human papilloma virus

Antibodies against HPV16 can develop up to 40 years before throat cancer is diagnosed

Source: www.eurekalert.org
Author: news release

An international group of researchers has found that antibodies to the human papilloma virus type 16 (HPV16) develop in the body between six to 40 years prior to a clinical diagnosis of throat cancer, and their presence indicates a strong increased risk of the disease.

The study, which is published in the leading cancer journal Annals of Oncology [1] today (Wednesday), also found that having HPV16 antibodies increased the risk of throat cancer far more in white people than in black: nearly 100-fold in white people, but 17-fold in black people.

Patients with HPV-associated throat cancer tend to respond better to treatment than those whose cancer is not associated with the infection; the researchers say this may partly explain the worse survival rates among black patients.

The main causes of throat cancer (known as oropharyngeal squamous cell carcinoma, OPSCC) are smoking, alcohol use and infection with HPV16. In the USA the proportion of OPSCCs attributable to HPV16 is around 70%; in some European countries a similar proportion is caused by HPV16, although this varies from country to country. [2]

Dr Mattias Johansson, a cancer epidemiologist at the International Agency for Research on Cancer (IARC) in Lyon, France, who led the research, said: “Importantly, the proportion of throat cancers caused by HPV16 has been increasing over the past few decades, particularly in men, and in some countries the overwhelming majority are now caused by the virus.

“Investigating the range in time prior to diagnosis in which HPV antibodies develop is important to understand how many years an individual who tested positive would be at increased risk, and also gives important insight into the natural history of the disease. In this study we found that antibodies can, in some cases, develop several decades prior to diagnosis of cancer. If rates of throat cancer continue to rise in the future, this biomarker could provide one means to identify individuals at very high risk of the disease who may benefit from specific preventive measures.”

The researchers from Europe, North America and Australia, who were part of the HPV Cancer Cohort Consortium, looked at 743 patients with throat cancer and compared them with 5,814 people without cancer who were the control group [3]. In the years before any diagnosis of cancer, all patients provided at least one blood sample, which was tested for antibodies against the HPV16 cancer-causing E6 protein, and 111 patients provided multiple samples over a period of up to 40 years. The median (average) time between first blood sample collection and a diagnosis of OPSCC was just over 11 years.

Specifically, they found that HPV antibodies were present in only 0.4% of people in the control group (22 out of 5814), but were detected in 26.2% of OPSCC patients (195 out of 743). Antibodies were present in 27.2% of white people before diagnosis with OPSCC (191 of 701) and in 7.7% of black people (3 of 39). This means that the presence of HPV16 antibodies was associated with a 98.2-fold increase in the risk of OPSCC in white people and a 17.2-fold increase in black people.

The first author of the study, Dr Aimée Kreimer, senior investigator at the Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, USA, said: “We also found that people diagnosed in more recent calendar years were more likely to have HPV antibodies, which is consistent with what we know about the increase in the proportion of throat cancers that are due to HPV16. Although there were some people with HPV antibodies detected prior to 1995, this was relatively rare.”

The researchers found that HPV16 antibodies tended to appear in people aged between about 40 to 80 years old – the median age at which antibodies were detected was 52 years, while the median age of diagnosis with OPSCC was 62. As there is no suitable, evidence-based way to test for OPSCC before symptoms appear, more research will be needed before HPV16 antibodies could be used to detect OPSCC in its early, pre-symptomatic stages.

Dr Kreimer said: “Although HPV16 antibodies could be a way to identify people at very high risk of cancer, we are currently missing the critical next steps in the screening process. Also, even though the antibody marker was very good at discriminating between those who would develop cancer and the controls who would not, with such a rare cancer, many people would still be likely to have a false-positive results.”

Dr Johansson concluded: “Future studies will focus on the most appropriate way to follow-up individuals who test positive for HPV16 antibodies and whether there is a way to identify pre-malignant lesions, as well as alternative ways of reducing the risk of eventually developing OPSCC. In other words, there is a long way to go before this biomarker can be used in clinical practice. While vaccination against HPV holds promise in preventing HPV-related cancers, we will not see a resulting reduction in throat cancers for several decades.”

