HPV

World Oral Health Day 2017: Signs and symptoms of oral HPV

Source: www.thehealthsite.com
Author: Sandhya Raghavan

In 2010, when actor Michael Douglas was diagnosed with throat cancer, he said something shocking about his condition. He revealed to a journalist that cunnilingus or oral sex was the reason why he got throat cancer. Quite naturally, his comments were met with disbelief and ridicule. But the only ones who weren’t laughing was the medical fraternity, who knew that there was a tremendous amount of truth in his statement. HPV or Human Papilloma Virus, one of the biggest risk factors for cancer, can be transmitted through an infected person’s genital fluids during oral sex. From here, it starts infecting the person’s oral and respiratory system, causing cancers of the mouth and neck in the long run.

What causes oral HPV?
Dr Gautam Bhansali, a consulting physician at Bombay Hospital, states, “Oral HPV is primarily spread through sexual contact and blood contact.” Unprotected vaginal, oral and anal sex, and open-mouthed kissing can cause the virus to proliferate. The risk factor is increased in people who have low immunity, like diabetics, smokers and those suffering from infectious diseases.

How to know if there is oral HPV residing in the body?
There is no way to find out because oral HPV is a sneaky virus. You may carry the virus for years and even transfer it to your partner without you knowing it. In most cases, the immune system sends the virus packing even before it sets shop in the body. But if it wins the war against your antibodies, it can increase the risk of cancers in the body.

When to see a doctor?
Oral HPV can develop into cancers of the oral cavity and the pharynx. Early symptoms include.
• Fever- “It is quite possible for a person infected with the oral HPV virus to have low-grade fevers,” says Dr Bhansali. Watch out for fevers that worsen during the evening hours.
• Trouble swallowing- If there is any obstruction in the throat while swallowing, immediately have it looked up.
• Mouth ulcers- Recurring mouth ulcers or lesions that refuse to go away can be indicators of cancer.
• Earache- “In severe cases, sometimes tumours press up against the Eustachian tube, causing earaches,” says Dr Bhansali.
• Hoarseness of voice- If tumours on one of the vocal cords end up paralysing it, the person’s voice can change to a great extent.
• Unexplained weight loss- With the immunity levels going down, someone with HPV infection may find his or her weight decreasing.
• Lump in the cheeks- “If the tumour starts developing on the parotid glands, lumps will be felt on the person’s cheeks,” reveals Dr Bhansali.
• Blood in cough – Coughing up blood is also an early symptom of oral HPV.

How can you prevent oral HPV?
Studies have proven that thorough oral hygiene can keep the virus at bay. “Following the correct oral hygiene routine is essential for preventing HPV infections. Brushing twice a day, flossing, cleaning the mouth and the genitals after sexual activity,” says Dr Bhansali. Know your sexual partner, use contraceptives and wear dental dams while performing oral sex on new sexual partners.

March, 2017|Oral Cancer News|

Throat cancer is becoming a national health epidemic say oral fitness experts

Source: californianewswire.com
Author: Raychel Harvey-Jones

As a dentist in practice for over 30 years, Dr. Gary Glassman (“Dr. G”) thought he had seen it all. “I have removed maggots from a child’s gums and a tomato plant that was growing from a seed in another patient. Oral fitness is as important as physical fitness, this week a young man died in California from a tooth infection that spread to his lungs,” says Dr. G.

I will admit I am a little nervous when it comes to visiting the dentist, over the years I have been lucky enough to find very patient dentists who have gradually rid me of my fear. After interviewing Dr. G, I plan on making it a priority to regularly visit the dentist. There is a much bigger problem in the U.S. that’s slowly becoming an epidemic – throat cancer.

Dr. G is concerned about the growing numbers of mouth and throat cancer caused by the Human Papillomavirus (HPV) that is transmitted during oral sex.

Dr. G, a leading global oral fitness expert, says, “The scary part about the growing concern of oral cancer among men is that we think of oral sex as a safer alternative to intercourse.”

According to the Centers For Disease Control and Prevention (CDC), the HPV virus is the most sexually transmitted infection in the United States, and it’s showing up in men aged 40-60 years old. Skeptical? Just ask actor Michael Douglas.

In an interview published in The Guardian newspaper in London, Douglas mentioned that his throat cancer could have been brought on by oral sex, a common way to become infected with HPV. (Douglas later admitted he actually had tongue cancer and “regrets blaming his wife’s vagina.”)

“We are seeing the HPV-positive throat cancer more in older men as they produce less saliva. Saliva acts as a natural coating that protects the mouth from infections. Also, there are a plethora of medications used everyday by older guys that cause dry mouth; medications like Ibuprofen and Amoxicillin,” says Dr. G.

There are about 200 different strains of HPV. Some cause common warts when they invade the skin. Others are the cause of sexually transmitted diseases.

“HPV can cause cervical cancer, as well as cancer in the back of the throat, including the base of the tongue and tonsils, though these are not the same strains of the virus. Cancer often takes years, even decades, to develop after a person gets HPV. More than half of American men who are having sex will get HPV at some point in their lives,” adds Dr. G.

