there is a good chance the end result of all the research will simply be that certain deintensification strategies are better for certain patient populations. Yom agreed. “One of our goals is to make deintensification acceptable within the standard of care,” she said. “But I’m not sure there’s going to be just 1 standard of care going forward.”

Even if these new strategies show equal or better success rates compared with the current standard ofcare, patients who undergo deintensified therapy might avoid the toxicities of more intense therapy at the cost of unexpected long-term AEs.

The 2 key takeaways from the study we put together are that, 1, there are a lot of different deintensification strategies, and in the short term, a lot of these different strategies don’t show any differences in outcomes or toxicity,” Patel said. “But the second point that is crucial is that longer-term follow-up is necessary for making judgments as to whether or not to do deintensified treatments.”

Nathan said 1 major concern is that patients with deintensified treatment regimens might facea higher risk of a subsequent cancer diagnosis. “HPV- associated cancers still have the same distant metastasis rate as HPV-negative cancers,” she said. “And the distant metastasis is occurring years later and sometimes in unusual locations.”

For example, lack of systemic therapy might not affect the current oropharyngeal tumor, but years later, could it lead to a cancer that might have been prevented? That type of question is impossible to answer at thispoint, andNathan says it is problematic to assume the answer is no.

Nathan also raised concerns about changes to the American Joint Commission on Cancer (AJCC) staging system. In the eighth edition of the AJCC Cancer Staging Manual, HPV-associated cancers were restaged because staging is generally meant to match prognoses, and HPV-associated cancers had been shown to have better prognoses, she said.The end result of the restaging, she said, is that some cancers previously deemed stage IV might now be reclassified as stage I or II. Nathan worries that the lower staging will result in even more deintensification because clinicians will not consider cases as serious as they once did, which would be a mistake, she said. “All the patients who did so well and have such good survival [in the existing de-escalation literature] were being treated like they were stage III or IV,” she said. “So, until you have the results of [ongoing clinical trials], you shouldn’t be doing it.”

Deintensification Today

Clearly, some level of deintensification is occurring withinclinics inthe United States.If itturnsout that 1 or more of the new, lower-intensity strategies is effective, the treatment paradigm for patients will be drastically different, Yom said:“To start talking about things like patient preferences and quality of life is foreign and different in oropharyngeal cancer.”

Patient preference is a key consideration,Patel said: “That’s why the data and being able to share with patients that these outcomes aren’t different at longer-term follow-ups is important.”

Different types of patients will likely favor different approaches, even if de-escalation is validated as a standard option, according to Yom. “I have patients who come to my clinic, and they’re like, ‘I have 2 kids. I’m staying alive. Hit me with everything you have,’” she said.

A large spectrum of Yom’s patient population is very highly educated about their cancers, she said, and that knowledge can inform the strategies they prefer. In many cases, education leads patients to be less concerned about mortality and more concerned about the impact of therapy on quality of life.

“There’s a large proportion of that population where their driving concern is this fear of long-term consequences,” she said.

Yom said radiation oncologists will need to better help patients, who until now had few treatment choices, think through their options. “We don’t have good structures and instruments to help people sort through the decision-making process ina way that makes sense to them,” she said. “I don’t think anybody does.”

Even if the data from the current trialsare positive, Nathan cautioned, the time horizon to evaluate outcomes must be longer than a few years. “Most of these trials are looking good, but follow-up is only about 3 to 4 years, she said. “A lot of our toxicities [that we have seen] have occurred 5 and 8 years later.”

That will require oncologists to be involved in decisions that might be thornier than those patients previously faced. “You’re going to have to be a much better oncologist,” Yom said.

Still, she and others say the challenge will be well worth it, but only if the ongoing scientific study findings support the optimism now shared by many in the field. “This deintensification movement will have huge implications [for] how the majority of patients with head and neck cancers will be treated in this country going forward,” Yom said.

