human papillomavirus

Scientists untangle the evolutionary history of the world’s most common STI

Source: www.iflscience.com
Author: Rosie McCall

Scientists have analyzed the genomes of viruses to reveal the surprisingly complex evolutionary past of the human papillomavirus (HPV), exposing the salacious details of our ancestors’ sexual history in the process.

HPV comes in several flavors but HPV16 is the most common subtype worldwide – and it is the one most frequently identified in cervical cancer. Together HPV16 and HPV18 are responsible for 70 percent of all cases, accord to stats from the World Health Organization (WHO).

The problem is, it isn’t exactly clear how HPV strains contribute to cervical cancer (and other types, including cancer of the anus, the throat, the base of the tongue, and the tonsils). Or why the virus naturally clears in some people but not others. Researchers hope that studying the evolution of the virus will expose biological insights and point at mechanisms that might explain how cervical cancer develops.

To try to untangle HPV16’s thorny evolutionary past, scientists led by the Chinese University of Hong Kong isolated and examined oral, perianal, and genital samples in 10 adult female squirrel monkeys (Saimiri sciureus) and eight adult rhesus monkeys (Macaca mulatta), half of whom were male and half of whom were female.

They found that the virus strains with most in common came from the same part of the body – meaning the oral samples from the squirrel monkeys and rhesus monkeys had more in common than oral and genital samples from the same species, for example. This, the authors say, implies the viruses adapted to a specific body part (or niche) where they co-evolved with their host for millions of years before passing to humans.

For the next part of the study, published in the journal PLOS Pathogens, the researchers compared 212 complete HPV16 virus genomes and 3,582 partial sequences to find out when exactly the HPV16 variants A, B, C, and D diverged from one another.

Schematic illustration of HPV16 codivergence with archaic hominins. Chen et al./PLOS Pathogens

Previous studies have shown that one (the HPV16 A variant) was a lover’s gift from our hominid relatives, the Neanderthals, transmitted to modern humans after a few too many nights of interspecies shagging. Now, it looks like this particular variant split from the virus’ “family tree”, setting off its own trajectory, just as modern humans and archaic hominins (Neanderthals and Denisovans) parted ways, evolutionarily speaking, 618,000 or so years ago.

While the HPV16 A variant co-evolved with its Neanderthal and Denisovan hosts, HPV16 B and HPV16 C variants co-evolved with modern humans. The different strains remained in their respective hosts for hundreds of thousands of years, the study authors say. Then, 100,000 years ago or thereabouts, a small band of Homo sapiens ventured outside of Africa and into Eurasia where they met – and intermingled – with other hominin species, contracting certain HPV16 A variants in the process.

The consequences of this can still be seen today and can help explain why certain variants are more commonly seen in certain groups, the HPV16 A variant in Europeans and Asians, for instance. Hopefully, the authors say, this new information will improve our understanding of why some variants of HPV16 may be inherently more carcinogenic than others.

November, 2018|Oral Cancer News|

A Look at Therapy Toxicities & Biology in Head & Neck Cancers

Source: journals.lww.com
Author: Valerie Neff Newitt

A measure of intrigue and discovery pertaining to head and neck cancer, spiked with compassion for patients struggling against treatment toxicities, helps quench the intellectual thirst of Yvonne Mowery, MD, PhD, Butler Harris Assistant Professor of Radiation Oncology at Duke University Medical Center, Durham, N.C.

Splitting time between the clinic and laboratory, Mowery is actively engaged in patient care as well as preclinical, translational, and clinical research. “I hope to get a better understanding of the biology of head and neck cancer and determine pathways that we can target to reduce metastatic spread of the disease and improve responsiveness to available treatments,” she told Oncology Times.

Long before reaching her current status as an award-winning investigator, Mowery grew up in Richmond, Va., in the midst of a “completely non-scientific” family. “I was an oddball,” she joked, while recalling her parents’ patience with her backyard composting experiments that became so foul-smelling that the health department was contacted. As a kid, her idea of a great present was an encyclopedia of science, and the thing that caught her eye at the toy store was a junior chemistry set.