Reasons why HPV16-driven throat cancer has increased in recent decades include changes in sexual practices that started in the middle of the 20th century and a decrease in tonsillectomy rates, which results in more tissue being available for infection by the virus.

The main limitation of the study is the difference between the groups of patients who took part in the study. For example, the group with the longest period of time between first collection of blood and diagnosis of OPSCC came from Norway, while other patient groups tended to have fewer blood samples collected over shorter timescales.

The research was carried out in collaboration with Dr Tim Waterboer, Head of Infection and Cancer Epidemiology, at the German Cancer Research Centre (DKFZ) in Heidelberg, Germany, who developed the HPV16 antibody test.

Notes:
[1] “Timing of HPV16-E6 antibody seroconversion before OPSCC: findings from the HPVC3 consortium”, by A.R. Kreimer et al. Annals of Oncology. doi:10.1093/annonc/mdz0138

[2] Oropharyngeal cancer starts inside the throat directly behind the nose, and can include the base of the tongue and tonsils. It is still a relatively rare cancer. Worldwide there are approximately 500,000 cases of head and neck cancers, of which OPSCC is one type. It is twice as common in men as in women.

[3] Of the 743 OSCC patients, 66% were from Europe, 30% from North America and 4% from Australia.

HPV infection may be behind rise in vocal-cord cancers among young nonsmokers

Source: www.eurekalert.org
Author: Public Release Massachusetts General Hospital

A remarkable recent increase in the diagnosis of vocal-cord cancer in young adults appears to be the result of infection with strains of human papilloma virus (HPV) that also cause cervical cancer and other malignancies. Investigators from Massachusetts General Hospital (MGH) describe finding HPV infection in all tested samples of vocal-cord cancer from 10 patients diagnosed at age 30 or under, most of whom were non-smokers. Their report appears in a special supplement on innovations in laryngeal surgery that accompanies the March 2019 issue of Annals of Otology, Rhinology and Laryngology.

“Over the past 150 years, vocal-cord or glottic cancer has been almost exclusively a disease associated with smoking and almost entirely seen in patients over 40 years old,” says Steven Zeitels, MD, director of the MGH Division of Laryngeal Surgery, senior author of the report. “Today nonsmokers are approaching 50 percent of glottic cancer patients, and it is common for them to be diagnosed under the age of 40. This epidemiologic transformation of vocal-cord cancer is a significant public health issue, due to the diagnostic confusion it can create.”

The researchers note that the increase in vocal-cord cancer diagnosis appears to mimic an earlier increase in the diagnosis of throat cancer, which has been associated with infections by high-risk strains of HPV. After initially attributing incidents of vocal-cord cancer in nonsmokers, which they began to see about 15 years ago, to increased travel and exposure to infectious diseases, Zeitels and his colleagues decided to investigate whether HPV infection might explain the diagnosis in younger nonsmokers.

To do so they examined the records of patients treated by Zeitels either from July 1990 to June 2004 at Massachusetts Eye and Ear Infirmary or between July 2004 and June 2018 at MGH. Of 353 patients treated for vocal-cord cancer during the entire period, none of the 112 treated from 1990 to mid-2004 were age 30 or younger. But 11 of the 241 patients treated from 2004 to 2018 were 30 or younger – 3 were age 10 to 19 – and only 3 of the 11 were smokers. Analysis of tissue samples from the tumors of 10 of the 11 younger patients revealed high-risk strains of HPV in all of them.

The authors note that these high-risk-HPV-associated vocal-cord cancers greatly resemble recurrent respiratory papillomatosis (RRP), a benign condition caused by common, low-risk strains of HPV. One of the 11 patients treated by Zeitels had previously been diagnosed at another center with vocal-cord cancer, and when it recurred after being surgically removed, she was misdiagnosed with RRP and treated with a medication that made the cancer worse, leading to the need for a partial laryngectomy.

