human papillomavirus

Which HPV vaccination schedule is best: 1, 2 or 3 doses?

Source: www.precisionvaccinations.com
Author: Don Ward Hackett

A new cervical cancer prevention study of women first offered Human Papillomavirus (HPV) vaccine found that 1-dose of quadrivalent HPV vaccine was as effective as 3-doses at preventing histologically confirmed, high–grade cervical lesions.

This Australian study’s finding published online on July 15, 2019, supports the hypothesis that the 1-dose HPV vaccination schedule may be a viable strategy when working towards the global elimination of cervical cancer.

These researchers said ‘If one dose could prevent precancerous cervical lesions, then global cervical cancer prevention would be greatly facilitated.’

This is an important goal since about 90 percent of cervical cancer cases are caused by HPV. This study included 250,648 women in Australia with 19.5 percent unvaccinated, 69.8 percent had received 3-doses, 7.3 percent 2-doses, and 3.4 percent just 1-dose of the HPV vaccine.

This study’s limitations include some degree of under–linkage and inaccurate data linkage because Australia does not have a unique national identifier, which impacts the classifications of vaccinated women as unvaccinated.

Additionally, these researchers said ‘we believe that these data support decision-makers to consider how a 1-dose HPV vaccination schedule, or a planned schedule with a 3–5 year interval between doses, could reduce vaccine demand globally, which currently exceeds vaccine supply.’

But the Gardasil 9 vaccine manufacturer appears to be resolving this supply/demand imbalance. During July 2019, Merck said it is spending $1.68 billion, opening 2 new Gardasil production plants, and adding 525 related jobs.

To clarify the Gardasil 9 vaccine dosing schedule, the Centers for Disease Control and Prevention (CDC) publish the following information:

Who should still receive a 3-dose schedule?
The CDC continues to recommend a 3-dose schedule for persons starting the HPV vaccination series on or after the 15th birthday, and for persons with certain immunocompromising conditions. The 2nd vaccine dose should be given 1–2 months after the 1st dose, and the 3rd dose, should be given 6 months after the first dose.

Who should receive just 2-doses?
Two doses of the HPV vaccine are recommended for all boys and girls at ages 11-12; the vaccine can be given as early as age 9. If you wait until they’re older, they may need three doses instead of two.

In the USA, HPV vaccines have been licensed for use among women since 2006 and among men since 2010.

HPV infections are so common that nearly all men and women will get at least one type of HPV at some point in their lives. Nearly 80 million Americans are currently infected with some type of HPV, says the CDC. About 14 million Americans, including teens, become infected each year. HPV is spread through intimate skin-to-skin contact. You can get HPV by having vaginal, anal, or oral sex with someone who has the virus.

Cervical cancer is the only type of HPV cancer with a recommended screening test. The other types of HPV cancer may not be detected until they cause health problems. HPV vaccination helps prevent these cancers by preventing infections that cause these cancers, says the CDC. HPV vaccines, like any medicine, can cause side effects, which you are encouraged to report to the CDC or a healthcare provider.

August, 2019|Oral Cancer News|

Updated HPV vaccine recommendations follow big HPV infection drops shown in new study

Source: www.forbes.com
Author: Tara Haelle

A vial of the human papillomavirus (HPV) vaccine Gardasil. (AP Photo/Charles Rex Arbogast)

Adults up to age 45 are now recommended to discuss with their doctors getting the human papillomavirus (HPV) vaccine, which prevents 3% of all cancer in women and 2% of all cancer in men—an estimated 34,000 cancers a year in the U.S. Following confirmation from the director of the Centers for Disease Control and Prevention (CDC), the recommendations also extend the age in men from age 21 to age 26, the same as in women.

The decision from the CDC’s Advisory Committee on Immunization Practices (ACIP) July 26 came the same day The Lancet published the largest study to date on the vaccine’s effectiveness. The meta-analysis of 65 studies found drops of 31%-83% of HPV infections and genital warts in men and women, depending on age and diagnosis.