Science was clearly her path when she headed to the University of Virginia. In her sophomore year, Mowery began working in a genetics lab. That’s where the lure of fruit flies took hold. “I looked at the development of their reproductive system and found that very interesting,” she recalled.

Nearing the completion of her undergraduate education, Mowery debated between attending medical school or graduate school. The eventual winner? Both. “I investigated physician-scientist training programs and arrived at Duke in 2004 to do a combined MD/PhD.” Today, Mowery spends 1 day a week in clinic where she sees patients, then moves to the lab for the remainder of the week to find strategies to improve patient care and develop therapies to deliver better outcomes for patients, both present and future.

Clinical Challenges
“I treat cancers primarily of the head and neck—such as oral cavity, larynx, tonsils, base of tongue, sinuses—with radiation therapy. I think of head and neck cancers as being in a ‘very high-stakes real estate’ area,” she said, “because they are often close to saliva glands, vocal cords, etc. This requires intricate planning for radiation treatment. Visualization of the tumor through fiberoptic laryngoscopy allows me to see a tumor responding to radiation and chemotherapy during the weeks of treatment; it is gratifying to watch it happen with your own eyes.”

Mowery said toxicity associated with treatment of this area of the body can be severe, partially due to the fact that it is typically “…one of the longer courses of radiation that we do—about 7 weeks, 5 days a week,” she explained. “Patients typically require pain medicine to eat and drink a soft diet, lose their sense of taste, and experience very dry mouth, sometimes requiring a feeding tube for nutrition. In addition, the skin on their neck often falls off.” Comparing it to severe sunburn, Mowery said skin typically blisters and peels off, leaving behind a neck that is “red, angry, and very uncomfortable. It just comes with the territory.”

In addition to these side effects, Mowery said there is also an unusual biological aspect to head and neck cancers which figures largely in her work. “Something very interesting scientifically drew me to these cancers,” she informed. “There are two main causes of cancer in this area: tobacco use and human papillomavirus (HPV). Outcomes for patients with HPV-positive oropharynx cancers are excellent; even when the cancer is locally advanced about 80-90 percent of patients are cured. But the tobacco-induced cancers, by contrast, do much worse (about 60% or less survival rate for locally advanced disease). Even if the tumor size is the same and the number of involved lymph nodes are the same, the biology is completely different for the HPV-related and the HPV-unrelated disease.”

In fact, the staging system was changed at the beginning of this year so that HPV-related cancers and HPV-negative cancers are staged differently. “HPV-positive cancers that used to be staged at IVA may now be staged at I or II, but they remain at stage IVA if the cancer is HPV-negative,” Mowery detailed.

Asked why tobacco-related cancer behaves so badly, Mowery answered, “We do not have a good understanding of that; it is something I am studying. We do know, however, that HPV-negative tumors exhibit a loss of function of the p53 gene, [which] is really the king of all tumor suppressors. In HPV-related tumors, p53 is usually genetically still intact but its activity is affected by HPV.”

She also commented that people still actively smoking during treatment tend to do much worse, likely due in part to having lower oxygen levels in the tumor, which in turn causes the radiation to work less effectively. “If we can figure out ways to make HPV-negative tumors behave more like HPV-positive tumors, outcomes would improve.”

From Clinic to Research
These realities on the clinical side have informed and inspired some of Mowery’s research efforts. One of her projects aims at reducing the toxicity of treatment while maintaining good outcomes in patients.

“A clinical trial that I am about to start will use PET/CT, a type of metabolic imaging, as an early litmus test to evaluate how patients are responding during treatment. If we find they are responding well, we will de-intensify and back off on the chemotherapy and radiation dose while still trying to achieve good outcomes,” Mowery explained.

