HPV

Early detection, treatment helps conquer oral cancer

Source: www.newsbug.info
Author: Bob Moulesong

According to the Oral Cancer Foundation, almost 50,000 cases of oral cancer will be diagnosed in the U.S. in 2018. The American Cancer Society reports that 10,000 people will die from the disease this year. Half of all people diagnosed with oral cancer will be alive in five years, according to both sources.

While those are disquieting statistics, Region physicians say routine checkups and early diagnosis improve the odds.

Oral cancer
Oral cancer includes cancers of the lips, tongue, cheeks, floor of the mouth, hard and soft palate, sinuses, saliva glands, and throat.

“People we see usually come to us for a lesion or ulcer found in the mouth or throat,” says Dr. Akta Kakodkar, an ear, nose and throat specialist with Community Healthcare System. “Some of them experience no pain but notice a growth or patch of discolored tissue in their mouth, cheek or gum.”

Kakodkar, who with her husband and fellow Community ENT physician, Dr. Kedar Kakodkar, treats oral cancer patients, is quick to point out that not every lesion, ulcer or mouth sore is cancer.

“We see hundreds of nervous patients who have bacterial or fungal infections,” she says. “Treatment with antibiotics or antifungal medications clear up many of these lesions. There are also many white and red patches that clear up on their own.”

The only way to know is a thorough examination.

Types and risk factors
“Most cases of oral cancer are linked to use of tobacco, alcohol and betel nuts, or infection with HPV,” Kakodkar says. “There are major risks associated with tobacco use, whether it’s smoking or chewing.”

There are two main types of oral cancer. Most prevalent is squamous cell carcinoma, accounting for more than 90 percent of cancers that occur in the oral cavity and oropharynx. Slow-growing verrucous carcinoma makes up more than 5 percent of oral cavity tumors.

First steps
Kakodkar says prevention is the best defense. “Your primary care physician may examine your head, neck, mouth and throat for abnormalities,” she says.

Self-exam may uncover a lesion or sore. “Remember, many of these are very treatable and are not cancer,” Kakodkar says. “But don’t wait. Cancer never goes away by itself.”

When Kakodkar discovers a suspicious lesion, she recommends a biopsy: “Depending on several variables, we might do the biopsy in clinic, or we may do it in a hospital setting.”

Once the results return, a plan of action can be established. “Usually, the next steps include imaging, such as a CT scan,” she says. “We also order a PET scan, which tells us what stage the cancer is in and whether or not it has spread.”

Treatment
Kakodkar says she prefers to go straight to surgery. “Many oral cancers are still small and local,” she explains. “Removing them completely is the best way to stop the spread of the cancer.”

Depending on the type and stage of the cancer, radiation and/or chemotherapy may be used.

“I want people to know that surgery for oral cancer is frequently a simple procedure,” Kakodkar says. “Oral cancer is frequently found early due to its visibility. Almost 90 percent of cancer patients in stage 1 or 2 recover and survive.”

A dental checkup
“Oral cancer screening is crucial during a dental examination,” says Dr. Ami Pandya, dentist at Family Dental Care in Valparaiso. “Recognizing abnormal tissue in a patient’s mouth could indicate precancerous tissues, and when identified early could save your life.”

A dentist will perform a thorough head and neck exam, which includes an oral cancer screening. “Dentists will complete extraoral examinations by palpating your jaw line to feel for any suspicious lumps that are not routinely present in these areas,” Pandya says.

A dentist will examine the intraoral tissues of your mouth and look for any suspicious lesions. “We examine the patient’s tongue, the floor of their mouth, and their gingival tissue,” Pandya says. Red and/or white patches can become cancerous.

Many doctors including Pandya have begun using VELscope, a light-based technology to detect precancerous tissues. It’s a wireless hand-held device that scans tissue, with abnormalities showing up as a dark black color.

“VELscope can detect abnormalities before they have a clinical presentation,” Pandya says. “It’s an incredible aid with oral cancer screening.”

Pandya recommends an annual VELscope examination for low-risk adults. Higher risk patients should get a VELscope exam each appointment.

Under the VELscope, cancer shows up as black, says Dr. Ami Pandya

If the dentist detects an abnormality, he or she informs the patient, noting the size, color and location of the lesion. A two-week follow-up is standard. “Oftentimes, these lesions resolve,” Pandya says. If it doesn’t resolve after two weeks, the patient is referred for further evaluation.

Note: This article originally ran on nwitimes.com.

November, 2018|Oral Cancer News|

Research Update: Vaccine Plus Checkpoint Inhibitor Combos for HPV-related Cancers

Source: MedPage Today
Author: Mark L. Feurst

Two new studies show the profound impact of a combined vaccine and anti-programmed death-1 (PD-1) antibody approach in the treatment of human papilloma virus (HPV)-related cancers.

