vaccine

Health department official on HPV vaccine: “What are we waiting for?”

Source: www.mynews13.com
Author: Rebecca Turco

Despite studies from the CDC showing the effectiveness of the HPV vaccine at preventing certain types of cancer, some parents are still hesitant to get their children vaccinated.

  • 92% of almost 35,000 cancers could be prevented by vaccine
  • Doctor: Some parents may think vaccine promotes sexual behavior
  • County Health Departments offer HPV vaccine for free

Dr. Raul Pino, the interim administrator of the Orange County Health Department, wants to change that.

Among the estimated 34,800 cancers probably caused by the human papilloma virus between 2012 and 2016, an estimated 92% could be prevented by the vaccine, according to the Centers for Disease Control and Prevention.

“We have a vaccine that prevents some type of cancers, and now we’re questioning if we should take the vaccine,” he said. “It will not only prevent penile cancer or vaginal cancer or cervical cancer, but also oral, esophagus and tonsils.

“So what are we waiting for?”

Pino thinks some parents might be hesitant because of the widely spread, but disproven, belief that vaccines are linked to autism. Then, there are other parents who think giving their child the vaccine is promoting sexual behavior. HPV is the most common sexually transmitted infection.

“The reality is, I think what the parents have to present to themselves in this debate, is what is the paramount objective here?” Pino said. “Is the paramount objective to offer protection to the individual, or is the paramount objective to prevent the behavior?”

Officials recommended that children receive the multi-dose HPV vaccine years before becoming sexually active, anywhere from 9 to 12 years old. A little more than half of teens, 51 percent, received all recommended doses of the vaccine last year, according to the CDC.

The HPV vaccine is not a required immunization for students in Florida. County health departments offer the vaccine for free.

October, 2019|Oral Cancer News|

Does HPV vaccine reduce HIV-positive men oral cancer risks?

Source: www.precisionvaccinations.com
Author: Don Ward Hackett, Fact checked by Robert Carlson, MD & Danielle Reiter, RN

Does the HPV vaccine protect against oral infections?

That’s the question a new National Cancer Institutes (NCI) funded clinical trial of the Gardasil 9 vaccine hopes to answer.

This extensive study will determine whether the Gardasil 9 vaccine can prevent persistent oral HPV infections among men who are Human Immunodeficiency Virus (HIV) positive, said the NCI online on October 8, 2019.

Oral HPV infections and HPV-related oral cancers are common in men and among HIV-positive individuals.

Gardasil 9 is the most recent formulation of the Human Papolivirus (HPV) vaccine, which covers 5 additional cancer-causing HPV types. There are over 100 types of HPV.

“We are hoping that if we show the efficacy of the vaccine, that vaccinating both males and females will ultimately reverse” the rising incidence of HPV-related oropharyngeal cancers, said one of the trial’s lead investigators, Anna Giuliano, Ph.D., of Moffitt Cancer Center.

The trial is one of several within the US–Latin American–Caribbean Clinical Trials Network (ULACNet), an NCI-led effort to reduce the burden of HPV-related cancers in HIV-positive individuals.

This new study intends to build relevant insights upon a June 2017 study found that vaccination against HPV may sharply reduce oral HPV infections that are a major risk factor for oropharyngeal cancer, a type of head and neck cancer, says the NCI.

The 2017 study found that the prevalence of oral infection with 4 HPV types, including two high-risk, or cancer-causing, types, was 88 percent lower in those who reported receiving at least 1-dose of an HPV vaccine, than in those who said they were not vaccinated.

The ULACNet international collaborative research network brings together institutions in the United States and counterparts in low- and middle-income countries (LMICs) in the Latin American and the Caribbean (LAC) region.

Funded in Fall 2019 via a U54 Partnership Centers Cooperative Agreement mechanism, ULACNet comprises of 3 Partnership Centers, each collaboratively conducting a multidisciplinary Clinical Trials Program supported via an infrastructure of an Administrative and Coordinating Core, a Data Management and Statistical Core, and a Central Laboratory Core.

ULACNet investigators collaborate with the NCI to design and conduct clinical trials on three key scientific areas across the continuum of prevention interventions for HPV-related cancers in people living with HIV, including:

  • optimizing dosing and delivery and evaluating new indications for HPV prophylactic vaccines
  • evaluating new biomarkers and technologies for improving the accuracy of cervical and anogenital cancer screening and triage
  • evaluating novel non-excisional treatments for HPV-related precancerous lesions

Outcomes of ULACNet clinical trials are expected to influence the development of clinical practice guidelines to improve preventive clinical care and reduce the burden of highly preventable HPV-related cancers in people living with HIV.