“Benign RRP of the vocal cords has been a well-known HPV disease for more than a century, and it is very remarkable that there is now an HPV malignancy that looks so similar, creating diagnostic and therapeutic confusion,” says Zeitels, the Eugene B. Casey Professor of Laryngeal Surgery at Harvard Medical School. “It should be noted that these HPV-associated vocal-cord carcinomas are not a malignant degeneration of the benign disease.”

Zeitels adds that HPV vocal-cord cancers are amenable to endoscopic treatment with the angiolytic KTP laser that he developed. “Large-scale studies are now needed to determine the pace of the increase in glottic cancer among nonsmokers, the incidence of high-risk HPV in these cancers and changes in the age and genders of those affected,” he says.

Note:
The lead author of the Annals of Otology, Rhinology and Laryngology paper is Semirra Bayan, MD, previously a fellow in laryngeal surgery at MGH and now at University of Chicago Medicine; William Faquin, MD, PhD, MGH Pathology, is a co-author. The study was supported by the Voice Health Institute, the National Philanthropic Trust, and the Eugene B. Casey Foundation.

March, 2019|Oral Cancer News|

No De-escalation of Therapy for HPV+ Throat Cancer

Source: www.medscape.com
Author: Alexander M. Castellino, PhD

Another trial has shown that de-escalating therapy does not work in patients with good prognosis human papillomavirus-positive (HPV+) oropharyngeal squamous cell carcinoma or throat cancers.

Results from the De-ESCALaTE HPV study show that using the targeted drug cetuximab with radiotherapy does not improve side effects and, more importantly, has worse survival compared with the standard of care — chemotherapy with cisplatin and radiotherapy.

The finding echoes the results from the US National Cancer Institute’s Radiation Therapy Oncology Group (RTOG) 1016 trial, the top-line results of which were released earlier this year, and details of which were presented this week at the American Society of Radiation Oncology (ASTRO) 2018 meeting.

“Do not change your clinical practice of using cisplatin with radiotherapy in these patients,” cautioned Hisham Mehanna, MBChB, PhD, chair of head and neck surgery at the University of Birmingham, United Kingdom, and lead investigator of the De-ESCALaTe study. He presented the results during a presidential session here at the European Society for Medical Oncology (ESMO) 2018 Congress (abstract LBA9).

“Cetuximab did not cause less toxicity and resulted in worse overall survival and more cancer recurrence than cisplatin. This was a surprise — we thought it would lead to the same survival rates but better toxicity. Patients with throat cancer who are HPV+ should be given cisplatin, and not cetuximab, where possible,” Mehanna said in a statement.

Hope for Fewer Side Effects
Cetuximab with radiation is already approved by the US Food and Drug Administration for use in head and neck cancer, including oropharyngeal cancer, and is an accepted standard of care, especially for patients who cannot tolerate cisplatin.

The hope behind de-escalation of therapy was that this regimen would offer similar efficacy but have fewer side effects than the standard regimen of cisplatin plus radiation.

“The side effects of treatment for patients with head and neck cancers are devastating. They experience loss of speech, loss of taste, and have trouble swallowing,” explained ESMO expert Jean-Pascal Machiels, MD, PhD, head of the department of medical oncology at the Cliniques Universitaires Saint-Luc, Brussels, Belgium.

“With HPV increasing rapidly in the Western world, HPV+ head and neck cancers are typically seen in younger patients who respond well to treatment and live for three to four decades. These patients would like to live without the toxicities associated with treatment,” he added.

“Based on a large study in 2006, many patients have been receiving cetuximab with radiotherapy on the assumption that it was as effective as chemotherapy with radiotherapy and caused fewer side effects,” Mehanna commented. That study showed that for patients with squamous cell carcinoma of the head and neck, treatment with cetuximab and high-dose radiotherapy improved locoregional control and reduced mortality. At the same time, side effects were no worse (N Engl J Med. 2006;354:567-578).