According to the CDC, there is no approved test to check for HPV in the mouth or throat; this is why regular visits to your dentist are critical. A dentist can monitor any changes in your mouth. There are HPV tests that can be used to screen for cervical cancer.

“Your mouth is crucial when it comes to your overall general health. Treat your dentist’s chair as an extension of your trips to the gym; it’s just as vital to your health and fitness,” adds Dr. G.

The HPV vaccine is a must before you are sexually active. However, if you haven’t had the vaccine there are measures you can take, ask your dentist. “It’s not worth the risk,” concludes Glassman.

February, 2017|Oral Cancer News|

Game changer’ HPV vaccine is now just 2 shots – not 3 – in bid to simplify

Source: www.dailymail.co.uk
Author: Mary Kekatos for dailymail.com

  • HPV vaccines will now be administered in two doses instead of three
  • The virus is the most common sexually transmitted infection in the US
  • But only 28% of boys and 42% of girls received the advised three doses in 2015
  • Doctors hope the new guidelines increase the number of kids who get the shot

The HPV vaccine will now be administered in two doses instead of three, new guidelines declare. The new rules, published on Monday, come after years of campaigns from cancer experts insisting an easier schedule would encourage more people to protect themselves from the sexually-transmitted infection.

Human papillomavirus (or, HPV) is the most common STI in the United States, affecting around 79 million people. It has been linked to numerous cancers – including prostate, throat, head and neck, rectum and cervical cancer.

Experts claim more widespread vaccine coverage of middle school children could prevent 28,000 cancer diagnoses a year. Currently, fewer than half the children eligible for the vaccine – given out as three doses over six months – are covered. Experts blame the lengthy, arduous schedule.

The American Cancer Society today endorsed the updated recommendations, which were released by the Advisory Committee on Immunization Practices (ACIP).  Dr Debbie Saslow, Senior Director, HPV Related and Women’s Cancers for the American Cancer Society, said: ‘In the past several years, studies have shown the vaccine is even more effective than expected.

‘This new two-dose regimen is easier to follow, and we now know is very effective in preventing HPV, which is linked to a half dozen types of cancer.’

Each year, about 14 million people become newly infected with HPV. According to the CDC, each year about 19,000 cancers caused by HPV occur in women in the US, with cervical cancer being the most common. And about 8,000 cancers caused by HPV occur each year in men in the US and oropharyngeal (throat) cancers are the most common. Besides cervical cancer, HPV has been linked to vaginal, vulvar, oropharyngeal, anal, and penile cancers.

Despite strong evidence of safety and effectiveness, vaccination rates in the US remains very low compared to other countries. Only 28 percent of boys and 42 percent of girls aged 13 to 17 years receiving the recommended three doses in 2015. The skewed figures between genders are largely attributable to the fact that the jab was only offered to boys as a standard vaccine as of last year.

Previously, it was believed HPV was most strongly linked with cervical cancer in women. Research since has shown links with penile, anal, mouth, throat and other cancers in men. However, the gender divide does not fully account for the staggeringly low levels of coverage overall.

Despite the three vaccines that are widely available, the number who choose to be vaccinated remains low, and the age they wait to do so has increased. Only Rhode Island, Virginia and the District of Columbia require the vaccine for students.

In response to these figures last year, the ACIP, along with the Centers for Disease Control and Prevention (CDC), conducted a thorough review of clinical trial data on HPV vaccines. They found that the vaccine in younger adolescents (aged nine to 14 years) produced an immune response similar or higher than the response in young adults (aged 16 to 26 years) who received three doses.

Generally, preteens receive the HPV vaccine at the same time as whooping cough and meningitis vaccines and it is administered before the likely chance of sexual contact.

The new schedule, approved by the FDA in October 2016, states that two doses of HPV vaccine given at least six months apart at ages 11 and 12 will provide ‘safe, effective, and long-lasting protection against HPV cancers’. Even adolescents between ages 13 and 14 are able to receive the HPV vaccination on the new two-dose schedule.
For patients who did not receive HPV vaccination before age 15, three doses are still required and may be given to females up to age 26 and males up to age 21.

February, 2017|Oral Cancer News|

NCI-Designated Cancer Centers Issue Statement in Support of New CDC Recommendations on HPV Vaccination

Source: The ASCO Post
Posted: 1/11/2017

The 69 National Cancer Institute (NCI)-designated cancer centers have issued a joint statement in support of recently revised recommendations from the Centers for Disease Control and Prevention (CDC) to improve national vaccination rates for human papillomavirus (HPV).

According to the CDC, incidence rates of HPV-associated cancers have continued to rise, with approximately 39,000 new HPV-associated cancers now diagnosed each year in the United States. Although HPV vaccines can prevent the majority of cervical, anal, oropharyngeal, and other genital cancers, vaccination rates remain low across the United States, with just 41.9% of girls and 28.1% of boys completing the recommended vaccine series.

New Recommendations

The new guidelines from the CDC recommend that children under age 15 should receive 2 doses of the 9-valent HPV vaccine at least 6 months apart. Adolescents and young adults older than 14 should continue to complete the 3-dose series.

