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HPV-related cancers in older adults could become among most common



Human papillomavirus (HPV) related throat and mouth cancers could soon be among the most common forms of the disease in adults between the ages of 45 and 65.

Experts in the United States are becoming increasingly concerned about the rapidly rising rates of middle throat cancer, known medically as oropharyngeal cancer.

If the trend continues they suggest it may grow to be one of the top three cancers in middle-aged men in the US by 2045 – and the most common form among elderly males within the next decade.

According to Dr Matthew Old, a head and neck surgeon at The Ohio State University Comprehensive Cancer Center – Arthur G James Cancer Hospital and Richard J Solove Research Institute (OSUCCC – James), the rise of middle throat cancers in this age group is a direct impact of HPV infection before modern vaccines were introduced in the mid-Noughties.

HPV is a large group of viruses passed on through skin-to-skin and oral contact that occurs during sexual activity.

The virus spreads easily, and an estimated 98% of the population has been exposed to it.

HPV can remain dormant for decades. High-risk strains of the virus have long been linked to an increased risk of cervical cancer. However, data from the past decade shows high-risk HPV is also strongly linked to cancers of the mouth, base of the tongue and the throat.

Gardasil, developed by Merck & Co, was widely introduced as an HPV vaccine in 2006, and is now recommended for use in both males and females from the age of nine to protect against the high-risk strains of the virus linked to cancer, including cervical, vulvar, throat, mouth, penis and anal. It is also administered for non-cancerous conditions, such as genital warts.

Although it has been available for nearly two decades, lack of awareness about it as a means of cancer prevention in later life has slowed progress in preventing these cancers.

The Centers for Disease Control and Prevention (CDC) in the US estimates that timely HPV vaccination could prevent 90% of cervical cancers alone. The National Cancer Institute believes that as of 2020 just 54.5% of young people in the US aged between 13 and 15 were vaccinated.

Dr Matthew Old

Dr Old said: “We have a long way to go in educating the public about the importance of HPV vaccination in youth, and of the risk factors and warning signs of HPV-related cancers for adults who did not have an opportunity to get vaccinated in childhood.

“I strongly encourage all parents with children of vaccination age to consider the HPV vaccine. Data increasingly show this is a powerful tool to prevent cancers later in life, and HPV is a risk factor that all genders should be aware of.”

Cervical cancer is the only type caused by HPV that has a recommended screening test to detect it at an early stage.  Currently, there are not recommended screening tests for cancers of the back of the throat, anus, vulva, penis and vagina caused by HPV, so they may not be detected until they cause serious health problems.

In the US alone, it is estimated there are 14,800 new HPV-related cancers of the back of the throat diagnosed every year, 6,900 of the anus, 2,900 of the vulva, 900 of the penis and 700 of the vagina. There are just over 11,000 new cervical cancer cases each year in the US – the most common HPV-related form of the disease in women.

Back of the throat is most common in men, accounting for 12,500 new cases annually, compared to 2,300 in women.

Electra Paskett, a cancer epidemiologist and co-leader of the OSUCCC – James Cancer Control Program, believes the conversation about the benefits of HPV vaccines among parents and health care providers needs to change.

“We need to shift the focus on HPV vaccination from preventing a sexually transmitted disease to preventing future cancers in order to stem the sharp increase in HPV-related cancers.

“The vaccine has historically been billed as a way to prevent infection risk related to sexual activity. It’s given in childhood not to encourage sexual activity at an early age, but because it is most effective at preventing HPV infection before the time of exposure and prevents cancer,” she said.

HPV vaccination is typically given in two doses between the ages of 9 and 14 and three doses in those aged 15 through to 26.

While HPV vaccination in adulthood is thought to provide less benefit because most people have already been exposed to the virus, it is now also available for individuals from ages 27 to 45 with a shared decision-making discussion with a health care provider.

According to data from the CDC, there is significant progress in one area. HPV infections and cervical precancers (abnormal cells in the cervix) have dropped since 2006, when the vaccines were first used in the United States.

Among teen girls, HPV types that cause most HPV cancers and genital warts have dropped 88%. Infections among young adult women have dropped 81%. Among vaccinated women overall, the percentage of HPV-related precancers have also dropped by 40%.

