HB-200 vaccines show promised in HPV16+ cancers

Source: www.targetedonc.com
Author: Sara Karlovitch

In an interview with Targeted Oncology, Marshall Posner, MD, discusses the use of the HB-201 and HB-202 vaccines in patients with human papillomavirus 16- positive cancers.

Adding pembrolizumab (Keytruda) to the HB-200 vaccines may help to improve efficacy in patients with human papillomavirus 16- positive (HPV16+) cancers, according to data from a phase 1 study.

HPV16+ cancers are caused by the expression of E7 and E6 oncoproteins, which is a source of immunogenic neoantigens. A tumor-specific T-cell response is induced by replicating arenavirus vectors HB-201 and HB-202.

The study (NCT04180215) assessed HB-201 monotherapy and HB-201 and HB-202 alternating 2-vector therapy intravenously with or without 1 intratumoral dose in HPV16+ cancers. An interim analysis looked at 38 patients with confirmed HPV16+ cancers. In total, 18 patients received HB-201 monotherapy, 9 received the monotherapy intravenously with or without 1 intratumoral dose and 11 patients received HB-201/HB-202 alternating therapy.

In an interview with Targeted Oncology™, Marshall Posner, MD, a professor of medicine, hematology and medical oncology at Mount Sinai, discusses the use of the HB-201 and HB-202 vaccines in patients with HPV16+ cancers.

TARGETED ONCOLOGY: Can you go over the safety, efficacy, and immunogenicity of arenavirus-based vectors HB-201 and HB-202 in patients with HPV16+ cancers?

POSNER: This is a first in human phase 1 trial with expansion cohorts, to occur later, of 2 vaccines. One is a lympho-choriomeningitis virus-based arenavirus vaccine and the other is a pichinde virus-based vaccine, both of which express the E6 and E7 proteins, and both are based on viruses infecting antigen presenting cells. The E6 and E7 proteins were going to be processed and presented to the immune system in the context of an inflammatory response to the virus. Neither of these viruses are human attacking viruses, so they won’t cause any significant pathology in humans. And these were the phase one studies looking at the HB-201 vaccine by itself, and then alternating regimen with Hb-201 and HB-202, which has been shown in animal models to be actually synergistic in anti-tumor activity. This particular presentation is about the safety and potential efficacy of combining these vaccines with pembrolizumab. So, the later on trials will include pembrolizumab in the process, but this was an early attempt to see what pembrolizumab could do, but primarily to look at the safety.

We presented the first 3 patients who have progressed on the vaccines and subsequently had pembrolizumab added to the treatment. This was a modification of the original protocol to allow us to really perform the phase 1 study in an earlier fashion. All the patients who were on this particular cohort had prior checkpoint blockade inhibitor and/or other chemotherapies and checkpoint blockade inhibitors. So, this was a heavily pretreated group who had failed multiple rounds of therapy in the recurrent metastatic setting. I personally know 2 of the patients had a really extensive visceral involvement with the cancer. So, this was really a group of patients for whom you would expect to see side effects, other problems related to the tumor itself and not expect a response. And yet with them, we saw some stabilization of disease, we saw minimal impact of adding pembrolizumab. No treatment emergent adverse events that were concerning or that led to modification or reduction of dose for stopping the pembrolizumab and other treatment.

What we did see was stabilization of disease, some evidence of a response, but not robust. And we also saw no change in a robust up regulation of responsive T cells. In an L spot test, which involves stimulating the T cells from a peripheral blood with protein. The protein targets the antigen. What they saw in the initial study inpatients with the vaccine, was a big upregulation of both T cell responses and CDA responses specifically. In the addition of pembrolizumab, they did not see a further increase. They saw a maintenance or a slight reduction. So, it’s unclear what that’s about. But it does indicate that we already have robust responses, and they certainly weren’t inhibited by adding the pembrolizumab in any significant fashion.

The results of the trial will allow us to move forward in the trial that we’re doing by adding pembrolizumab to more patients. Moving forward, when we hit our recommended phase 2 dose of either the single vaccine or the double vaccine treatment, we added pembrolizumab. In the subsequent phase 1 and phase 2 expansion. I think the aim here is to go forward with a combination, rather than to do the expansion cohort with just the vaccine, but that’s up to the company and not up to me. It proved to be reasonably tolerable. There was a good safety signal and a good signal of some evidence of at least clinical responsiveness in the patients. So that was the end result of the study.

What was the reasoning behind adding pembrolizumab to the HB-200 vaccines in this patient population?

There’s some suggestion that given the patients don’t make a robust response to HPV by itself, that adding pembrolizumab would boost the response obtained with a vaccine by blocking inhibitory signals in the tumors. That is going to take some more work, you’re not going to see that early on in these kinds of trials. Although the data is suggested that it will, it’s really a small number of patients. So, that’s the rationale for doing that. It’s possible that pembrolizumab isn’t the right immune stimulant and that we need to simulate some other part of the immune system and I think as further studies go on, looking at the combination of pembrolizumab with other immune modulating drugs, that we’ll see some changes that will suggest other agents to combine with the vaccines.

What is the mechanism of action of the HB-200 vaccines with pembrolizumab and without pembrolizumab?

The presumption is that the vaccines will enhance CDH stimulation. And you’ll have activated CDA cells entering the tumor and killing the tumors based on their immune activation from the vaccine. Adding pembrolizumab would hopefully eliminate intertumoral, PD0-L1 and PD-1, inhibition of that immune response as well as inhibition of immune response with the T cells. So, those are the gross mechanisms of action. But really micro analysis of that is going to take some look at the material that the company has collected and some of the scientific laboratory investigation that they’re doing to look at that. We’re at the dawn of immunotherapy. I think the question goes right back to why do we only see a small fraction of patients responding to immunotherapy with head and neck cancer? Not as many as you would see, for example, with melanoma, but it’s still a fabulous result. But the question is really basically why are HPV-negative and HPV-positive patients not responding and are their mechanisms the same or different? Do we need to really look different modulators to the immune system in these patients?

