Even when treated with a combination of chemotherapy, surgery and radiotherapy, survival rates for lung cancer, especially small cell lung cancer, are very low: on average only around 20% to 40% of patients diagnosed with Stage 2 lung cancers, at which point tumours are around 5cm in size, can expect to survive for five years or more with treatment.
Bringing together some of Europe’s leading specialists on genetics, epigenetics, pathology and oncology, the CURELUNG initiative has identified several epigenetic lung cancer biomarkers that could be potentially useful to target new therapies and early diagnosis.
The research is also contributing to the development of innovative tools to detect and characterise different types of lung cancer, and identify the most aggressive cancers in early-stage patients, as well as furthering clinical trials of new drugs.
“Not all cancers are the same, and not all patients will respond the same way to treatment. By identifying genetic alternations associated with specific cancer types we can create a list of biomarkers that can help determine the most effective, targeted treatment strategy for each individual patient while minimising the effect on healthy cells,” explains CURELUNG coordinator Manel Esteller, head of the Epigenetics and Cancer Biology Programme at Bellvitge Biomedical Research Institute (IDIBELL) in Spain.
“One of the factors that makes lung cancer the most lethal type of cancer in the world is that it is usually diagnosed late, often after it has already metastasised and spread to other regions of the body. By identifying the biomarkers associated with lung cancer we can screen for them, allowing cancer to be detected and treated sooner, which should improve the effectiveness of therapies and increase survival rates,” Esteller says.
With that aim in mind, project partner MRC Holland, a biotech company, is building on work conducted in CURELUNG to develop screening tools for use in a clinical setting.
Equally important is determining the most effective course of treatment by identifying how drugs or combinations of drugs affect distinct forms of lung cancer brought on by different genetic alterations. In that regard, the biomarkers identified in CURELUNG are contributing to ongoing clinical trials in Germany run by pharmaceutical firms Novartis and AstraZeneca.
“The biomarkers we identified are being used by clinical researchers to determine if and how cancers with certain genetic alterations are affected by the drugs being tested, which should contribute to the development of new treatments for those cancer types,” the CURELUNG coordinator says.
With lung cancer accounting for 20% of all forms of cancer and causing the death of 1.6 million people worldwide each year – the most of any cancer – Esteller points out that if one drug is proven to be effective against 10% of lung cancers, and a second against another 10%, then the impact will only increase incrementally until a majority of lung cancers can be treated with targeted therapies.
Stunted growth, impaired development of the nervous system, abnormal sensitivity to UV light and premature ageing are just some of the symptoms that young CS patients start to exhibit just a few months after birth or in the early years of their lives. In most cases, patients die in their teens or early adulthood.
“When I was doing my first postdoc in England, I had the opportunity to meet children who were suffering from this disease,” Maria Fousteri, beneficiary of the CHROMOREPAIR research grant, recalls. “This encounter really made me want to find out what happens and made me want to help these children.”
The molecular biology of the syndrome remains poorly understood. However, some 20 years ago, researchers did find out that CS sufferers have difficulty repairing lesions from UV light that are induced in genes, i.e. damage to actively transcribed DNA. “As a result, their cells will not be able to restore gene expression and will ultimately lack some proteins that are very important for the cells to operate,” explains Fousteri.
While CS is rather rare, DNA damage and deficiencies in repairing such damage are relevant to a range of human diseases, from neurodegenerative disorders to cancer. Improving our understanding of the underlying genome maintenance mechanisms, such as the transcription-coupled nucleotide excision repair (TC-NER) mechanism, which is affected in CS patients, will help researchers assess risks posed by environmental hazards and provide insight into the causes of ageing, age-related health problems and more.
Specifically, Fousteri looked into the role of chromatin remodelling in TC-NER that might be affected in CS. DNA is packaged tightly into chromatin – a complex of molecules – so that it fits in the cell. Chromatin plays a central role in the repair of DNA damage and controls gene expression and DNA replication, among other things.
Tight packaging of DNA into chromatin impedes access to DNA for repair purposes. In healthy people, the chromatin structure is therefore remodelled to allow access to the damage sites, allowing repair and DNA transcription (or copying) to continue. Failure to repair this damage and resulting prolonged interruption of transcription activity may lead to genomic instability or cell death. This, in turn, probably contributes to CS symptoms.
Similar but different
Through their research, Fousteri and colleagues in Rotterdam with whom she collaborated during CHROMOREPAIR characterised the functions of a novel gene, UVSSA, which plays an important role in the TC-NER mechanism – a process critical to restoring gene expression after damage.
People with mutations to this gene exhibit UV sensitivity, just like CS patients. But they do not have CS patients’ neurodegenerative problems, says Fousteri.