She noted that because HPV-positive and HPV-negative cancers are still treated exactly the same way when not on a clinical trial, investigators also hope to find out if treatment can be de-intensified for the HPV-positive patients who tend to have more successful outcomes by virtue of their cancer type, thus allowing them to avoid some of the severe side effects.

“Of course, even in HPV-positive cancers, not every patient is cured,” cautioned Mowery, “so we want to see if we can identify, early on, who is going to do well and who, in contrast, still needs that full 7-week intensive course of radiation therapy and chemotherapy.”

Another clinical trial ongoing at Duke in which Mowery is involved is testing a drug called BMX-001 given to patients through a subcutaneous injection during radiation. “We hope the drug will reduce the—the inflammation and irritation of the lining of the mouth and throat during radiation—and dry mouth,” she said.

Mowery is also busy in lab with intensive work in developing new mouse models of both HPV-related and HPV-unrelated squamous cell carcinoma of the head and neck. “My objective is to develop a platform in which I can develop radiation with immunotherapy, as well as with chemotherapy and various novel systemic agents, to try to improve outcomes particularly for HPV-negative disease,” noted Mowery, also the winner of a 2017 Conquer Cancer Young Investigator Award. “I want to discover if there are ways that we can make our bodies and our immune system realize that these cells are not ‘self’ and activate the immune system to attack and eliminate them.”

Tobacco-related cancer is induced in mice by giving them a carcinogen present in tobacco, “… causing them to become like a tobacco chewer or smoker,” Mowery explained. “Having that exposure causes mutations in cells in the lining of their mouth.”

Mowery further said her research is taking advantage of large sequencing projects in which various head and neck tumors have been sequenced. These data are publicly available and published primarily by The Cancer Genome Atlas organization. “I have been able to see which genes are most commonly mutated and then can genetically engineer mice to have those mutations. In other words, I can specifically knock out certain genes in the head and neck to model the cancer in mice.”

This is extremely important because it allows Mowery and team to interrogate the biology of the mutations, and determine which genetic changes and pathways lead to the cancer spreading from its site of origin to the lymph nodes or the lungs. “It helps us to develop therapies to block the cancer and keep it at bay, and to determine if there are better ways to sensitize the cancer to radiation and chemotherapy,” she detailed. “And we have an opportunity to test drugs that we hope will help with side effects of radiation. We must make sure that drugs protecting normal tissue are not also protecting the tumor. Having great animal models of human cancer is really important to making progress.”

As if her work in head and neck cancer were not enough, Mowery is continuing an earlier effort begun in the lab of her research mentor David G. Kirsch, MD, PhD, by acting as radiation oncology principal investigator for a multi-site, international prospective randomized clinical trial investigating the combination of the immune checkpoint inhibitor pembrolizumab (anti-PD-1 antibody) and radiation therapy for patients with high-risk soft tissue sarcoma of the extremities. The researchers are also examining the biology behind the effects of radiation combined with pembrolizumab in a co-clinical trial using primary mouse models of sarcoma.

“We saw promising results combining them in this model. Our hope is by using this combination during the early stage of disease we may be able to eliminate those cells that have escaped the primary tumor before they cause a problem.”

Who Has Time for Hobbies?
Asked about her life outside of the clinic and lab, Mowery admitted that little time is left for hobbies. “I used to play tennis, but now I just enjoy watching it,” she said through a chuckle. “I splurged on a Labor Day vacation to the U.S. Open in New York. In my off time, I mostly read and spend time with my family. I am married; my wife is a nurse at Duke working in bone marrow transplant. We have no children.”

But the couple does have the patter of little feet in their midst. “We have two small dogs, Heidi and Cassie, a Maltese and a Maltese Shih Tzu mix—both less than 10 lbs.,” Mowery offered. “We live in downtown Durham, N.C., which is a burgeoning area. It’s kind of cool, and a little bit grungy—but in a good way. I love going for walks and checking out new restaurants. And I love food,” she added brightly.

After a brief pause, Mowery turned her thoughts again to patients. “There is one other clinical trial we’ve recently opened in the head and neck space. We are looking at financial toxicity of patients,” she said. “We are very concerned about the bills patients incur for cancer care and how that affects their quality of life.

