Long-term implant failure in patients treated for oral cancer by external radiotherapy: a retrospective monocentric study

Source: Journal of Oral Medicine and oral Surgery, JOMOS
Date: October 10th, 2018
Authors: Aline Desoutter, Sophie Deneuve, Sophie-Charlotte Condamin and Anne-Gaëlle Chaux-Bodard

Abstract

Introduction: The placement of dental implants in irradiated bone has allowed functional rehabilitation for many oral cancer patients. Nonetheless, there is only few data about implant failure in irradiated tissues and their consequences. This retrospective study aims to highlight the rate and circumstances of implant failure.

Material and method: Patients treated with external radiotherapy for oral carcinoma and who received dental implants were included. Patients reconstructed with free bone flaps were excluded.

Results: Eighteen patients were included. Forty implants were placed between 2004 and 2007, 8 failed, of whom one osteoradionecrosis was observed. Time interval between radiotherapy and implantation was 44.6 (6–182) months. Mean dose was 51.8 (50–66) Gy.

Discussion: In the series, the implant failure rate is 20%, which corroborates the literature’s data. Failures occur more often for doses over 50 Gy. The placement of dental implant in irradiated bone leads to soft tissue complications but also increases the risk of osteoradionecrosis. The recent reimbursement of dental implants in oral cancer patients by the National Social Health system will probably increase the indications. Multidisciplinary staffs should be aware of benefit/risk ratio for each patient.

Introduction

Dental implants in patients treated for upper aerodigestive tract (UADT) cancers have facilitated the functional and aesthetic rehabilitation of patients whose postoperative anatomy did not allow for the placement of conventional prostheses. Several studies have been conducted and the success rates have varied from 62.5% to over 90% [1]. These success rates would be similar to those found in a healthy patient’s mandible, which is reported to be 92.6% [2]. However, there is little information regarding the types of failures that occur with these implants, as well as the consequences and circumstances surrounding their occurrence, especially when the radiation dose at the implant site is >40 Gy. Indeed, most of the published studies are case studies in which there is great heterogeneity in the initial tumor sites and in the radiation doses received at the implant site. It is therefore difficult to precisely determine the failure risk in patients who have received large radiation doses in the oral area. The expected complications are mainly peri-implantitis, loss of implants, and even osteoradionecrosis (ORN) [3]. The aim of this study was to highlight long-term implant failures in patients who were treated with radiotherapy for oral cancer and to observe the circumstances and consequences of these failures.

Material and methods

The clinical records of oral cancer patients treated between 2004 and 2007 by radiotherapy (exclusively or not) and who received implants were reviewed. In the interest of maintaining the homogeneity of the study sample, patients treated with a microanastomosis fibula flap were excluded.

The following information was extracted from the case records: tumor location, tumor stage, and type of treatment received, the duration between radiotherapy and implantation, the type of implants placed, the surgical and operative protocol, the patient’s medical history (excluding oncology) as well as any implant or peri-implant clinical events and their time of occurrence. Failure was defined as loss of implant osseointegration resulting in implant loss or removal. Surgical and implant loading failures were considered. Statistical analysis was performed using XLSTAT® software (Microsoft).

Results

Eighteen patients, consisting of 14 males (77%) and four females (13%) were eventually included. The mean age at the time of implant placement was 57.5 years (range: 42–78 years).

The initial tumor locations, the initial tumor stage, and the treatments received are presented in Table I.

Table I : Population studied: sites, tumor stages, and treatments received.
Table II : Implant failures as a function of the radiation dose received, initial tumor site, and failure onset delay.

Discussion

Cervicofacial radiation is one of the primary causes of implant loss [1,4] regardless of whether it is administered early or late [5]. Several failure factors specific to implant placement in irradiated areas have been identified; these include the duration after radiotherapy and the radiation dose received.