The three ULACNet Partnership Centers include the following collaborations between institutions in the United States and partners in Mexico, Puerto Rico, Brazil, Peru, and the Dominican Republic:

  • University of California, San Francisco (UCSF) in San Francisco, CA (PI: Joel Palefsky, MD) in partnership with University of Puerto Rico in San Juan, Puerto Rico (PI: Anna Patricia Ortiz, PhD, MPH) and National Institute of Public Health (INSP) in Cuernavaca, Morelos, Mexico (PI: Jorge Salmeron, MD, DSc)
  • Weill Medical College of Cornell University in New York, NY (PI: Timothy Wilkin, MD, MS) in partnership with Moffitt Cancer Center, in Tampa, FL (PI: Anna Giuliano, PhD, MPH), University of Sao Paulo in Sao Paulo, Brazil (PI: Luisa Villa, PhD), National Institute of Public Health (INSP) in Cuernavaca, Morelos, Mexico (PI: Eduardo Lazcano-Ponce, MD, PhD), and the University of Puerto Rico in San Juan, Puerto Rico (PI: Jorge Santana-Bagur, MD)
  • Fred Hutchinson Cancer Research Center in Seattle, WA (PIs: Margaret Madeleine, PhD, MPH, and Ann Duerr, MD, PhD) in partnership with Asociacion Civil Via Libre in Lima, Peru (PI: Robinson Cabello, MD), National Institute of Infectious Diseases Evandro Chagas-Oswaldo Cruz Foundation (FIOCRUZ) in Rio de Janeiro, Brazil (PI: Beatriz Grinsztejn, MD, PhD), PATH in Seattle, WA (PI: Silvia de Sanjose, MD, PhD), and Instituto Dermatologico Dominicano y Cirugia de Piel (IDCP) in Santo Domingo, Dominican Republic (PI: Yeycy Donastorg, MD).

For more information about this important clinical trial, please contact the ULACNet Program Director is Vikrant Sahasrabuddhe, MBBS, DrPH in the NCI Division of Cancer Prevention.

References:
US-Latin American-Caribbean Clinical Trials Network (ULACNet) for Prevention of HPV-related Cancers in People Living with HIV
HPV Vaccine May Provide Men with “Herd Immunity” against Oral HPV Infections
HPV Vaccination Linked to Decreased Oral HPV Infections
HPV-Related Cancer Prevention and Control Programs at Community-Based HIV/AIDS Service Organizations: Implications for Future

October, 2019|Oral Cancer News|

HPV ‘Herd Immunity’ Is on the Rise Among Adults

Source: www.webmd.com
Author: Dennis Thompson, HealthDay Reporter

The United States could be approaching a state of herd immunity against human papillomavirus (HPV), a virus linked to several cancers.

Oral HPV infections declined by 37% among unvaccinated 18- to 59-year-old men between 2009 and 2016, according to a Sept. 10 report in the Journal of the American Medical Association.

That included a decline in infections of HPV16, the strain found in more than 9 out of 10 cases of head and neck cancer related to the virus, said senior researcher Dr. Maura Gillison, a professor of medicine at MD Anderson Cancer Center in Houston.

Researchers say men are benefitting from increased HPV vaccination rates among American women, who receive the vaccine to prevent virus-caused cervical cancer.

“In contrast to cervical cancers, we have no means by which to screen for HPV-positive head and neck cancers,” Gillison said. “The vaccine is our best hope for prevention.”

HPV vaccination has been recommended for girls since 2006 and for boys since 2011. The virus has been linked to cancers of the cervix, penis, anus, mouth and throat.

Vaccination rates among boys and girls are steadily rising, according to the U.S. Centers for Disease Control and Prevention.

About half of teens were up to date on the HPV vaccine in 2017, and two-thirds of 13- to 17-year-olds had received the first dose to start the series. On average, the percentage of teens who started the HPV vaccine series rose by 5 percentage points each year between 2013 and 2017, the CDC says.

“At least 75% vaccine coverage of boys and girls would be necessary to eradicate HPV16, the HPV type that is most likely to lead to cancer development,” Gillison said.

But vaccination rates have lagged among males.

To see if males are receiving some protection from greater HVP vaccination among females, Gillison and her colleagues reviewed U.S. federal health survey data gathered between 2009 and 2016.

They found that by 2016, about 15% of women and 6% of men had received the vaccine.

Despite lower vaccination rates among males, oral HPV infections declined from 2.7% to 1.6% in men between 2009 and 2016.

Interestingly, prevention of oral HPV infections and the head and neck cancers they cause is not listed as a reason to get the vaccine, Gillison said. No clinical trials have been undertaken to show that the HPV vaccine could prevent such cancers.

The decrease in HPV infections among the unvaccinated men is consistent with a decline in genital HPV infections among unvaccinated women between 2004 and 2014, the researchers noted.

“This study demonstrates that even with suboptimal uptake of the HPV vaccine, important gains are being made in herd immunity against oral HPV types included in the vaccine,” said Dr. Amesh Adalja, a senior scholar at the Johns Hopkins Center for Health Security in Baltimore. He was not involved with the study.