The team studied the importance of the protein produced by this gene – as well as the genes that carry mutations in CS sufferers – for the TC-NER mechanism. The researchers analysed how the results, i.e. very severe CS and the relatively mild UV-sensitive syndrome (UVSS), can be so different from one another, although the same mechanism, namely TC-NER, is compromised.
The findings from CHROMOREPAIR, as well as data gathered in the process, are the foundations for Fousteri’s work today.
The project gave her the opportunity to prove her mettle as an independent researcher, giving impetus to her career and ultimately leading to her election as research group leader at the Biomedical Sciences Research Center ‘Alexander Fleming’ in Greece. There she continues her research to the benefit of patients suffering from CS and other DNA damage-related disorders.
Marine microbiologist Laura Alonso-Sáez has studied the composition of the bacterial communities thriving in coastal waters of the Bay of Biscay and analysed a variety of functions carried out by individual species.
Her findings indicate that the roles of the various species may not overlap as much as previously thought. She has also concluded that some species only perform their particular tasks at specific times of the year, when seasonal changes in environmental conditions kickstart these processes.
“The main problem we have as marine microbiologists is that the vast majority of the microbes that live in the seawater cannot be cultured in the lab. So it’s hard to study what they do,” Alonso-Sáez explains.
However, she adds, the advent of high-throughput technologies for genetic analyses has opened up new horizons. Taking water samples from the ocean and sequencing their genetic material has become a viable proposition.
Alonso-Sáez, then working at the Spanish Oceanographic Institute, put this possibility to good use in the Fundiversity project, for which she benefited from a Marie Curie Reintegration Grant. This funding was awarded to help her re-establish her career in her native Spain after a post-doc assignment in Sweden on a Marie Curie mobility scheme.
The two grants helped Alonso-Sáez pursue her specialisation and acquire additional scientific skills, she notes, listing the genomics expertise that underpinned Fundiversity as one example. They have also allowed her to develop the coordination know-how required to run a molecular biology laboratory, adding to the promising CV that then helped her to secure a tenure-track position in Spain.
Diversity and demarcation
Fundiversity enabled Alonso-Sáez to shed new light on the ocean’s briny bacteria. Over a period of three years, she regularly sampled the waters at a coastal station in the Bay of Biscay within the Spanish time-series programme Radiales.
Every lucky dip brought up specimens of hundreds of species. By studying their DNA and RNA – their genetic coding and the genes that are actually expressed – Alonso-Sáez managed to establish the seasonal variations in the composition and functioning of bacterial communities in this part of the Atlantic.
While some species are strongly represented at all times, others appear to come and go with the seasons. Some grow and carry out their specific functions only at particular times of the year. Alonso-Sáez cites the example of species involved in ammonia oxidation, the transformation of ammonia into nitrite as part of the marine nitrogen cycle, which only expressed the relevant genes in autumn.
A hot topic
There is still a lot to learn about individual species’ contributions to the biogeochemical processes that keep our environment going. However, says Alonso-Sáez, comparing their genes to similar ones from other, well-characterised species makes it possible to infer their functions. A key step in Fundiversity was then to see if the various copies of a particular gene in the samples belonged exclusively to related specimens, or to several types.
Understanding these roles and the vulnerability of the species performing them is crucial. Seasonality reflects a reaction to variations in environmental conditions such as temperature and the availability of nutrients. A lasting change in these parameters, for example as a result of global warming, might jeopardise seasonal species and processes.
Fundiversity ended in August 2013, having unleashed a torrent of data which Alonso-Sáez and her colleagues continue to analyse and exploit. Alonso-Sáez has since moved on to the marine research Institute AZTI, also in Spain. Her work on the functioning of marine bacteria continues in a new project (Teccam) that will explore the impact of changing environmental conditions on model marine bacteria. For this particular study, she will be focusing on species that can be cultured in the lab.
Fellow Laura Alonso in O/V José de Rioja
© nestor arandia
Mistrustful of politicians and voting, young people are turning to street demonstrations, charity events, consumer activism and social media to express their political and civic views. The EU-funded Processes Influencing Democratic Ownership and Participation (PIDOP) project tried to uncover why young people feel this way.
The issue is complex, says the PIDOP project coordinator Professor Martyn Barrett. “For this reason, the research explored how psychological drivers interact with social, demographic and institutional factors to determine people’s civic and political behaviour,” explains Barrett. The project focused on gathering data from 16- to 26-year-old men and women from ethnic majority and minority groups in nine European countries.