For successful implantation, the minimum time after radiotherapy before implantation should be 6–12 months [6]. A delay of >12 months would improve implant success rates [7]. In the current study, a minimum period of 6 months was selected after the multidisciplinary consultation with the surgical oncologists and radiotherapists. After excluding the two patients who were treated several years ago, missed their follow-up, and then reappeared for prosthetic rehabilitation, the average implantation time after radiotherapy in our study was 20.37 months (range: 6–49 months). One study [8] showed that the failures are less severe in patients receiving implants a later stage of oncological treatment (17.1% failure rate for intraoperative implants versus 4.6% for those placed postoperatively). Of course, the idea of early rehabilitation encourages the surgical team to perform implantation along with tumor removal, before additional treatments are administered. Although this technique has the advantage of decreasing treatment duration, it is not always feasible because of the constraints of tumor management.

The radiation dose received at the implant site is also a major cause of implant failure, with doses <50 Gy being more favorable [9,10]. Animal studies and literature reviews show that the implant failure rate is directly correlated with the radiation dose received [9,10]. In the study, implant sites that received estimated doses >55 Gy had failure (mean: 59.33 Gy). In fact, all implant failures occurred in patients who received treatment for cancer involving the anterior aspect of the floor of the mouth. The therapeutic target was therefore very close to the implant site, and the dose administered at the implant site was close to the therapeutic dose delivered.

The biggest challenge consists in evaluating the radiation dose received at the implantation site. In most studies, the initial tumor sites involved all the UADTs, including the oropharynx, with low radiation doses of about 30 Gy at the symphyseal and parasymphyseal level. It therefore seems more appropriate to limit the evaluation of failure rates to patients treated for cancer of the oral cavity, as the radiation doses at the implant site are therefore more homogeneous. In published studies, only a few authors [11] highlight the antecedents or lack thereof of radiation, with irradiated tissue implants having osseointegration rates of 83% at 5 years.

Long-term implant survival rates reported by the previous clinical studies are nonhomogeneous, with values of 72.8% at 10 years [9], 24% at 5 years [10], or 72% at 8 years [11]; however, these values support the results of our present study. Thus, Wagner [12] reports a 5-year osseointegration rate of 97.5% and at 10 years of 72.8%, whereas other authors report success rates of 48.3% [3]. Another study reports complications in 41.5% patients [13].

Seven out of eight failures encountered in the series began with peri-implantitis. Werkmeister [14] observed a soft-tissue complication rate of 28.6% in irradiated areas versus 8.3% in nonirradiated areas. These complications can be explained in part by the small amount of keratinized gingiva, along with the predisposing factors of radiotherapy-related sensitization and dry mouth. The occurrence of peri-implantitis should be carefully monitored to avoid ORN [15].

An increased loss of marginal bone was reported by many authors, with 2–9 mm variations for a period of 3 years after implant surgery [16]. According to Tanaka [17], early failures are more frequent. In the studies, all failures occurred >1 year after implant placement.

In the present series, a case of loss of osseointegration resulted in extensive ORN at a rate of 2.5%. Treatment of ORN required a subsequent free vascularized bone transfer reconstruction. This patient had been treated for a mouth floor lesion in the past and had received a postoperative radiation dose of 64 Gy (See Patient 3, Tab. I). This implant failed 1 year previously, and a reimplantation was proposed because of the impossibility of prosthetic rehabilitation without bone anchorage. Thus, there were two interventions on adjacent parasymphyseal mandibular bone sites. The patient had reverted to smoking regularly despite tobacco counseling. The risk of triggering ORN following implant placement was estimated to be 1.6%–5% [9,16,18,19]. Some authors advocate the use of hyperbaric oxygen therapy before and after implantation to stimulate or optimize healing and decrease ORN risk [20,21]. Others believe that the risk/benefit/cost ratio is not sufficiently favorable. More recently, the use of low-intensity pulsed ultrasound to increase healing capacity has been advocated [22]. Animal studies are currently underway [23].