HPV causes nearly all cervical cancers, as well as most oropharyngeal, anal, penile, vulvar, and vaginal cancers. HPV16 and HPV18 are the leading viral genotypes that increase cancer risk. Given the viral cause of these cancers, immunotherapy has been considered a strong potential approach.

Many patients with the HPV16 and HPV18 subtypes of head and neck squamous cell carcinoma have good outcomes from treatment that includes surgery or chemotherapy and radiation. Although anti-PD-1 therapy is approved for patients who do not respond to treatment or who develop metastatic disease, it benefits only about 15% of patients. The theory, therefore, is that a vaccine could potentially boost the immune systems of patients with HPV-related head and neck cancer, opening the door for better responses to other existing therapies.

Vaccine + Nivolumab in Phase II Study

In the first study, a phase II trial, a tumor-specific vaccine combined with the immune checkpoint inhibitor nivolumab was found to shrink tumors in patients with incurable HPV-related cancers.

“Ours are the first results with this particular approach,” Bonnie Glisson, MD, of the Department of Thoracic Head and Neck Medical Oncology at the University of Texas MD Anderson Cancer Center in Houston, told the Reading Room. “The rates of response and survival are approximately double what have been observed with nivolumab given alone to similar patients. These results will lead to larger, randomized clinical trials of this combination.”

Vaccines specific to HPV antigens found on tumors had previously sparked a strong immune response, but had not by themselves been active against established cancers, she noted.

“Vaccines are revving up the immune system, but the immunosuppressive tumor microenvironment probably prevents them from working. Our thinking was that inhibition of programmed death-1 (PD-1) would address one mechanism of immunosuppression, empowering the vaccine-activated T lymphocytes to attack the cancer.”

Glisson and colleagues combined the vaccine ISA101, which targets peptides produced by the strongly cancer-promoting HPV16 genotype of the virus, along with nivolumab, a checkpoint inhibitor that blocks activation of PD-1 on T cells.

The single-arm, single-center clinical trial included 24 patients with incurable HPV-16–positive cancer who were followed for 12.2 months. The vaccine was given subcutaneously on days 1, 22, and 50. A nivolumab dose of 3 mg/kg was given intravenously every 2 weeks beginning on day 8 for up to 1 year. Of the 24 patients with recurrent HPV16-related cancers, 22 had oropharyngeal cancer, one had cervical cancer, and one had anal cancer. The overall response rate was 33% (eight patients), and the median duration of response was 10.3 months. Five of eight patients remain in response, the team reported.

The overall median survival was 17.5 months, progression-free survival was 2.7 months, and 70% of patients survived to 12 months.

Grades 3 to 4 toxicity occurred in two patients (asymptomatic grade 3 transaminase level elevation in one patient and grade 4 lipase elevation in one patient), requiring discontinuation of nivolumab therapy. The researchers observed side effects expected from the two treatments separately, but said they were encouraged to see no sign of synergistic side effects caused by the combination.

“The combination was very well tolerated as opposed to other immunotherapy combinations such as combined blockade of PD-1 and CTLA-4,” Glisson said. “The vaccine did stimulate a strong HPV-specific immune response in peripheral blood T cells, although this was not correlated with response or survival. This suggests that other immune-suppressive factors in the tumor environment are contributing to immune evasion.”

Randomized clinical trials of the vaccine and anti-PD1 combinations for cervical and oropharyngeal cancer are ongoing, she added. “These are promising data that will be confirmed in a randomized trial. Positive results could lead to marketing of the first therapeutic HPV vaccine.”

Vaccine Helps T cells Infiltrate HPV-related Head and Neck Cancer

In the second study, another vaccine was shown to boost antibodies and T cells to help them infiltrate tumors and fight off HPV-related head and neck cancer. This approach might complement PD-1 or programmed death-ligand 1 inhibition in HPV-associated head and neck cancers to improve therapeutic outcomes, explained the study’s lead author, Charu Aggarwal, MD, MPH, of the Perelman School of Medicine at the University of Pennsylvania.

“We wanted to know if this vaccine can boost the immune systems of patients with HPV-related head and neck cancer, potentially opening the door for better response rates to other existing therapies. Our findings show that we can.”

Aggarwal and colleagues conducted a Phase Ib/II safety, tolerability, and immunogenicity study of immunotherapy with MEDI0457, a DNA immunotherapy targeting HPV16/18 E6/E7 with interleukin-12 encoding plasmids. The vaccine was delivered via electroporation to 21 patients. One group of patients received one dose before surgery, followed by three doses after surgery. The second group received four doses following chemotherapy and radiation.