 

OCF NOTE: The foundation’s donors were funders of the RTOG 1016 clinical trial over several years.

Patients with HPV-positive oropharynx cancer should receive chemoradiation

Source: medicalxpress.com
Author: provided by European Society for Medical Oncology

Patients with human papilloma virus (HPV)-positive throat cancer should receive chemoradiotherapy rather than cetuximab with radiotherapy, according to late-breaking research reported at the ESMO 2018 Congress in Munich.

“Many patients have been receiving cetuximab with radiotherapy on the assumption that it was as effective as chemotherapy with radiotherapy and caused less side effects but there has been no head-to-head comparison of the two treatments,” said study author Prof Hisham Mehanna, Chair, Head and Neck Surgery, Institute of Cancer and Genomic Sciences, University of Birmingham, UK.

Throat cancer is rapidly becoming more common in Western countries. For example in the UK, incidence was unchanged in 1970 to 1995, then doubled in 1996 to 2006, and doubled again in 2006 to 2010.The rise has been attributed to HPV, a sexually transmitted infection. Most throat cancer was previously caused by smoking and alcohol and affected 65-70 year-old working class men. Today HPV is the main cause and patients are around 55, middle class, working, and have young children.

HPV-positive throat cancer responds well to a combination of cisplatin chemotherapy and radiotherapy, and patients can survive for 30-40 years, but the treatment causes lifelong side effects including dry mouth, difficulty swallowing, and loss of taste. Patients deemed unable to tolerate chemotherapy, for example because of poor kidney function or older age, receive cetuximab, an epidermal growth factor receptor (EGFR) inhibitor, and radiotherapy.

This study compared side effects and survival with the two treatments in 334 patients with HPV-positive throat cancer enrolled from 32 centres in the UK, Ireland, and the Netherlands. Patients were randomly allocated to radiotherapy and either cisplatin or cetuximab. Eight in ten patients were male and the average age was 57 years.

During the two-year study there were ten recurrences and six deaths with cisplatin compared to 29 recurrences and 20 deaths with cetuximab. Patients on cisplatin had a significantly higher two-year overall survival rate (97.5%) than those on cetuximab (89.4%; p=0.001, hazard ratio [HR] 4.99, 95% confidence interval [CI] 1.70-14.67). Cancer was over three times more likely to recur in two years with cetuximab compared to cisplatin, with recurrence rates of 16.1% versus 6.0%, respectively (p=0.0007, HR 3.39, 95% CI 1.61-7.19).

There were no differences between groups in the overall number of side effects, or of acute or late severe (grade 3-5) toxic events including dry mouth and difficulty swallowing. There were significantly more serious adverse events such as renal and haematological problems with cisplatin than with cetuximab.

Mehanna said: “Cetuximab did not cause less toxicity and resulted in worse overall survival and more cancer recurrence than cisplatin. This was a surprise—we thought it would lead to the same survival rates but better toxicity. Patients with throat cancer who are HPV positive should be given cisplatin, and not cetuximab, where possible.”

Commenting on the study for ESMO, Dr. Branislav Bystricky, Head, Medical and Radiation Oncology Department, University Hospital Trencin, Slovakia, said: “It was believed that cetuximab causes less side effects and was therefore a good option for HPV-positive throat cancer patients who are young and expected to survive for several decades, as well as those less able to tolerate chemotherapy. This study shows that the best treatment choice for patients with HPV-positive throat cancer is cisplatin and radiotherapy. This combination gives ‘double’ the benefit since it is more effective in terms of survival and does not worsen all grade toxicity compared to cetuximab with radiotherapy.”

Bystricky noted that the results were in agreement with interim findings of the US National Cancer Institute’s RTOG 1016 trial, which is scheduled to report this month. He said: “We now have two studies showing that these patients should not be given cetuximab. Future research should examine whether genotyping for the KRAS-variant can select a group of patients that will benefit from cetuximab treatment with radiotherapy.”