Conclusion

It is widely accepted that the use of implant techniques in cancer patients is sometimes essential to ensure functional prosthetic rehabilitation. This retrospective study, which was conducted on patients who had specifically received oral radiotherapy, confirmed that it was a reliable therapeutic treatment for radiation doses of 45–50 Gy. However, the small number of patients in this study prevents the extrapolation of results to larger populations, considering the significant morbidity and lower success rate than patients who were not irradiated. Thus, the inherent risk of a past history of radiotherapy must be taken into account. The use of software like Dentalmaps® [24] allows a better evaluation of the doses received at potential implantation sites. This software is based on the automatic segmentation and delineation of the dental zones, making it possible to estimate the dose received at different points of the dental arch to the nearest 2-Gy fraction. However, the software is expensive, the work is laborious, and this device cannot be routinely used. Considering that health organizations are responsible for the cost management of implants in patients with cancer of UADT, there will be a definite increase in the indications for implantation [25]. It is up to the members present at the multidisciplinary consultation meetings to evaluate the benefit/risk ratio on a case-by-case basis.

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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.

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October, 2018|Oral Cancer News|

Adam Kay picks the best books about living with cancer

Source: www.theguardian.com
Author: Adam Kay

As Orson Welles so cheerily put it, we are born alone, we live alone and we die alone. But none of us has to struggle through cancer alone, thanks to a vast pool of literature, non-fiction and poetry that tackles the subject.

In C: Because Cowards Get Cancer Too, columnist and self-confessed hypochondriac John Diamond writes with almost unbearable honesty about his fears as he is diagnosed with throat cancer. As he puts it, this is his “attempt to write the book I was looking for the night I got the bad news”, and it explains “what it’s like to be a person with cancer, to deal with the pain and the fear and the anger”. While his feelings vacillate between hope and despair, his dark humour sings through. Taking the reader on a gripping and emotional journey, this account captures the unpalatable but essential truth that not all those living with cancer are “bravely battling” – some are just plain scared. Diamond is one of a handful of writers who can make me snort out loud in public through the magic of their words, and is much missed.

The true story beautifully told by Rebecca Skloot in The Immortal Life of Henrietta Lacks is astonishing. Henrietta was a penniless black tobacco farmer who died in 1951, but whose cervical cells changed the shape of medicine. Taken without permission, cells from her tumour have since been multiplied and shared around the world to advance our understanding of cancer. Skloot’s book was inspired by a science lesson in which her teacher told the class that if they went to almost any cell culture lab in the world and opened its freezers, they might find billions of Henrietta’s cells in small vials on ice. The biography examines how those cells enabled scientists to make advances in fields ranging from cancer and gene mapping to IVF. Skloot confronts issues of racism, poverty, consent and the anguish of Henrietta’s family.

Clive James wrote in this paper about living with late-stage cancer in his weekly column, Reports of My Death. One of his latest (and, he assumed, last) books of poetry, Sentenced to Life, and its surprise sequel, Injury Time, are filled with verses that address the feeling of wanting to live life to its fullest while waiting for death to knock. “Now, not just old, but ill, with much amiss / I see things with a whole new emphasis,” he reflects. In these volumes, he describes his sense of loss, and guilt at leaving behind the people he loves, and draws on his trademark humour.

There are many cancer blogs out there, but to my mind one of the best was The C Word, subsequently turned into a book and a TV series starring Sheridan Smith. Lisa Lynch has a gloriously witty turn of phrase in dealing with the emotional ups and downs of living with breast cancer – or, as she put it, The Bullshit. Made all the more poignant as she died after the book was published, it is no-nonsense, funny, moving and entirely devoid of self-pity.

If we trust the Pulitzer prize panel about this kind of thing, and I suspect we should, then read The Emperor of All Maladies by oncologist Siddhartha Mukherjee. It is an in-depth, but clear and at times poetic depiction of the “lethal, shape-shifting entity” – its past, present and putative future.

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October, 2018|Oral Cancer News|

AN E-CIGARETTE COMPANY PUT VIAGRA AND CIALIS IN ITS VAPING LIQUIDS, AND THE FDA IS NOT PLEASED

Source: newsweek.com
Date: 10/13/18
Author: Kelly Wynne

A vape company, HelloCig Electronic Technology Co., has included Viagra and Cialis in its liquids, and has raised the ire of the Food and Drug Administration.