HPV is responsible for nearly all cervical cancer, over 90% of anal cancer, 70% of oral, throat and neck cancers and over 60% of penile cancer. Though HPV is primarily transmitted through sexual contact, non-sexual transmission occurs as well.

Previously, the HPV vaccine had been recommended for females and males in a series of two doses up to age 14 or three doses up to age 26 in women and age 21 in men. Men ages 22-26 could also get the vaccine.

ACIP’s unanimous vote to extend the recommendation to age 26 in men corresponds to evidence showing the vaccine’s substantial benefits for men. In fact, research shows men to be up to six times more likely than women to develop an oral infection with the highest risk strain of HPV.

ACIP’s 10-4 vote regarding adults ages 27-45 who haven’t received the HPV vaccine emphasizes shared decision-making with their providers. The HPV vaccine is not licensed by the FDA for adults older than 45 since data on its effectiveness does not exist for this age group.

The “decision from ACIP emphasizes what the data has shown—that the HPV vaccine is safe and effective for use in patients ages 27 to 45, and that use of the vaccine in this age group should be the result of shared decision-making between patients and their trusted physicians,” Christopher M. Zahn, M.D., vice president of Practice Activities at the American College of Obstetricians and Gynecologists (ACOG) said in a statement.

“Obstetrician-gynecologists are encouraged to discuss with their patients ages 27 to 45 the potential benefits of HPV vaccination, addressing the reduced efficacy compared to vaccination within the younger target age range as well as the reduced risk of high-grade disease and cervical cancer,” Zahn said, adding getting the vaccine at the recommended age of 11-12 years offers the most benefit.

“Women’s decisions will also likely consider their individual circumstances, preferences, and concerns, and the role of the obstetrician-gynecologist is to provide unbiased information in a balanced, thorough way in order to aid that decision-making,” he said.

New research finds big drops in HPV-related infections

The new study found that HPV infections with strains 16 and 18 dropped 83% among girls ages 13-19 and by 66% among women ages 20-24 up to eight years after vaccination.

The HPV 16 and 18 strains in Gardasil cause 70 percent of all cervical, vaginal, vulvar and anal cancers. Gardasil 9 also protects against HPV 6 and 11, which cause 90% of genital warts, and against five other strains (31, 33, 45, 52, and 58). Together, the strains in Gardasil 9 represent 90% of HPV-related cancers.

HPV infections caused by HPV 21, 33 and 45 cut in half (54%) among vaccinated girls ages 15-19, according to the new research. Similarly, genital warts diagnoses fell by 67% in these girls and by 48% in boys of the same age. Older men (up to 24) and women (up to 29) also saw declines in genital warts by 31%-54%.

Rates of grade 2 cervical neoplasia, a precursor to cancer, also dropped by half (51%) in screened girls 15-19 and by 31% in women 20-24 years.

Cervical cancer can take up to 20 years to develop, so the vaccine, first approved in 2006, has not been available long enough for a sizable evidence base showing a reduction in cancer incidence. Dramatic declines in HPV infection rates, however, are expected to translate to similar declines in HPV-caused cancer rates, and immunity from the vaccine is long-lasting.

Multiple large reviews of the HPV vaccine have found it to be among the safest vaccines available. While the actual shot itself can be particularly painful, the only regularly reported side effects are pain, redness and soreness at the injection site and, in some teens, temporary fainting, which is common with many vaccines in adolescents. Among 13,000 people in the clinical trials for Gardasil 9, five people also reported fever, allergy to the vaccine, asthmatic crisis, headache and tonsillitis, though not all of these were determined to be caused by the vaccine.

The most effective way to reduce cervical cancer has been and remains regular screenings. However, screenings only detect early development of abnormal tissue that could become cancerous whereas the HPV vaccine prevents the viral infections that leads to those tissue abnormalities in the first place.

Since there is no current way to screen for throat/mouth/neck or anal cancer in women or men (or penile cancer in men), the HPV vaccine remains the only way to prevent those cancers.