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May, 2020|Oral Cancer News|
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An Occult HPV-Driven Oropharyngeal Squamous Cell Carcinoma Discovered Through a Saliva Test

Source: Frontiers in Oncology
Date: March 31st, 2020
Authors: Kai Dun Tang, Sarju Vasani, Touraj Taheri, Laurence J. Walsh, Brett G. M. Hughes, Lizbeth Kenny, and Chamindie Punyadeera

Oropharyngeal cancer (OPC) caused by human papillomavirus (HPV) is a rising global concern. Early lesions are small and are often located in difficult to access areas (such as the crypts of the tonsils or base of tongue). Unlike cervical cancer, there is no standard or routine screening program for HPV-driven OPC. HPV DNA from OPC tumors may shed directly into saliva, and this can be used as a biomarker for early diagnosis. In this study, we report the first-ever clinically occult OPC in an asymptomatic patient discovered through a saliva test. This case relied upon serial measurements of HPV-16 DNA in saliva, which fell to undetectable levels following low morbidity, curative treatment.

Introduction

The incidence of high-risk human papillomavirus (HR-HPV−16,-18,-33) driven oropharyngeal cancer (OPC) is rapidly increasing in developed countries (1–3). HPV-driven OPCs have surpassed cervical cancer as the most common HPV-driven cancer in the USA. The prevalence of HR-HPV has been reported as 3.7% of the USA population, with a bimodal age distribution of incidence (4). It remains unclear why some individuals go on to develop OPC, while others clear the initial HPV infection (5). The strong association between HR-HPV infection and cervical cancer has led to screening programmes in primary healthcare settings, resulting in earlier diagnosis and a reduction in cancer deaths (6). Unlike cervical cancer, no screening test is available for OPC and current HPV vaccines have yet to demonstrate any reduction in future OPC development (7). Here, we report the first ever case of occult OPC detected as a direct result of a theoretical screening test—in this case HPV-16 DNA analysis in salivary oral rinse samples. Our clinical and pathological findings increase our understanding of both the natural history of the disease and the potential for wider screening to identify early stage OPC, facilitating less morbid treatments.

Cases Presentation

An ongoing HPV-16 DNA prevalence study was approved by institutional ethics committees from the University of Queensland; Queensland University of Technology and the Royal Brisbane and Women’s Hospital. A total of 665 cancer-free healthy individuals from Queensland Region, Australia between May 2016 and October 2017 were recruited. All participants gave written informed consent prior to sample collection.

Six hundred and fifty cancer-free healthy individuals with sufficient amount of DNA were tested for oral HPV-16 DNA. Of these 3 have been identified to have persistent oral HPV-16 DNA infection. Following discussion with our ethics team we have approached these three participants and offered them consultation with an Ear, Nose, and Throat (ENT) surgeon. A 63-year-old caucasian male was assessed as part of this consultation process. He had consistently been HPV-16 DNA positive for a period of 36 months, with a steadily rising HPV-16 viral load in his salivary oral rinse samples (Figure 1A). He was invited to attend the ENT clinic for assessment and discussion.

FIGURE 1
www.frontiersin.orgFigure 1. Occult oropharyngeal microcarcinoma detected based on a screening test through the serial measurements of salivary HPV-16 DNA. (A) HPV-16 DNA viral load in salivary oral rinse samples over time. B (Baseline); F1 (6 month follow-up); F2 (12 month follow-up); F3 (36 month follow-up); PT (2-week post-tonsillectomy). (B) Sections of the left tonsillar tissue found a 2 mm non-keratinising squamous cell carcinoma, with focal stromal invasion <1 mm, excised with clear margins. The remainder of the left tonsil showed follicular lymphoid hyperplasia. Hematoxylin-eosin (H&E x200) (C) HPV-16 DNA was only positive in left tonsillar tissue. (D) p16INK4a immunohistochemistry staining (IHC) x20: Diffuse positive brown staining for p16INK4a in tumor region comparing non-affected area in the left tonsil.

He is an ex-smoker, having quit 15 years ago, with a 45 pack year history of smoking. He drinks two standard drinks (2.5 units of alcohol) per day. He is heterosexual, and his social history includes multiple oral sex partners in the past (>5), followed by a long term monogamous relationship. Initial clinical examination of the oropharynx including palpation and white light revealed no significant abnormalities. Both tonsils were irregular due to mucous retention cysts and there was slight tonsillar asymmetry (Left < Right) but no evidence of any malignant lesions. Narrow band imaging (NBI) showed some mild vascular changes at the left glosso-tonsillar sulcus. There were no palpable lymph nodes in the neck. An MRI examination of the oropharynx and neck demonstrated no occult lesions of the tonsils or the base of tongue and no cervical lymphadenopathy.