“We monitor women for HPV, but this should be a concern for people of all genders because partners expose partners,” Dr Old said.


Europe: Improving access to early-stage lung cancer care



Europe: Improving access to early-stage lung cancer care

Researchers from Amsterdam UMC Cancer Center Amsterdam have looked at inequalities in access to early-stage lung cancer care in Europe.

Early-stage lung cancer has stark differences between European countries regarding access and reimbursement.

There are also differences in reimbursement times and indications between the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA).

Researchers from Amsterdam UMC Cancer Center Amsterdam analysed the landscape, publishing their results in The Lancet Regional Health Europe as part of a series on the latest developments in the treatment of this lung cancer.

“Tackling inequalities in access to care must be a common European priority,” says Amsterdam UMC pulmonologist Idris Bahce. In collaboration with colleagues from seven European countries, Bahce used a literature review to map out the latest developments and analyse access to these new treatments from a European perspective.

“The existing differences in healthcare systems and reimbursement structures between European countries threaten to exacerbate healthcare inequalities at both European and national level. We therefore call for a collective European approach to reduce these inequalities,” says Bahce.

He suggests measures such as more international cooperation between the EMA and other registration authorities, harmonising cost-effectiveness procedures in European countries, a more critical evaluation of reimbursement criteria and improving multidisciplinary collaborations around the patient.

The standard treatment for fit patients with early-stage lung cancer has always been surgery, sometimes combined with pre- or post-operative chemotherapy. Recently, the EMA has approved new treatments such as immunotherapy, which appear to significantly improve survival rates after surgery. More approvals of innovative treatments are expected, potentially further exacerbating existing inequalities within Europe.

In addition to the Dutch hospitals Amsterdam UMC and Erasmus MC, colleagues from Spain, France, Germany, England, Italy and Poland also contributed to this international study as well as a Review and a Viewpoint in The Lancet Regional Health Europe.

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Study looks at link between adversity and cognitive decline



A new paper has examined the relationship between childhood adversity and psychiatric decline, as well as adult adversity and psychiatric and cognitive decline. 

The findings revealed just one instance of adversity in childhood can increase cases of mental illness later in life. It also revealed that adverse events in adults can lead to a greater chance of both mental illness and cognitive decline later in life. 

The paper has been published by Saint Louis University associate professor of health management and policy in the College for Public Health and Social Justice, SangNam Ahn, Ph.D., in Journal of Clinical Psychology.

Ahn stated: “Life is very complicated, very dynamic. I really wanted to highlight the importance of looking into the lasting health effect of adversity, not only childhood but also adulthood adversity on health outcomes, especially physical health and psychiatric and cognitive health. 

“There have been other studies before, but this is one of the first that looks into these issues comprehensively.” 

Ahn, along with his team of researchers, examined data from nearly 3500 individuals over the course of 24 years. The group took the longitudinal data and evaluated it using a list of lifetime potential traumatic events.

The research team included childhood adversity events such as moving due to financial difficulties, family requiring financial help, a parent experiencing unemployment, trouble with law enforcement before the age of 18, repeating school, physical abuse and parental abuse of drugs or alcohol. 

Adulthood adversity events included the death of a child, the death of a spouse, experiencing a natural disaster after age 17, firing a weapon in combat, a partner abusing drugs or alcohol, being a victim of a physical attack after age 17, a spouse or child battling a serious illness, receiving Medicaid or food stamps and experiencing unemployment. 

The study determined that nearly 40% of all individuals experienced a form of childhood adversity, while that number climbed to nearly 80% for adulthood adversity. Those who experienced childhood adversity were also 17% more likely to experience adulthood adversity. Only 13% of individuals sampled reported two or more forms of childhood adversity, while 52% of adults experienced two or more forms of adult adversity. 

In cases of either childhood adversity or adulthood adversity, researchers found individuals who experienced adversity were also more likely to experience anxiety and depression later in life, and in the case of adulthood adversity, were also more likely to experience cognitive decline later in life. 

Individuals with one childhood adversity experience saw a 5% higher chance of suffering from anxiety, and those with two or more childhood adversity experiences had 26% and 10% higher chances of depression and anxiety, respectively. Individuals who experienced two adulthood adversities had a 24% higher chance of depression, while also experiencing a 3% cognitive decline later in life. 