Eighteen of the 21 patients (86%) showed elevated T cell activity that lasted at least 3 months after the final vaccine dose, the team reported. Five tumors were biopsied both before and after one dose of the vaccine, and there was evidence of T cells reacting with antigens contained in the vaccine in all five of these samples. One patient who developed metastatic disease and was treated with anti-PD-1 therapy developed a rapid and durable complete response that has lasted more than 2 years.

“We have not seen that kind of infiltration with just one dose of a vaccine before. These findings open the door for utilizing targeted immunotherapy approaches against specific cancer-causing targets like HPV,” said Aggarwal, adding that the vaccine was well tolerated, with no serious side effects reported.

“This response suggests that the vaccine may, in some manner, prime the immune system, potentially boosting the effects of subsequent anti-PD-1 therapy,” she explained, noting that a multi-site clinical trial is now open to patients with metastatic HPV-associated head and neck cancer, who will receive a combination of the vaccine with anti-PD-1 therapy.

Previously, the CheckMate-141 trial tested nivolumab in 361 patients with recurrent or metastatic, chemotherapy-refractory squamous cell head and neck cancer, and the results led to FDA approval in that setting. Sixty three of these patients were HPV16-positive, and the overall response rate among this group was 15.9%, with a median overall survival of 9.1 months.

 

November, 2018|Oral Cancer News|

Cultural barriers still stand in the way of HPV vaccine uptake

Source: arstechnica.com
Author: Cathleen O’Grady

Every year, nearly 34,000 cases of cancer in the US can be attributed to HPV, the human papillomavirus . The CDC estimates that vaccination could prevent around 93 percent of those cancers. Yet HPV vaccination rates are abysmal: only half of the teenagers in the US were fully vaccinated in 2017.

Cultural barriers play a role in that low rate. Vaccinating pre-teens against a sexually transmitted infection has had parents concerned that that this would encourage their kids to have sex sooner, with more partners, or without protection or birth control. And vaccine rates vary across different social and cultural groups: for instance, rural teenagers are less likely to be vaccinated than urban ones.

Two recent studies explore different facets of the cultural barriers standing in the way of better HPV vaccine uptake. The first, a paper published last month in the Canadian Medical Association Journal, looks at the data on whether the vaccine encourages riskier sexual behavior and finds no evidence that it does. And the second, an early draft of a paper presented at an American Association for Cancer Research meeting this week, reports the results of a culturally-targeted intervention aiming to increase vaccine uptake among low-income Chinese Americans.

The kids are alright
Although the vaccine is now recommended for both boys and girls, the initial drive was to get teenage girls vaccinated, given the link between HPV and cervical cancer. That’s why girls are the focus of the recent study on risky sexual behavior: the researchers used data from high school girls in Canada, where a huge survey on adolescent health is administered every few years.

A team of researchers was able to use this data to compare results from the survey before and after a large-scale HPV vaccine program was implemented across high schools in Canada in 2008. The researchers compared data from 2003, before the program began, to data from 2008 and 2013. Altogether, nearly 300,000 girls’ survey responses were analyzed.

The researchers found that, on every measure they looked at, risky sexual behaviors either decreased or stayed the same. The number of girls who had ever had sex decreased from 21.3 percent in 2003 to 18.3 percent in 2013. The girls who’d had sex before age 14 decreased from 14.3 percent to 10.2 percent, and girls who’d ever been pregnant went from 5.9 percent to 3.4 percent. The use of condoms increased, as did the use of birth control pills.

The researchers are careful to point out that they don’t think the HPV vaccine caused the increase in safe sex among the teenagers. That shift was already underway, they write, pointing to data showing “a downward trend in risky sexual behaviors since before 2003.” But it does suggest that the introduction of the vaccine in 2008 wasn’t associated with an increase in risky sexual behaviors.

Survey data like this has its problems, especially when the questions involve sex. It’s likely that the girls aren’t telling all, even when the survey is anonymous. But because all three years of the survey are likely to suffer from the same problem, the comparison is still apples with apples. And it’s possible that in a parallel universe without the vaccine, the risky behaviors could have plummeted even further; there’s simply no way to tell.

The researchers plan to explore whether risky behavior looks different in girls who had been vaccinated compared to those who hadn’t. To do this, they will introduce a new question in the survey, which asks girls about their HPV vaccination status. But in the meantime, these results fit in well with a growing body of literature: a study in the US that compared girls who were and weren’t vaccinated found no differences in pregnancy or STD rates between the two groups, while a different Canadian study found similar results.

Some research has even found that girls who’ve had the vaccine have safer sex than those who haven’t. That could be because HPV vaccine programs often go hand-in-hand with sex education, and teasing apart those influences is extremely difficult. But it seems unlikely that a significant change in risky behavior is lurking hidden in the data.