Even though it is difficult to identify patterns that drive behaviour across diverse groups of people, the research identified three key factors affecting civic and political participation:
Encouraging democratic citizenship in young people
“When governments are more accountable, democratic and uphold the rule of law, their citizens are more engaged,” says Barrett. These political institutions must also take effective action against discrimination and be embedded in a culture of democracy. If people feel that they are discriminated against or they have little opportunity to get the attention of government, they will feel more dissatisfied and disengaged.
The PIDOP project revealed that young people feel that politicians aren’t willing to listen to their concerns, and this is the primary reason they aren’t interested in voting. However, young people are passionate about other issues — problems affecting people in other countries, racism, recycling and global warming. They actively sign e-petitions, volunteer and raise money for charity.
“The challenge for politicians is to listen to and understand young people’s concerns, make them feel that they can make a difference, and engage them in politics,” emphasises Barrett.
Civic education and active membership of organisations, such as Amnesty International and youth clubs, can also make a difference. “Teaching children about the history of democracy doesn’t help them become engaged citizens,” says Barrett. Children must have concrete experiences. “If children have the opportunity to discuss a local issue and then write to their parliamentarian, and receive a response, they are more likely to believe that participating will make a difference,” adds Barrett.
Using the PIDOP findings to improve curricula in schools
The PIDOP findings have led to the creation of the Competencies for Democratic Culture (CDC) project. Launched by the Education Department of the Council of Europe, the initiative is designing a new education framework. Countries can tailor the framework to their unique requirements to help educators develop children’s democratic attitudes and values, encourage autonomous learning, and foster analytical and critical thinking skills. The Council’s 47 member states can use the framework to rewrite their national curricula to further promote civic and political participation.
PIDOP has provided the insights that politicians, educators and citizens need to promote democratic citizenship among young people in Europe.
Strangers into Citizens Rally, Trafalgar Square, London ,7 May 2007
© David Garbin
Central and Eastern European countries (CEECs) that joined the EU between 2004 and 2007 saw their economies grow fast after accession. But much of the growth was concentrated among urban areas and better-educated citizens. And with its base in low production costs rather than innovative products and services, the growth proved fragile in most countries during the 2008-2009 financial crisis.
To find out how CEECs could achieve their full growth potential, the GRINCOH project investigated different economic, social and institutional aspects of their development. Its results suggest that more inclusive and stable growth would come from policies supporting local potential for innovation, and tailored to different regions, which would also allow more efficient use of imported innovation than has been the case up to now.
Project coordinator Grzegorz Gorzelak of Poland’s Uniwersytet Warszawski says there is a new understanding in the EU institutions that the traditional approach to cohesion – which targets key regions, welfare and uniform development goals – eventually leads to an inability to grow. “GRINCOH looked at how to reform cohesion policy after 2020.”
Research focused on the 10 CEECs – Bulgaria, the Czech Republic, Estonia, Hungary, Latvia, Lithuania, Poland, Romania, Slovakia and Slovenia. Although there are differences in development between and within these countries, they have much in common.
“They joined as a group and came from a socialist tradition that is different from the economic tradition of the older Member States,” explains Gorzelak. “Factors that initially allowed fast growth are now almost fully exploited – these countries need to find changes of direction to compete in a world economy driven by innovation.”
In the first 18 months of the project, policy and economic specialists from both Eastern and Western Europe researched changes in these countries that were linked to joining the EU. They gathered evidence from a wide spectrum of academic literature and their own case studies of past EU programmes for the CEECs.
In particular, the project focused on structural changes, international trade and foreign investment (an important source of growth for the CEECs), innovation and entrepreneurship, labour markets and skills, social cohesion and welfare, regional development, institutions, cohesion policy and development scenarios.
In the second half of the project, researchers tested how different political frameworks, institutional conditions and development strategies could impact growth up to 2020. For this, they used the MAAST 3 macro-regional model, developed by the Politecnico di Milano, one of the project partners.
“We concluded that one policy does not fit all cases; policies should be adapted more to suit the type of region,” says Gorzelak. He cites focusing more on secondary cities rather than developed, main cities as an example of a targeted policy.
However, the project also showed that the different regions of the EU impact each other, which should be taken into account in policy formation for the whole of the European Union. And GRINCOH recommends a longer-term focus rather than “fire-fighting”, along with stronger coordination of thematic policies, including those on education, industry and social policy.
Help to turn R&D into new businesses and prepare people for jobs would improve cohesion, while continued reform of institutions to bring them in line with EU norms is also important.
Indeed, stronger inter-regional scientific networks and home-grown potential for adopting – and efficiently adapting and developing – imported innovation has more potential to boost growth than hunting for foreign investment, which often adds little new knowledge to local economies, researchers found.