Twitter lends insight to HPV-associated oral cancer knowledge

Source: www.oncnursingnews.com
Author: Brielle Benyon

The incidence of human papillomavirus (HPV)-associated oral cancer has risen in recent years, and the virus has now surpassed tobacco and alcohol use as the leading cause of the disease. In fact, while the HPV vaccine is typically associated with preventing cervical cancer, there have been more cases of HPV-associated oral cancer than there have been cervical cancer.1

While the link between oral cancer and HPV may be well-known to healthcare professionals, researchers at Howard University recently took to Twitter to get a glimpse into the public’s knowledge about the topic.

“By looking at the social media data, we wanted to know what people are hearing about oral cancer – especially HPV-caused oral cancer,” study co-author Jae Eun Chung, PhD, associate professor in the Department of Strategic, Legal & Management Communication at Howard University, said. “We wanted to see what the gaps are between the knowledge of the healthcare professionals and the public.”

The researchers collected 3,229 unique tweets over the course of 40 weeks using search terms such as “HPV or papilloma” and “mouth or oral or throat or pharyngeal or oropharyngeal.” They then used a program called nVivo 12.0 to conduct a content analysis that looked at certain phrasing, terms, and themes that commonly appeared.

More than half (54%; 1679 total) of the tweets had information about prevention, while 29% (910) were about the causes of oral cancer. Far fewer tweets were about treatment (5%; 141), diagnosis (3%; 97), symptoms (1%; 42), and prognosis (1%; 25).

Interestingly, the researcher discovered a prominence on the risk of HPV-associated oral cancer in men, with tweets that referred to males outnumbering tweets that referred to females in a 3:1 ratio. Also, the most popular hashtag used in the dataset was #jabsfortheboys, appearing in 89 tweets.

“There was a heavy emphasis on the risk of HPV-associated (oropharyngeal cancer) among men, which is different than what we see with HPV vaccination among girls,” Chung said. “That was very positive news to us, because HPV-associated (oral cancer) rates are higher among the male population and HPV vaccination rates are higher among girls.”

While spreading HPV vaccination and oral cancer is important on a global scale, the United States might have some catching up to do, as the 5 most mentioned Twitter users discussing the topic were located outside of the US–1 in New Zealand, 2 in Australia, and 2 in the United Kingdom.

“That’s kind of sad, because there are more Twitter users from the United States than from any other country,” Chung said.

Ultimately, Chung explained, these findings outlined an area where the country can benefit from more education and social media campaigns.

“In conclusion, this study provides some insight as to how the public makes sense of HPV-associated oral cancer,” she said. “More education and campaigns are needed, and US residents can benefit from more active involvement of US-based health education.”

Reference
1. Chung JE, Mustapha I, Gu X, Li J. Understanding public perception about human papillomavirus (HPV)-associated oropharyngeal cancer (OPC) through Twitter. Presented at: D.C. Health Communication Conference; Fairfax, Virginia; April 26-27, 2019.

April is Oral Cancer Awareness Month: Self-exams, early detection can save lives

Source: www.prnewswire.com
Author: press release

Because early detection of oral cancer offers a greater chance of a cure, the American Association of Oral and Maxillofacial Surgeons (AAOMS) is reminding the public during Oral Cancer Awareness Month of the importance of performing monthly self-exams.

AAOMS promotes self-exams and screenings every April with the Oral Cancer Foundation, which predicts about 53,000 new cases of oral cancer will be diagnosed in 2019 in the United States – leading to more than 9,000 deaths.

“A monthly self-exam takes only minutes and could potentially save your life,” said AAOMS President A. Thomas Indresano, DMD, FACS. “If done on a regular basis, you’re increasing the chances of identifying changes or new growths early. The survival rate for oral cancer is between 80 and 90 percent when it’s found at early stages of development.”

Oral and maxillofacial surgeons (OMSs) encourage a six-step oral cancer self-exam that involves looking and feeling inside the mouth for suspicious sores and feeling the jaw and neck for lumps. Using a bright light and a mirror:

  1. First remove any dentures.
  2. Look and feel inside the lips and the front of the gums.
  3. Tilt the head back to inspect and feel the roof of the mouth.
  4. Pull the cheek out to inspect it and the gums in the back.
  5. Pull out the tongue and look at its top and bottom.
  6. Feel for lumps or enlarged lymph nodes in both sides of the neck, including under the lower jaws.