Different tactics for different groups
The obvious benefits of the vaccine make it important for us to understand why its uptake isn’t higher. The rate is even lower among certain groups, says Grace X. Ma, director of the Center for Asian Health in Philadelphia. While Asian American teenagers have rates similar to the average, “there are certain subgroups, such as Chinese Americans whose parents are low-income and have limited English proficiency, for whom uptake is much lower.” According to Ma, different sources placed the rate at between 10 and 30 percent at the time she started her research.

Ma designed a program to reach these parents through doctors, using materials written in their own languages and delivered through a source they were inclined to trust. In a small pilot study, Ma engaged pediatricians working in low-income Asian communities in Philadelphia and New York. By the end of the study, 110 parents had been reached by the materials, while a control group of 70 hadn’t. More than 70 percent of the teenagers of those 110 parents “had at least one dose of the HPV vaccine, compared with 10 percent of adolescents whose parents did not receive the intervention,” Ma reports.

Without a lot more information, it’s difficult to know what was driving this difference: it could be the cultural specificity of the materials, it could simply be access to the information in a language the parents understand, or a longer and more focused conversation with the doctor might drive the change.

But research in this vein, exploring the effects of different kinds of interventions, could give important clues to how vaccine uptake could be improved in a wider range of population groups. The potential barriers could range from cultural attitudes about sex to language issues to financial access to medical care. But clearly, simple access to the vaccine isn’t enough to encourage widespread adoption.

Source: Canadian Medical Association Journal, 2018. DOI: 10.1503/cmaj.180628 (About DOIs).

November, 2018|Oral Cancer News|

HPV vaccine gains support of ADA

Source: Multi Briefs
Date: October 24th, 2018
Author: Tammy Adams

The American Cancer Society estimates there will be more than 50,000 new cases of oral cancer in 2018. And between 70 to 80 percent of these cases will be attributed to the human papillomavirus virus (HPV), a virus that has types associated with oropharyngeal cancer.

These staggering numbers call for action; action the American Dental Society is willing to take. Why? Because the HPV vaccine could prevent the vast majority of these new cases, but compared to other vaccines in the U.S., it is underutilized.

According to a resolution passed recently by the ADA House of Delegates, the ADA urges dentists to support the use and administration of the human papillomavirus virus vaccine, recognizing it as a way to help prevent infection of the types of HPV associated with oropharyngeal cancer.

Resolution 53H-2018 cites recommendations from the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices. It states that the vaccination is a “safe and effective intervention to decrease the burden of oral and oropharyngeal HPV infection.”

The policy is the result of a multifaceted ADA council proposal that includes input from the Council on Scientific Affairs, the Council on Advocacy for Access and Prevention and the Council on Dental Practice. A workgroup committed to the HPV issue and led by ADA volunteer members developed an evidence-based background report to help write the policy.

Dr. Paul Eleazer, past chair of the ADA Council on Scientific Affairs, said that he is encouraged to see the ADA “get behind” this growing crisis, referring to the rising number of HPV-associated cancers being reported. “There is incontrovertible evidence that this virus is responsible for the sharp uptick in oropharyngeal cancers, especially in younger patients and young adults,” said Dr. Eleazer.

In 2017, the ADA Council on Scientific Affairs and Center for Evidence-Based Dentistry published “Evidence-based Clinical Practice Guideline for the Evaluation of Potentially Malignant Disorders in the Oral Cavity” to inform dental professionals about the potential use of adjuncts as triage tools for the evaluation of lesions, including potentially malignant disorders, in the oral cavity. To view this guideline, visit ADA.org/OralCancer.

To read the full resolution related to the HPV vaccine, members can log in to the Member Center on ADA.org and click on “Committee C—Dental Education, Science and Related Matters” under Reports and Resolutions. It is Resolution 53.

October, 2018|Oral Cancer News|

Lowering Radiation Dose Could Improve QoL, Cut Costs in Oral Ca

Source: MedPage Today, Medpage.com
Date: October 25th, 2018
Author: Elizabeth Hlavinka

SAN ANTONIO — Radiation de-intensification was tied to a quicker rebound in a number of quality of life (QoL) measures and reduced costs for patients with HPV-associated oropharyngeal cancer, a pair of studies found.

With lower doses of radiotherapy (RT), QoL measures including speech, pain, and socialization still generally worsened after treatment, but returned to baseline within 3 to 6 months, reported Kevin Pearlstein, MD, of the University of North Carolina in Chapel Hill.

And more aggressive de-intensification led to a 22% cost reduction for treatment overall ($45,884 versus $57,845 with standard care), with 33% lower costs for RT itself and 50% lower costs for post-treatment care (P=0.01), according to findings presented by Mark Waddle, MD, of the Mayo Clinic in Jacksonville, Florida.

The studies were presented here at the American Society for Radiation Oncology (ASTRO) meeting during a session on improving outcomes while minimizing toxicity in oropharyngeal cancer.