One liquid was called e-Cialis, a popular erectile dysfunction drug, and was displayed with photos of the real product, according to Ars Technica. A weight loss drug, whose brand was banned in Europe, was allegedly adapted into the liquid form as well, though FDA testing proved it instead contained the erectile dysfunction medication found in Viagra.

The FDA sent a warning letter to HelloCig on Thursday. It urged the company to make the necessary changes to properly market their products and asked they comply with FDA regulations to continue selling any type of drug.

HelloCig alleged they responded to the FDA in a statement sent to USA Today Saturday. “Our aim is to fully comply with all FDA regulations, both in letter and spirit,” the statement read.

The FDA also released a statement, written by FDA Commissioner Scott Gottlieb, on the illegal sale of these liquids on Thursday. “There are no e-liquid products approved to contain prescription drugs or any other medications that require a doctor’s supervision,” the statement read. “Prescription drugs are carefully evaluated and labeled to reflect the risks of the medications and their potential interactions with other medicines, and vaping active drug ingredients is an ineffective route of delivery and can be dangerous.”

Gottlieb considers the e-cigarette usage among teenagers an epidemic, he clarified in a statement last month. “E-cigs have become an almost ubiquitous—and dangerous—trend among teens,” he wrote. “The disturbing and accelerating trajectory of use we’re seeing in youth, and the resulting path to addiction, must end. It’s simply not tolerable. I’ll be clear. The FDA won’t tolerate a whole generation of young people becoming addicted to nicotine as a tradeoff for enabling adults to have unfettered access to these same products.”

HelloCig is based in China but sells vaping products in America. The brand carries over 150 flavors of e-liquid among other products like “e-herbs, e-healthcare and e-beverages smoke liquid.”

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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.

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October, 2018|Oral Cancer News|

New risk factor for mouth cancer uncovered

Source: www.medicalnewstoday.com
Author: Tim Newman, fact checked by Paula Field

In some regions, mouth cancer incidence has risen. A recent study investigates a new risk factor for mouth cancer. In certain parts of the world, over the past couple of decades, mouth cancer rates have soared. For instance, in the United Kingdom, rates of mouth cancer have increased by 68 percent. They rose from eight cases per 100,0000 in 1992–1995 to 13 cases per 100,000 in 2012–2014.

In the United States, mouth cancer and mortality rates have declined overall. However, when examined at a state level, the data reveal a more complex picture. For instance, mouth cancer deaths have risen significantly in Nevada, North Carolina, Iowa, Ohio, Maine, Idaho, North Dakota, and Wyoming.

Some known risk factors for mouth cancer include smoking tobacco, drinking alcohol, human papillomavirus (HPV), and chewing betel quid, which is a mix of natural ingredients wrapped in a betel leaf that is popular in some parts of Southeast Asia.

In India, mouth cancers are the most common cause of cancer-related deaths in men aged 30–69 years old. Scientists think that chewing betel quid could be responsible for many of these deaths.

New risk factor for mouth cancer
Although scientists have confirmed some risk factors, there is still much to learn about how and why mouth cancer affects certain individuals and not others. Recently, scientists set out to investigate another potential risk factor: air pollution.

The researchers, funded by the Ministry of Science and Technology in Taiwan, published their findings this week in the Journal of Investigative Medicine.

In particular, the team focused on the impact of fine particulate matter, also known as PM2.5. These are particles of liquid or solid matter that measure 2.5 micrometers in diameter or under. Scientists already knew that PM2.5 has a negative impact on cardiovascular and respiratory health, but they wanted to find out whether exposure to higher levels of PM2.5 might also increase mouth cancer risk.

To investigate, they collated information from 482,659 men aged 40 years old or above. All participants had attended health services and given information about smoking and chewing betel quid.

The scientists next gathered data from 66 air quality-monitoring stations across Taiwan. By referring to the participants’ health records, the scientists could estimate each person’s exposure to PM2.5.