“Oral HPV infection is a major factor in the development of head and neck cancer, and this vaccine has the potential to be game-changing as more individuals are vaccinated,” Adalja said.

HPV-positive head and neck cancers are the most rapidly rising cancers in the United States among men under age 60, Gillison said.

She called on doctors to use the data from this and other studies to promote HPV vaccination.

“I can guarantee that all of my patients diagnosed with HPV-positive head and neck cancer would exchange two or three shots for three months of toxic cancer therapy in a heartbeat,” she said.

“The HPV vaccine, together with the hepatitis B vaccine, are the two most important advances in the history of cancer prevention, period,” Gillison concluded.

September, 2019|Oral Cancer News|

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.

Cancer ‘vaccine’ shown to be effective in small trial

Source: www.upi.com
Author: Dennis Thompson, HealthDay News

A new method of brewing a cancer vaccine inside a patient’s tumor could harness the power of the immune system to destroy the disease, researchers report.

Immune stimulants are injected directly into a tumor, which teaches the immune system to recognize and destroy all similar cancer cells throughout the body, said senior researcher Dr. Joshua Brody. He is director of the Lymphoma Immunotherapy Program at the Icahn School of Medicine at Mount Sinai in New York City.

“We’re injecting two immune stimulants right into one single tumor,” Brody said. “We inject one tumor and we see all of the other tumors just melt away.”

Eight out of 11 lymphoma patients in a small, early clinical trial experienced partial or complete destruction of the tumor that received the initial injection, according to the report published April 8 in the journal Nature Medicine.

The vaccine also halted overall cancer progression in six patients for three to 18 months, and caused significant regression or actual remission in three patients, the investigators found.

The results were solid enough that the research team is expanding its next clinical trial to include lymphoma, breast, and head and neck cancer patients, Brody said. That trial started in March.

Prior efforts at unleashing the immune system to fight cancer have focused on T-cells, which Brody calls the “soldiers” of the immune army because they directly attack harmful invaders in the body.

Drugs called checkpoint inhibitors help T-cells identify cancer cells as the bad guys and kill them off.

“We call them the ‘Jimmy Carter’ medicines because that’s what Jimmy got when he had very advanced-stage melanoma,” Brody said.

But the checkpoint inhibitors have typically only been able to help about one in five cancer patients significantly, “so there’s lots of room for improvement,” he added.

This new vaccine approach focuses on dendritic cells, which Brody calls the “generals” of the immune system’s army. Dendritic cells guide the response of T-cells to fight off invaders.

“We’re trying to mobilize these immune generals to tell the soldiers what to do,” Brody said.

Patients first received nine daily injections of an immune stimulant intended to “recruit” dendritic cells by teaching them how to recognize cancerous cells, the study authors said.

The patients then received eight injections of a second stimulant that “activates” the dendritic cells, prompting them to instruct T-cells to hunt and destroy the now revealed cancer cells in the body.

Essentially, the method turns the injected tumor into a cancer vaccine factory, the researchers explained.

The approach differs from traditional vaccines for the flu or measles because those are preventive, teaching the body beforehand how to fight off an infectious disease, Brody pointed out.

This vaccine is therapeutic. “We’re trying to teach the immune system to get rid of the thing even after you’ve already got the problem,” he said.

Lab tests involving mice show that this vaccine approach could be at least three times more powerful if combined with checkpoint inhibitors, Brody added.

Because of this, patients in the new trial will receive both the vaccine and checkpoint inhibitors, the researchers said.

Susanna Greer, scientific director of clinical cancer research and immunology for the American Cancer Society, said that “priming” dendritic cells inside a person’s tumor to produce the best anti-tumor immune response “suggests a promising immunotherapy strategy.”

“Additional human studies are warranted to confirm these findings,” Greer said.

Dr. Catherine Diefenbach, director of clinical lymphoma at the NYU Langone Perlmutter Cancer Center in New York City, said the vaccine approach is “novel and extremely interesting,” and could help explain why checkpoint inhibitors usually don’t help patients with non-Hodgkin lymphoma.

However, she noted that really only three of the 11 patients in the initial clinical trial had truly meaningful responses to the vaccine.

“These are indolent lymphoma patients,” said Diefenbach, an expert for the American Society of Clinical Oncology. “The fact there was stable disease doesn’t really mean anything because these cancers don’t grow fast.”

April, 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|

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

Source: MedPage Today
Author: Mark L. Feurst

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

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

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

Vaccine + Nivolumab in Phase II Study

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

 

November, 2018|Oral Cancer News|

Cultural barriers still stand in the way of HPV vaccine uptake

Source: arstechnica.com
Author: Cathleen O’Grady

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

November, 2018|Oral Cancer News|

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|