Reference:
Ho A, Posner M, Niu J, et al. First report of the safety/tolerability and preliminary antitumor activity of HB-201 and HB-202, an arenavirus-based cancer immunotherapy, in patients with HPV16+ cancers. Jour. Clin. Oncol. 2021;39(15):2502 doi: 10.1200/JCO.2021.39.15_suppl.2502.

FDA gives ISA101b fast track designation for HPV 16+ oropharyngeal cancer

Source: www.cancernetwork.com
Author: Hayley Virgil

The first patients with human papillomavirus 16–positive oropharyngeal cancer have been dosed with ISA101b, which was given a fast track designation by the FDA, as part of a phase 2 study.

ISA101b has received a fast track designation from the FDA for the treatment of patients with recurrent and metastatic human papillomavirus (HPV) 16–positive oropharyngeal cancer, according to a press release from drug developer ISA Pharmaceuticals.1

The fast track designation is intended to facilitate the development of investigational therapies that may help to address unmet medical needs for serious or life threatening diseases. An ongoing randomized, double-blind phase 2 trial is examining cemiplimab (Libtayo) with or without ISA101b and has an estimated enrollment of 194 patients (NCT03669718).

“Recurrent and metastatic HPV16-positive OPC is a form of head and neck cancer with a high unmet medical need. The Fast Track designation for ISA101b underlines the potential benefit of this immunotherapy for patients suffering from this disease,” Leon Hooftman, chief medical officer at ISA Pharmaceuticals, said in a press release.

ISA101b elicits strong and specific immune responses to HPV16 virus proteins and creates a robust T-cell immune response against cancerous cells or tissues. In the ongoing trial, patients in the experimental arm will receive ISA101b 3 times over 3 weeks plus cemiplimab every 3 weeks for up to 24 months, and the control arm will receive a matched placebo plus cemiplimab at the same dose.

The primary outcome measures are overall response rate and safety, with a key secondary end point of duration of response.

To be eligible for the trial, patients need to be 18 years or older, have a diagnosis of histologically confirmed recurrent or metastatic HPV16-positive oropharyngeal cancer with tumors that express PD-L1, and be candidates for anti–PD-L1 therapy. Patients who have experienced disease progression on or after a platinum-based chemotherapy regimen are also eligible. Additionally, an ECOG performance status of 0 or 1 is required, as well as measurable disease by CT or MRI imaging.

Patients with untreated metastatic or unresectable tumors that do not express PD-L1 and aren’t candidates for an anti–PD-L1 therapy are not eligible for enrollment. Additionally, those with known brain metastases or leptomeningeal metastases or a serious or uncontrolled medical disorder are not allowed. Patients with a history of other malignancies 3 years or fewer prior to entry are also excluded, with the exception of basal cell or squamous cell carcinoma of the skin that was treated with local resection only, carcinoma in situ of the cervix, prostate or breast cancer, or low grade non-muscle invasive superficial bladder cancer in situ.

The compound is currently being studied in HPV16-positive cancers in combination with cemiplimab in several phase 2 clinical trials. Similarly, ISA101b is also being examined as a single agent in HPV16-positive cervical cancer, an indication for which the compound has received an orphan drug designation.2

References
1. ISA Pharmaceuticals receives fast track designation for lead product ISA101b. News release. ISA Pharmaceuticals. September 14, 2021. Accessed September 14, 2021. https://bit.ly/3Aac1Je
2. ISA Pharmaceuticals receives US orphan-drug designation for ISA101b in HPV16-positive cervical cancer. News release. ISA Pharmaceuticals. July 1, 2020. Accessed September 14, 2021. https://prn.to/3zlfun7

2021-09-15T06:04:52-07:00September, 2021|Oral Cancer News|

Study: HPV vaccination will reduce throat and mouth cancers, but overall impact will take 25-plus years to see

Source: www.newswise.com
Author: Johns Hopkins Bloomberg School of Public Health

Vaccinations against human papillomavirus (HPV), a major cause of throat and back of mouth cancers, are expected to yield significant reductions in the rates of these cancers in the U.S., but will not do so until after 2045, according to a new modeling study from researchers at the Johns Hopkins Bloomberg School of Public Health. HPV is the most common sexually transmitted infectious virus worldwide. HPV infections are often silent, and while most infections clear, some are chronic and can trigger cancers including mouth and throat (oropharyngeal), and cervical cancer because they disrupt DNA and inhibit tumor-suppressor proteins in the cells they infect. Although there is no cure for existing HPV infections, new infections are preventable with vaccines, the first of which entered use in the U.S. in 2006.

In the new study, the Bloomberg School researchers analyzed national databases on oropharyngeal cancer cases and HPV vaccinations, and projected the impact of HPV vaccination on the rates of these cancers in different age groups. They estimated that the oropharyngeal cancer rate would nearly halve between 2018 and 2045 among people ages 36–45. However, they also projected that the rate in the overall population would stay about the same from 2018-2045, due to still-rising rates of these cancers in older people, where most of these cancers occur.

The study appears online September 2 in JAMA Oncology.

“We estimate that most of the oropharyngeal cancers from 2018 to 2045 will occur among people who are 55 years and older and have not been vaccinated,” says study lead author Yuehan Zhang, a PhD candidate in the research group of Gypsyamber D’Souza, PhD, professor in the Department of Epidemiology at the Bloomberg School.

