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|

Calls grow for treatment deintensification of HPV-positive OPC

Source: ww.pharmacytimes.com
Author: Bryan Fitzgerald, PharmD, BCOP
Health-System Edition, July 2021, Volume 10, Issue 4

Oropharyngeal cancer (OPC) is a type of head and neck cancer that affects structures in the back of the throat, including the base of the tongue, the posterior pharynx, the soft palate, and the tonsils.1 In the United States, rates of OPC are increasing each year, with an estimated 54,010 new cases in 2021.2 Well-established risk factors include alcohol abuse; exposure to tobacco, including chewing tobacco, cigarettes, and pipes; and infection with human papillomavirus (HPV).

With an estimated 43 million infections in 2018, HPV is the most common sexually transmitted infection in the United States.3 HPV infection is causally linked with cancers of the anogenital region, including anal, cervical, penile, vaginal, and vulvar cancers. When HPV is spread orally, infections can also lead to the development of OPC. In the United States, more than 70% of OPC cases are caused by HPV.4

HPV is a group of more than 100 viruses, including certain high-risk strains associated with the development of cancer. The HPV-16 strain is responsible for causing the majority of HPV-positive (HPV+) OPC cases, with HPV-18, HPV-33, and HPV-35 also contributing, albeit significantly less than HPV-16.1 In these high-risk HPV strains, the viral genome encodes several oncogenic proteins that inhibit tumor suppressor proteins, leading to chromosomal instability and malignancy in infected cells.

HPV+ OPC is considered a genetically distinct form of OPC. Compared with HPV-negative (HPC–) OPC cases, HPV+ OPC is associated with a favorable prognosis with improved rates of response prognosis with improved rates of response to treatment and overall survival. Because of the difference in tumor biology, the National Comprehensive Cancer Network (NCCN) has adopted different staging criteria for HPV+ and HPV– disease and recommends that HPV status be used to stratify patients with OPC.1

The treatment landscape for localized OPC typically involves a multidisciplinary approach consisting of chemotherapy, radiation, and/or surgery. For fit patients with locally advanced OPC who are able to tolerate intensive therapy, concurrent radiation with systemic high-dose cisplatin chemotherapy is the preferred treatment regimen.1 Unfortunately, treatment of OPC is associated with a high risk of treatment-related morbidity, which may leave patients cured of their malignancy but with lifelong complications, such as dysgeusia, dysphagia, and xerostomia, but also systemic complications from cisplatin chemotherapy, including hearing loss and neurotoxicity.

Because patients with HPV+ OPC are generally younger with more favorable prognoses, clinicians have hypothesized that less intensive treatment could result in fewer long-term complications from treatment but with continued favorable cancer-related outcomes.5 This concept, called deintensification, has become popular in recent years. Several strategies for treatment deintensification have been proposed, including reducing the dose of radiation; substituting cisplatin for an alternative agent with less toxicity, such as cetuximab; and surgical resection. Several phase 3 comparison trials have been conducted, and other trials are ongoing.

Aptly named De-ESCALaTE (NCT01874171), this phase 3 trial randomized patients with 334 HPV+ OPC to receive radiation plus cetuximab or cisplatin.6

Unfortunately, the trial results did not favor substitution of cisplatin with cetuximab. At 2 years, the incidence of severe toxicities did not significantly differ between cetuximab and cisplatin (P = .98), nor did rates of overall toxicities (P = .49). Significant differences in 2-year overall survival rates and recurrence rates were seen. However, these results favored cisplatin (HR, 5.0; P = .001 for overall survival; HR, 3.4; P = .0007 for recurrence).6

RTOG-1016 (NCT01302834) was a second phase 3 trial published comparing cetuximab with cisplatin in HPV+ OPC patients.7 This trial analyzed 805 patients who were randomized to receive radiation plus cetuximab or cisplatin. Similar to the De-ESCALaTE trial, the RTOG-1016 trial results favored cisplatin over cetuximab, with 5-year overall survival rates of 84.6% versus 77.9%.8