“Unfortunately, some people just can’t afford to fill their whole prescription. Some take their drugs every other day because they are worried about cost. Some patients just do not follow through on therapy. We need to get a better sense of how much of that is going on and if there are early warning signs we can detect allowing us to intervene.”

Mowery added that better communications between health care providers and patients are needed to help patients better understand costs they face and identify resources that can help them.

“We just opened this survey-based pilot trial in June. We hope to have data next year and be able to develop a follow-up plan to employ the strategies that we find,” said Mowery. “There are a lot of ways we can try to help our patients.”

November, 2018|Oral Cancer News|

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

October, 2018|Oral Cancer News|

Why oral cancer threatens men

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

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

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

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

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

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

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

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

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

October, 2018|Oral Cancer News|

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

Source: www.cancertherapyadvisor.com
Author: Bryant Furlow

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

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

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

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

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

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

HPV vaccination rates are improving, Dr Ramondetta noted.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

October, 2018|Oral Cancer News|

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.

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.

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.”

October, 2018|Oral Cancer News|

HPV-related cancer rates outpace vaccinations

Source: www.ctpost.com
Author: Cara Rosner, Conn. Health

Cancers linked to the human papillomavirus, commonly called HPV, rose dramatically in a 15-year period, even as the rates of young people being vaccinated climbed, the Centers for Disease Control and Prevention reported.

The 43,371 new cases of HPV-associated cancers reported nationwide in 2015 marked a 44 percent jump from the 30,115 cases reported in 1999, according to a CDC analysis. HPV vaccination rates have improved over the years, but not fast enough to stem the rise in cancers, the CDC said.

Oropharyngeal, or throat, cancer was the most common HPV-associated cancer in 2015, accounting for 15,479 cases among males and 3,438 among females. HPV infects about 14 million people each year. Between 1999 and 2015 rates of throat and vulvar cancer increased, vaginal and cervical cancer rates declined, and penile cancer rates were stable, according to the CDC.

“The (overall rise) seems to be mostly driven by oropharyngeal cancers,” said Dr. Sangini Sheth, assistant professor of obstetrics, gynecology and reproductive sciences at Yale School of Medicine.

“Vaccination is key to preventing those cancers,” said Sheth, who also is an associate medical director and director of colposcopy and cervical dysplasia at Yale New Haven Hospital’s Women’s Center. “Oropharyngeal cancer is most common in men, and HPV vaccination rates, while they are rising in the U.S. and Connecticut, became routine for boys later (than girls). And the rate of vaccinations among boys has definitely lagged that of girls. Hopefully, we will see vaccinating our boys have an impact on oropharyngeal cancer, but that’s going to take time.”

The push to vaccinate adolescents against HPV is a relatively recent development. The vaccination was included in the routine immunization program for females in 2006 and for males in 2011, according to the CDC.

At one time, the HPV-vaccine was viewed largely to prevent sexually transmitted diseases, and some parents “resented” it and thought it was unnecessary for their children, according to Dr. Richard Brauer, section head of otolaryngology at Greenwich Hospital. Now it’s marketed as a cancer vaccine and parents have become more receptive, said Brauer, who also has a private practice, Associates of Otolaryngology, in Greenwich.

In 2017, 65.5 percent of adolescents aged 13 to 17 nationwide had at least one dose of the HPV vaccine, up 5.1 percentage points from 2016, according to CDC data released in August.

In Connecticut, 75.4 percent of girls aged 13 to 17 had one dose of the vaccine, 67.1 percent had two doses and 58.4 received three doses. Among males, 67.3 percent received one dose, 58.8 percent got two and 37.8 percent got three, the 2017 data show. But even amid overall gains, hurdles remain. Gender disparity persists, and many teens received the first vaccine dose but failed to get necessary subsequent doses.