Risk increased by 43 percent
The researchers collected the data in 2012–2013. During this time, 1,617 men developed mouth cancer. As expected, both tobacco smoking and chewing betel quid increased mouth cancer risk. After taking a range of influencing factors into account, the scientists demonstrated that exposure to PM2.5 also increased mouth cancer risk.

The scientists compared PM2.5 levels of below 26.74 micrograms per cubic meter (ug/m3) with those above 40.37 ug/m3. They associated the higher levels of PM2.5 with a 43 percent increase in the risk of developing mouth cancer. According to the authors:

“This study, with a large sample size, is the first to associate mouth cancer with PM2.5. […] These findings add to the growing evidence on the adverse effects of PM2.5 on human health.”

Alongside PM2.5’s relationship with mouth cancer, the authors identified a correlation between higher levels of ozone and an increased risk of developing the disease.

The next challenge will be to understand how particulate matter might cause mouth cancer. Although this will require more detailed studies, some theorize that carcinogenic compounds found in PM2.5, including polycyclic aromatic hydrocarbons and heavy metals, might be part of the answer.

Because these particles have such a small diameter, the body absorbs them relatively easily, potentially causing damage as they travel through the body.

However, the authors also remind us to be cautious — this is an observational study, so it cannot definitively prove that pollution causes mouth cancer. Also, it is not clear exactly how much PM2.5 enters the mouth.

This interaction needs further investigation, but the large size of the current study makes their conclusions worthy of follow-up.

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October, 2018|Oral Cancer News|

FDA approves expanded use of Gardasil 9 to include individuals 27 through 45 years old

The U.S. Food and Drug Administration today approved a supplemental application for Gardasil 9 (Human Papillomavirus (HPV) 9-valent Vaccine, Recombinant) expanding the approved use of the vaccine to include women and men aged 27 through 45 years. Gardasil 9 prevents certain cancers and diseases caused by the nine HPV types covered by the vaccine.

“Today’s approval represents an important opportunity to help prevent HPV-related diseases and cancers in a broader age range,” said Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research. ”The Centers for Disease Control and Prevention has stated that HPV vaccination prior to becoming infected with the HPV types covered by the vaccine has the potential to prevent more than 90 percent of these cancers, or 31,200 cases every year, from ever developing.”

According to the CDC, every year about 14 million Americans become infected with HPV; about 12,000 women are diagnosed with and about 4,000 women die from cervical cancer caused by certain HPV viruses. Additionally, HPV viruses are associated with several other forms of cancer affecting men and women.

Gardasil, a vaccine approved by the FDA in 2006 to prevent certain cancers and diseases caused by four HPV types, is no longer distributed in the U.S. In 2014, the FDA approved Gardasil 9, which covers the same four HPV types as Gardasil, as well as an additional five HPV types. Gardasil 9 was approved for use in males and females aged 9 through 26 years.

The effectiveness of Gardasil is relevant to Gardasil 9 since the vaccines are manufactured similarly and cover four of the same HPV types. In a study in approximately 3,200 women 27 through 45 years of age, followed for an average of 3.5 years, Gardasil was 88 percent effective in the prevention of a combined endpoint of persistent infection, genital warts, vulvar and vaginal precancerous lesions, cervical precancerous lesions, and cervical cancer related to HPV types covered by the vaccine. The FDA’s approval of Gardasil 9 in women 27 through 45 years of age is based on these results and new data on long term follow-up from this study.

Effectiveness of Gardasil 9 in men 27 through 45 years of age is inferred from the data described above in women 27 through 45 years of age, as well as efficacy data from Gardasil in younger men (16 through 26 years of age) and immunogenicity data from a clinical trial in which 150 men, 27 through 45 years of age, received a 3-dose regimen of Gardasil over 6 months.

The safety of Gardasil 9 was evaluated in about a total of 13,000 males and females. The most commonly reported adverse reactions were injection site pain, swelling, redness and headaches.

The FDA granted the Gardasil 9 application priority review status. This program facilitates and expedites the review of medical products that address a serious or life-threatening condition.