October, 2018|Oral Cancer News|

FDA approves expanded use of Gardasil 9 to include individuals 27 through 45 years old

The U.S. Food and Drug Administration today approved a supplemental application for Gardasil 9 (Human Papillomavirus (HPV) 9-valent Vaccine, Recombinant) expanding the approved use of the vaccine to include women and men aged 27 through 45 years. Gardasil 9 prevents certain cancers and diseases caused by the nine HPV types covered by the vaccine.

“Today’s approval represents an important opportunity to help prevent HPV-related diseases and cancers in a broader age range,” said Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research. ”The Centers for Disease Control and Prevention has stated that HPV vaccination prior to becoming infected with the HPV types covered by the vaccine has the potential to prevent more than 90 percent of these cancers, or 31,200 cases every year, from ever developing.”

According to the CDC, every year about 14 million Americans become infected with HPV; about 12,000 women are diagnosed with and about 4,000 women die from cervical cancer caused by certain HPV viruses. Additionally, HPV viruses are associated with several other forms of cancer affecting men and women.

Gardasil, a vaccine approved by the FDA in 2006 to prevent certain cancers and diseases caused by four HPV types, is no longer distributed in the U.S. In 2014, the FDA approved Gardasil 9, which covers the same four HPV types as Gardasil, as well as an additional five HPV types. Gardasil 9 was approved for use in males and females aged 9 through 26 years.

The effectiveness of Gardasil is relevant to Gardasil 9 since the vaccines are manufactured similarly and cover four of the same HPV types. In a study in approximately 3,200 women 27 through 45 years of age, followed for an average of 3.5 years, Gardasil was 88 percent effective in the prevention of a combined endpoint of persistent infection, genital warts, vulvar and vaginal precancerous lesions, cervical precancerous lesions, and cervical cancer related to HPV types covered by the vaccine. The FDA’s approval of Gardasil 9 in women 27 through 45 years of age is based on these results and new data on long term follow-up from this study.

Effectiveness of Gardasil 9 in men 27 through 45 years of age is inferred from the data described above in women 27 through 45 years of age, as well as efficacy data from Gardasil in younger men (16 through 26 years of age) and immunogenicity data from a clinical trial in which 150 men, 27 through 45 years of age, received a 3-dose regimen of Gardasil over 6 months.

The safety of Gardasil 9 was evaluated in about a total of 13,000 males and females. The most commonly reported adverse reactions were injection site pain, swelling, redness and headaches.

The FDA granted the Gardasil 9 application priority review status. This program facilitates and expedites the review of medical products that address a serious or life-threatening condition.

The FDA granted approval of this supplement to the Gardasil 9 Biologics License Application to Merck, Sharp & Dohme Corp. a subsidiary of Merck & Co., Inc.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

October, 2018|Oral Cancer News|

Doctors push HPV vaccine, Merck asks FDA to expand Gardasil 9 age range

Source: www.drugwatch.com
Author: Michelle Llamas, Emily Miller (editor)

Doctors, national cancer organizations and 70 nationally recognized cancer centers banded together in June to increase HPV vaccinations and improve cervical cancer screening. But they’re not the only ones pushing for more vaccinations.

HPV vaccine maker Merck requested the FDA expand the recommended age range for Gardasil 9. Gardasil 9 is currently the only HPV vaccination available in the U.S.

Nearly 80 million Americans get HPV infections each year. Of those people, about 32,500 get HPV-related cancers, according to the CDC.

Studies show the HPV vaccine is effective in protecting against the human papilloma virus. The virus can lead to several cancers. These include cervical, vaginal, vulvar, anal, penile or throat cancers.

HPV vaccination rates in the U.S. remain low. Doctors and cancer centers say low vaccination rates are a public health threat.

“HPV vaccination is cancer prevention,” Dr. Deanna Kepka, assistant professor in the University of Utah’s College of Nursing, said in a statement. “It is our best defense in stopping HPV infection in our youth and preventing HPV-related cancers in our communities.”

