Tech innovation offers hope for head/neck cancer treatment

Source: www.miragenews.com Author: University of Colorado Anschutz Medical Campus Over the past decade, human papillomavirus (HPV) has increasingly been identified as a significant cause of certain head and neck cancers – for example, evidence suggests it causes 70% of oropharyngeal cancers in the United States. Further, over the past three decades, incidence of HPV-driven cancers has increased substantially worldwide and in the U.S. While there are well-established screening tools, as well as vaccines, for HPV-driven cancers such as cervical cancer, there are fewer resources for HPV-driven head and neck cancers. As a result, researchers are working with a sense of urgency to develop innovative therapeutics to treat them. One groundbreaking therapeutic has shown significant promise in a phase 1 clinical trial led by Antonio Jimeno, MD, PhD, co-leader of the University of Colorado Cancer Center Developmental Therapeutics Program and the CU Cancer Center head and neck cancer SPORE grant. Research results published today show that a microfluidic squeezing technology used on peripheral blood mononuclear cells (PBMCs), a type of immune cell, helps stimulate anti-tumor activity in a subtype of HPV16-positive cancers, including head and neck, cervical, and anal cancers. “This technology is quite novel,” Jimeno explains. “As opposed to other cell therapies that require a patient’s cells to be genetically modified, this involves a different way of manipulating cells that does not lead to genetic modifications. It makes the process faster and perhaps more agile as to what you can direct the cells against.” “Sending them to boot camp” This [...]

HPV, PD-L1 move to the forefront of biomarkers for head and neck cancers

Source: www.onclive.com Author: Silas Inman The frontline treatment for patients with head and neck cancer is largely dominated by surgery and radiation therapy, with ongoing efforts to find biomarkers and other strategies to better individualize care. The leading markers used to tailor therapy are human papillomavirus (HPV) status, which typically signals the aggressiveness of the disease, and PD-L1 expression level, which may help guide selection of immune checkpoint inhibitor (ICI) therapy. These markers are gaining notice in different settings. HPV status has broad applicability across head and neck cancers, whereas the clinical utility of PD-L1 expression remains a more nuanced question. HPV-Positive Tumors Approximately 70% of head and neck cancers, specifically oropharyngeal cancers, are positive for HPV, with most cases associated with the HPV-16 subtype. These tumors appear most commonly in nonsmoking White men with a mean age of diagnosis of 60.3 years (SD, 10.8) for oropharyngeal cancer and 63.2 years (SD, 12.7) for other types of head and neck cancers.1,2 Moreover, HPV-positive tumors typically fall into a low- to intermediate-risk category, with 5-year overall survival (OS) outcomes far superior compared with rates for HPV-negative tumors, which are typically caused by smoking. For patients with HPV-associated head and neck cancers, the 5-year OS rate ranges from 75% to 80% compared with 45% to 50% for those with HPV-negative tumors.3 In many cases, although the prognosis is more favorable for patients with HPV-positive tumors, the treatment is the same as it is for HPV-negative tumors. However, with the introduction of ICIs [...]

CUE-101 gets fast tracked for recurrent/metastatic head and neck squamous cell carcinoma

Source: www.onclive.com Author: Kristi Rosa The FDA has granted a fast track designation to CUE-101 for use as a monotherapy and in combination with pembrolizumab (Keytruda) in patients with human papillomavirus (HPV16+) recurrent or metastatic head and neck squamous cell carcinoma (HNSCC).1 CUE-101 is an off-the-shelf therapy that was designed to trigger and expand HPV16 tumor-specific T cells by exhibiting 2 cues to T cells. The first signal includes the HPV E7 protein, which is harbored by HPV-induced cancer cells and interacts with the HPV-specific T-cell receptor to offer selectivity. The second signal is comprised of an engineered interleukin-2 variant that fuels T cell activity. “We are very pleased to have received fast track designation from the FDA for CUE-101. This designation not only underscores the large unmet need for patients with recurrent/metastatic head and neck cancer who currently rely on available non-targeted therapies, but also highlights the potential of CUE-101 to provide a significant clinical benefit,” Matteo Levisetti, MD, senior vice president of Clinical Development at Cue Biopharma, Inc., stated in a press release. Previously, investigators evaluated the potential of CUE-101 to selectively activate and expand HPV16 E7–specific CD8-positive T cells in patients with HPV-driven cancers, including HNSCC, cervical cancer, and anal cancer.2 To showcase the activity of the product, human E7-specific T cells and peripheral blood mononuclear cells (PMBCs) were tested. To evaluate the in vivo activity of CUE-101, investigators evaluated the product in HLA-A2 transgenic mice. The agent was found to selectively bind, activate, and expand HPV16 [...]