Because of the De-ESCALaTE and RTOG-1016 results, experts advise against the substitution of cisplatin for chemoradiation regimens for patients with localized HPV+ OPC, and cisplatin plus radiation continues to be the preferred systemic treatment option per the NCCN guidelines.1,5 Because cisplatin continues to be standard of care for the treatment of localized OPC, the role of deintensification for patients with HPV+ OPC may lie in adjustments to surgical strategies or radiation therapy. Treatment deintensification should be pursued only through clinical trials, and experts encourage clinicians to conduct and analyze phase 2 trials before moving on to phase 3 studies.1,5

CONCLUSION
The treatment landscape of cancer is ever-changing. Specifically in localized HPV+ OPC, the difference in tumor biology presents a unique clinical area where reducing the intensity of treatment may be warranted, particularly with long- and short-term toxicities associated with cisplatin. Interestingly, phase 3 data have shown evidence of harm in removing cisplatin from chemoradiation regimens for HPV+ OPC; therefore, cisplatin-based chemoradiation remains the standard of care for these patients. Future trials may support treatment deintensification in ways other than removing cisplatin.

REFERENCES
1. NCCN. Clinical Practice Guidelines in Oncology. Head and neck cancers, version 3.2021. Accessed June 16, 2021. https://www.nccn.org/professionals/physician_gls/pdf/head-and-neck.pdf

2. Cancer stat facts: oral cavity and pharynx cancer. National Cancer Institute. Accessed June 16, 2021. https://seer.cancer.gov/statfacts/html/oralcav.html

3. Genital HPV infection – fact sheet. CDC. Updated January 19, 2021. Accessed June 17, 2021. https://www.cdc.gov/std/hpv/stdfact-hpv.htm
4. HPV and oropharyngeal cancer. CDC. Updated September 3, 2020. Accessed June 17, 2021. https://www.cdc.gov/cancer/hpv/basic_info/hpv_oropharyngeal.htm

5. Mehanna H, Rischin D, Wong SJ, et al. De-escalation after DE-ESCALATE and RTOG 1016: a head and neck cancer intergroup framework for future de-escalation studies. J Clin Oncol. 2020;38(22):2552-2557. doi:10.1200/JCO.20.00056

6. Mehanna H, Robinson M, Hartley A, et al; De-ESCALaTE HPV Trial Group. Radiotherapy plus cisplatin or cetuximab in low-risk human papillomavirus-positive oropharyngeal cancer (De-ESCALaTE HPV): an open-label randomised controlled phase 3 trial. Lancet. 2019;393(10166):51-60. doi:10.1016/S0140-6736(18)32752-1

7. Gillison ML, Trotti AM, Harris J, et al. Radiotherapy plus cetuximab or cisplatin in human papillomavirus-positive oropharyngeal cancer (NRG Oncology RTOG 1016): a randomised, multicentre, non-inferiority trial. Lancet. 2019;393(10166):40-50. doi:10.1016/S0140-6736(18)32779-X

8. Gardasil 9. Prescribing information. Pfizer; 2017. Accessed June 23, 2021. https://www.fda.gov/fi les/vaccines,%20blood%20&%20biologics/published/Package-Insert—Gardasil.pdf

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.

Naveris’ new saliva test detects head and neck cancer

Source: www.biospace.com/
Author: staff

A new clinically-validated saliva test has been shown to detect HPV-associated head and neck cancer with high accuracy, a first-of-its-kind study result.

Researchers at Washington University School of Medicine in St. Louis used the Naveris, Inc. test to analyze saliva for sequences of the human papilloma virus (HPV) genome that are specific for HPV DNA released from malignant tumors. The test successfully distinguishes this tumor-tissue modified virus from non-cancerous sources of HPV DNA and precisely measures the number of tumor-tissue modified viral HPV (TTMV-HPV) DNA strands present in a saliva sample.

The study results point to the potential for a significant improvement in early detection of the most common type of head and neck cancer, HPV-associated oropharyngeal squamous cell carcinoma.

“Naveris’ patient-friendly saliva test has the potential to radically advance early detection of HPV-positive head and neck cancer, which has been growing rapidly among men in the United States. Early detection of these cancers would make a dramatic difference in patient outcomes,” said Piyush Gupta, PhD, CEO of Naveris.

The study quantified participants’ tumor-tissue modified viral HPV DNA in saliva samples and compared it to the levels found in their blood by utilizing Naveris’ NavDx® test. The results showed that TTMV-HPV DNA was commonly found in the saliva of HPV-associated head and neck cancer patients (44/46 cases), and at 18 times higher levels in the saliva samples than in the blood samples. One sample had undetectable TTMV-HPV and one was indeterminate for HPV DNA.