“HPV vaccination is going to work to prevent oropharyngeal cancers, but it will take time to see that impact, because these cancers mostly occur in middle age,” D’Souza says.

Oropharyngeal cancer is the most common HPV-related cancer, and according to the Oral Cancer Foundation there are more than 50,000 new cases of it in the U.S. each year. Alcohol and tobacco use also are risk factors, but are seen as increasingly less important than HPV.

Vaccination is a powerful medical weapon against this family of viruses, but has one major shortcoming: It can prevent, but not treat. In other words, it does not work against established HPV infections or against cells that have been transformed by HPV and are on their way to forming tumors. Thus it is recommended chiefly for the young who are not yet exposed to sexually transmitted HPV. (Most people who were already adults when HPV vaccination became available have never been vaccinated, and thus remain at risk for these cancers.)

For the study, the researchers estimated current and future HPV vaccination rates using data from surveys conducted by the U.S. Centers for Disease Control and Prevention, and projected oropharyngeal cancer rates based on past and current incidence data from the National Cancer Institute.

They estimated that the rates of vaccination by 2045, for different age groups—given the emphasis on vaccinating the young—will amount to about 72 percent of people ages 36–45, 37 percent of those ages 46–55, 9 percent of those ages 56–69, and 0 percent of people ages 70–83 being vaccinated.

These projections show continuing high oropharyngeal cancer rates in older, mostly unvaccinated groups, and almost no change in the overall U.S. rate of these cancers—14.3 per 100,000 assuming no vaccination; and 13.8 per 100,000, with vaccination, in 2045.

However, they foresaw the rates of new oropharyngeal cancers would fall substantially in the relatively well vaccinated 36–45 and 46–55 age groups during the 2018–2045 period: from 1.4 to 0.8 per 100,000; and from 8.7 to 7.2 per 100,000, respectively.

The results suggest, though, that by 2045 HPV vaccination will have begun to make a significant impact. “Our projections suggest that by around 2033, nearly 100 cases of oropharyngeal cancer will be prevented each year, but by 2045 that figure will have increased by about ten times,” Zhang says.

Notes:
“Projected Impact of HPV Vaccination on Oropharynx Cancer Incidence in the United States: 2020-2045” was co-authored by Yuehan Zhang, Carole Fakhry, and Gypsyamber D’Souza.

Funding was provided by the National Institute of Dental and Craniofacial Research (R35DE026631).

2021-09-03T12:26:37-07:00September, 2021|Oral Cancer News|

Immunotherapy for HPV+ head and neck cancer: Awakening the force within

Source: medicalxpress.com
Author: Emory University

A new study from scientists at Emory Vaccine Center and Winship Cancer Institute of Emory University reports that the immune cells that are the major targets of immune checkpoint inhibitors are present in tumors from head and neck cancer patients.

The study focuses on head and neck tumors that are positive for human papillomavirus (HPV), which is becoming one of most common types of head and neck cancers treated in the Western world. The results are scheduled for publication in Nature.

It suggests checkpoint inhibitors, which have transformed the treatment of several types of cancer, could be uniquely effective against this type of head and neck cancer. The results also indicate that the experimental approach of therapeutic vaccination for HPV+ cancer could be broadened to include more elements of the virus, to potentially trigger a broader and stronger immune response.

Researchers from Rafi Ahmed’s lab at Emory Vaccine Center collaborated with the co-directors of the Winship Head and Neck Cancers working group, oncologists Nabil Saba, MD and Mihir Patel, MD, to obtain samples from patients with head and neck tumors early in the course of treatment.

“About five years ago, we began to have an influx of patients that sought out our center for surgical treatment,” Patel says. “We often heard some variation of a similar story: I was sick with cold-like symptoms and once that resolved this I noticed swelling in a lymph node on the side of my neck. Stories like this made us think about how the immune system might play a unique role, different than typical smoking-related head and neck cancers.”

The team wanted to learn more about the different kinds of CD8 or “killer” T cells present within the cancers; CD8 T cells are specialized immune cells capable of detecting and killing virus-infected or tumor cells, if they are not constrained by regulatory signals. The inhibitory receptor PD-1 is highly expressed on exhausted CD8 T cells in chronic viral infections and cancer, and stem-like PD-1+ CD8 T cells are crucial for maintaining tumor-specific CD8 T cell responses. The majority of currently available checkpoint inhibitors, such as pembrolizumab and nivolumab, block the PD-1 signaling pathway.

“Our results show that a subset of HPV-specific CD8 T cells in the tumor exhibits a striking resemblance to the stem-like CD8 T cells our lab has previously defined in mouse models as proliferating in response to PD-1 blockade,” says Andreas Wieland, Ph.D., co-lead author of the paper and an instructor in Ahmed’s lab.

“It is reasonable to assume that these cells would similarly provide a proliferative burst in response to PD-1 blockade in these patients. However, this remains to be formally tested.”

HPV-positive tumors do have a relatively good response to conventional forms of treatment such as radiation and chemotherapy, Wieland adds. The group of patients studied at Winship was treatment-naïve when tumor samples were obtained; how radiation and chemotherapy affect the number and phenotype of T cells in the tumor needs additional investigation.

“These findings greatly enhance our understanding of CD8 T cell responses in the tumor micro-environment in HPV-related oropharynx cancers, and likely other virally mediated tumors,” Saba says. “It confirms the existence of the different lineages necessary for an effective T cell specific anti-tumor response. Taking advantage of the local immune-response by avoiding its possible early elimination by traditional therapeutic modalities may pave the way to an improved clinical outcome for patients. It may have implications for how best to incorporate immunotherapy in the treatment of other virally mediated tumors.”