Oral cancer symptoms may include one or more of the following if they are persistent and not resolving:

  • Red, white or black patches in the soft tissue of the mouth.
  • A sore in the mouth that fails to heal within two weeks and bleeds easily.
  • An abnormal lump or hard spot in the mouth.
  • A painless, firm, fixated mass or lump felt on the outside of the neck that has been present for at least two weeks.
  • Difficulty in swallowing, including a feeling food is caught in the throat.
  • Chronic sore throat, hoarseness or coughing.
  • A chronic earache on one side.

The risk factors for oral cancer include smoking and tobacco use, alcohol consumption and the human papillomavirus (HPV).

“About 25 percent of oral cancer patients have no known risk factors,” Dr. Indresano said. “It’s important that everyone perform a monthly self-exam. And if you have any of the symptoms for more than two weeks, promptly contact an oral and maxillofacial surgeon. OMSs are experts in diagnosing and surgically treating oral cancer.”

April, 2019|Oral Cancer News|

Flossing and going to the dentist linked to lower risk of oral cancer

Source: www.livescience.com
Author: Yasemin Saplakoglu, Staff Writer

Regularly flossing and going to the dentist may be tied to a lower risk of oral cancer.

That’s according to findings presented March 31, here at the American Association for Cancer Research (AACR) annual meeting.

In the new study, researchers analyzed the dental health behaviors of patients who were diagnosed with oral cancer between 2011 and 2014 at the ear, nose and throat clinic at The Ohio State University Comprehensive Cancer Center. The patients’ behaviors were compared to those of non-cancer patients who came to the clinic for other reasons, such as dizziness or an earache. [7 Odd Things That Raise Your Risk of Cancer (and 1 That Doesn’t)]

All of the patients in the study had responded to a survey that included questions about how often they flossed, how often they went to the dentist, how sexually active they were and if they smoked or drank alcohol.

Oral cancer can be divided into two categories: those driven by the sexually transmitted human papillomavirus (HPV) and those that aren’t, said lead study author Jitesh Shewale, a postdoctoral fellow at the University of Texas MD Anderson Cancer Center in Houston. (Smoking and drinking are both risk factors for non-HPV oral cancers.)

After adjusting for factors such as age, gender, socioeconomic status and race, the researchers found that oral HPV-negative people who went to the dentist less than once a year had nearly twice the risk of developing oral cancer than those who went once a year or more. Similarly, oral HPV-negative people who flossed less than once a day had over twice the risk than those who flossed more. In other words, poor oral hygiene was linked to increased non-HPV oral cancer risk.

The study didn’t find an association between poor dental hygiene and oral cancer in those who also had oral HPV, however.

The researchers hypothesize that the oral microbiome may play a role in the association between oral hygiene and cancer risk. In previous research, scientists from the same team found evidence that “poor oral hygiene practices causes a shift in your oral microbiome,” Shewale told Live Science. That shift “promotes chronic inflammation and [can lead to] the development of cancers.” HPV-positive oral cancers mostly affect the base of the tongue and the tonsils region, while HPV-negative cancers mostly affect oral cavities, which are more affected by oral hygiene, he added.

Denise Laronde, an associate professor in dentistry at the University of British Columbia who was not a part of the study, said that the new research was “interesting” but added that it was too early to draw conclusions. (The study found an association between oral hygiene and cancer risk, but did not show cause-and-effect.)

Still, “a lot of the times people look at their oral health as almost disconnected from the rest of their body,” Laronde told Live Science. “But so many systemic diseases are reflected in your oral health and vice versa.”

Laronde added that the new research will hopefully raise awareness about the importance of flossing. “We all know people say they floss way more than they do,” she said. But studies like this raise awareness that “you’re not just flossing to keep your teeth, you’re flossing to maintain your health.”