Washington University researchers are presenting an abstract of the study at the American Society of Clinical Oncology (ASCO) 2021 annual meeting.

“The results of our study highlight the potential of accurately analyzing saliva to improve the early detection of HPV-associated oropharyngeal squamous cell carcinoma. If validated in larger studies, this test could lead to earlier diagnosis and treatment,” said the study’s principal investigator Jose P. Zevallos, MD, chief of the division of Head and Neck Surgery in the Department of Otolaryngology at Washington University School of Medicine.

Naveris’ new saliva test is based upon the proprietary technology employed by the NavDx® blood test that is in use at centers of excellence treating HPV-associated oropharyngeal cancer across the United States. NavDx® is a liquid biopsy test that detects HPV-associated head and neck cancer earlier than is possible with imaging and is provided exclusively in the United States through the Naveris national reference CAP-accredited laboratory.

About Oropharyngeal Cancer:
Oropharyngeal cancer, which can develop at the base of the tongue, tonsils, and the middle part of the throat, used to be closely associated with smoking and heavy drinking. Today, however, oropharyngeal cancer is primarily caused by human papillomavirus (HPV) infection, 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.1

Cases of HPV-positive oropharyngeal cancer have been increasing at an exponential rate among men in the United States over the last two decades2. About 54,000 cases of oropharyngeal and oral cavity cancer are expected in the nation this year and more than 10,000 deaths.3

Oropharyngeal cancers usually are not identified early because they grow slowly in locations that are not easy to see. By the time the cancers are recognized they frequently have spread to the lymph nodes and are difficult to treat. Early detection, however, enables highly effective treatment.

About Naveris, Inc.
Naveris, Inc. is a molecular diagnostics company developing and commercializing novel blood and saliva tests to enhance the early detection and clinical management of viral-associated cancers. The company’s NavDx® blood test, which uses proprietary technology to detect tumor tissue modified HPV, is in use at leading cancer treatment centers and academic medical centers throughout the United States.

New therapy shortens treatment for HPV-related cancers of the tonsils, tongue

Source: medicalxpress.com
Author: From Mayo Clinic News Network, Mayo Clinic News Network

Patients with HPV-related oropharyngeal cancer who undergo surgery and are treated with chemotherapy, may be able to forgo significant radiation therapy without increasing the risk of their cancer spreading, according to the results of a clinical trial led by researchers at Mayo Clinic.

“We found that decreasing the amount of radiation therapy after a minimally invasive robotic surgery improved the quality of life of patients with HPV-related oropharyngeal cancer while delivering excellent cure rates,” says Dr. Eric Moore, a Mayo Clinic otolaryngologist. “In essence, we found exactly the right amount of treatment to deliver without over-treating these patients.”

Dr. Moore and his colleagues compared 79 patients treated at Mayo Clinic for HPV-related tonsil and tongue cancer with surgery and two weeks of radiation therapy to a group of 115 patients with the same cancer who were treated with surgery, and the standard six weeks of radiation therapy and chemotherapy.

Dr. Moore and his colleagues found no decrease in survival or cancer recurrence in the group that received two weeks of radiation therapy, compared to the group that received six weeks of radiation therapy. He says that by decreasing the amount of radiation therapy after minimally invasive robotic surgery, physicians were able to improve the quality of life of patients and achieve excellent cure rates.

“In essence, we found exactly the right amount of treatment to deliver without overtreating,” says Dr. Moore.

Dr. Moore says Mayo Clinic now offers dose de-escalation radiation therapy to appropriately selected patients with HPV-related cancers of the tonsils and tongue.

“This approach shortens the treatment time for these patients by several weeks and reduces side effects without sacrificing the effectiveness of the treatment,” Dr. Moore says.

Genetic changes in head and neck cancer, immunotherapy resistance identified

Source: MedicalXPress
Date: April 26th, 2021
Author: University of San Diego-California

A multi-institutional team of researchers has identified both the genetic abnormalities that drive pre-cancer cells into becoming an invasive type of head and neck cancer and patients who are least likely to respond to immunotherapy.