In the research from Pearlstein’s group, patients reported global QoL scores of 81 at baseline (using the 100-point EORTC QLQ-C30 questionnaire, where higher scores connote better health), which dipped to 69 at 3 months post-treatment, then rose to 75 at 6 months. Global QoL scores increased to 82 and 84 by months 12 and 24, respectively.

Common long-term side effects such as sticky saliva, taste, and ability to swallow did not return to baseline within months 3 to 6, but continued to improve between months 12 and 24. Pearlstein noted that swallowing took longer to return to baseline, typically between 1 to 3 years.

“This highlights the possibility that there can be improvement in these symptoms with longer-term follow-up,” he said.

Although oropharynx cancers associated with HPV generally have a more favorable prognosis compared with those that are not, the treatment is similar for both. As a result, these lower-risk patients still typically experience symptoms of dysphagia, dry mouth, and taste changes for upwards of 1 year after treatment, Pearlstein said.

While standard treatments typically include 70 Gy RT along with 100 mg/m2cisplatin, this study investigated whether patients given 60 Gy RT along with weekly 30 mg/m2 doses of cisplatin would result in improved QoL. Cisplatin-intolerant patients were treated with cetuximab, and patients who could not tolerate either did not receive chemotherapy.

The authors also conducted a multivariate analysis that controlled for type of chemotherapy, gender, and age. Those with with worse baseline symptoms of dry mouth, taste, and sticky saliva were more likely to return to baseline function at 12 months (ORs of 1.06, 1.09, and 1.02, respectively). Similar associations for sticky saliva and swallowing were found among patients who underwent unilateral neck RT.

“One obvious limitation is that we don’t have a direct comparison with standard intensity chemotherapy/radiotherapy,” Pearlstein said. “However, when we view these findings in the context of what we already know for patients with head and neck cancer, we do feel our findings suggest that patients who receive de-intensified chemotherapy/radiotherapy may benefit from faster return to baseline quality of life, continue improvement in symptoms over time, and less long-term morbidity.”

To conduct the study, the researchers collected data from two de-intensification phase II trials that took place from 2012 to 2017. A total of 126 patients were included, a majority of which were ages 60 and over (53%) and were non-smokers (63%). Patients were followed for an average of 25 months.

Cost of Treatment

De-intensification of radiation may also benefit these patients by decreasing total treatment costs, according to an analysis of a prospective phase II study.

“Several studies have or are investigating de-escalation of treatment to reduce toxicity while maintaining outcomes,” Waddle said during his presentation. “However, those studies haven’t investigated the cost of care that may be associated with de-escalation of treatment.”

He reported that the median cost was $17,309 for RT among those who received de-escalated doses compared with $28,161 with standard treatment (P<0.0001). The per-patient costs were $797 versus $933 per month, respectively, in the first 6 months after treatment and $518 versus $611 in the 16 to 24 months after treatment.

Among the post-treatment savings, gastrointestinal-related costs were 79% lower (P<0.01), hospitalization costs were 40% lower, and emergency department visit costs were 90% lower.

This study obtained data from the MC1273 trial, in which 68 patients received aggressive de-escalated doses of RT (30-36 Gy), and then compared the costs to 84 patients treated with standard of care (60-66 Gy). The average patient age was 58.5 years and the majority of them were white men.

October, 2018|Oral Cancer News|

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

October, 2018|Oral Cancer News|

Patients with HPV-positive oropharynx cancer should receive chemoradiation

Source: medicalxpress.com
Author: provided by European Society for Medical Oncology

Patients with human papilloma virus (HPV)-positive throat cancer should receive chemoradiotherapy rather than cetuximab with radiotherapy, according to late-breaking research reported at the ESMO 2018 Congress in Munich.

“Many patients have been receiving cetuximab with radiotherapy on the assumption that it was as effective as chemotherapy with radiotherapy and caused less side effects but there has been no head-to-head comparison of the two treatments,” said study author Prof Hisham Mehanna, Chair, Head and Neck Surgery, Institute of Cancer and Genomic Sciences, University of Birmingham, UK.

Throat cancer is rapidly becoming more common in Western countries. For example in the UK, incidence was unchanged in 1970 to 1995, then doubled in 1996 to 2006, and doubled again in 2006 to 2010.The rise has been attributed to HPV, a sexually transmitted infection. Most throat cancer was previously caused by smoking and alcohol and affected 65-70 year-old working class men. Today HPV is the main cause and patients are around 55, middle class, working, and have young children.

HPV-positive throat cancer responds well to a combination of cisplatin chemotherapy and radiotherapy, and patients can survive for 30-40 years, but the treatment causes lifelong side effects including dry mouth, difficulty swallowing, and loss of taste. Patients deemed unable to tolerate chemotherapy, for example because of poor kidney function or older age, receive cetuximab, an epidermal growth factor receptor (EGFR) inhibitor, and radiotherapy.