Children who are 11 or 12 years old should get two shots of HPV vaccine six to 12 months apart, according to the CDC. Adolescents who get their shots less than five months apart need a third dose of the vaccine, as do all children older than 14. Three doses also are recommended for people ages nine to 26 who have certain immunocompromised conditions.

“It falls on the parent” whether children get vaccinated, said Dr. Bradford Whitcomb, chief of gynecologic oncology at UConn Health. “People associate HPV with female stuff. It needs to be pushed that we’re not just preventing female cancers.”

While it’s encouraging that vaccination rates are climbing, “we just may not see the benefit of that for years to come,” Whitcomb said. “It’s going to take a longer time, especially with the development of cancer, to see the effect. After the HPV infection, it can take years for a cancer to develop.”

Many people exposed to HPV will never get cancer, doctors said. The most common HPV-associated cancer among women is cervical cancer. Data show rates of that cancer are falling, but there are racial disparities.

Between 2011 and 2015, Hispanic women had the highest incidence rates of cervical cancer at 8.9 percent, according to an analysis by the Kaiser Family Foundation. That compares with 8.4 percent among black women, 7.4 percent among white women and 6.1 percent among Asian and Pacific Islander women.

Cervical cancer mortality rates also showed racial disparities during that time. Black women had the highest mortality rate at 3.7 percent, compared with 2.6 percent among Hispanics, 2.2 percent among whites and 1.8 percent among Asians and Pacific Islanders, data show.

It is crucial for doctors to talk to young patients and their parents about the HPV vaccine, even if it spurs conversations parents may feel awkward having, Sheth said.

“Clinicians need to feel comfortable normalizing the HPV vaccine and really present the HPV vaccine as a cancer prevention tool,” she said.

Note:
This story was reported under a partnership with the Connecticut Health I-Team, a nonprofit news organization dedicated to health reporting. (c-hit.org)

September, 2018|Oral Cancer News|

E-cigarettes and smokeless tobacco can put you at a greater risk of oral cancer, says study

Source: www.thehealthsite.com
Author: Sreemoyee Chatterjee

Not just cigarette smokers, those smoking e-cigarettes as well as consuming smokeless tobacco like chewing tobacco and more are at greater risk of developing oral cancer, shows a recent study conducted by University of California.

In case you think only cigarette smokers are at a higher risk of getting oral cancer, you are widely mistaken. A recent study has found that a wide majority of non-cigarette tobacco users as well those using electronic cigarettes are exposed to considerable level of carcinogen, as much as a cigarette user is exposed to. Not just that, shockingly smokeless tobacco users were found at a greater exposure to tobacco-specific nitrosamines (TSNA). The study has been conducted by the scholars from University of California, San Francisco.

Starting from cigarettes to cigar, waterpipes, pipes, marijuana containing cigar to smokeless products like moist snuff, chewing tobacco, e-cigarettes, snus and other nicotine replacement products can increase your chance of getting oral cancer, revealed the study.

What is Oral cancer?
Belonging to the head and neck cancer group, oral cancer is a type of cancer that grows in mouth or throat tissues and mostly hit the squamous cells of your mouth, tongue and lips. Oral cancer can of several types – lip cancer, tongue cancer, cancer in the inner lining of your cheek, gums, floor of the mouth and hard and soft palate. It is important to go to a dentist for a biannual check-up for early detection of oral cancer, experts say. Due to lack of awareness and adequate check-ups, oral cancer gets detected only after they spread to the lymph nodes of the neck.

The other risk factors
Apart from tobacco consumption, both smoke and smokeless and excessive alcohol consumption, there are several other risk factors that can put you to greater risk of developing oral cancer. Human papillomavirus (HPV) infection, chronic facial exposure to sun, a former diagnosis of oral cancer, a family history of oral or any other types of cancer, a depleted body immune system, inadequate nutrition, genetic syndromes are other risk factors for oral cancer. Shockingly, being male is another potent risk factor as studies have found males to be at a higher risk of developing oral cancer, twice as likely compared to women.