OmniPathology announces the launch of its oropharyngeal HPV PCR test

Source: www.globenewswire.com Author: press release OmniPathology, an independent, physician-owned and operated pathology lab, today announced the launch of a new oral test for human papillomavirus (HPV) that can cause cancer. The Oral HPV Test is a lab-developed test (LDT) performed on a Roche cobas® 6800 and 8800 high-throughput platforms. The Oral HPV Test detects 14 high-risk strains of HPV. It is performed via a throat swab submitted to OmniPathology, a CLIA-certified laboratory in Pasadena, for testing. Patients who test positive are advised to undergo a thorough examination by an ear, nose, and throat (ENT) doctor and may require close follow-up. Detection and removal of early oral and oropharyngeal premalignant lesions can help significantly reduce the risk of progression to cancer. This test will be offered to primary care and GYN physicians, LGBTQIA+ clinics, dentists, oral surgeons, and ENT practices across the country as part of routine examinations of patients. “Launching this oropharyngeal HPV test is an exciting milestone for OmniPathology, especially since this is an underserved area for diagnostic testing. As an organization led by science and driven by service, OmniPathology continues to offer state-of-the-art molecular testing that can impact patient care and enhance the quality of the services our physician clients offer to their patients,” said Mohammad Kamal M.D., founder and CEO of OmniPathology. “We continue to build our testing menu to target sexually transmitted infections and other viral diseases.” Oral HPV has no symptoms and is spread through skin-to-skin contact. Risk factors for oral HPV include oral sex, [...]

NF-κB over-activation portends improved outcomes in HPV-associated head and neck cancer

Source: medicalxpress.com Author: staff, Impact Journals LLC A new research paper has been published in Oncotarget, titled "NF-κB over-activation portends improved outcomes in HPV-associated head and neck cancer." Head and neck squamous cell carcinoma (HNSCC) is a devastating disease that impairs fundamental tissues involved in respiration, phonation and digestion. HNSCC is primarily caused by exposure to either ethanol and tobacco or the human papillomavirus (HPV). Among patients with HPV+ HNSCC, there is a growing clinical demand to develop robust stratification tools to accurately identify patients with good or poor prognosis. According to the research, "While oncologic outcomes for HPV+ HNSCC are generally favorable, treatment paradigms developed for HPV-negative disease burden many survivors of HPV+ HNSCC with lifelong debilitating treatment-associated side effects. On the other hand, ~30% of HPV+ HNSCC patients exhibit a more aggressive disease course and suffer recurrence." Somatic mutations or deletions in TRAF3 or CYLD identified a subset of HPV+ HNSCC associated with improved outcome. A cross talk between canonical and non-canonical NF-κB signaling suggests that TRAF3 and CYLD affect both NF-κB pathways. "Herein, we demonstrate that an RNA-based classifier trained on tumors harboring these mutations may improve prognostic classification," state the researchers. To improve on genomic classification, the researchers designed the current study to provide a foundation for development of NF-κB related, RNA based classification strategies to better identify HPV+ HNSCC patients with good or poor prognosis that could potentially aid in future efforts towards treatment personalization. "This report validates and expands on our findings that significant [...]