“We now have an inclination that incorporating immune therapy with PD-1 blockade prior to surgery or radiation may benefit patients,” Patel says. “We are actively in the process of developing ‘window of opportunity’ studies to understand this.

Looking at both primary tumors and metastatic lymph nodes, the researchers were able to detect both tumor-specific stem-like CD8 T cells, which can proliferate in response to HPV peptides, and more terminally differentiated cells that do not proliferate. In contrast to significant numbers of tumor-specific CD8 T cells in the tumors, tumor-specific cells appeared at a very low abundance in patients’ blood, suggesting that they preferentially reside in tumors. The team also found that the different CD8 T cell subsets in the tumor microenvironment differ in their localization, with stem-like cells residing in distinct niches within the stroma and away from the tumor cells themselves.

Concentrating on HPV-positive tumors in this study facilitated the study of tumor-specific T cells with defined specificities across several patients as the virus is providing a defined set of tumor-associated antigens, whereas in other types of cancer the antigens caused by mutations will vary from individual to individual.

Note:
Co-first authors of the paper are Haydn Kissick, Ph.D., assistant professor of urology and microbiology and immunology, and Christiane Eberhardt, MD, a former postdoctoral fellow in Ahmed’s lab who is now at the University of Geneva. Patel is also associate professor of otolaryngology at Emory University School of Medicine. Saba is professor and Vice Chair in the Department of Hematology and Medical Oncology.

2021-09-02T20:07:01-07:00September, 2021|Oral Cancer News|

Natick company develops test to detect head and neck cancer that could lead to earlier diagnosis

Source: www.bostonherald.com
Author: Alexi Cohan

A saliva-based diagnostic test that can detect HPV-related head and neck cancer has the potential to catch the disease earlier and even serve as a standard screening method, which the medical community currently lacks.

Oropharyngeal squamous cell carcinoma, a cancer caused by human papillomavirus that develops in the mouth and throat, is expected to cause more than 10,000 deaths this year, according to the American Cancer Society. Cases have been increasing significantly in men in recent years.

But there is no screening method for this cancer right now, said Charlotte Kuperwasser, chief of clinical operations at Natick-based diagnostics company Naveris. She said most men who contract it will notice a lump in their throat and go to the doctor. But by that time, the cancer could be quite advanced.

The new saliva test developed by Naveris has been shown to detect HPV-associated head and neck cancer with high accuracy, which is a first-of-its-kind study result and could offer a patient-friendly way to catch the cancer early.

“Saliva is actually a very easy source, very non-invasive. It doesn’t require a medical professional to collect, it could even be done at home so there’s a lot of advantages to saliva,” Kupperwasser told the Herald.

Researchers at Washington University School of Medicine in St. Louis used the test to successfully analyze saliva for HPV genomes that are specific for DNA released from cancerous tumors. The study results highlighted the potential to use the test to catch the cancer early.

“Then, you can actually intervene and make a difference and prevent these cancers from showing up,” Kupperwasser said.

The saliva test builds off a Naveris blood test that detects HPV-associated head and neck cancer earlier than is possible with cancer imaging. That technology is already being used by hundreds of doctors.

Finding a way to detect HPV-related cancer early can’t come soon enough. Kupperwasser said by 2035, HPV cancers are expected to become the third leading cancer type among white men.

“The incidence is going up dramatically and the prevalence is getting to be so high,” Kupperwasser said.

Human papillomavirus is the most common sexually transmitted virus and infection in the United States. More than one of five U.S. adults are infected with a high-risk strain of HPV that can potentially develop into cancer.

But many people might not have any symptoms of HPV, which can take decades to turn into cancer.

Kupperwasser said a similar situation unfolded with cervical cancer in the United States. Cases were going up and a screening mandate was put into place, helping significantly.

She said the same thing could happen with the saliva test if it were used as a standard screening method.

The saliva test could be available to patients within 18 months, but it remains in clinical trials, said Kupperwasser.

‘On the rise:’ Immunotherapy options for head and neck cancer

Source: www.curetoday.com
Author: Kristie L. Kahl

On behalf of the Head and Neck Cancer Alliance, Dr. Michael Moore spoke with CURE® about emerging therapies that potentially offer exciting new options for the future.

Although rates of head and neck cancer have risen, in part because of the human papillomavirus (HPV), emerging therapies such as targeted agents and immunotherapies are paving the way for future treatment of the disease, according to Dr. Michael Moore.

“I would say (immunotherapy) is probably one of the more exciting parts of what we’ve learned about head and neck cancer in recent years,” he told CURE® as a part of its “Speaking Out” video series.

On behalf of the Head and Neck Cancer Alliance, CURE® spoke with Moore, associate professor of otolaryngology-head and neck surgery and chief of head and neck surgery at Indiana University School of Medicine in Indianapolis, about targeted therapies, immunotherapy and how clinical trials are leading the way for future treatments.

How have genomics and targeted therapies played a role in head and neck cancer treatment?

Well, I would say it’s an emerging role. And it’s not used as commonly in head-neck cancer as it is in some other areas. So molecular testing or targeted therapies essentially are looking at a very specific part of the tumor to see if we can develop a specific drug that will target just that; (the goal is to) weaken the cancer’s defense — that is one way to say it — and try to very specifically treat that cancer in a way that will give us the best chance of getting rid of it and potentially try to limit the side effects related to the treatments. This has become a little bit more common now that the ability to analyze these tumors has become more widely available across the country. But still, the majority of these types of treatment approaches will be in the context of a clinical trial.

Do we have any currently approved targeted therapies for head and neck cancer?