Research shows there are a number of barriers to overcome to improve vaccination rates, including a lack of strong recommendations from physicians and parents not understanding that this vaccine protects against several types of cancer. In an effort to overcome these barriers, NCI-designated cancer centers have organized a continuing series of national summits to share new research, discuss best practices, and identify collective action toward improving vaccination rates.

The original joint statement, published in January 2016, was the major recommendation from a summit hosted at The University of Texas MD Anderson Cancer in November 2015, which brought together experts from the NCI, CDC, American Cancer Society, and more than half of the NCI-designated cancer centers.

The updated statement is the result of discussions from the most recent summit, hosted this past summer by The Ohio State University Comprehensive Cancer Center. Nearly 150 experts from across the country gathered in Columbus to present research updates and plan future collaborative actions across NCI-designated cancer centers.

 

“This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.”

January, 2017|Oral Cancer News|

Feds, cancer centers aim to boost HPV vaccinations

Source: www.dispatch.com
Author: JoAnne Viviano

Faced with getting her daughter the HPV vaccine, which helps protect against cervical and other cancers, Anaraquel Sanguinetti paused.

The human papillomavirus is spread through sexual contact, and the Westerville mom didn’t want her now-18-year-old daughter to think she was promoting promiscuity. So Sanguinetti did some research. And she had a long talk with her daughter, and another with her doctor.

In the end, daughter Celine got the vaccine last year.

“We are discovering every day new reasons why people obtain cancer, so it’s just another added layer of protection for my daughter for her future, because you just never know,” Sanguetti said. “ I didn’t want to have a regret.”

Sanguetti is in the minority. Though vaccinating against HPV is recommended by the Centers for Disease Control and Prevention, and countless cancer centers and health-care providers, most children in the United States have not been vaccinated against HPV.

Calling that “a serious public health threat,” dozens of cancer centers released a joint statement on Wednesday urging more parents and pediatricians to get onboard.

The statement endorses the CDC’s recent revisions to its HPV vaccine recommendations. Vaccinating, the statement says, could help prevent the nearly 40,000 cases of HPV-associated cancers diagnosed in the United States each year.

“Get the HPV vaccine for your child so they don’t have to hear those words: ‘You have cancer,’ “ said Electra Paskett, co-leader of cancer control at Ohio State University’s Comprehensive Cancer Center, which is among the institutions participating in the effort.

The CDC estimates that as many as 79 million Americans are infected with HPV, which can cause cervical, genital, anal, rectal and throat cancers as well as genital warts. Fourteen million new infections occur each year.

A 2016 CDC report says that only about 42 percent of girls and 28 percent of boys had completed the recommended vaccination series. In Ohio, 35 percent of girls and 23 percent of boys have completed the vaccination course.

In all, 69 National Cancer Institute-designated cancer centers are participating in the effort.

The recommendations issued last year say that kids who are 11 or 12 should receive two shots of the HPV vaccine, delivered at least six months apart. The previous recommendation was for three shots, which is still advised for people 15 to 26 years old.

Simplifying the process likely will increase participation and move the nation toward the U.S. Department of Health and Human Service’s goal of having 80 percent of young people vaccinated by 2020, said Dr. Li Li, associate director for prevention research at Case Western Reserve’s Comprehensive Cancer Center.

“This is one of the few preventable cancers,” he said. “There’s a very unique opportunity for us nationwide to get together to put this forward.”

Li said he’d like to see the state mandate that children receive the vaccine at age 11 or 12 to enroll in school. That’s the rule in three states, he said.

Paskett said recommendations also call for bundling the HPV vaccine with other vaccines given at that age.

“The public has been clamoring for a cancer vaccine for decades, and we now have one and we need to use it,” she said.

Sanguetti said she wanted to make sure her daughter was vaccinated before going off to college. She said she would recommend that other parents do their own research and have their children vaccinated even if it is uncomfortable thinking about their sons or daughters having sex.

“It’s for their future,” she said. “It’s more toward their well-being. It’s not promoting anything other than a preventative for cancer.”

For more information, go to www.cdc.gov/hpv.

January, 2017|Oral Cancer News|

Immunotherapies Form New Frontier in Treating Head and Neck Cancers

Source: OncLive.com

Date: January 2nd, 2017

In August 2016, the FDA approved pembrolizumab (Keytruda) for patients with platinum-refractory squamous cell carcinoma of the head and neck (SCCHN).1 Not only was it the first immunotherapy approved for head and neck cancer (HNC), but it marked the first new drug approval for HNC in the United States in 20 years.

“Now we have an agent that really changes the paradigm—a new class of treatment—and we are seeing amazing benefit in some patients,” said Tanguy Seiwert, MD, during an OncLive Peer Exchange® panel held during the 2016 European Society for Medical Oncology (ESMO) Annual Meeting.

Less than a month later, the menu of immunotherapy options expanded as the FDA approved nivolumab (Opdivo) for the treatment of patients with recurrent or metastatic SCCHN with disease progression on or after a platinum-based therapy.