This study compared side effects and survival with the two treatments in 334 patients with HPV-positive throat cancer enrolled from 32 centres in the UK, Ireland, and the Netherlands. Patients were randomly allocated to radiotherapy and either cisplatin or cetuximab. Eight in ten patients were male and the average age was 57 years.

During the two-year study there were ten recurrences and six deaths with cisplatin compared to 29 recurrences and 20 deaths with cetuximab. Patients on cisplatin had a significantly higher two-year overall survival rate (97.5%) than those on cetuximab (89.4%; p=0.001, hazard ratio [HR] 4.99, 95% confidence interval [CI] 1.70-14.67). Cancer was over three times more likely to recur in two years with cetuximab compared to cisplatin, with recurrence rates of 16.1% versus 6.0%, respectively (p=0.0007, HR 3.39, 95% CI 1.61-7.19).

There were no differences between groups in the overall number of side effects, or of acute or late severe (grade 3-5) toxic events including dry mouth and difficulty swallowing. There were significantly more serious adverse events such as renal and haematological problems with cisplatin than with cetuximab.

Mehanna said: “Cetuximab did not cause less toxicity and resulted in worse overall survival and more cancer recurrence than cisplatin. This was a surprise—we thought it would lead to the same survival rates but better toxicity. Patients with throat cancer who are HPV positive should be given cisplatin, and not cetuximab, where possible.”

Commenting on the study for ESMO, Dr. Branislav Bystricky, Head, Medical and Radiation Oncology Department, University Hospital Trencin, Slovakia, said: “It was believed that cetuximab causes less side effects and was therefore a good option for HPV-positive throat cancer patients who are young and expected to survive for several decades, as well as those less able to tolerate chemotherapy. This study shows that the best treatment choice for patients with HPV-positive throat cancer is cisplatin and radiotherapy. This combination gives ‘double’ the benefit since it is more effective in terms of survival and does not worsen all grade toxicity compared to cetuximab with radiotherapy.”

Bystricky noted that the results were in agreement with interim findings of the US National Cancer Institute’s RTOG 1016 trial, which is scheduled to report this month. He said: “We now have two studies showing that these patients should not be given cetuximab. Future research should examine whether genotyping for the KRAS-variant can select a group of patients that will benefit from cetuximab treatment with radiotherapy.”

October, 2018|Oral Cancer News|

Why oral cancer threatens men

Source: www.scientificamerican.com
Author: Claudia Wallis, Scientific American November 2018 Issue

Back in 2006, when the vaccine for human papillomavirus (HPV) was introduced, I rushed to get my teenage daughters immunized. Here, amazingly, was a vaccine that could actually prevent cancer. By blocking HPV infection, it protects girls from the leading cause of cervical malignancies. I didn’t give much thought to my son, and neither did the medical establishment. It wasn’t until 2011 that health authorities recommended the vaccine for boys.

In hindsight, that delay was a mistake, though perfectly understandable: the vaccine was developed with cervical cancer in mind and initially tested only in girls. Today, however, we see a rising tide of cancers in the back of the throat caused by HPV, especially in men, who are three to five times more vulnerable than women. This surge of oropharyngeal cancers, occurring in many developed nations, took doctors by surprise. Oral cancers were expected to decline as a result of the drop in smoking that began in the 1960s.

Smoking-related oropharyngeal cancers are, in fact, down. But making up the difference, particularly in men, are those related to HPV, which have more than doubled over the past two decades. With cervical cancer waning (thanks to screening and prevention), this oral disease is now the leading HPV-related cancer in the U.S. Nearly 19,000 cases were reported in 2015, according to a recent report by the Centers for Disease Control and Prevention. Roughly nine out of 10 involve a nasty strain called HPV-16.

Researchers link the rise of these cancers to changing sexual practices, perhaps dating back to the 1970s. “People have more partners than they had in the past, and they initiate oral sex at an earlier age than previous generations did,” says Gypsyamber D’Souza, associate professor of epidemiology at the Johns Hopkins Bloomberg School of Public Health. Greater exposure to oral sex means that the nearly ubiquitous virus gets transferred from the genitals to the mouth.

Studies suggest that most women develop protective antibodies to HPV after having a few sexual partners, but for men, it may take more than 10 partners. A likely reason for the difference, says oncologist Maura Gillison of the University of Texas MD Anderson Cancer Center, is that “in women, the infection is vaginal-mucosal; in men, it’s entirely on the skin,” where it is much less likely to trigger an antibody response. Males can get an active infection again and again, and it lingers longer than in women, making them the “Typhoid Marys of HPV,” as Gillison puts it. The path from infection to cancer may take decades and is not well understood.