He was offered continued surveillance, or a biopsy of the area of NBI change with bilateral tonsillectomy. The patient elected for bilateral tonsillectomy and biopsy of the base of tongue with NBI guidance under general anesthetic and informed consent was obtained. The surgical specimens were sent for histology and tissue HPV-16 DNA testing. The patient was discharged from hospital the same day. He had a routine postoperative course with a sore throat for 1 week and recovered fully. An ultrasound scan of his neck was performed 2 months post-surgery which showed no cervical lymphadenopathy. He is currently under routine oncological surveillance. The patient has a very high likelihood of cure with minimal morbidity from single modality treatment.

Clinical Specimens’ Collection and Processing

Salivary oral rinse samples of this individual were collected at baseline, 6, 12, 36 month, and 2 weeks after his bilateral tonsillectomy using previously published method (8–10). Briefly, participants were asked to swish and gargle for 1–2 min with 2 × 10 mL volumes of 0.9% saline, prior to expectorating the rinse sample into a 50 mL falcon tube. Tissue biopsies from the tonsil and base of tongue were obtained after surgical resection. All samples were immediately frozen on dry ice upon collection and transported back to the laboratory for subsequent processing.

HPV-16 DNA QPCR Analysis

Total DNA was extracted from salivary oral rinse and tonsillar tissue samples using the QIAmp DNA Mini Kit (Qiagen, Germantown, MD, USA) as per manufacturer’s protocol. For detection of HPV-16 genotyping, the qPCR assay targeting the opening reading frame (ORF) region of HPV16 E6/7 was carried out with the QuantStudio™ 7 Flex Real-Time PCR System (Applied Biosystems, Foster City, CA, USA) as described previously (11, 12). For quantification of HPV-16 DNA viral copies in salivary oral rinse and tissue samples, a standard calibration curve was generated using qPCR by plotting threshold cycle (Ct values) against the logarithm of the copy number of 8-fold serially diluted (1 × 101-1 × 108 copies) of pHPV-16 plasmid DNA [American Type Culture Collection (ATCC)® 45113™].

Immunohistochemistry

H&E (Haemotoxylin and Eosin stains) staining on formalin-fixed paraffin-embedded (FFPE) slide was performed to investigate the cellular and tissue structure/morphology. HPV status was evaluated using CINtec® p16INK4a Histology Kit (E6H4 clone) (Roche MTM Laboratories, Heidelberg, Germany) according to manufacturer’s instructions. p16INK4a was considered positive by two independent pathologists when there was a strong, diffuse nuclear and cytoplasmic staining pattern in the majority (>70%) of tumor cells.

Salivary HPV-16 DNA as a Biomarker-Based Tool for HPV-Driven OPC Screening

Salivary oral rinse samples from this individual had been collected at baseline, 6, 12, and 36 month follow-up as well as 2 weeks after his bilateral tonsillectomy. HPV-16 DNA genotyping and viral loads in all samples were analyzed using an in-house developed qPCR assay. HPV-16 DNA viral load in saliva increased exponentially across the 36 month follow-up period (from 3.43 to 1,281.69 copies/50 ng) and subsequently declined to undetectable levels post-tonsillectomy (Figure 1A).

Histologically Confirmed Diagnosis of an Occult P16INK4A Positive OPC

This individual was diagnosed as having a 2 mm squamous cell carcinoma (T1N0M0) in the left tonsil (Figure 1B) using Haemotoxylin and Eosin (H&E) staining. He had only foci of stromal invasion with a depth of <1 mm. The remainder of the left tonsil showed follicular lymphoid hyperplasia. Further, HPV-16 DNA was only positive in left tonsillar tissue (Figure 1C). Immunohistochemistry (IHC) staining for p16INK4a demonstrated diffuse and strong staining in more than 70% of tumor cells (Figure 1D). However, the non-affected remainder of the left tonsil as well as the right tonsil were negative for p16INK4a with usual mosaic pattern of staining. The excision margins of the left tonsillar malignancy were widely clear. No atypia or malignancy could be identified in the right tonsil and bilateral tongue base specimens all of which were negative for HPV-16 DNA.