Right now, the vaccination rate among teens ages 13 to 17 is 60 percent. Doctors are pushing for an 80 percent HPV vaccination rate in pre-teen boys and girls.

“[Vaccination] combined with continued screening and treatment for cervical pre-cancers … could see the elimination of cervical cancer in the U.S. within 40 years,” Dr. Richard Wender, chief cancer control officer for the American Cancer Society, said in a news release. “No cancer has been eliminated yet, but we believe if these conditions are met, the elimination of cervical cancer is a very real possibility.”

Gardasil 9 requires two to three doses to be complete. Only 43 percent of teens get all required doses.

Studies show the vaccine is safe for most people. The most common side effects are headache, nausea, vomiting and fever.

But, the HPV vaccine may cause rare but serious side effects. The FDA’s Vaccine Adverse Event Reporting System has reports of autoimmune diseases, deaths and premature ovarian failure linked to the vaccine.

The National Vaccine Injury Compensation Program (VICP) has paid out millions to a few people who said the vaccine injured them. Since 2006, VICP has paid out or settled 126 HPV claims and dismissed 157.

Current campaigns urge pre-teens and teens to get the HPV vaccine. Merck wants more adults to get the vaccine, too.

At the beginning of June, the FDA accepted Merck’s application to expand the age range for Gardasil 9. The agency granted it priority review. The FDA originally approved Gardasil 9 for people ages 9 to 26. But Merck wants that age range expanded to include adults ages 27 to 45.

“Women and men ages 27 to 45 continue to be at risk for acquiring HPV, which can lead to cervical cancer and certain other HPV-related cancers and diseases,” Dr. Alain Luxembourg, Merck Laboratories’ director of clinical research, said in a statement.

HPV is a group of about 150 related viruses. Gardasil 9 protects against nine strains. The FDA hopes to reach a decision on the application by Oct. 2, 2018.

Be your own advocate

Source: www.wvnews.com
Author: Mary McKinley

The importance of dental care goes beyond cavities — it’s also about preventing cancer. The week of April 8 is National Oral, Head and Neck Cancer Awareness Week, and your dentist or dental hygienist may be your first line of defense against oral cancer.

More than 50,000 Americans are expected to be diagnosed with oral or oropharyngeal cancer (cancer of the back of the throat, including the base of the tongue and the tonsils) in 2018, and 350 will be diagnosed in West Virginia alone.

Routine dental exams can detect cancer or pre-cancers during the early stages. If you notice a persistent sore or pain, swelling or changes in your mouth, or red or white patches on the gums, tongue, tonsils or lining of the mouth, visit a doctor or dentist so they can examine your mouth more closely.

Some people diagnosed with oral cancer have no risk factors, so it’s important for everyone to keep those dental appointments.

If you use tobacco, drink alcohol in excess, or have the human papillomavirus (HPV), you have an increased risk for oral cancer. Oral cancer is more common in older adults, particularly men, but oropharyngeal cancer is on the rise in middle-aged, nonsmoking white men between the ages of 35 and 55. The majority of these types of cancer cases are caused by HPV.

Take charge of your health and reduce your risk of oral cancer. If you smoke or chew tobacco, quit now (it’s never too late). Moderate your alcohol consumption to no more than one drink a day for women or two for men.

If you have children, make sure they receive the HPV vaccine, which is recommended for all girls and boys ages 11 and 12; a “catch-up” vaccine is also available for young women up to age 26 and most young men up to age 21.

You can be your own best advocate. Check the inside of your mouth in the mirror each month, and speak up to your dentist or dental hygienist if you notice any changes that concern you.

Ask about cancer screenings when making your dental appointments. And to learn more about cancer prevention, be sure to visit www.preventcancer.org.

April, 2018|Oral Cancer News|

Accurately identifying aggressive head and neck cancers

Source: www.eurekalert.org
Author: press release

The Case Western Reserve-led research team will analyze computerized images of tissue samples for patterns which could become “biomarkers,” or predictors, for determining relative risk for recurrence in one particularly common type of head and neck cancers.