The findings have not yet been published in a peer-reviewed journal.

April, 2019|Oral Cancer News|

The epidemic of throat cancer sweeping the industrialized world

Source: www.mercurynews.com
Author: Dr. Bryan Fong

Tonsils – Angina Pectoris

Over the past three decades, a dramatic increase in a new form of throat cancer has been observed throughout the industrialized world. The good news is that it’s potentially preventable — if parents get their children vaccinated.

The disease shows up primarily in men, typically between the ages of 45 and 70. Those who are affected often lead healthy lifestyles. They do not have extensive histories of smoking tobacco or consuming alcohol, which are risk factors for traditional throat cancers.

The rate of this new cancer has been increasing 5 percent per year and today, it is more than three times as common as in the mid-1980s. If you think this scenario sounds like a slow-moving infectious medical drama (think Contagion or World War Z), you would be right.

The source of this cancer is a virus, the human papillomavirus (HPV) — the same virus that causes most cervical cancer in women. It’s widely known that parents should get their girls vaccinated. Now, with the surge in oral HPV cancers, especially in men, parents should get their boys vaccinated too.

Currently, vaccination against HPV is recommended by the Centers for Disease Control for children and young adults ages 9-26. The vaccination includes a series of two or three injections; the side effects are mild.

Ideally, the vaccinations should be administered before someone becomes sexually active. That’s because HPV is spread via sexual activity. Risk of HPV infection and throat cancer increases with the number of lifetime partners.

Men have a lower immune response to the virus than women, which explains the predilection of this disease for men. It’s difficult to know if someone has an active oral HPV infection because there are no symptoms. Currently, there is no widely accepted test for HPV in men.

Chronic infection leads to cellular changes within the lymphatic tissues in the throat, specifically the tonsils and base of tongue. Over the course of 20-30 years, these changes can result in the formation of cancer.

Throat cancer caused by HPV is insidious. The primary tumor in the tonsil or base of tongue often causes little to no symptoms. Early signs of this cancer may be a mild sore throat, occasional blood-tinged oral saliva, or increased or new snoring.

Often, the first sign of the cancer is a lump in the neck after the cancer has spread into the lymphatic system. The lump may arise quickly and then shrink to varying degrees, lulling one into complacency.

Early stage cancer can be treated with surgery or radiation. More advanced cancers are treated with combined therapy such as surgery followed by radiation therapy, or chemotherapy in conjunction with radiation therapy.

Finally, some good news. Treatment for HPV-related throat cancer is successful in about 90 percent of cases and is significantly more successful than treatment of non-HPV related throat cancer.

But, as successful as medicine has been in treating this cancer, an even better alternative is prevention via vaccination. Initial studies have shown that vaccination produces an immune response to HPV and reduces the rate of HPV infection. Given time and good vaccination coverage, a decline in throat cancer is expected.

In summary, here are a few simple take-home messages: If you have a lump in the neck or a chronic sore throat, don’t procrastinate. Have your doctor check it out. If you are a partner of someone with these symptoms, strongly encourage your partner to see his or her doctor.

If you have children ages 9-17, talk to your pediatrician about HPV vaccination. If you are 18-26 years old, talk to your primary care doctor about vaccination. These simple steps may save your life or the life of your loved one.

Note: Dr. Bryan Fong is the senior practicing head and neck surgical oncologist for Northern California Kaiser Permanente.

February, 2019|Oral Cancer News|

Why salivary diagnostics for dental practices?

Source: www.dentistryiq.com
Author: Barbara Kreuger, MA, RDH

I recently had the opportunity to visit OralDNA Labs and learn more about the process of running salivary diagnostic tests. Admittedly, when I first heard about salivary diagnostics, I didn’t immediately embrace the tests and what they had to offer. I was not convinced that they were necessary, believing they would not change how we treat dental disease.

However, we’ve been fortunate to use salivary diagnostics in practice and see the benefits in our patients firsthand. These tests have proven to be a great addition to our prevention tool box. Salivary diagnostics can play an important role in helping us produce high quality outcomes for patients and create awareness of their oral-systemic risk factors.