During the Peer Exchange, the panelists provided an overview of the immunotherapy terrain in HNC, a discussion that was filled with considerable hope and excitement. “When we try immunotherapies in the second-line setting, we see objective responses—sometimes deep, clinically meaningful, extremely durable responses—and we’re beginning to think that maybe, on some occasions, we may be able to cure patients with relapsed metastatic head and neck cancer,” said Kevin Harrington, MD, PhD. This is especially remarkable since such patients have generally had a survival of ≤1 year.

The panelists concurred that the care of patients with HNC will evolve significantly over the next 5 to 10 years, as the tip of the immunotherapy iceberg is just starting to be scratched. During the Peer Exchange, they provided a rationale for using immunotherapies in HNC, including human papillomavirus (HPV)-positive and HPV-negative disease; outlined key immunotherapy studies; and offered their thoughts on the future of immunotherapies in HNC, including use of biomarkers to guide therapy and the opportunity to improve response by using combination treatments.

“Next-generation sequencing efforts are beginning to shed light on the hidden complexities of these tumors, leading to the identification of multiple molecular subtypes,” said Ezra Cohen, MD, who served as moderator for the session. “As key differences between tumors, with and without HPV infection, are beginning to emerge, the challenge is to find ways to use this information to personalize treatment for individual patients.”

Rationale for Immunotherapy in HNC

In patients with locally advanced HNC, HPV status has generally determined outcomes, with HPV-positive patients having a good prognosis and higher likelihood of cure, and HPV-negative patients having a poorer prognosis and a lower likelihood of cure.

However, outcomes with conventional therapy in recurrent metastatic disease have been poor across the board, especially in the setting of platinum- refractory disease, indicating a tremendous unmet need. Before pembrolizumab was approved in this setting, the recommendation was to use a taxane, such as methotrexate or cetuximab (Erbitux), as a single agent, but the outcomes have been unsatisfactory. In contrast, immunotherapy studies have shown promising results in these patients, with HPV-negative patients also benefiting.

“The rationale for [using immunotherapies] for HPV-positive tumors may be the virus, as well as mutations, and for HPV-negative tumors, it’s likely the mutation load,” said Seiwert. He explained that HPV-negative tumors are often smoking-associated tumors and, therefore, have high mutation loads, a factor that has been associated with good response to immunotherapy, whereas HPV-positive tumors resemble melanoma, with significant inflammation, another factor associated with good response.

Although efficacy was found to be the same for HPV-positive and HPV-negative tumors in KEYNOTE-012, which was the study that led to pembrolizumab’s approval for HNC, some CheckMate-141 subanalyses suggest there might be slightly more activity in HPV-positive patients, noted Seiwert.

Despite such findings, he said, “HPV status should not actually dissuade us one way or the other from using immunotherapy—it’s clearly active in both HPV-negative and HPV-positive tumors.” And, as Harrington pointed out earlier in the discussion, since nothing else works well in the second-line setting, “why not try it?”

Key Pembrolizumab Studies

The panelists proceeded to provide an overview of several instrumental pembrolizumab studies, including the KEYNOTE-012 expansion study and KEYNOTE-055 studies, and of the phase III CheckMate-141 study, which paved the way for nivolumab’s approval.2-4 They also discussed a subanalysis of CheckMate-141 presented at ESMO that demonstrated good patient-reported outcomes following nivolumab therapy, lending further support to its use in SCCHN.5

KEYNOTE-012 Expansion Study

The phase Ib KEYNOTE-012 expansion study administered 200 mg of pembrolizumab intravenously once every 3 weeks to 132 patients with recurrent or metastatic SCCHN, irrespective of their programmed death-ligand 1 (PD-L1) or HPV status.2 Primary endpoints included overall response rate (ORR), and safety and secondary endpoints included progression-free survival (PFS), overall survival (OS), and PD-L1 expression’s impact on response.

Pembrolizumab was well tolerated, and yielded a clinically meaningful ORR with evidence of durable responses; median duration of response was not reached. The ORR was 18% by central imaging vendor review and 20% by investigator analysis. A statistically significant increase in ORR was observed for PD-L1–positive versus PD- L1–negative patients (22% vs 4%, respectively; P = .021).

At 6 months, PFS and OS rates were 23% and 59%, respectively. “And we have patients living far beyond what we usually expect for metastatic disease…we now have patients who have completed 2 years of treatment in a setting with a median life expectancy of about 6 months,” revealed Seiwert, who is involved with the study.

Pembrolizumab was also well tolerated. Grade ≥3 events occurred in 9% of patients. “[This is] within the range of toxicities that we have seen in other studies,” said Viktor Grünwald, MD. “Because we’re approaching a very sick and morbid patient population, we might expect different toxicity outcomes, so I think it’s very reassuring that we’re seeing the same amount of toxicity as in other studies,” he explained.

While checkpoint inhibitors are generally well tolerated and have favorable toxicity profiles, the panelists warned that severe side effects can occur and careful patient monitoring is required. A key concern they discussed is pneumonitis.