That’s a great question. I think these are kind of different and are emerging all the time. There are ones that are focused on very specific mutations, such as what’s called the BRAF mutation, which is one that can be present in melanoma or certain aggressive cancers, such as thyroid cancer. And other ones will target things like tyrosine kinase inhibitors that have a more focused route to try to combat these tumors. And then there are ones that will be discussed a little later, such as immuno-oncology drugs that focus on the program cell death ligand and the receptor to try to turn the body’s immune system back on. Another example is what’s called Erbitux (cetuximab), which is focusing on a specific receptor on cancer cells, really trying to exploit this particular difference in cancer cells compared with normal tissue to try to give the best chance of getting rid of the tumor, but minimizing the side effects of the treatment.
What role has immunotherapy had in head and neck cancer treatment?

Cancer has a way of almost turning off the local immune system. It blocks many of the local immune responses to it. Normally, the body would say, “Yeah, that’s not part of our normal tissue, we want to get rid of it.” And some cancers have a way of blocking that. These immunotherapies have a way of almost inhibiting that blockage, if you will, or turning the immune system back on and allowing your own body’s immune system to fight these tumors. These can be incredibly effective. The challenge is if they’re only effective in a small minority of cancers. And so, when they do work, they can work extremely well and can give really good and long-lasting results. But in a high percentage of patients, the responses are much more modest or (patients) may not even respond at all.

Can you discuss the currently available immunotherapies for head and neck cancer?

There are two. Opdivo (nivolumab) is one that can be used in patients who have not responded or progressed despite standard therapy, including recent treatment with chemotherapy, including cisplatin. And then Keytruda (pembrolizumab) is another similar amino therapy that can be used and has actually achieved approval for use in the primary setting. When cancer comes back in an area that can’t be treated with either definitive surgery or definitive radiation therapy, you can use that as a next avenue for treatment. These are the two (Food and Drug Administration)-approved drugs that are out there. They also have ongoing studies where they’re being combined with other standard-of- care, primary treatments for head and neck cancer. I think in the next five to 10 years, they’ll likely be integrated much more on the front end of cancer therapy, rather than just offering them to those who don’t have other treatment options.

How do clinical trials help to advance these therapies, and why should patients consider joining one?

These are really what allows us to make our cancer treatment better. We constantly are. It’s not just going out and experimenting on people but, rather, we’re comparing these treatments to see how we can improve on the current standard approach to therapy. If you were to look back 50 to 60 years ago, all we had were big, morbid surgeries that people were put through and possibly adding radiation therapy. And then we added cisplatin, which is a drug that can be effective in enhancing the effects of radiation therapy. Now, as we add these other treatments, such as immunotherapy and other targeted therapies, the only way we know if they have any advantage over what we have to offer, currently, is to compare them in a clinical trial.

And with these clinical trials, those who have designed them have been very thoughtful in trying to do so in a way that compares them and then looks to see: Does that give us a benefit in getting rid of the cancer or curing the cancer, or at a minimum, slowing it down or giving a longer life? And/or does it give better quality of life or reduce the level of side effects? That’s what many of these clinical trials are. Some are adding new agents to see if those work better than other ones. For example, in the HPV-related cancer, some of the clinical trials are saying these respond fairly well to treatment. Can we actually back off on the severity of treatment, give them just as good of a cancer cure but (with) fewer long-term side effects? I think they’re critical as the only way we’re going to figure out how best to manage these types of cancers.

Five reasons boys and young men need the HPV vaccine, too

Source: www.mskcc.org
Author: Memorial Sloan Kettering Cancer Center, News and Information

Rich Delgrosso found the lump while shaving. It was on the left side of his neck and it seemed to grow bigger by the day. He made an appointment with his ear, nose, and throat doctor.

“He said the odds were 50/50 that it was an infection,” recalls the 56-year-old father of two from Pleasantville, New York. “I asked, ‘What’s the other 50?’”

It was a possibility no one wanted to hear: Cancer. Rich underwent a biopsy and learned he had squamous cell carcinoma that had originated on the base of his tongue. His cancer, the doctor told him, was caused by the human papillomavirus (HPV).

Rich was shocked. “I knew HPV could cause cancer,” he says, “but I thought it was only cervical cancer in women.”

It’s true that HPV, a sexually transmitted virus, does cause the majority of cervical cancer cases in women. But it can also cause a variety of cancers in men, too, some of which are on the rise.

HPV led to a five-fold increase of head and neck cancers in young men from 2001 to 2017, according to data released at the 2021 American Society for Clinical Oncology annual meeting.

Memorial Sloan Kettering’s David Pfister, a medical oncologist who cares for people with head and neck cancer, says these cancer cases are just now emerging in people infected with the virus many years ago.

“Once the association between HPV infection and throat cancers was established, we better understood the significant increase in the rate of these cancers,” he says. “There is a delay between infection and the development of cancer, so there is a big reservoir of people already potentially at risk.”

But there is a way to prevent more than 90% of cancers caused by this virus: Get the HPV vaccine. It protects against head and neck cancers as well as anal cancer in both men and women. In men, it also protects against penile cancer, and in women, cervical cancer, vaginal cancer, and vulvar cancer. The vaccine is recommended for all children and can be given as early as age 9. It’s also approved for adults up to age 45.

Amidst growing concern about falling vaccination rates, MSK joined other National Cancer Institute-designated cancer centers in a May 2021 statement urging physicians, parents, and young adults to begin or keep up with HPV vaccinations, after they were interrupted by COVID-19. Early in the pandemic, HPV vaccination rates among adolescents fell by 75%. Since March 2020, an estimated one million doses of HPV vaccine have been missed by adolescents who have public insurance. That’s a decline of 21% from pre-pandemic levels.