The FDA granted approval of this supplement to the Gardasil 9 Biologics License Application to Merck, Sharp & Dohme Corp. a subsidiary of Merck & Co., Inc.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

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October, 2018|Oral Cancer News|

HPV vaccine expanded for people ages 27 to 45

Source: www.nytimes.com
Authors: Denise Grady and Jan Hoffman

About 14 million women and men become infected with the human papillomavirus each year in the United States, according to the Centers for Disease Control and Prevention. CreditCreditKeith Bedford/The Boston Globe, via Getty Images

The HPV vaccine, which prevents cervical cancer and other malignancies, is now approved for men and women from 27 to 45-years-old, the Food and Drug Administration said on Friday.

The vaccine is Gardasil 9, made by Merck, and had been previously approved for minors and people up to age 26.

It works against the human papillomavirus, HPV, which can also cause genital warts and cancers of the vulva, anus, penis and parts of the throat. The virus has many strains. It is sexually transmitted, and most adults encounter at least one strain at some point in their lives. The vaccine protects against nine strains, including those most likely to cause cancers and genital warts.

“Today’s approval represents an important opportunity to help prevent HPV-related diseases and cancers in a broader age range,” Dr. Peter Marks, director of the F.D.A.’s Center for Biologics Evaluation and Research, said in a statement.

The approval was based on a study in women ages 27 to 45, showing that an earlier version of the vaccine was highly effective in preventing persistent HPV infection, genital warts, vulvar and vaginal precancers, cervical precancers and cervical cancers related to the virus types covered by the vaccine.

The vaccine’s effectiveness in men ages 27 to 45 is inferred from the data in women, from its efficacy in younger men and from evidence that it created immunity in a study of men 27 to 45-years-old.

The most common side effects of the vaccine include soreness at the injection site, swelling, redness and headaches.

If a person has already been exposed to a particular strain of HPV, the vaccine will not work against that strain. For that reason, vaccination has been strongly recommended for young people before they become sexually active.

But even someone who has already been exposed to a few strains — but not to all nine in the vaccine — can still gain protection against the strains they have not encountered.

“This is great,” Dr. Lois M. Ramondetta, a professor of gynecologic oncology at MD Anderson Cancer Center in Houston, said in an interview. “It’s a prevention vaccine. The best time to get it is before you turn 13 and have any intimate activity at all. But, that said, it protects against nine types of HPV, so if you have one of the types, you still can be protected from other HPV types.”

She added: “There is a whole generation of people we were missing who didn’t know about it. Doctors weren’t good at talking about it.”

She and Dr. William Schaffner, an infectious disease expert at Vanderbilt University, said people over 26 began asking doctors about the vaccine. Some were leaving marriages or monogamous relationships, expected to begin dating and realized they might be exposed to the virus.

“They want to feel protected to some extent,” Dr. Ramondetta said. “Now they have the opportunity.”

Younger people need two shots, but the older ones will need three, spaced a few months apart.

Dr. Ramondetta noted that tumors affecting part of the throat — called oropharyngeal cancers — caused by HPV are rising, particularly in men. The vaccine is believed to help prevent them.

Dr. Schaffner said a panel that advises the Centers for Disease Control and Prevention has already been discussing the data on using the vaccine in older people, and is expected to make a recommendation about it. The recommendation could be universal, meaning that everyone in that age range should receive it, or it could be “permissive,” meaning that the decision is up to doctors and patients.

Once that group, the Advisory Committee on Immunization Practices, recommends a vaccine, insurers generally cover it.

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October, 2018|Oral Cancer News|

HPV16 vaccine yields added benefit in recurrent throat cancer

Source: www.medpagetoday.com
Author: Ian Ingram, Deputy Managing Editor, MedPage Today

Adding a tumor-specific vaccine to PD-1 checkpoint inhibition was safe and effective in HPV16-positive patients with recurrent or metastatic oropharyngeal cancer, a small phase II trial found.