“Although it only occurs in about 1% to 2% of patients, you must screen for it because it’s life threatening,” said Seiwert. “If somebody says, ‘I am short of breath’ or ‘I have a little bit of a cough,’ I scan them right away to look for it,” he said, explaining that immediate treatment with high-dose steroids is warranted.

KEYNOTE-055 Preliminary Results

KEYNOTE-055 enrolled 172 patients with recurrent or metastatic SCCHN to receive pembrolizumab 200 mg every 3 weeks after progression on platinum plus cetuximab. The preliminary analysis, which reported on 92 evaluable patients, was initially presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting.3 Primary endpoints include ORR and safety.

As with KEYNOTE-012, pembrolizumab was found to be well tolerated and to have significant antitumor activity, with 17% to 18% response rates. Evaluation of the full study cohort will include analyses of HPV status and response by anatomic site. “I think that’s the story we’re seeing for pembrolizumab in head and neck cancer—patients are already being treated in single-arm clinical studies, which is somewhat unusual, but reflects the speed of knowledge that we’re gaining that is leading to approvals,” said Grünwald.

Nivolumab also had a lower incidence of treatment-related adverse events (TRAEs) than IC. Any grade TRAEs occurred in 59.3% and 77.5% of patients on nivolumab or IC, respectively. Grade 3/4 TRAEs occurred in 13.6% and 35.1% of patients, respectively, indicating the treatment is well tolerated, which also translated to improvements in quality of life in the patient-reported outcomes study.5

“A very detailed analysis of patient-reported outcomes using 3 well-validated questionnaires showed nivolumab was able to maintain good patient-re- ported outcomes in terms of their quality of life, their functioning, and their symptom scores, whereas IC showed serious detriment in those scores,” said Harrington.

In the study,5 patients treated with nivolumab had delayed worsening of functioning and symptoms compared with IC at approximately 4 months of follow-up, with patients receiving nivolumab reporting longer maintenance of function and less pain, fatigue, and dyspnea on treatment, as compared with those receiving IC.

“So not only do we have clear evidence that these drugs can work in terms of improving survival and delivering meaningful responses, but they do so with fewer episodes of treatment-related toxicity and disease-associated morbidity,” said Harrington.

Future of Immunotherapy in HNC

The panelists noted that use of biomarkers and combination therapies are key areas of future development for HNC. Both areas are already being examined in clinical trials and have relevance across the vast HNC spectrum, from those with minimal disease to those with previously treated advanced disease, potentially offering a curative pathway to more patients.

“It’s fantastic to have drugs that work in second-line relapsed metastatic or first-line metastatic setting, but what I want and what patients want is to be cured at the time they first present with their disease so they never have treatment in relapsed metastatic setting,” said Harrington.

Biomarkers

Although biomarkers such as PD-L1 expression are already being used and can help identify patients who are more likely to respond, high PD-L1 expression does not guarantee response, nor does no or low PD-L1 expression ensure lack of response or lack of durable response.

Subsequently, use of pembrolizumab and nivolumab is without use of this biomarker for patient selection. “While [a PD-L1 assay] can help inform patients of their likelihood to respond, it is not an assay that can select patients,” said Seiwert, who is working to identify novel biomarkers.

“I’ve been involved in looking at a novel biomarker called interferon gamma signature, which can be assayed quite easily with a rapid turn-around, and seems to perform somewhat better than PD-L1 expression,” said Seiwert. “It seems to have a high negative predictive value, and it may eventually allow us to exclude some patients who have no chance of having benefit, but it needs further validation.” He said that other biomarkers are also under investigation, including mutational load, immunogenic mutations, and dynamic biomarkers, but all are still experimental.

“What we really need is a biomarker that would predict progressive disease,” said Grünwald. “To me, that would be much more usable than an assay that just allows us to say to patients ‘your chance of response is 30%.’ I see biomarkers as having the potential to guide development of treatment algorithms,” he said.

Combinations

Currently, PD-L1–targeted agents have seen the greatest development, and studies are starting to suggest that response with these agents can be enhanced when they are combined with other treatments, including chemotherapy, CTLA-4 blockade, and radiotherapy. “About 70% of HNCs have some level of PD-L1 expression—some level of inflammation—but we only see responses in 15% to 18% of patients, so the pool of patients who might benefit from combinations is huge,” said Seiwert.

He noted that the melanoma and lung cancer settings have already shown combining PD-1 inhibitors with chemotherapy or a second checkpoint inhibitor to be particularly promising in the front line, and he suspects one or both combinations will eventually receive approval in these settings and warrant serious investigation for patients with SCCHN.

“Some of our patients do not benefit from a checkpoint inhibitor, and we can’t identify these patients in advance, but giving them chemotherapy might buy us time,” he said. “It’s almost like a pharmacodynamic effect, where we have more time for the immunotherapy to work, and maybe, also make the immune system stronger and expose antigens.”