Trial underway for novel agent plus immunotherapy for HPV-related head and neck cancer

Source: www.curetoday.com Author: Brielle Benyon Results from a phase 2 clinical trial demonstrated promise for the combination of the novel agent PDS0101 plus Keytruda (pembrolizumab) in treating human papillomavirus (HPV)-associated head and neck cancer. As such, the trial will now progress to full enrollment of 54 patients who have not been previously treated with a checkpoint inhibitor. The trial, VERSATILE-002, involves two groups of HPV16-positive patients with head and neck cancer that is either metastatic or has returned after treatment. One group consists of patients who have no prior treatment with checkpoint inhibition immunotherapy, while the other group is made up of 21 patients whose disease failed checkpoint inhibition — assessment for this group is still ongoing. In the checkpoint inhibitor-naïve group, four or more of the 17 patients achieved an objective response, which was classified by a 30% or more reduction in tumor size. “The achievement of this important milestone in the VERSATILE-002 phase 2 clinical trial strengthens the evidence of our novel Versamune platform’s potential ability to induce high levels of tumor-specific CD8+ killer T-cells that attack the cancer to achieve tumor regression,” commented Dr. Lauren V. Wood, Chief Medical Officer of PDS Biotech, the developer of PFS101, in a statement. “The initial data solidifies our belief that PDS0101’s demonstrated preclinical efficacy when combined with Keytruda has the potential to significantly improve clinical outcomes for patients with advanced HPV16-positive head and neck cancers.” PDS0101 works by inducing large quantities of CD4+ helper and CD8+ killer T cells, a [...]

2022-02-03T10:51:38-07:00February, 2022|Oral Cancer News|

New MSK radiation approach means fewer side effects for more patients with HPV-related head and neck cancer

Source: www.mskcc.org Author: Memorial Sloan Kettering Cancer Center Robert Rosenfeld thought the lump he felt in his neck in late 2018 was just a symptom of a cold that wouldn’t go away. He visited an ear, nose, and throat specialist who saw nothing upon first examination, but Robert knew something was wrong and asked for a CT scan. The specialist called him with the bad news: It was almost certainly cancer. A biopsy confirmed he had stage 2 cancer at the base of his tongue and 2 nearby lymph nodes. The tumor was positive for the human papillomavirus (HPV). Robert, then a 69-year-old car salesman on Long Island, met with cancer doctors near his hometown of Hauppauge, New York, to learn about treatment options. He realized he faced a tough road: Standard treatment would be 7 weeks of radiation, during which he also would receive 3 rounds of chemotherapy. The standard radiation dose would likely cause mouth sores, difficulty swallowing, dry mouth (from damage to salivary glands), loss of taste, and nausea. Robert wanted a second opinion, and his medical oncologist strongly recommended Memorial Sloan Kettering Cancer Center. When Robert called, he was able to get in to see radiation oncologist C. Jillian Tsai the very next day. “When I met Dr. Tsai, she was amazing,” Robert says. “She told me what I was up against but also that the cancer I had was curable.” There was another major plus: Dr. Tsai was able to offer a significantly reduced radiation [...]

Molecular profiling identifies potential prognostic biomarker for treatment response in HNSCC