Discussion

Long-term persistence of HPV-16 infection is likely to be a prerequisite for the development of malignancy (13, 14). Women with persistent HPV-16 infection in the cervix for <1 year have a 40% risk of developing cervical intraepithelial neoplasia grade 2 or more within 3 years (13). Indeed, the natural history of HPV in the oropharynx from initial infection to carcinogenesis is not known with many questions remaining unanswered. Several studies have evaluated the prevalence of HPV-16 DNA in saliva (15–18) without clinical assessment of positive individuals. Studies aimed at clinical assessment of those with persistence for premalignancy or microscopic carcinoma have failed to detect significant abnormalities (19). This has led to the assertion that screening for early occult or premalignant oropharyngeal lesions is not feasible. Here, we report the first ever histologically confirmed diagnosis of an asymptomatic occult OPC (T1N0M0) discovered by a theoretical screening test through the serial measurements of HPV-16 DNA in salivary oral rinse samples.

The impact of the pattern of salivary HPV persistence including changes in the absolute HPV viral DNA copies over time has never been investigated. The pattern of salivary HPV-DNA detection in this case demonstrates an exponential upward trend with the titer at first sample being 3.43 copies per 50 ng and the final titer before surgery of 1281.7 viral copies per 50 ng. This may represent progression of the lesion with subsequent shedding of increasing levels of HPV-16 DNA into the saliva. In future cases the presence of this pattern should be evaluated, as it may provide a critical marker for the progression of disease and hence a signal for intervention; indeed the pattern of viral copies in serial measurement may have more importance than the persistence itself.

This case also has important implications with regards to the natural history of the disease. The left tonsil was strongly positive for HPV 16 DNA outside the region of malignancy and as anticipated was p16INK4a positive only within carcinoma. This implies that the malignancy is likely to have developed in a wider field of HPV infection with only a component undergoing malignant change. The existence of a precursor lesion to OPC has long been doubted and is cited as one of the obstacles to OPC screening (16). This case demonstrates that very early lesions can be found in asymptomatic individual, and that they can potentially be eradicated with minimal morbidity.

The quest for a sensitive and specific screening test for HPV-driven OPC is of great importance. The uptake of HPV immunization in developed countries is variable and the developing world remains largely unimmunised. As sexual habits change in the developing world (20, 21) there is likely to be the same rapid expansion in this disease that we have witnessed in the United States and Europe and global burden will continue to rise. As the first singular case, this report does not act as direct evidence of the value of screening in a general population, however, it demonstrates a possible salivary screening test and pathway for the detection of microscopic OPC. It demonstrates that a screened individual can receive significantly less morbid treatment than would be required for the standard presentation at a more advanced stage. This report and previous studies (8, 11, 12, 22), support the value of a salivary oral rinse test as a potential screening tool. Unlike previously published work, our study is the first to demonstrate that continuous monitoring of HPV-16 DNA in salivary oral rinse samples can detect occult OPC.

Data Availability Statement

All datasets generated for this study are included in the article.

Ethics Statement

This study was approved by institutional ethics committees from the University of Queensland (UQ) [HREC No: 2014000679 and 2014000862]; Queensland University of Technology [HREC No: 1400000617 and 1400000641]; and the Royal Brisbane and Women’s Hospital (RBWH) [HREC/16/QRBW/447]. Written informed consent was obtained from this participant for publication of this case report.

Author Contributions

All authors have read and agree to the published version of the manuscript. KT and CP: conceptualization. All authors: methodology, validation, formal analysis, data curation, investigation, and writing—review and editing. KT, SV, and CP: writing—original draft preparation. CP: funding acquisition.

Funding

The prevalence study was funded by Janssen Biotech Inc.

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Acknowledgments

We thank Dr. Gert Scheper from Janssen Vaccines & Prevention B.V. We would also like to thank Lilian Menezes for her assistance in the recruitment of study patient and collection of clinical samples.

 

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Revealed: How cancer unit kept theatres open and saved lives despite coronavirus lockdown

Source: www.sundaypost.com
Author: Janet Boyle

Patients with head and neck malignancies have continued to get vital surgery at Queen Elizabeth University Hospital in Glasgow under strict infection vigilance set up by its maxillofacial surgery unit.

More than 40 patients have been treated for head and neck ­cancer during lockdown. Others have undergone procedures for facial skin cancer and facial injuries.

The Royal College of Surgeons Edinburgh says 87% of its members in cancer surgery had stopped operating altogether or significantly reduced the number of procedures due to the danger of patients contracting the virus. And experts fear deaths from cancer could rise by a fifth over the next year as a result of scores of treatments and consultations being cancelled.