In the locally advanced setting, animal studies have shown promise combining chemoradiotherapy with immunotherapy, but results of a small study presented at ESMO revealed some dosing challenges in humans.6

In the study, 18 patients with various forms of intermediate- or high-risk SCCHN received ipilimumab, an anti–CTLA-4 antibody, in addition to standard intensity-modulated radiotherapy with cetuximab. Dermatologic immune-related adverse events limited dosing. “There are some safety hints that it may not be a piece of cake getting through radiotherapy, and maybe cetuximab might not be the optimal part now, but I think there is still a lot of promise combining radiochemotherapy with immunotherapy,” said Grünwald. “It could be a future way in how we successfully treat early forms of localized SCCHN.”

Combining checkpoint inhibition with radiation is another intriguing combination, and one that has the potential to act like an in situ vaccination that can lead to abscopal responses (ie, responses at distant sites), noted Harrington, something he has, thus far, only observed rarely with radiation.

“The idea behind combining checkpoint inhibition and radiation is that we could use the confluence of the two different mechanisms to make abscopal responses more predictable and more effective at a distant site, while engendering an immunologically relevant response that allows us to treat macroscopic metastatic disease while also getting rid of micrometastatic disease that could lead to metastatic failure,” he said.

Although immunotherapy combinations are showing promise in SCCHN and other cancers, the panelists warned that they should only be attempted as part of clinical trials. “There are still a lot of question marks about combinations, so they must be done as part of a clinical trial,” said Seiwert. Not only are toxicities and immunosuppressive effects best managed in clinical trials, but trials are essential in advancing these therapies and identifying the next breakthroughs in the field, he said.

 

“This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.”

January, 2017|Oral Cancer News|

Reducing Radiation Successfully Treats HPV-Positive Oropharynx Cancers and Minimizes Side Effects

Source: Yale Cancer Center, http://www.newswise.com/articles/reducing-radiation-successfully-treats-hpv-positive-oropharynx-cancers-and-minimizes-side-effects

Released: 12/26/2016

Newswise — Human papillomavirus-positive oropharynx cancers (cancers of the tonsils and back of the throat) are on rise. After radiation treatment, patients often experience severe, lifelong swallowing, eating, and nutritional issues. However, new clinical trial research shows reducing radiation for some patients with HPV-associated oropharyngeal squamous cell carcinomas can maintain high cure rates while sparing some of these late toxicities.

“We found there are some patients have very high cure rates with reduced doses of radiation,” said Barbara Burtness, MD, Professor of Medicine (Medical Oncology), Yale Cancer Center, Disease Research Team Leader for the Head and Neck Cancers Program at Smilow Cancer Hospital, and the chair of the ECOG-ACRIN head and neck committee. “Radiation dose reduction resulted in significantly improved swallowing and nutritional status,” she said.

The study, published in the December 26 issue of the Journal of Clinical Oncology, showed that patients treated with reduced radiation had less difficulty swallowing solids (40 percent versus 89 percent of patients treated with standard doses of radiation) or impaired nutrition (10 percent versus 44 percent of patients treated with regular doses of radiation).

“Today, many younger patients are presenting with HPV-associated squamous cell carcinoma of the oropharynx,” said Dr. Burtness. “And while traditional chemoradiation has demonstrated good tumor control and survival rates for patients, too often they encounter unpleasant outcomes that can include difficulty swallowing solid foods, impaired nutrition, aspiration and feeding tube dependence,” said Dr. Burtness. “Younger patients may have to deal with these side effects for decades after cancer treatment. We want to help improve our patients’ quality of life.”

The study included 80 patients from 16 ECOG-ACRIN Cancer Research Group sites who had stage three or four HPV-positive squamous cell carcinoma of the oropharynx, and were candidates for surgery. Eligible patients received three courses of induction chemotherapy with the drugs cisplatin, paclitaxel, and cetuximab. Patients with good clinical response then received reduced radiation.

Study results also showed that patients who had a history of smoking less than 10 packs of cigarettes a year had a very high disease control compared with heavy smokers.

 

Other authors on the paper include: Shanthi Marur (Johns Hopkins Medicine) and Anthony Cmelak (Vanderbilt University).

“This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.”

January, 2017|Oral Cancer News|

Genetic variants are associated with susceptibility to mouth and throat cancer

Source: www.eurekalert.org
Author: news release

A number of genetic variants associated with susceptibility to oral cavity and pharyngeal cancer have been described in an international study published in the journal Nature Genetics.

The most noteworthy finding was an association between cancer of the oropharynx and certain polymorphisms (alternative versions of a given DNA sequence) found in the human leukocyte antigen (HLA) genomic region. HLAs, proteins found on the surface of most cells in the body, play an important role in recognizing potential threats and triggering the immune response to foreign substances.

According to Eloiza Helena Tajara, a professor at the São José do Rio Preto Medical School (FAMERP) in São Paulo State, Brazil, and co-author of the article, a specific group of variants in this region, located on chromosome 6, is associated with enhanced protection against oropharyngeal cancer caused by human papilloma virus (HPV).

“Previous research showed that these same variants confer protection against cancer of the uterine cervix, which is known to be associated with HPV,” Tajara said. “Our findings suggest that the genes that control the immune system play a key role in predisposition to HPV-related tumors. This discovery points to the possibility of clarifying the mechanisms whereby such tumors develop and of designing methods for monitoring risk groups.”