Moreover, parents of boys are increasingly hesitant to have their sons vaccinated, according to a study in the journal Pediatrics.

MSK’s HPV Center is working to increase vaccination rates for everyone. Here are five reasons why it’s especially important for males.

1. Men get cancers caused by HPV in large numbers, too.
From 2013 to 2017, there were approximately 25,000 cases of HPV-associated cancers in women and 19,000 in men, according to the Centers for Disease Control and Prevention. More than four out of every ten cases of cancer caused by HPV are in men.

“HPV should be of concern to all since men and women are affected virtually the same by this virus,” says Abraham Aragones, an MSK physician who also studies public health.

2. There are now more cases of head and neck cancers than cervical cancers in America; HPV causes 70% of them, according to the CDC.
“My doctor told me that tumors of the neck and throat were getting more common in men,” Rich recalls.

Head and neck cancers are four times as common in men as they are in women.

3. There is no test for HPV cancers in males.
A Pap test detects early-stage cervical cancer in women. No such test exists for penile, anal, or head and neck cancers.

“Developing something like a Pap test for throat cancer would be a game-changer,” says Dr. Pfister. “When you compare the throat to the cervix, the anatomy of sites like the tonsils and the base of the tongue have hard-to-reach crevices the virus can hide in. Until an effective and reliable screening test is developed, patients should stay up to date on their HPV vaccines, know how the disease is acquired, and take any suspicious symptoms like a lump in the neck or blood in the phlegm to their doctor or dentist.”

4. The odds of getting HPV-related cancer increases with age.
“Today’s men are living longer than ever before, and that gives cancer more time to develop,” Dr. Aragones says. “Vaccination protects men from HPV-related cancers in the short and long term.”

5. The vaccine is just as safe for boys as it is girls.
The HPV vaccine went through years of rigorous safety testing before it was approved in 2006 to prevent cervical cancer in women and in 2009 to prevent HPV-related cancers in males. Since then, more than 100 million doses of the HPV vaccine have been given in the United States. Like any vaccine, there can be side effects, but they are minor, like arm soreness and fatigue. “The benefits of vaccinating against HPV far outweigh any potential risk of side effects,” says Dr. Aragones.

Rich made sure his teenage son got the HPV vaccine and says his younger daughter will follow suit.

“I didn’t want them to go through what I went through,” he says. After radiation and chemotherapy three years ago, Rich thankfully has shown no evidence of disease.

HPV-related cancers are usually able to be treated successfully. But preventing a cancer is far better than treating it, which makes the HPV vaccine a valuable weapon against cancer.

HPV vaccine leads to more than 80% drop in infections: What parents need to know

Source: Good Morning, America
Date: April 2nd, 2021
Author: Katie Kindelan

 

A new study has shown the effectiveness of the HPV vaccine, and found a dramatic decline in human papillomavirus infections in both vaccinated and unvaccinated teen girls and young women in the United States.

“This study shows that the vaccine works very well against a common virus, HPV,” Dr. Hannah Rosenblum, lead author of the study and medical epidemiologist at the Centers for Disease Control and Prevention (CDC), told “Good Morning America.”

“HPV can cause serious health problems later in life, including some cancers in both women and men,” she said. “HPV vaccination is cancer prevention — by vaccinating children at age 11 or 12, we can protect them from developing cancers later in life.”

HPV is the most common sexually transmitted infection in the United States and can cause health problems like genital warts in addition to cancer, which are most commonly cervical cancer in women and throat cancer in men, according to the CDC.

The HPV vaccine was first authorized in the U.S. for females in 2006, and for males in 2011. There has since been a more than 80% decline in HPV infections nationally, according to the CDC study.

The newly-released data from the CDC shows an 88% decrease in HPV infections among 14 to 19-year-old females and an 81% decrease among 20 to 24-year-old females.

There has also been a drop in unvaccinated females, according to Rosenblum, who warned that does not mean people should let their guard down.

“We also see an effect among unvaccinated females in these age groups due to less spread of the virus, however, unvaccinated persons are not immune and are still at risk of getting HPV,” she said. “They should talk to their doctor about getting vaccinated if they are 26-years-old or younger.”

HPV viruses are found in 80 million people in the United States, according to the CDC. There are hundreds of subtypes of HPV, and 1 in 4 people in the U.S. are infected with HPV at some point in their lives.

The CDC recommends two doses of the HPV vaccine, taken six to 12 months apart, for all girls and boys ages 11 to 12, but says the vaccine can be given to children as young as 9.

Teens and older who are not vaccinated are encouraged to do so by the age of 26. People ages 15 and older need three doses of the vaccine, according to the CDC.

The timing of the vaccine has to do with the state of children’s immune systems and also trying to vaccinate pre-teens before they are sexually active, Dr. Laura Riley, chair of obstetrics and gynecology at Weill Cornell Medicine and New York-Presbyterian in New York City, told “GMA.”

“Your immune system [at ages 11 and 12] is such that you have a robust response to this vaccine, and it lasts for a really long time,” she said. “But if you haven’t had it, still continue talking to your doctor about getting it up to age 26.”

Riley said she hopes the CDC’s new data — which stands out for being a 10-year study — combined with the safety of the HPV vaccine eases any remaining concerns parents may have about getting their children vaccinated against HPV.

“When [the HPV vaccine] first rolled out, the message wasn’t quite clear, so instead of people recognizing that you were going to prevent your kid from getting cancer, people were focused on the fact that HPV is a sexually transmitted disease,” she said. “The education has to continue so that parents can understand the real benefit of this vaccine.”