Now it is hoped the protocols ­followed by the Glasgow team can be adopted to allow more surgery to resume. Critical to the safety of the operations is that the patients are tested for coronavirus twice before the procedure – once 48 hours beforehand, and then again immediately before surgery begins.

Patients are also asked to ­self-isolate for two weeks before surgery, the surgical team works in a separate building to the main hospital and some surgical techniques have been modified to reduce the risk of infection.

Operating on head and neck malignancies poses considerable risk to theatre teams because the work is closely associated with patients’ faces and respiratory systems, making the virus easily transmissible.

Further risk lies in the head and neck surgeon having to abandon a face shield to use the operating microscope vital to navigate and sew together tiny nerves and blood ­vessels in the face and throat.

Professor Jim McCaul, a ­consultant maxillofacial surgeon at the QEUH, said: “We never stopped working for our cancer patients. We have been doing major surgery throughout, with massive support from trainees and all of the outpatient, ward and theatre staff and nurses and administration team.

“Recent announcements about introducing a two-week lockdown on patients is what we have been doing from the start. There has been amazing support in theatre and no one hesitated at all about continuing surgery on patients.

“It would not have happened ­without the six other maxillofacial head and neck surgeons, outpatient, ward and administrative staff and many others.

“Our theatre nurses all wear full PPE, even though the patients have tested negative. Some staff are even isolating from their families. I cannot wear a visor at the microscope and that raises the risk, but it is a calculated risk.”

Patients will also need radio and chemotherapy, if the disease is more advanced.

“We also very worried about patients sitting on cancer and ­infection symptoms which will present later. It means more life-­changing treatment and we cannot cure them all,” Professor McCaul added.

Survival from head and neck ­cancer – between 50% and 60% depending on the area of head and neck affected and how advanced when it is diagnosed – has lagged behind other cancers such as breast and leukaemia.

“Cases diagnosed later can need extensive surgery, which can change patients’ appearance and ability to chew, swallow food and speak,” Professor McCaul added.

The Scottish Government is ­working to resume treatment halted during the Covid pandemic.

Discussions are ongoing as to how to take Scotland’s cancer surgery and other operations forward. Surgeons believe the way ahead almost certainly involves continual testing of staff and patients.

Hospitals in other countries have strived to create Covid-free units but emergency admissions of patients with the virus have made that challenging.

Besides operating on cancer patients, the QEUH’s head and neck cancer team has been treating those with facial injuries caused by trauma.

Professor McCaul said: “Only the super-urgent trauma cases have to go to theatre and we can get a test in 24 hours and wear full PPE for that.

“If we need to use plates and screws we use self-drilling screws because the drill generates aerosol.”

Nursery teacher Mandy Peebles was devastated to be diagnosed with mouth cancer at the age of 30.

“Everyone is scared when they are told they have cancer and I was prepared to go to any lengths to get the surgery needed to remove it,” said Mandy, from Cowglen, Glasgow. “I came across the pea-sized lump by accident, while looking for a wisdom tooth coming through. A referral to Glasgow Dental Hospital and a biopsy in December led to an appointment at the maxillofacial unit at the Queen Elizabeth University Hospital in Glasgow.

“Results confirmed it was cancer in January, just as Covid was spreading across mainland Europe to the UK.”

Mandy had two operations, in March and April. She said: “The government warnings about cancer patients being at extra risk made me lock down at home and when I was told by Professor McCaul that I would have to completely isolate I did everything possible to ensure I remained Covid-free. Catching the virus would mean my operation would be cancelled.

“My fiancé Calum is a railways maintenance engineer who works in isolation with PPE so all possible transmission was sealed off.

“I could only see my parents by waving to them when they passed my garden gate and that was heartbreaking.

“Not being able to hug my mum before undergoing surgery was painful for us both. But that’s what it took to get the surgery and I can only thank the surgical team for everything they did.

“I was fully aware that mouth cancer was a hill to climb and early treatment was vital.

“I was isolated in hospital for two days before the op and tested before going into theatre.

“The minutes seemed like hours as I waited for the Covid test results. When they returned negative the feeling of relief was amazing.”

Mandy added: “Calum and I are marrying in exactly a year and I now have everything to live for.”