The study was coordinated by the International Agency for Research on Cancer (IARC) and involved 40 research groups in Europe, the United States, and South America. The Brazilian participants are members of the Head & Neck Genome Project (GENCAPO), a consortium of scientists affiliated with several institutions.

In a recent study, GENCAPO evaluated more than 7 million genetic variants in samples from 6,034 patients with head and neck cancer. The cases comprised 2,990 oral cavity tumors, 2,641 oropharyngeal tumors, 305 tumors in the hypopharynx (the bottom part of the pharynx near the esophagus), and 168 tumors in other regions or more than one region concurrently. The study population also included samples from 6,585 people without cancer as controls.

The researchers detected eight loci (genomic sites) associated with susceptibility to these types of tumor. Seven had not previously been linked to mouth or throat cancer.

According to Tajara, the IARC set out to focus on analyzing oral cavity and oropharynx tumors because there are no genome-wide association studies of these two tumor types. Although these cancers are predominantly caused by tobacco and alcohol use, the importance of HPV, particularly HPV16, as a cause of oropharyngeal cancer has become more evident in recent years.

“The throat is the most affected area among head and neck cancer subsites, likely because its tissue is more receptive to the virus,” Tajara said.

In the article, the researchers note that the proportion of HPV-related oropharyngeal cancer cases is estimated to be approximately 60% in the US and 30% in Europe but lower in South America.

“One finding that was expected to some extent was the absence of HLA associations with oropharyngeal cancer, which may be due to the fact that the frequency of HPV-positive oropharyngeal cancer is less than 10% in South America,” Tajara said. “The same factor appears to account for the weak association between the variants identified and HPV-positive oral cavity cancer, which is also far less frequent than HPV-negative oral cavity cancer.”

In her view, the strong rise in cases linked to HPV in the US could be partly due to a change in sexual habits, especially regarding the practice of oral sex. “It’s possible that Brazil is still in a transition stage and that the habits that favor infection are only starting to become more common. If so, the effects will appear in a few years’ time,” she said.

Previous studies have already shown that HPV-associated head and neck cancers affect younger people and develop rapidly. By contrast, cases associated with tobacco and alcohol use as well as poor oral hygiene are more prevalent in those over fifty years old and progress more slowly but are harder to treat.

In addition to DNA in tissue samples taken from participants of the study, data were also collected on environmental and clinical factors possibly associated with the development of this type of cancer, such as smoking, alcohol consumption, and age.

According to Tajara, thanks to the joint efforts of 40 research groups it was possible to obtain data on a significant number of patients, thus enhancing the impact and reliability of the results. The GENCAPO team contributed some 1,000 samples from tumors for analysis.

“Based on these results, we can try to understand from the molecular standpoint how the observed polymorphisms interfere with the response to HPV infection,” Tajara said. “This may give us clues as to how to protect people and how to reduce the incidence of this type of tumor.”

December, 2016|Oral Cancer News|

Predicting throat cancer recurrence with a blood test

Source: knowridge.com
Author: from University of Michigan Health System

A new study suggests the possibility of predicting at its earliest stages when a type of head and neck cancer will come back.

Oropharyngeal cancer — which occurs in the throat, tonsils and back of the tongue — is frequently linked to the human papilloma virus. That’s good news, in a way, as HPV-related cancers are generally more responsive to treatment.

But for about 15 to 20 percent of these patients, the treatment won’t work and their cancer will return. There are no known biomarkers to predict when treatments are likely to fail.

In a new study in Clinical Cancer Research, researchers found that patients whose oropharyngeal cancer recurred had higher levels of antibodies for two proteins, E6 and E7, which are found in HPV-fueled cancers. The finding suggests a potential blood-based marker that could predict when cancer is likely to return.

For this study, researchers looked back at 52 patients with advanced oropharyngeal cancer who had enrolled in a prior study: 22 who had developed recurrence and 30 who had not. The two groups were similar in age, cancer classification and smoking status. All tumors were linked to the human papilloma virus.

On average, cancer recurred 13 months after a patient’s treatment ended. Serum was measured via a blood test at diagnosis or start of treatment, then repeated after treatment ended and about every three months after.

Initially, there was no difference in E6 and E7 antibody levels between those patients who recurred and those who didn’t. All patients showed a decline in their antibody levels three months after treatment.

That makes sense, says study author Matthew E. Spector, M.D., assistant professor of otolaryngology at the University of Michigan Health System. After three months, all or most of the cancer had been wiped out. Since oropharyngeal cancer almost never recurs three months after treatment, antibody levels declined in all the patients studied.

“Most patients recur within the first two years, so the window to catch it is two years after treatment. Everyone’s level goes down over time, but some start to go up a little — and those are the ones we have to focus on,” Spector says.

Finding answers in antibodies

When the researchers looked at E6 and E7 antibody levels over time, they found that in patients whose cancer recurred, the levels of E7 were not decreasing as quickly as patients who did not recur. And they could begin to detect that prior to the point when the recurrence was discovered.

“If we can monitor someone through blood markers, then instead of a patient coming for a clinic visit every two to three months, they could get blood drawn near home. If there’s evidence of high E7, we can tell the patient to come in for more evaluation,” Spector says.