“Through a series of surprises, we followed clues that focused more and more tightly on specific genetic imbalances and their role in the effects of specific immune components in tumor development,” said co-principal investigator Webster Cavenee, Ph.D., Distinguished Professor Emeritus at University of California San Diego School of Medicine.

“The genetic abnormalities we identified drive changes in the immune cell composition of the tumors that, in turn, dictates responsiveness to standard of care .”

Reporting in the April 26, 2021 online issue of the Proceedings of the National Academy of Sciences, researchers describe the role of somatic copy-number alterations—abnormalities that result in the loss or gain in a copy of a gene—and the loss of chromosome 9p in the development of human papillomavirus (HPV)-negative and .

The loss of chromosome 9p and the deletion of JAK2 and PD-LI, two neighboring genes found on chromosome 9p, was associated with resistance to immune checkpoint inhibitors, a type of cancer immunotherapy that uses antibodies to make tumor cells visible to a patient’s immune system.

“Although programmed death-1 (PD-1) immune checkpoint inhibitors represent a major breakthrough in , only 15 percent of patients with HPV-negative head and neck cancer respond to treatment,” said co-principal investigator Scott M. Lippman, MD, senior associate dean, associate vice chancellor for and care and Chugai Pharmaceutical Chair in Cancer at UC San Diego School of Medicine.

“The ability to predict a patient’s response or resistance to this class of therapies, a major unmet clinical need, is a unique and novel discovery. Knowing who will not respond avoids losing several months to ineffective therapy with huge financial costs and impacts to quality of life,” said Lippman, director of UC San Diego Moores Cancer Center and medical oncologist who specializes in the treatment of patients with head and neck cancer at UC San Diego Health, San Diego’s only National Cancer Institute-designated comprehensive cancer center.

For this study, co-led by New York University Langone Health’s Teresa Davoli, Ph.D., and The University of Texas MD Anderson Cancer Center’s William N. William, MD, with co-investigator Steve Dubinett, MD, of UCLA Jonsson Comprehensive Cancer Center, researchers prospectively followed 188 patients at MD Anderson Cancer Center to study genomic and immune drivers of the transition to invasive HPV-negative head and neck cancer. They reviewed comprehensive genomic and transcriptomic data of 343 HPV-negative head and neck cancer patients from The Cancer Genome Atlas and 32 HPV-negative head and neck cancer cell lines from the Cancer Cell Line Encyclopedia project, and analyzed patient survival after immunotherapy in real-world evidence cohort data from Caris Life Sciences.

In 2021, the National Cancer Institute estimates approximately 54,000 new cases of head and neck cancers will be diagnosed in the United States, with 10,850 deaths. HPV-negative head are the most common, increasing and lethal subtype of this malignancy worldwide, said Lippman.

“The data serves as a powerful predictive marker, transforming standard of care for precision immunotherapy for patients with advanced, recurrent head and ,” said Lippman. “And, while we focused in an unprecedented extensive interrogation of the most globally lethal form of head and neck squamous cancer, accounting for more than 300,000 deaths annually, the application may be useful in a wide variety of solid tumors for which immune checkpoint inhibitors comprises standard of care.”

Dental Professionals Should Remember the HPV Vaccine Too

Source: Dentistry Today
Date: April 13th, 2021
Author: Jo-Anne Jones

We live in a viral world as we patiently await the end of the COVID-19 pandemic. Many people already have chosen to be vaccinated to protect themselves from getting the virus, or, at the very least, minimize its severity.

The harsh nature of the pandemic has led to expediency in developing the vaccine, which has not been typical, historically speaking. While the COVID-19 vaccine took less than a year to develop, the mumps vaccine took four years. The polio vaccine took 13 years. The human papillomavirus (HPV), flu, and chicken pox vaccines took 17, 27, and 28 years, respectively.

Looking back in the annals of history, we have the remarkable work of Edward Jenner to thank for his development of the first vaccine. His work involved deliberately infecting a human being with a mild dose of smallpox. His rigorous trials were controlled, repeatable, and documented in his 1798 publication, “An Inquiry Into the Causes and Effects of the Variolæ Vaccinæ.”

Jenner devoted the remainder of his life advocating for the safe and effective administration of the vaccine. In 1972, routine smallpox vaccination ended in the United States, followed by the World Health Organization declaring the disease’s elimination in 1980.