While most of the results were expected or unsurprising, one area that stood out to Ahn was education. Those individuals studied who reported higher levels of education saw a reduction in the number of adversity experiences. Ahn hopes to study this avenue more to learn how education may be able to mitigate or prevent these declines. 

“Before including education, there was a significant association between childhood adversity and cognitive impairment,” Ahn said. 

“But when including education as a covariate, that significant association disappeared. Interesting. So there were important implications here. Education and attending school, people could be better off even if they were exposed to childhood adversity. They’re likely to learn positive coping mechanisms, which may help avoid  relying on unhealthy coping mechanisms, such as smoking or excessive drinking or drug use.

“Education is quite important in terms of health outcomes. If I am educated, I’m likely to get a better job, have a higher income, and live in areas with less crime. I’m likely to buy gym membership or regularly exercise. I’m likely to shop at Whole Foods and get proper nutrition. All of which help combat these adversities we hinted at in the study. So the education and health outcomes are already closely related, and that is what we saw in our study.”

Ahn also encourages clinicians and everyday people alike to discuss their stress. Clinicians can learn more about their patients and have a better approach when it comes to their physical and mental health, while others could potentially relate to shared experiences. But through awareness and recognition, these adverse experiences could potentially have less serious, lasting effects. 

“Public health is very interested in stress,” Ahn said. “But we’re still examining how daily stress impacts our long term health outcomes. So to see the effects here in the study, I want people to pay attention to their stress and proactively address it. Clinicians should have deep discussions with their patients about their stress and mental state. And those topics can be approached in other areas too, like the classroom or the dining room table. The more we are aware of stress and discuss our stress, the better we can handle any adversities we find in life.”

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New tool to explore mechanisms of age-related diseases



New tool to explore mechanisms of age-related diseases

A new screening tool has been developed that will investigate the mechanisms behind conditions such as cancer, arthritis, neurodegeneration and cardiovascular disease.

Wellcome Sanger Institute researchers and their collaborators at Open Targets and EMBL’s European Bioinformatics Institute (EMBL-EBI) have developed the screening tool called scSNV-seq.

The tool has been designed to uncover how genetic changes affect gene activity that can lead to diseases such as cancer, autoimmunity, cardiovascular disease and neurodegenerative diseases such as Alzheimer’s and Parkinson’s. 

The tool enables the investigation of thousands of DNA mutations identified by genetic studies in one experiment, and will help to guide the development of advanced diagnostics and treatments.

scSNV-seq allows the rapid assessment of the impact of thousands of genetic changes in cells that have never been screened before, directly connecting these changes to how those same cells operate. 

This technique helps researchers to pinpoint mutations that contribute to disease, which will offer crucial insights for developing targeted therapies.

In a new study, published in Genome Biology, the team applied scSNV-seq to the blood cancer gene, JAK1, accurately assessing the impact of JAK1 mutations.

The assessment revealed for the first time that certain mutations caused a “halfway house” phenotype cycling between different states which was not possible under previous approaches.

The technique is designed to demonstrate versatility across cell types, including hard-to-culture primary cells like T cells and stem-cell derived neurons, as well as various editing methods such as base editing and prime editing. 

Applied on a large scale, scSNV-seq could transform understanding of the genetic changes driving cancer and decoding genetic risk for Alzheimer’s, arthritis, diabetes and other complex diseases.

Dr Sarah Cooper, first author of the study at the Wellcome Sanger Institute, stated: “In an era where the rate of genetic variant discovery outpaces our ability to interpret their effects, scSNV-seq fills a major gap for studying challenging cells like T cells and neurons. 

“We are already using it to shed light on the impact of Alzheimer’s and Parkinson’s risk variants on brain cells.”

Dr Andrew Bassett, senior author of the study at the Wellcome Sanger Institute, said: “Our technique is able to directly connect effects of mutations to how a cell behaves, revealing downstream impacts that previous technologies alone cannot deliver. 

“The technique speeds up the identification of causal genetic mutations, which will allow better diagnosis and deepens our molecular understanding of diseases, paving the way for more targeted and effective treatments.”

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