“The real benefit is to prevent your child from getting cervical cancer,” Riley said. “The fact that you can prevent [cervical cancer] with a vaccine that has been used for years and has shown to be safe, why wouldn’t you do it?”

Long-lasting infection with certain types of HPV is the main cause of cervical cancer, which has the best survival rates if detected early according to the CDC. Doctors routinely screen for cervical cancer with the Pap test and HPV DNA testing depending on age and risk factors.

“We need to make sure that the teenagers and pre-teens are getting the benefit of the HPV vaccine, because it really is an anti-cancer vaccine,” said Riley. “[Cervical cancer] is a really devastating disease.”

Globally, a woman loses her life to cervical cancer every two minutes, according to a 2019 article published in the medical journal The Lancet.

In the U.S., doctors on the frontlines like Riley said more must continue to be done to educate parents about the HPV vaccine and make sure that all children across the country have access to the vaccine. As of 2018, nearly 40% of adults ages 18 to 26 reported receiving one or more doses of the HPV vaccine, according to the CDC.

“We need to make sure that we work on access to this vaccine and make sure that all girls of all races and ethnicities have the access,” said Riley. “And we need to be sure that the message is clear so that everyone gets the two doses of the vaccine, because that’s what is associated with the best protection.”

2021-05-11T10:31:22-07:00May, 2021|Oral Cancer News|

Addressing unmet needs for head and neck cancer awareness month

Source: www.targetedonc.com
Author: Sara Karlovitch

Head and neck cancers, also known as squamous cell carcinomas of the head and neck, account for nearly 50,000 cases of cancer per year in the United States.

April is head and neck cancer month. According to the American Association for Cancer Research (AACR), alcohol and tobacco use are major risk factors for developing head and neck cancers. However, infection with the cancer-causing types of the human papillomavirus (HPV) also increases the risk for certain forms of the cancer, as well as eating preserved or salted foods, poor oral hygiene, occupational exposure to wood dust, asbestos, and synthetic fibers, radiation exposure, and Epstein-Barr virus infection in endemic regions, including southeast Asia.

Head and neck cancers are more common among men than women. Additionally, most patients who are diagnosed with this type of cancer are 50 years or older. Symptoms include a lump or sore on that does not go away or heal, difficulty swallowing, changes in voice, or a sore throat that does not resolve or heal.

Trials such as the KEYNOTE-048 study (NCT02358031), which investigated the use of pembrolizumab (Keytruda) as a first line treatment for recurrent or metastatic squamous cell cancer of the head and neck, have changed how head and neck cancers are treated. While many patients recover, many are still affected by life-long disabilities as the result of their disease and treatment.

Stuart J. Wong, MD, a medical oncologist, professor, and director of the Center for Disease Prevention Research at the Medical College of Wisconsin, discussed the KEYNOTE-048 trial, advances in head and neck cancers, and current unmet needs in this patient population in an interview with Targeted Oncology.

TARGETED ONCOLOGY: Can you discuss the evolution of treatments for patients with head and neck cancer?

WONG: Probably the biggest evolution is the integration of immune oncology into our treatment of head and neck cancer. We now have a first line indication for the use of an immune checkpoint inhibitor for patients with recurrent/metastatic head and neck cancer. This has been very successful in improving the overall survival for this patient population. Based upon the success of these agents in the recurrent and metastatic setting, there have been many new studies launched to test immune oncology agents into earlier stages of disease and to test novel immunotherapy combinations. The results of many of those studies are still anxiously being awaited.

TARGETED ONCOLOGY: What are your preferred first-line and later-line treatments in this setting?

WONG: My preferred first line is off of a clinical trial, pembrolizumab. The results of the KEYNOTE-048 study are very exciting and a huge help for patients, however we’re still not satisfied with that. My first choice, if at all possible, is to enroll patients in a clinical trial. Roughly about 20% of the patients with recurrent metastatic disease may have long-term survival with the use of pembrolizumab. Other patients receive benefits that may improve their survival, which is fantastic, but we’re not satisfied with those results and want to have higher response rates and more patients who would benefit from this therapy and more patients that have long-term survival. The only way we can do this is enroll patients in clinical trials and push the envelope even further and find strategies to improve the outcome of our patients.

TARGETED ONCOLOGY: What are some clinical trials of therapies in this setting right now, including for PD-L1 inhibitors and EGFR inhibitors?

WONG: The most exciting area of research are studies for patients who have progressed on an immune checkpoint inhibitor or have shown initial refractory disease. The most intriguing studies out there are for cellular therapies or other immune strategies. These novel therapies alone or in combination with an immune checkpoint inhibitor may overcome that initial resistance or subsequent resistance. There are many different strategies that are being explored. We are anxiously awaiting their results. As of yet, none of these strategies have proven to be successful compared with standard strategies. But I think in the next few years, we’re going to have some really dramatic results; something that will improve the outcome of this population of patients.

TARGETED ONCOLOGY: Can you talk about the role of low dose radiation for these patients?

WONG: This is an exciting area of research. The idea is that many of our patients with HPV-associated cancer have a favorable outcome and that you might be able to decrease the intensity of therapy and improve their outcome is a very promising strategy. A group from Memorial Sloan Kettering Cancer Center has led an interesting pilot study in which they decrease the intensity of the radiation using a significantly lower dose but kept cisplatin in the treatment regimen. Those results are very promising. The subsequent study of this paradigm and a larger multicenter trial would potentially warrant a sea of change in the way we manage patients. There are other strategies that are attempting to do the same thing. But this is an exciting area of research and something that patients seem to be very interested in exploring. We look forward to clinical trials that employ this technique.

TARGETED ONCOLOGY: Please go into detail on some of the unmet needs that are still relevant in the space.