Fortunately, the HPV vaccine should prevent these oral cancers, just as it protects against cervical cancer (as well as virus-related cancers of the vulva, labia, penis and anus). After lagging for years, U.S. rates of vaccination of boys are catching up with that of girls. New CDC data show that in 2017, 68.6 percent of girls and 62.6 percent of boys, ages 13 to 17, had received at least one dose of the vaccine—up from 65.1 and 56 percent, respectively, in 2016. If the trend continues, HPV-related cancers will ultimately become a scourge of the past in the U.S.

The tough question is what to do in the meantime for the large number of people, especially at-risk men, who have never been immunized. The CDC recommends the vaccine for children as young as nine and up to age 21 for boys and 26 for girls. Merck, which makes the only HPV vaccine now used in the U.S., is seeking approval to make it available up to age 45, but the $130-a-dose vaccine is less cost-effective in older populations. “It’s best given before people are sexually active,” explains Lauri Markowitz, team lead and associate director of science for HPV at the CDC. “The vaccine is not therapeutic; it’s prophylactic.” A vaccine advisory committee meeting this fall will weigh whether to revise current recommendations. One possibility, she says, is raising the upper age for boys to 26, matching that for girls.

D’Souza, Gillison and others are investigating ways to identify and screen people who may be at an especially high risk for oral HPV cancers—a significant challenge. There is no Pap-smear equivalent for this devastating disease, no reliable way to spot precancerous or early-stage lesions. And research by and her colleague Carole Fakhry shows that even if you focus on a high-risk group such as men in their 50s—8 percent of whom are infected with one of the noxious HPV strains—only 0.7 percent will go on to develop the cancer. There’s little point in terrifying people about the small odds of a bad cancer, D’Souza says, so “we’re working on understanding which tests would be useful.”

October, 2018|Oral Cancer News|

As HPV-related cancer rates climb, experts scrutinize barriers to HPV vaccination

Source: www.cancertherapyadvisor.com
Author: Bryant Furlow

Oropharyngeal squamous cell carcinomas (SCCs) are now the most commonly diagnosed human papillomavirus (HPV)-associated cancers in the United States, with 15,479 men and 3438 women diagnosed in 2015, according to an analysis by the Centers for Disease Control and Prevention (CDC).1

Between 1999 and 2015, cervical cancer and vaginal squamous cell carcinoma (SCC) rates declined, by 1.6% and 0.6% per year, respectively. But rates for vulvar SCC increased by 1.3% annually during the same period. Anal SCC rates also climbed by approximately 2% a year among men and 3% among women.1

Rates of oropharyngeal SCC — cancers of the throat and tongue — climbed as well, particularly among men (2.7% a year vs 0.8% in women).

All told, more than 43,000 Americans were newly diagnosed with HPV-related cancers in 2015, the analysis showed, up from 30,115 in 1999.1 Most people diagnosed with HPV-associated malignancies are older than 49 years.1 Most women diagnosed with cervical cancer are older than 30 years.1

“We don’t actually know what caused the increase in HPV infections but we know now that we have a safe and effective vaccine that can prevent infections,” said Lois Ramondetta, MD, professor of gynecologic oncology and reproductive medicine at the University of Texas MD Anderson Cancer Center, Houston.

“We’re seeing people who were infected decades ago developing these cancers,” Dr Ramondetta said. “We’ll see rates continue to rise over the coming years because the vaccine wasn’t available before 2006.”

HPV vaccination rates are improving, Dr Ramondetta noted.

Overall, approximately half of adolescents in the United States have completed the HPV vaccine dose-series — well shy of the 2020 herd immunity goal of 80%.

“That’s the overall up-to-date vaccination rates for adolescents aged 13 to 17,” Dr Ramondetta explained. “That’s definitely not where we want it to go but it is 5% higher than last year. If you look at the one-completed-dose vaccine initiation rate, that’s 65.5%.”

HPV vaccination rates are improving more rapidly among boys than girls.

“For some reason, safety is not as big a concern for boys and their parents,” Dr Ramondetta said. “It shouldn’t be a concern at all. This vaccine has been studied more than just about any other vaccine. But if you ask parents why girls are not vaccinating, safety seems to be a concern for some.”

There appears to be less stigma among parents about sons becoming sexually active than there is about the sexual activity of daughters, said Debbie Saslow, PhD, senior director of HPV-related and women’s cancers at the American Cancer Society in Atlanta, Georgia.

Vaccination rates vary geographically, both between countries and within the US. Only a handful of states require that public school students receive the HPV vaccine. Vast expanses of the rural US have few or no pediatricians and limited access to the vaccine.

Australia introduced HPV vaccines at the same time as the US, nearly a decade ago, but Australia achieved 80% vaccination rates in just a year, Dr Saslow said. That was largely because the Australian government paid for the vaccines and they were administered in schools. As a result, this year, Australia changed cervical cancer screening recommendations to reflect the reduced risk: at age 25, women start undergoing HPV testing (rather than pap tests) every 5 years.