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Study: Regular drinkers can curb chance of getting alcohol related diseases with exercise

Source: www.express.co.uk
Author: Richard Percival

The scientists revealed that heavier drinkers needed to produce greater physical output to offset other deadly diseases associated with drink. Meanwhile, people who recently gave up alcohol could also reduce their chances of getting sick if they exercised more too.

Researchers from the University of Sydney used data from participants aged 30 years and over in ten British population-based health surveys. They then compared this with death rates of alcohol-related cancers which included oral cavity, throat, larynx, oesophagus, liver, colorectal, stomach and additionally pancreas and lung

Using models, they discovered a strong direct association between alcohol consumption and mortality risk of alcohol-related cancers, with a significantly higher risk among ex-drinkers.

They discovered people who drank excessive amounts of alcohol every week (more than 14 units for women and 21 for men) but who did at least seven hours of exercise were less likely to die from these cancers.

The study published in the International Study of Cancer last week added: “Engaging in a recommended level of physical activity attenuated the negative effects of alcohol consumption on alcohol-related cancer mortality.

“This provides valuable evidence of the potential of promoting physical activity as an adjunct risk minimisation measure for alcohol-related cancer prevention.”

It is the first time analysts have looked at the link between exercise and surviving cancers linked with alcohol. Anne McTiernan, a cancer prevention expert at the Fred Hutchinson Cancer Research Centre, said that the evidence between exercise and alcohol “was clear”.

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A new tool to predict delays in post-surgical radiotherapy for head and neck cancer

Source: www.eurekalert.org
Author: Medical University of South Carolina news release

More than 65,000 Americans are diagnosed annually with head and neck cancer, which most often occurs inside the mouth and throat. For patients who undergo surgery to treat this cancer, guidelines recommend that prompt initiation of radiotherapy — within six weeks — is critical for best outcomes.

Unfortunately, delays in initiating post-operative radiotherapy (PORT) are far too common. Patients do not always understand the importance of prompt initiation of radiotherapy and may have to overcome other barriers, such as lack of social support and insurance. In addition, health care providers do not always communicate with one another or coordinate care. These avoidable delays have a negative impact on outcomes in a disease that claims almost 15,000 lives in the U.S. each year.

To ameliorate this crisis, a research team at the Medical University of South Carolina has developed and validated tools known as nomograms to help predict treatment delays in high-risk patients based on individualized risk factors. The team was led by Evan Graboyes, M.D., an assistant professor in the Department of Otolaryngology-Head & Neck Surgery at MUSC and a member of the Cancer Control Program at Hollings Cancer Center. The results of the nomogram study were reported in JAMA Otolaryngology-Head & Neck Surgery.

“A nomogram is a graphical representation of a mathematical model that we are using to predict how likely it is that a patient with head and neck cancer may have a treatment delay,” explained Graboyes. “We hope that these nomograms can be used to identify patients at highest risk for treatment delays so that we can target interventions to them to decrease the risk of delay.”

Standard-of-care treatment for patients with head and neck cancer combines surgery, radiation and chemotherapy. However, treatment outcomes remain very poor, and only about 50% of head and neck cancer patients with advanced disease will survive after 5 years.

With the goal of improving the survival rate of patients with head and neck cancer, Graboyes and his team developed and validated two types of nomograms for predicting delays in PORT. The study examined pre- and post-surgical data from 60,766 adult patients with head and neck cancer, grouped into different cohorts.

The first nomogram is based on information available to both the clinician and patient during the surgical consultation. At this point, the patient will know whether he or she is likely going to have surgery followed by radiation therapy. “This type of nomogram will provide a personalized estimate of the risk of delay commencing PORT and can be used to enhance counseling and guide interventions for patients with higher risks of delay,” explained Graboyes.

The findings of Graboyes’ study suggest that stage 4 cancer and oral cavity sites are two of the main variables associated with delayed PORT initiation. Knowing this type of information beforehand will enable patients to obtain pre-surgical dental oncologic treatment referrals and may greatly improve timely PORT introduction.

The second nomogram incorporates information from before and after surgery. According to Graboyes, this nomogram can be used by health care systems to compare their rates of PORT delay in a risk-adjusted fashion that acknowledges differences in the types of patients being treated.

In addition, the nomogram may guide quality improvement initiatives. For example, one of the key factors associated with delayed PORT was prolonged length of stay after surgery. This information may help physicians to reduce the length of time patients stay in the hospital after surgery, eliminating one hurdle to prompt initiation of radiation treatment.