Another such vaccine victory is the polio vaccine, which was first available in the United States in 1955. Thanks to its widespread use, the United States has been polio-free since 1979.

And while the United States government has said that dentists can now administer the COVID-19 vaccine, there is another vaccine that we should bring to the attention of every adult who visits our practice: the HPV vaccine.

The Rise of Oropharyngeal Cancer

The fastest-growing segment of oropharyngeal cancers is attributed to HPV. Yet it can be prevented by the Gardasil HPV nine-valent vaccine (Gardasil 9 [9vHPV]). More than 270 million doses of the Gardasil HPV vaccine have been given worldwide, including 120 million doses in the United States.

Gardasil 9 is a non-infectious recombinant vaccine prepared from virus-like particles (VLPs) of the protein of HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58.

We accept vaccination due to perceived risk. Are your patients aware of the ubiquitous nature of this virus and the fact that merely being alive and sexually active may place them at inherent risk? Many of our patients who do not possess a history of tobacco or alcohol use do not perceive a risk of oral or oropharyngeal cancer.

But according to the Centers for Disease Control and Prevention, more than 70% of oropharyngeal cancers are related to HPV. HPV-related oropharyngeal cancer has now surpassed HPV-related cervical cancer as the leading HPV-associated cancer.

Cervical cancer used to be the leading cause of cancer death for women in the United States. But in the past 40 years, the number of cervical cancer cases and the number of cervical cancer deaths have decreased significantly. This decline is primarily the result of opportunistic screening practices and the HPV vaccine.

Most sexually active Americans will clear the virus without consequence. Many of them will not be aware of even having the virus. However, for persistent infection with a high-risk strain such as HPV-16, the risk for malignant transformation is real.

In 2020, the Food and Drug Administration approved an expanded indication for Gardasil 9 for the prevention of oropharyngeal and other head and neck cancers caused by HPV types 16, 18, 31, 33, 45, 52, and 58. The vaccine is also indicated to prevent cervical, vulvar, vaginal, anal, and penile cancer.

2021 is a year defined and impacted by an overstretched healthcare system. We have longer wait times and backlogs for cancer treatments than ever before. For a cancer that is essentially preventable by a vaccine, it is frustrating beyond words to know that many of our dental patients are unaware of its existence.

HPV is responsible for a small number of oral cancers, as the vast majority are caused by lifestyle behaviors including smoking and alcohol use—once again, preventable.

We are not powerless. Our patients do not have to fall victim to the collateral damage of COVID-19. We can encourage our patients to perform a self-examination of the oral cavity between professional visits. We can educate them about the subtle symptoms that may be associated with HPV-related oropharyngeal cancer.

A North American campaign entitled Check Your Mouth was developed to educate the public about the importance of oral self-examination. It is the result of collaboration between the Oral Cancer Foundation and Holland Healthcare, developer of the Throat Scope and TelScope.

The Throat Scope is the world’s first all-in-one illuminated tongue depressor. The TelScope is a seamless oral telehealth delivery system capable of capturing real-time high-resolution images and emailing them to an oral healthcare provider via encrypted email.

Empower your patients. Share the science that we are most fortunate to have and recognize that we can proactively fight back in a viral world.

Ms. Jones is an award-winning speaker who has given over a thousand presentations across the United States, Canada, England, Ireland, and Bermuda. She also joins the Dentistry Today’s Leaders in Continuing Education for the eleventh consecutive year. With her frank and open lecture style, focus on direct knowledge translation to practice, and educational and clinical resources, she has earned many loyal followers both nationally and internationally. She may be reached at jjones@jo-annejones.com.

 

2021-04-13T12:57:09-07:00April, 2021|OCF In The News|

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

Source: Good Morning, America
Date: April 2nd, 2021
Author: Kathleen Kindalen

 

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.”

More parents balking at giving kids cancer-fighting HPV vaccine

Source: www.usnews.com
Author: Steven Reinberg

From 2012 to 2018, more doctors recommended their patients get vaccinated with the HPV vaccine — from 27% to 49%. But at the same time, the number of parents who were reluctant to have their kids vaccinated increased from 50% to 64%, researchers found.