Among 24 patients treated with nivolumab (Opdivo) and the ISA101 long peptide vaccine, 22 of whom had oropharyngeal cancer, 33% responded and median overall survival was 17.5 months, Cornelis Melief, PhD, of ISA Pharmaceuticals in the Netherlands, reported here at the 4th annual Cancer Immunotherapy Conference.

All eight of the responders had oropharyngeal cancer (36%), with two complete and six partial responses. The median duration of response among these patients was 10.3 months, and responses were seen in both platin- and cetuximab-refractory patients, and those refractory to both.

Melief noted that one of the partial responders had total clearance of the primary tumor, but a solitary lung metastasis remained, but was stable at 2.5 years.

Rate of overall survival at 6 and 12 months was 75% and 70%, respectively. The combination was well tolerated and safe, said Melief, with no increase in the rate of serious adverse events. A randomized trial is planned to confirm the findings.

“The results of our trial are among the first clinical data to support the general concept of combining cancer vaccination with immune checkpoint blockade to enhance efficacy of vaccine-activated T cells in the immunosuppressive tumor environment,” Melief’s group wrote in JAMA Oncology, where the findings were also published.

The findings compare favorably to outcomes in a larger group of p16-positive patients in CheckMate 141, which tested nivolumab in recurrent or metastatic, chemotherapy-refractory squamous cell head and neck cancer, and led to FDA approval in that setting.

Overall response among the 63 p16-positive patients in that trial was 15.9%, and median overall survival was 9.1 months.

Median progression-free survival (PFS) in the current study was just 2.7 months, similar to that in CheckMate 141: 2.0 months in nivolumab-treated patients, which was no different from the PFS with standard therapy at 2.3 months (HR 0.89, 95% CI 0.70-1.13, P=0.32).

“These findings are nearly double the response rate and median overall survival reported in the CheckMate 141, KEYNOTE-012, and KEYNOTE-055 trials,” said Theodoros Teknos, MD, of Seidman Cancer Center in Cleveland, calling the study an important incremental discovery in the burgeoning field of immunotherapy for head and neck cancer.

In KEYNOTE-012, the rate of overall response rate was 12% in a similar patient group (survival was not reported). In KEYNOTE-055, the rates were 20% and 8 months, respectively.

“Based on the findings reported in this study, additional investigation in the form of a larger randomized clinical trial evaluating the contribution of HPV16 vaccination to PD-L1 inhibition is warranted,” he told MedPage Today. “Nested in this trial, it would be advisable to perform robust analysis of immunologic subsets and cytokine profiling to identify biomarkers of response to this treatment approach.”

Teknos, who was not involved in the study, noted that the subgroup analysis again calls into question the use of PD-L1 as a biomarker. While 43% of the PD-L1 ≥1% group were responders, 18% of the PD-L1 < 1% group were as well.

Melief also presented data on the ISA101 vaccine in 62 late-stage HPV-positive cervical cancer patients treated with the ISA101 vaccine in combination with chemotherapy and highlighted the survival difference among those with a vaccine-induced T-cell response. Median overall survival was 22.7 months in those that had an HPV-specific response above the median versus 12.9 months for those with a response below the median (HR 0.286, 95% CI 0.149-0.551, P=0.0066).

He noted that this was not due just to immunocompetence differences between patients, as the effect was found to be independent of patients’ immune status.

The current study enrolled 24 patients from 2015 to 2016 — 20 men and four women. Outside of the oropharyngeal cancer patients, there was one patient with anal and cervical cancers each. Patients received three 100 μg doses of the subcutaneous ISA101 vaccine (days 1, 22, and 50). Starting on day 8, intravenous nivolumab was given every 2 weeks for a year or until disease progression or unacceptable toxicity.

Toxicities were of the expected variety: fever and injection site reactions with ISA101, and diarrhea, fatigue, and hepatoxicity with nivolumab. Two patients had grade 3 and 4 adverse events that led to discontinuation of nivolumab (an asymptomatic transaminase level elevation and a lipase elevation, respectively).