Bacterial identification
There are numerous salivary diagnostic tests available. The most widely used test from OralDNA Labs is MyPerioPath, which tests for the 11 pathogens that are known to contribute to periodontal destruction.(1) Once the test reveals which pathogens are contributing to the patient’s periodontal disease, it also offers antibiotic recommendations that target these specific bacteria.

When combined with periodontal maintenance visits and patient homecare, this test can lower a patient’s bacterial load, thus increasing positive outcomes. Retesting has shown that this reduction in bacteria can have a dramatic effect. We’ve seen tough cases—patients who were compliant with homecare but still exhibited clinical signs of periodontal disease—that improved dramatically after being treated with the test’s recommended systemic antibiotic. Periodic monitoring with MyPerioPath combined with periodontal maintenance treatment can help keep patients’ oral health stable.

Genetic predisposition
In addition to bacterial profile testing, various tests from OralDNA labs can tell us a patient’s genetic predisposition toward inflammation. This can reveal one of the reasons why some patients continue to experience periodontal destruction after treatment despite compliance and lower quantities of periodontal pathogens. In addition, much of the research connecting oral health to systemic conditions reveals that it is a patient’s total inflammatory burden that puts someone at risk for a host of health problems.(2,3)

While the patient’s genetic profile cannot be changed, the knowledge that the person has an overactive inflammatory response can help the practitioner and patient understand that there is a need for more frequent continuing care, adjunctive therapies, or treatment with a periodontist. This information can also help patients manage and control their systemic health with the help of their physician.

Caries risk assessment
When we look beyond the patient’s periodontal health, salivary diagnostics can also test for the bacteria that are known to contribute to caries. When we have an objective measure of the quantity and types of cariogenic bacteria in the patient’s mouth, we can once again tailor treatments to reduce his or her caries risk and motivate the patient toward behavioral change. If we then combine the test with a caries risk assessment tool, we can use the test to monitor the effectiveness of these behavior changes. Knowing the patient’s risk allows us to encourage the person to use interventions, such as fluoride to re-mineralize teeth and xylitol to inhibit the bacterial metabolism.

Oral cancer screening
Finally, salivary diagnostics can also test for the presence of various human papillomavirus (HPV) strains that have been shown to cause oral cancer. According to the American Cancer Society, oral cancer will take the lives of 10,860 people this year, and HPV is now seen as the leading cause.(4,5) Early diagnosis is key and increases survival from a dismal 20% when discovered after it has metastasized to distant sites, to 93% when discovered early.(6)

Knowing a patient’s HPV status may prompt us to increase the frequency of someone’s oral cancer screenings, or to use adjunctive diagnostic tools such as oral anomaly detection devices to more closely monitor the patient and potentially catch the cancer at an earlier stage.

More and more research studies are correlating the various bacteria that cause periodontal disease to systemic conditions. The more we understand about a patient’s bacterial load and risk factors, the better equipped we can be to help manage periodontal disease and improve overall health. Salivary diagnostics can help us provide optimal care for patients, increasing our ability to provide them with positive outcomes through tailored treatment and patient education.

Barbara Kreuger, MA, RDH, earned a Bachelor of Science in dental hygiene from the University of Minnesota and holds a Master of Arts in organizational leadership from St. Mary’s University of Minnesota. She spent more than 18 years as a clinical dental hygienist before moving to her current role as dental hygiene senior specialist for Pacific Dental Services. Barbara is currently serving as president of the Minnesota Dental Hygienists’ Association.