Although the two nomograms were developed in one cohort of patients and validated in a second cohort of patients with head and neck cancer from across the U.S., the study still had some key limitations. The nomogram didn’t account for individual patient education, income, social support, dental disease, smoking or alcohol consumption. Therefore, more research will be needed to understand the degree to which these factors lead to delays in PORT initiation. A future study will help to address some of these limitations.

Graboyes believes that the current study will help head and neck cancer patients get the treatment they need and improve their chance of survival.

“I would love it if patients and clinicians would be able to use the nomogram website to get more precise, quantitative information about the risk of PORT delay and use it to educate patients, counsel them before treatment and communicate risk precisely,” said Graboyes. “We know that getting patients timely head and neck cancer care that follows guidelines is a promising strategy to improve survival among these patients. I hope these nomograms will be a practical and useful tool as we work toward the goal of decreasing treatment delays.”

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World-first saliva test detects hidden throat cancer

Source: www.miragenews.com
Author: staff

A simple saliva test developed by Queensland University of Technology (QUT) biomedical scientists has detected early throat cancer in a person who had no symptoms, and no clinical signs of cancer. QUT researchers Associate Professor Chamindie Punyadeera and Dr Kai Tang.

  • A series of saliva HPV tests detected an asymptomatic throat cancer during a trial of a new saliva diagnostic
  • Further validation studies are needed to confirm this finding
  • It is a world-first discovery, previously there was no screening test for HPV-DNA oropharyngeal cancers
  • The patient had surgery in which a 2mm cancer was removed and has had no recurrence of HPV-DNA in his saliva.

In what is believed to be a world-first, the non-invasive test picked up HPV-DNA in a saliva sample from an infected healthy person. Persistent human papillomavirus (HPV) infection is now the leading cause of cancers in the oropharynx (tonsils and tongue base area of the throat).

“The series of saliva tests raised the alert and detected an early cancer before the person had any symptoms,” said QUT Faculty of Health’s Associate Professor Chamindie Punyadeera, who, with Dr Kai Tang developed the test.

“This enabled removal of the tonsil which had a 2mm cancer in it, by straightforward local surgery alone.

“The incidence of high-risk human papillomavirus (HPV)-driven throat cancers is on the rise in developed countries and, unfortunately, it is often discovered only when it more advanced, with patients needing complicated and highly impactful treatment.

“In the US, HPV-driven throat cancers have surpassed cervical cancers as the most common cancer caused by HPV but unlike cervical cancer, up until now, there has been no screening test for this type of oropharyngeal cancer.”

Professor Punyadeera said the discovery was made during an HPV-prevalence study which included 665 healthy individuals.

“To take the test all the person has to do is give a salivary oral rinse sample. When the test shows HPV-16 DNA, it is repeated and if the presence of HPV-16 is persistent over a period of time we would be suspicious that there may be underlying cancer.

“The person whom we reported in this study had been consistently HPV-16 DNA positive for 36 months, with a steadily rising count of HPV-16 DNA after testing at 6, 12 and 36 months.

“The patient was found to have a 2mm squamous cell carcinoma in the left tonsil, treated by tonsillectomy. This has given our patient a high chance of cure with very straightforward treatment.

“Since the surgery, the patient has had no evidence of HPV-16 DNA in his saliva.”

Professor Punyadeera said this was the first-ever case of histologically confirmed diagnosis of an asymptomatic, hidden throat cancer, diagnosed with a saliva screening test and that wider validation studies were required to confirm this finding.

“The presence of this pattern of elevated salivary HPV-DNA must be fully evaluated, as it may provide the critical marker for early cancer detection.

“We now have the promise of a screening test for oropharynx cancer and there is an urgent need to undertake a major study to validate this test and the appropriate assessment pathway for people with persisting salivary HPV-DNA.

This research is part of a collaboration with Royal Brisbane and Women’s Hospital’s Professor Liz Kenny, Dr Sarj Vasani, Dr Touraj Taheri and Associate Professor Brett Hughes and University of Queensland’s Professor Laurence J. Walsh.

Source:
The study, An Occult HPV-Driven Oropharyngeal Squamous Cell Carcinoma Discovered Through a Saliva Test (https://www.frontiersin.org/articles/10.3389/fonc.2020.00408/full), was published in Frontiers in Oncology.

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