WONG: The biggest one, I think, is that in clinical research, we still have a small minority of patients with head and neck cancer who enroll in clinical trials. There are many causes for this, but we cannot make progress in the treatment of these cancers unless we have more opportunities for patients to go on clinical trials and more clinical trials to offer to patients. It is frustrating that our progress is slow and that we cannot offer more advances to patients. There are some diseases where a much higher percentage of patients are treated on clinical trials initially and then when they recur, clinical trials are really part and parcel of the standard management of certain diseases. We don’t have that luxury in head and neck cancer, and this is something that we need to overcome. There is a desire for patients and for their physicians to make quicker progress. We cannot do that unless we have more resources at our fingertips to allow that to happen, and to make more progress on our patients.

I think the other big area that is in need of progress is supportive care oncology. Many of the treatment modalities that we utilize to cure or attempt to cure our patients have significant morbidity. The adverse effects linger with patients, sometimes for the rest of their life. While we’re happy that our patients are able to have their lives extended, or in some cases be cured, it makes us very frustrated that they do so at the expense of, sometimes, lifelong disabilities. We need more research into supportive care and survivorship issues. Many of us are very dedicated to this. But again, that runs into the issue that we have limited resources; there’s not as much funding for this kind of research. This is, I would say, a very big unmet need and frequently doesn’t rise to the top of discussion when we talk about cancer therapy and clinical trials.

TARGETED ONCOLOGY: Are there any specific upcoming trials or therapies that you think show promise in head and neck cancer?

WONG: If you would ask me in 2 months, I might have some really good ideas for you. I always look forward to our upcoming American Society of Clinical Oncology Annual Meeting. I’m sure this one promises to show some really exciting results. I guarantee in the next few years, we’re going to be making some exciting progress with respect to new technologies, especially cellular therapy strategies and immune oncology strategies. I can’t put bets on one line of research as being the most promising but there are many exciting lines of evidence that are being explored in ongoing clinical trials and clinical trials that are on the drawing board. I simply would say stay tuned and hopefully we’ll have some exciting news in the near future.

Reference:
Head and Neck Cancer Awareness Month. AACR. Accessed April 13, 2021. https://bit.ly/3sgeRHA

Head-and-neck surgeons buoyant about new, just-right robot

Source: newsroom.uw.edu
Author: Brian Donohue

You know how great it feels when someone makes a pie or cake just for you? University of Washington Medicine head and neck surgeons have been feeling that kind of love lately, and on Feb. 5 they shared the first slice, so to speak, with patient Steven Higley.

Surgical assistants work near patient Steven Higley on Feb. 5. Lead surgeon Jeff Houlton is obscured by the robotics.

The cake in this story is actually a da Vinci robotic-assist system built especially for head and neck procedures. It is easier to maneuver than the robotic device they’ve used for the past decade, which was designed for operations to the chest and abdomen.

Higley underwent surgery to have a cancerous tonsil and part of his throat removed. Sitting at a console a few feet from the patient, Dr. Jeff Houlton manipulated the miniature surgical tools emanating from the robot’s single port, positioned just outside Higley’s open mouth. It was UW Medicine’s first trans-oral surgery with the new tool.

“If you think about laparoscopic surgery in the belly area, robotics provides the advantage of multiple mechanical arms approaching from different angles,” Houlton said. “But it’s a challenge to have three robotic arms that all need to go through a patient’s mouth. With this machine, the three arms are designed to come through one garden hose-like entry port and then articulate out from there.

“Pretty interesting, though, that in the past 10 years we built a nationally recognized practice for robotic head and neck surgery with a device designed for a different part of the body,” he added, laughing.

The new robot’s single port, left, through which all surgical instruments travel. At right, Dr. Jeff Houlton manipulates the instruments from a distant console. Photos by Randy Carnell, UW Medicine

Higley’s radical tonsillectomy entailed the removal of a margin of tissue beyond the visible tonsil and tumor. Houlton’s incisions exposed cranial nerves and branches of the carotid artery. Working in tight quarters with such vital anatomy, Houlton and his head-and-neck colleagues in surgery, Brittany Barber and Neal Futran, welcome the improvement in maneuverability.

Head and neck cancers represent only 3% of all oncology cases in United States. But case numbers are rising, Houlton said, with increased incidence of throat cancer involving human papillomavirus (HPV), as was the case with Higley, 68.

“Most of these cancers are HPV-mediated rather than smoking- and drinking-related,” Houlton said. “We call it an epidemic because it’s a viral cancer that’s gone up significantly since about the year 2000. In terms of HPV, cancer of the oropharynx (mouth, throat and tongue) is actually more common than cervical cancer now.”

Higley’s cancer came to light last fall after a yearly physical with his Olympia-based physician.

“I had no trouble swallowing, no pain,” Higley recalled. “I didn’t notice anything until my doctor said, ‘Hey, this looks like something we should check out.’ ” His referral to UW Medicine led to a biopsy in mid-December, and on Dec. 23, he learned that he had cancer.

“I’m glad they found it early and so is my wife,” Higley said. “If I could’ve had surgery the next day, it would’ve been OK with her.”

After the robotic part of the surgery, Houlton incised Higley’s neck and removed more than a dozen lymph nodes to be biopsied for cancer cells. Higley hopes they’ll concur with the pre-surgery PET scan that indicated his cancer was constrained to the tonsil.

Patient outcomes data suggests Higley’s prognosis is encouraging: 90-95% of patients who undergo surgery for this cancer survive five years or more.

Higley is already swallowing liquids and soft foods, but he’ll manage sore throat for about a month, Houlton said.

2021-02-12T18:43:12-07:00February, 2021|Oral Cancer News|
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