References

1. Oral DNA tests. OralDNA website. https://www.oraldna.com/tests.html. Accessed February 1, 2019.
2. Hunter P. The inflammation theory of disease. The growing realization that chronic inflammation is crucial in many diseases opens new avenues for treatment. EMBO Rep. 2012;13(11):968-70.
3. Minihane AM, et al. Low-grade inflammation, diet composition and health: current research evidence and its translation. Brit Jour Nutrition. 2015;114(7):999–1012.
4. Key Statistics for Oral Cavity and Oropharyngeal Cancers. American Cancer Society website. https://www.cancer.org/cancer/oral-cavity-and-oropharyngeal-cancer/about/key-statistics.html. Accessed February 1, 2019.
5. HPV/Oral Cancer Facts. Oral Cancer Foundation website. https://oralcancerfoundation.org/understanding/hpv/hpv-oral-cancer-facts/. Accessed February 1, 2019.
6. Survival Rates for Oral Cavity and Oropharyngeal Cancer. American Cancer Society website. https://www.cancer.org/cancer/oral-cavity-and-oropharyngeal-cancer/detection-diagnosis-staging/survival-rates.html. Accessed February 1, 2019.

February, 2019|Oral Cancer News|

HPV discovery raises hope for new cervical cancer treatments

Source: www.eurekalert.org
Author: press release – University of Virginia Health Syste

Researchers at the University of Virginia School of Medicine have made a discovery about human papillomavirus (HPV) that could lead to new treatments for cervical cancer and other cancers caused by the virus.

HPV is responsible for nearly all cases of cervical cancer and 95 percent of anal cancers. It is the most common sexually transmitted disease, infecting more than 79 million Americans. Most have no idea that are infected or that they could be spreading it.

“Human papillomavirus causes a lot of cancers. Literally thousands upon thousands of people get cervical cancer and die from it all over the world. Cancers of the mouth and anal cancers are also caused by human papillomaviruses,” said UVA researcher Anindya Dutta, PhD, of the UVA Cancer Center. “Now there’s a vaccine for HPV, so we’re hopeful the incidences will decrease. But that vaccine is not available all around the world, and because of religious sensitivity, not everybody is taking it. The vaccine is expensive, so I think the human papillomavirus cancers are here to stay. They’re not going to disappear. So we need new therapies.”

HPV and Cancer
HPV has been a stubborn foe for scientists, even though researchers have a solid grasp of how it causes cancer: by producing proteins that shut down healthy cells’ natural ability to prevent tumors. Blocking one of those proteins, called oncoprotein E6, seemed like an obvious solution, but decades of attempts to do so have proved unsuccessful.

Dutta and his colleagues, however, have found a new way forward. They have determined that the virus takes the help of a protein present in our cells, an enzyme called USP46, which becomes essential for HPV-induced tumor formation and growth. And USP46 enzyme promises to be very susceptible to drugs. Dutta calls it “eminently druggable.”

“It’s an enzyme, and because it’s an enzyme, it has a small pocket essential for its activity, and because drug companies are very good at producing small chemicals that will jam that pocket and make enzymes like USP46 inactive,” said Dutta, chairman of UVA’s Department of Biochemistry and Molecular Genetics. “So we are very excited by this possibility that by inactivating USP46 we’ll have a way to treat HPV-caused cancers.”

Curiously, HPV uses USP46 for an activity that is opposite to what the oncoprotein E6 was known to do. E6 has been known for more than two decades to recruit another cellular enzyme to degrade the cell’s tumor suppressor, while Dutta’s new finding shows that E6 uses USP46 to stabilize other cellular proteins and prevent them from being degraded. Both activities of E6 are critical to the growth of cancer.

The researchers note that enzyme USP46 is specific to HPV strains that cause cancer. It is not used by other strains of HPV that do not cause cancer, they report.

Notes:
(1) The researchers have published their findings in the scientific journal Molecular Cell. The team included Shashi Kiran, Ashraf Dar, Samarendra K. Singh, Kyung Yong Lee and Dutta. All are from UVA’s Department of Biochemistry and Molecular Genetics.

(2)The work was supported by the National Institutes of Health, grant R01 GM084465.

December, 2018|Oral Cancer News|

Standard chemotherapy treatment for HPV-positive throat cancer remains the most effective, study finds

Source: www.eurekalert.org
Author: press release, University of Birmingham

A new study funded by Cancer Research UK and led by the University of Birmingham has found that the standard chemotherapy used to treat a specific type of throat cancer remains the most effective.