The key is to look at the ratio of E7 antibodies. Every patient had a different baseline level, and the absolute level was not an indication.

“It’s very patient-specific,” Spector says. “Each patient will have different levels, but the question is what happens when you track it over time. If it rises, that suggests recurrence.”

Oropharyngeal cancer most commonly recurs in the throat, neck or lungs. If recurrence is caught early, surgery to remove the cancer in the throat or neck can eliminate the disease and is likely to be a cure. If the cancer spreads to the lungs, offering targeted therapies earlier might improve outcomes.

The test for E6 and E7 antibodies is a standard laboratory test that any cancer treatment facility could perform, so it would likely be inexpensive to implement.

More testing among a larger number of patients is needed. The U-M team has opened a phase II trial to assess the potential for E7 antibodies as a biomarker for recurrence. For information, call the U-M Cancer AnswerLine at 800-865-1125.

December, 2016|Oral Cancer News|

Blood-borne HPV antibodies indicate head, neck cancer prognosis

Source: medicalxpress.com
Author: provided by Brown University

People with head and neck cancers with evidence of human papillomavirus (HPV) infection generally have a better prognosis than people without evidence of infection. A new study in JAMA Oncology suggests that to produce a strong, reliable prognostic signal, all that’s needed is a blood serum test for two specific HPV antibodies, rather than lab work on a biopsy. Further, the researchers said, the study shows that this blood-based biomarker is predictive of outcome for all types of head and neck cancer.

bloodbornehp

The human papillomavirus causes not only cervical cancer but also cancers of the head and neck. Credit: National Cancer Institute

“What this adds is that it helps us know how best to measure clinically the HPV contribution to this disease,” said study senior author Karl Kelsey, a professor of epidemiology and of pathology and laboratory medicine at Brown University. Kelsey collaborated with lead author Heather Nelson of the University of Minnesota Masonic Cancer Center in making the findings.

Moreover, Nelson, Kelsey and their colleagues wrote, referring to the common HPV16 strain of the virus: “These data are among the first to demonstrate a convincing relationship between HPV16 and improved patient survival for tumors of the larynx and oral cavity.”

Appraising antibodies
The study examined blood serum samples and five-year survival rates among more than 1,000 Boston-area head and neck cancer patients diagnosed between 1999 and 2011. Overall, those who tested positive for antibodies to the oncogenic HPV proteins E6 or E7 were less likely to die during the five year follow-up period after diagnosis compared to those who tested negative for the antibodies. Based on the analysis, the researchers estimated that those with evidence of an immune response to HPV were 25% less likely to die during the course of follow-up compared to those with no immune response to HPV.

The study’s purpose was to determine whether the antibodies provide a reliable indication of prognosis. In ongoing trials, doctors are testing whether patients with HPV-associated cancers can be treated less aggressively—and hopefully with fewer negative side effects—than people with non-HPV-associated cancers, Kelsey said. If trials prove successful, then it will be particularly important to determine whether cancers are HPV-associated.

“The assessment of a patient’s HPV status likely will affect treatment,” he said. “That’s why there’s real interest in getting it right; for instance, how do you test?”

Better prognosis across the board
Prior studies have focused primarily on the role of HPV in the oropharynx—the area of the throat right behind the mouth. An important contribution of the current study, Nelson said, is demonstration that an immune response to HPV is important for all forms of head and neck cancer, although the benefit does show some variance based on the exact cancer location. Those patients with an HPV immune response with tumors located in the oropharynx and larynx had a similar risk of dying during the follow-up period, though the reduced risk was slightly attenuated for those patients with tumors located in the oral cavity.

The results didn’t depend significantly on whether people had high or low levels of the antibodies, so long as they had some, the researchers found, though testing positive for both E6 and E7 was better than for just one.

The reduced chance of dying by five years carried through for people who tested positive for the antibodies even if they consumed tobacco and alcohol. But the worst prognoses in the study were among smokers whose cancers could not be traced to HPV.

In all, the findings controlled for the statistical influences not only of tobacco and alcohol exposure, but also of age, race, gender, education and how far advanced the cancer was.

Relates to broader advances
Kelsey said the findings could help bring head and neck cancer treatment closer into line with two emerging practices of fighting the disease: personalized medicine and immunotherapy.

“To me, personalized medicine really reflects using all the information you can glean about an individual tumor to treat it appropriately,” Kelsey said. “Here HPV is an example of a causal factor that delineates the mechanism of the tumor suppressor genes that drive the tumor and that gives you insight into the differences in the tumor.”

Meanwhile, the study might help shed light on why immunotherapy—in which the body’s immune system is marshaled to attack cancer—appears to help for some head and neck cancers, Kelsey said. It may not be coincidence, for instance, that the prognosis is better among people whose cancers are associated with a virus that promotes a robust immune response, in the form of antibodies, than among people without a viral cause for their cancer.

If HPV-related cancers can indeed be treated differently, Kelsey said, then serum-based testing to determine the role of the virus could soon be available, too.

December, 2016|Oral Cancer News|