Those tumors, known as oropharyngeal cancers, occur primarily at the base of the tongue and in the tonsils.

Currently, however, oncologists tend to treat all of these tumors with the same aggressive level of therapy. This is the case even though many of the oropharyngeal tumors which are caused by the human papilloma virus (HPV) tend to have favorable outcome-regardless of treatment-while another subset of the tumors progress and metastasize, or spread.

“Right now, it’s a one-size-fits-all therapy for all of these patients with HPV head and neck cancers,” said Anant Madabhushi, MD, the F. Alex Nason Professor II of Biomedical Engineering, founding director of the CCIPD at the Case School of Engineering and primary investigator in the new research.

“There are currently very few validated biomarkers and approaches that are accurate enough to be able to identify which of these cancers are more aggressive or which ones are less aggressive,” he said. “That has limited the ability of clinicians to even hold clinical trials to find out if they can de-escalate therapy for some of these patients-or who needs more aggressive therapy.”

The National Cancer Institute (NCI) recently awarded a $3.15 million, five-year academic-industry partnership grant to Madabhushi and his team to pursue the research and build toward establishing those clinical trials.

Co-primary investigator on the grant is Vanderbilt University’s James Lewis Jr., MD, whose specialty is head and neck pathology, while Cleveland Clinic’s Shlomo Koyfman, MD, and David Adelstein, MD, are co-investigators with expertise in radiation and medical oncology.

Additionally, Pingfu Fu, an associate professor of population and quantitative health statistics at Case Western Reserve, brings expertise in biostatistics. Cheng Lu, a senior research associate in CCIPD is also involved with the project.

Madabhushi’s team is again working with Mark Lloyd, MD, of industry partner Inspirata Inc., the Florida-based company also teaming up with the lab on studies of breast and lung cancer-work supported by more than $6.3 million in NCI funding.

The team presented its data at the 2018 United States and Canadian Association of Pathology (USCAP) meeting in Vancouver this month and has generated data to suggest that the approach could soon become a clinically actionable tool.

Initial results on almost 400 oropharyngeal cancer patients suggests that the technology is independently prognostic of disease progression-meaning that it could stand alone in helping clinicians figure out how aggressive the disease is and then make a more informed decision on how aggressively to treat the cancer.

“In those cancers, they’ve established whether you can modulate your therapy based on the risk profile for those tumors,” Madabhushi said. “But in head and neck, clinicians might have a sense that there are different risk profiles for different patients, but nobody knows for certain. We want to change that by giving them the risk stratification tools to better help the patient.”

March, 2018|Oral Cancer News|

Biofilms in tonsil crypts may explain HPV-related head and neck cancers

Source: www.genengnews.com
Author: staff

Human papilloma virus (HPV) encased in biofilms inside tonsil crypts (pictured) may explain why the roughly 5% of HPV-infected people who develop cancer of the mouth or throat are not protected by their immune systems. Tonsil crypts with HPV are shown in green; epithelial and biofilm layers are shown in red. [Katherine Rieth. M.D.]

How can human papilloma virus (HPV) be prevalent in otherwise healthy people not known to carry it? A just-published study concludes that the virus may be lurking in small pockets on the surface of their tonsils.

Researchers from University of Rochester Medical Center (URMC) found HPV encased in biofilms inside tonsil crypts, where HPV-related head and neck cancers often originate. HPV is shed from the tonsil during an active infection and gets trapped in the biofilm, where it may be protected from immune attack.

In the crypts, the virus likely lays in wait for an opportunity to reinstate infection or invade the tonsil tissue to develop cancer.

“The virus gains access to the basal layer of stratified squamous epithelium through structural breaks in the stratified epithelial superstructure,” the investigators reported in the study. “Tonsillar crypt reticulated epithelium itself has been shown to contain numerous small blood vessels and has a discontinuous basement membrane, which may facilitate this infection and reinfection process.”