The findings of the trial, which aimed to compare for the first time the outcomes of using two different kinds of treatment for patients with Human papillomavirus (HPV)-positive throat cancer, are published today (November 15th) in The Lancet.

Throat cancer is one of the fastest rising cancers in Western countries. In the UK, incidence was unchanged between 1970 and 1995, then doubled between 1996 and 2006, and doubled again between 2006 and 2010. The rise has been attributed to HPV, which is often a sexually transmitted infection. Most throat cancers were previously caused by smoking and alcohol and affected 65 to 70 year old working class men. Today, HPV is the main cause of throat cancer and patients are middle class, working, have young children and are aged around 55.

HPV-positive throat cancer responds well to a combination of cisplatin chemotherapy and radiotherapy, and patients can survive for 30 to 40 years, but the treatment causes lifelong side effects including dry mouth, difficulty swallowing, and loss of taste.

The De-ESCALaTE HPV study, which was sponsored by the University of Warwick, compared the side effects and survival of 164 patients who were treated with radiotherapy and cisplatin, and 162 who were given radiotherapy and cetuximab. The patients were enrolled between 2012 and 2016 at 32 centres in the UK, Ireland, and the Netherlands. Patients were randomly allocated to be treated with radiotherapy and either cisplatin or cetuximab. Eight in ten patients were male and the average age was 57 years.

Importantly, the results found that there was very little difference between the two drugs in terms of toxicity in patients and side effects such as dry mouth, however, there was a significant difference in the survival rates and recurrences of cancer in patients taking part in the trial.

They found that the patients who received the current standard chemotherapy cisplatin had a significantly higher two-year overall survival rate (97.5%) than those on cetuximab (89.4%). During the six-year study, there were 29 recurrences and 20 deaths with cetuximab, compared to 10 recurrences of cancer and six deaths in patients who were treated with the current standard chemotherapy cisplatin.

And cancer was three times more likely to recur in two years following treatment with cetuximab compared to cisplatin, with recurrence rates of 16.1 per cent versus six per cent, respectively.

Study lead Professor Hisham Mehanna, Director of the University of Birmingham’s Institute of Head and Neck Studies and Education, said: “Many patients have been receiving cetuximab with radiotherapy on the assumption that it was as effective as cisplatin chemotherapy with radiotherapy and caused fewer side effects but there has been no head-to-head comparison of the two treatments.

“Cetuximab did not cause less toxicity and resulted in worse overall survival and more cancer recurrence than cisplatin.

“This was a surprise – we thought it would lead to the same survival rates but better toxicity. Patients with throat cancer who are HPV positive should be given cisplatin, and not cetuximab, where possible.”

Dr Emma King, Cancer Research UK Associate Professor in head and neck surgery at the University of Southampton, said: “Studies like this are essential for us to optimise treatments for patients. We now know that for HPV-positive throat cancer, the standard chemotherapy treatment remains the most effective option.

“However, we must keep testing new alternatives to ensure patients always have access to cutting-edge and kinder treatments. Chemotherapy and radiotherapy can leave head and neck cancer patients with long term pain and difficulties swallowing, so we should always strive to minimise side effects.”

Professor Janet Dunn from the University of Warwick, whose team ran the De-ESCALaTE HPV trial, said: “In the current trend for de-escalation of treatment, the results of the De-ESCALaTE HPV trial are very important as they were not as we expected. They do highlight the need for academic clinical trials and are an acknowledgement of the key role played by Warwick Clinical Trials Unit at the University of Warwick as the co-ordination and analysis centre for this important international trial.”

The patients on the De-ESCALaTE trial Steering Committee endorsed the importance of research findings.

Malcom Babb, who is also President of the National Association of Laryngectomee Clubs, said: “From a patient perspective, De-ESCALaTE has been a success by providing definitive information about the comparative effectiveness of treatment choices.”

November, 2018|Oral Cancer News|

Cultural barriers still stand in the way of HPV vaccine uptake

Source: arstechnica.com
Author: Cathleen O’Grady

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

November, 2018|Oral Cancer News|