“Overall, more U.S. teens are getting the HPV vaccine, and the nation is making progress towards reaching the HPV vaccination goals; however, if parental reluctance continues to grow, the current rate of our progress might plateau or possibly decline,” said lead study author Kalyani Sonawane. She’s an assistant professor in the department of management, policy and community health at the University of Texas Health Science Center in Houston.

“In the long term, the lost opportunity to protect our teens from HPV might contribute to cases of HPV-associated cervical, oropharyngeal, penile, anal, vaginal and vulvar cancers in the future,” Sonawane said.

Parents’ reluctance to have their kids vaccinated rose more for girls, from 54% to 68%, compared with 44% to 59% for boys, the researchers noted. The report was published online Feb. 9 in the journal Pediatrics.

To increase the number of boys and girls who get vaccinated, doctors need to strongly recommend it, Sonawane said.

“Further improvements in provider recommendations can be made, given that it is the most important factor for improving HPV vaccine uptake,” she said. “Providers should be prepared to tackle hesitancy by conveying the importance of HPV vaccination to parents and debunking vaccine misinformation. Increasing vaccine confidence in parents will be key to attaining HPV vaccination goals in the U.S.”

The reluctance is largely due to safety concerns, Sonawane said. In a study, she and her colleagues found that the most common reason parents cite for their reluctant to HPV vaccine is concerns regarding adverse effects.

“The public message about the HPV vaccine should highlight that the vaccine protects against cancers. It is important to emphasize to parents that the vaccine offers protection for up to six cancers, because data indicates that many people are not aware of this fact,” Sonawane said.

In another study, Sonawane found that less than one-third of Americans know that HPV causes anal, penile and oral cancers.

Sonawane added that the anti-vaxxer movement is likely contributing to the growing reluctance of parents to have their children vaccinated, and she is concerned that the “negative coverage of the COVID vaccine will trickle down to HPV vaccine and affect perceptions regarding vaccines.”

HPV is a sexually transmitted infection that is the cause of most cervical, vagina and vulva cancers, penis cancer and cancer in the back of the throat. It can take years for these cancers to develop, but children can be protected by getting the HPV vaccine at ages 11 to 12, according to the U.S. Centers for Disease Control and Prevention.

One pediatrician unconnected to the study noted the importance of the marketing for the vaccine.

“When this vaccine first hit the market, they didn’t focus the messaging around it being a cancer preventer vaccine. They focused on the sexually transmitted infections,” said Dr. David Fagan, vice chairman of pediatric administration-ambulatory at Cohen Children’s Medical Center in New Hyde Park, N.Y.

Fagan believes, however, the message should be that the vaccine prevents cancer. “Wouldn’t you, as a parent, want to do everything you could for your child to prevent the possibility of your child getting a cancer — this vaccine does that,” he said.

He also thinks that the quality of the recommendation is key to convincing parents to vaccinate their children.

The American Academy of Pediatrics is doing a lot to educate pediatricians in motivational interviewing techniques, Fagan said.

The tetanus booster, the meningitis vaccine and the HPV vaccine are those recommended for adolescence.

Evidence shows, if you offer the HPV in first or second place as opposed to third place, parents are more likely to opt for it, Fagan said.

“If you do tetanus, meningitis, HPV, they are less likely to accept HPV, but if you put HPV first or even second, there’s evidence that there’s better uptake. So messaging is really, really important,” he said.

The vaccine is safe, Fagan said. A study has shown that no serious side effects have been seen since the vaccine was released.

“You know these things on social media about the safety of the vaccine, obviously that’s crazy stuff,” he said.

“I tell parents if this vaccine was unsafe, it would have been pulled from the market,” Fagan said. “Additionally, you would be reading about multimillion dollar legal settlements in the press, and that has not happened. So the take-home message is this vaccine is safe and effective in preventing cancers caused by HPV.”

More information
For more on the HPV vaccine, go to the U.S. Centers for Disease Control and Prevention.

Sources:
Kalyani Sonawane, Ph.D., assistant professor, department of management, policy and community health, University of Texas Health Science Center at Houston; David Fagan, MD, vice chairman, Pediatric Administration-Ambulatory, Cohen Children’s Medical Center, New Hyde Park, N.Y.; Pediatrics, Feb. 9, 2021, online

2021-02-10T10:56:54-07:00February, 2021|Oral Cancer News|
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