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October, 2018|Oral Cancer News|

Oral sex and ‘deep kissing’ linked to increase in HPV-positive head and neck cancer

Source: www.sbs.com.au
Author: Amelia Dunn

Jake Simpson was 22 when he started to get painful toothaches. Trips back and forth to the dentist couldn’t seem to fix the growing lump at the back of his mouth It came as a total surprise to Jake, his partner Carly, and their newborn son Noah, when oncologists in Brisbane told him he had stage four head and neck cancer, and would need to start treatment immediately.

“We didn’t know what any of it meant. He was so young and healthy, we couldn’t believe it,” Carly said.

Despite rigorous treatment and surgery that removed more than two-thirds of his tongue, Jake’s cancer was too aggressive and spread to his lungs. He died within eight months of his diagnosis.

These cancers, known as oropharyngeal cancers in the back of the tongue and tonsils, are on the rise in young men, and are caused by the sexually transmitted disease HPV – human papillomavirus. While doctors believe it is most commonly passed on through oral sex, some argue it’s now as easy as ‘deep kissing’.

“Jake wasn’t tested for HPV because it was too aggressive from the day one, but that age bracket that he fell in, more than likely, the cause was HPV,” Carly said.

HPV has been dubbed the ‘common cold’ of STDs. Over 80 per cent of Australian adults will get HPV at one point in their lives, and most will clear it without even knowing.

But two particular strains, P16 and P18 are closely linked with cancer, not just in the cervix like widely known, but increasingly in the head and neck.

Two strains of HPV, P16 and P18 are closely linked with cancer, not just in the cervix like widely known, but increasingly in the head and neck.
Source: The Feed

Researchers across the US, UK and Australia say changing sexual practices over the last 50 years, and an increase in sexual partners has prompted the rising incidence rate of this cancer.

Oncologist Brett Hughes has witnessed the significant shift in the patient demographic, who says nearly 80 per cent of his patients now have HPV positive cancers.

“We now see an age group of people who generally live very healthy lifestyles; that don’t necessarily have to have drunk or smoke and the other risk factors that we’d normally associate with cancers in the mouth or throat.”

The cancer is also eight times more likely to present in men. Dr Hughes said oropharyngeal cancers are now the most common HPV related cancer in Australia, trumping cervical cancer, and are continuing to rise.

“It’s predicted for Australia and it may even be as late as in the 2030s that we might see the peak incidence which is a little bit scary considering how common this cancer is becoming.”

While this cancer is increasing, many take comfort in Australia’s strong vaccination program to fight HPV related cancers.

The Gardasil vaccine, developed by Australian of the year Professor Ian Frazer, was first administered to Australian girls in 2007, and then to boys in 2013 after it became clear HPV was affecting them as well. But Professor Frazer said people need to be given the vaccine before they’re sexually active.

“All the vaccines that we currently use are vaccines to prevent infection. A vaccine to cure an infection is a different beast all together,” he said.

Without a therapeutic vaccine, sexually active adults who missed out on the vaccine at school are still at risk of contracting persisting HPV, with Prof Frazer insisting “the big challenge now is to get something for oropharyngeal cancer.”

Right now, there is no vaccine for adults and no way of testing or preventing HPV positive oropharyngeal cancers. But there are people out there trying to change that.

After Jake Simpson passed away in 2016, he donated $20,000 for research into early intervention for these cancers.

His family chose a saliva research program currently underway at the Institute of Health and Biomedical Innovation in Brisbane lead by Professor Chamindie Punyadeera. The lab work is aimed at creating a simple and easy test everyone can do to monitor their HPV status at the dentist or GP.

“What we want to do is early intervention and detection,” she said.

“If you detect early, 80 per cent of patients survive. If you detect late, 20 per cent of them survive.”

But as the technology is still five years away from public use, and a therapeutic vaccine is perhaps even further away, Carly and Professor Punyadeera agree young people just need to be aware that this cancer exists, and is on the rise.

“Young boys think it’s a women’s cancer type. It’s not at all,” Prof Punyadeera said.

“It’s really sad and we all need to be aware of HPV associated head and neck cancers.”

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October, 2018|Oral Cancer News|