That will eventually happen in the US as well, Dr Saslow predicted.

“It’s going to happen but the question is when,” she said. “What will happen is we’ll start screening later, at age 25 and maybe eventually 30, and screening will get away from Pap testing, because Pap tests are not as effective in vaccinated people: they’ll detect a bunch of cervical changes unrelated to cancer. It will all be false positives. We’ll need to go to strictly HPV-based testing” or potentially some new type of screening test, according to Dr Saslow.

In the US, there appear to be socioeconomic or class barriers at play regarding HPV vaccination. Completion rates tend to be higher among more affluent groups, meaning that those who get the first vaccine are more likely to complete the series.

But there’s also a “reverse disparity” in initiating HPV vaccination at all Dr Saslow noted. “Poor and minority kids have higher rates of [the] first dose. Providers might be doing their own risk-based recommendations to parents, which they should not be doing, saying these kids are at higher risk.”

In high-socioeconomic-status urban and suburban communities, vaccine hesitance and prevalent “anti-vax” conspiracy theories may be barriers to vaccination. In rural areas, religious conservativism about sex and sexually transmitted disease — as well as the political climate — are likely factors, Dr Ramondetta added. Rates of HPV vaccination are worse than those for, say, polio or measles, suggesting that hesitance is related to the sexual nature of HPV transmission.

“There’s still a stigma about HPV infection, which is crazy, since most people are exposed,” said Dr Ramondetta. “Normalizing HPV is important — it’s just an aspect of the human condition, like flu.”

“There is ample evidence of the efficacy, safety and durability of this vaccine,” Dr Ramondetta said. “We need to find new ways to educate the public. We can talk to one another all we want in journals but meanwhile, social media is filled with [misinformation] … We need to take a larger role in social media, flooding it with accurate information.”

“Most parents just need reassurance,” she added. “Their motivation is to keep their kids safe.”

Doctors should recommend HPV vaccination every time they see adolescent patients and their parents, Dr Saslow emphasized. And, oncologists need to reach out to family physicians and pediatricians, she said.

References
1. Van Dyne EA, Henley SJ, Saraiya M, Thomas CC, Markowitz LE, Benard VB. Trends in human papillomavirus-associated cancers — United States, 1999-2015. MMWR Morb Mortal Wkly Rep. 2018;67(33);918–924.

October, 2018|Oral Cancer News|

Oral treatment may not be far off for head and neck cancer patients

Source: app.secure.griffith.edu.au
Author: staff, Griffith University

A highly promising approach to treating HPV-driven head and neck cancer is on the way, and it could be in the shape of a simple oral medication. This is according to new breakthrough research led by Griffith University, which has conducted trials showing that the drug, Alisertib, tested in trials to treat other cancers such as lung and kidney, can also successfully destroy the cancer cells associated with head and neck cancer.

Human Papilloma Virus (HPV) is the main culprit in head, neck and oral cancers. The virus is thought to be the most common sexually transmitted infection (STI) in the world, and most people are infected with HPV at some time in their lives.

The latest trials – which have taken place over the past three years at Griffith’s Gold Coast campus – have shown a particular enzyme inhibitor in the drug, has the ability to prevent proliferation of HPV cancer cells in advanced head and neck cancers.

A 100 per cent success rate
Led by Professor Nigel McMillan, program director from Griffith’s Menzies Health Institute Queensland, the trials have shown a 100 per cent success rate in the drug eradicating the cancerous tumours in animals.

“Head and neck cancers can unfortunately be very difficult to treat, just by the very nature of where they are located in and around the throat, tongue and mouth,” says Professor McMillan.

“This part of the body contains some delicate areas such as the vocal chords and areas relating to speech, taste, smell, saliva etc, therefore there can be some significant side effects with the current treatment options.

“Quality of life is a major consideration in this patient group and therefore a simple oral treatment regimen will have massive benefit over other treatments in terms of reducing some quite drastic side effects.”

In Australia, there are over 5000 new cases of head and neck cancer each year. First line treatments include radiation and surgery (increasingly of the robotic type), followed by chemotherapy, however survival rates of around 70 per cent have remained unchanged for the past 35 years.

Half of all head and neck cancers are known to be caused by the HPV virus, with four times as many men (784) as women (250) estimated to have already died from the disease in Australia during 2018.

In the United States, there are now more cases of head and neck cancer than there are cervical cancer, a disease which is now set to become much more rare in Australia due to the introduction a decade ago of the world-leading national (HPV) vaccination program for schoolchildren.

Professor McMillan says the next step in the research is for the drug to be extended to human trials at the Gold Coast with patients for whom other treatments have so far proved unsuccessful.

October, 2018|Oral Cancer News|