Source: www.ajmc.com Author: Matthew Gavidia Human papillomavirus surrogate marker p16 was identified as a potential prognostic biomarker for standard-of-care immune checkpoint blockade therapy response in non-oropharyngeal head and neck squamous cell carcinoma. Real-world overall survival among patients with oropharyngeal squamous cell carcinoma (OPSCC) and non-OP head and neck squamous cell carcinoma (HNSCC) differed significantly based on the presence of the human papillomavirus (HPV) surrogate marker p16, with further implications identified regarding time on treatment with immune checkpoint blockade (ICB) therapies. Findings were published in Cancers. Identified as the sixth most common cancer worldwide with incidence expected to increase by 32% in the next 2 decades, patients with recurrent and/or metastatic HNSCC typically have a poor prognosis. Although diagnosis of HNSCC is typically related to tobacco and alcohol use, incidence of HPV-associated HNSCC has risen substantially, in which those positive for the virus whose HNSCC stems in the oropharynx have exhibited better survival outcomes. Researchers sought to further investigate the association of HPV and/or its surrogate marker p16 with response to standard-of-care ICB therapies in patients with OPSCC and non-oropharyngeal (non-OP) HNSCC. “We also investigated other potential biomarkers and mutations that may predict improved response to ICB in both HPV-positive and -negative patients with HNSCC,” they added. Patients registered in the Caris Life Sciences CODEai database with non-OP HNSCC and OPSCC were recruited and identified by comprehensive molecular profiling to be positive or negative for p16. In total, 2905 HNSCC (OPSCC, n = 948) cases were identified. Of those tested for [...]

Achieving an 80% HPV vaccination rate could eliminate nearly 1 million cases of male oropharyngeal cancer this century

Source: medicalxpress.com Author: University of Texas Health Science Center at Houston A nationwide effort to adequately vaccinate 8 in 10 adolescents against the human papillomavirus (HPV) could prevent 934,000 cases of virus-associated, male oropharyngeal cancer over this century, reported investigators at The University of Texas Health Science Center at Houston (UTHealth Houston) School of Public Health in The Lancet Regional Health—Americas. At the start of each decade, the Healthy People program of the U.S. Department of Health and Human Services establishes goals to reduce the most significant preventable threats to health, which include an 80% target for the HPV vaccination program. However, in the U.S., just 54% of adolescents and only 21% of young adults were adequately vaccinated as of 2019. To gage the effect of accomplishing an 80% target on male oropharyngeal cancer, the most common cancer caused by HPV, UTHealth Houston researchers created a simulation model to project the development of this cancer over a lifetime and to measure the impact of the HPV vaccination. "Our study is the first to develop and validate a comprehensive mathematical modeling framework of the natural history of oral HPV infection and its progression to oropharyngeal cancer," said Ashish A. Deshmukh, Ph.D., MPH, the study's senior author and an associate professor in the Department of Management, Policy and Community Health and associate director of the Center for Health Services Research at UTHealth School of Public Health. "Achievement of the 80% goal by 2025 and maintaining it could lead to the prevention of [...]

2021-12-16T08:47:19-07:00December, 2021|Oral Cancer News|

Liquid biopsy provides accurate, fast Dx of HPV-associated head and neck cancer

Source: www.medpagetoday.com Author: Mike Bassett, Staff Writer, MedPage Today The use of liquid biopsy for the diagnosis of human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) was more accurate, faster, and less expensive than standard tissue-based biopsies, according to a prospective observational study. The sensitivity and specificity of this circulating tumor HPV DNA-based approach were 98.4% and 98.6%, respectively, with positive and negative predictive values of 98.4% and 98.6%, reported Daniel L. Faden, MD, of Massachusetts General Hospital and Harvard Medical School in Boston, and colleagues. The diagnostic accuracy of this non-invasive approach was significantly higher than standard of care (Youden index 0.968 vs 0.707, P<0.0001), they noted in Clinical Cancer Research. In addition, liquid biopsy reduced the time to diagnosis from a median of 41 days to 15 days, and estimated costs associated with this method were about 36% to 38% less than the traditional biopsy approach. "Currently the way we diagnose HPV-associated cancer is either with a needle biopsy of a neck lymph node or a tissue biopsy from the oropharynx -- and these approaches have a couple of different limitations," Faden told MedPage Today. Not only are they invasive and painful for patients, but needle biopsy of a neck lymph node has high failure rates due to a lack of adequate cellular material. "So, patients might have to undergo a repeat biopsy to get the diagnosis we are waiting for," he noted. "That adds time to diagnosis, and we know that time from presentation to [...]

2021-12-03T05:54:26-07:00December, 2021|Oral Cancer News|
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