The URMC researchers said their finding could help prevent oropharyngeal cancers that form on the tonsils and tongue—and may explain why the roughly 5% of HPV-infected people who develop cancer of the mouth or throat are not protected by their immune systems.

HPV 16 and 18, high-risk strains that are known to cause cervical cancer, also cause head and neck cancers. While verified tests can detect HPV in people before they develop cervical cancer, that’s not the case with head and neck cancers, which according to a 2016 study are expected to outnumber cervical cancer cases by 2020.

“Far-Reaching Implications”
“Given the lack of universal HPV immunization and the potential for the virus to evade the immune system, even in individuals with detectable HPV in their blood, our findings could have far-reaching implications for identifying people at risk of developing HPV-related head and neck cancers and ultimately preventing them,” Matthew Miller, M.D., associate professor of otolaryngology and neurosurgery at URMC, said in a statement.

Dr. Miller and six colleagues detailed their findings in “Prevalence of High-Risk Human Papillomavirus in Tonsil Tissue in Healthy Adults and Colocalization in Biofilm of Tonsillar Crypts,” published online January 25 in JAMA Otolaryngology-Head & Neck Surgery, and announced by URMC today. The study’s corresponding author is Katherine Reith, M.D., an otolaryngology resident at URMC.

The researchers carried out a retrospective, cross-sectional study using samples obtained from tonsils archived at a university hospital following elective nononcologic tonsillectomy from 2012 to 2015. The samples consisted of formalin-fixed, paraffin-embedded samples of tumor-free tonsil tissue from 102 adults who had elective tonsillectomies and were between ages 20 and 39. More than half the patients (55, or 53.9%) were female.

Five of the samples contained HPV and four contained HPV 16 and 18. In every case, HPV was found in tonsil crypts biofilms.

HPV status was assessed by polymerase chain reaction (PCR), and high-risk subtypes 16 and 18 were assessed with quantitative PCR assay. Samples that demonstrated presence of HPV were then analyzed by in situ hybridization to localize the viral capsid protein.

These samples were then stained with concanavalin A to establish biofilm presence and morphology and with 4′,6-diamidino-2-phenylindole (DAPI) to visualize location of the virus in relation to cell nuclei. Data was assembled for aggregate analysis to colocalize HPV in the biofilm of the tonsillar crypts, the URMC researchers reported.

The research team plans to develop topical antimicrobials designed to disrupt the biofilm and allow the immune system to clear the virus—part of their investigation of potential screening tools, such as an oral rinse, to detect HPV in the mouth and throat.

February, 2018|Oral Cancer News|

7 million American men carry cancer-causing HPV virus

Source: www.nytimes.com
Author: Nicholas Bakalar

The incidence of mouth and throat cancers caused by the human papilloma virus in men has now surpassed the incidence of HPV-related cervical cancers in women, researchers report.

The study, in the Annals of Internal Medicine, found that 11 million men and 3.2 million women in the United States had oral HPV infections. Among them, 7 million men and 1.4 million women had strains that can cause cancers of the throat, tongue and other areas of the head and neck.

The risk of infection was higher for smokers, for people who have had multiple sex partners, and for men who have sex with men. Frequent oral sex also increased the risk. The rate was higher among men who also had genital HPV. (Almost half of men aged 18 to 60 have a genital HPV infection, according to the Centers for Disease Control and Prevention.)

Neither age nor income made a difference in high-risk oral infection rates, but rates among non-Hispanic blacks were higher than other races and ethnicities.

HPV vaccination is recommended starting at age 11 or 12 and is effective, said the senior author, Ashish A. Deshmukh, an assistant professor at the University of Florida, and “it’s crucial that parents vaccinate boys as well as girls.”

The lead author, Kalyani Sonawane, also at the University of Florida, said that behavioral change is important, too, particularly smoking cessation. “The difference in oral HPV infection between smokers and nonsmokers is staggering,” she said.

October, 2017|Oral Cancer News|