“Our findings have been well-received by the Commission’s DG Regional Policy,” says Gorzelak. “They are launching, in cooperation with ERSA, a series of lectures for scientists and policy-makers in October or November 2015 in Brussels.”
GRINCOH’s research is publicly available on the project website in a series of presentations, detailed working papers and case studies, with a possible book in the pipeline, he adds. Each of the consortium’s 12 institutes is continuing its research, with further collaboration possible.
“We didn’t reinvent the wheel,” he concludes. “But we provided evidence for our concept of how to achieve cohesion – understood as growth, innovation and competitiveness, and not simply traditionally as convergence.”
©SOHO (ESA & NASA)
From time to time, the Sun ejects plasma and magnetic fields in a massive burst. The phenomenon is known as a coronal mass ejection (CME), and can occur up to five times every day.
We earthlings are usually oblivious to these cosmic goings-on. But for those rare occasions when a CME makes its presence felt on Earth – in a worst case scenario by temporarily shutting down electricity supplies – it makes sense to understand the origins of the beast, and when it will arrive.
Spiros Patsourakos took on this challenge when he received one of the EU’s Marie Curie reintegration grants to allow him to continue research in his field on returning to his native Greece after more than 10 years abroad. Over four years, the grant enabled him and his colleagues – through the SEP project – to shed new light on the genesis of CMEs, to solve an age-old discussion on some ‘disturbances’ observed on the Sun’s surface, and to take great strides towards predicting when CMEs will arrive on Earth.
CMEs are an “interesting physics problem”, says Patsourakos. “And we don’t yet know the details.” What we do know is that CMEs are major drivers of space weather.
Not every CME will reach Earth. And not every CME reaching Earth will have a visible impact. A CME would need to be particularly powerful and transporting a south-facing magnetic field if it is to disrupt the Earth’s magnetic fields, disrupt currents and switch off electricity. But it can happen, and it did in the Canadian province of Quebec in 1989. A geomagnetic storm tripped circuit breakers on the power grid, leaving the region without power for nine hours.
“These events are not frequent, but you only need one with the appropriate conditions to cause major disruption,” says Patsourakos.
Knowing the ropes
Before a CME is expelled, sets of magnetic field lines – known as flux rope – begin to twist and turn around the future CME launch pad. A “hot topic” within solar physics is whether these flux ropes are a pre-requisite to an eruption or not.
While Patsourakos’ research hasn’t quite provided an answer to this debate once and for all, it did provide radical new insights into the build-up to a CME. By observing images of the Sun at various temperatures through a powerful telescope providing very regular and high-resolution images, Patsourakos was able to witness the formation of magnetic flux rope and then – seven hours later – the eruption.
Traditional studies involve going back and looking at images from one hour before a CME took place, while Patsourakos’ approach showed that the build-up starts much earlier. “If you only focus on smaller temporal intervals, you may interpret the data differently,” says Patsourakos. He believes that his revelation could change the way scientists approach observations.
As for whether flux ropes are necessary for a CME to take place – Patsourakos and his colleagues are now working on statistical studies in a bid to see how common the flux ropes are, and eventually to answer this all-important question.
Another question dividing space scientists is whether or not the disturbances travelling across the solar surface during the initial stages of a CME are caused by CME-driven waves, or whether they are simply a shadow of the fledgling CME.
“The debate has been settled,” says Patsourakos – and the answer will please both camps. “During the same phenomenon, there are some elements that can be explained as being waves, others as non-wave,” he says.
Estimating arrival time
Predicting when a CME will arrive on Earth still requires a little more work, says Patsourakos. Speed can vary from a few hundred kilometres per second to more than 2000 kilometres per second. By looking in depth at the factors affecting the speed at which a CME travels, and in particular perturbed solar wind, he has already improved on previous methodologies. More extensive testing is now needed – and planned.
Since the SEP project ended in 2014, Patsourakos and his colleagues have continued to work on the many open questions from his lab in the physics department at the University of Ioannina. The next steps are statistical studies of CMEs’ pre-eruptive configuration and propagation.
Many common cancers are now treatable with radiotherapy, chemotherapy and surgery. But the 5-year survival rate of pancreatic cancer is still less than 5%, in part because it is difficult to detect early, according to the World Health Organization. The cancer has few unique early-stage symptoms and none that are easy to spot, while the pancreas’ location deep in the abdomen often hides tumours from conventional imaging.
The SaveMe project has engineered nanoparticles – particles less than 100 000 billionths of a metre across – that could one day improve early detection. The EU-funded project’s team has shown it is possible both to create nanoparticles that can home in on cancer cells in the lab and to track these nanoparticles with standard imaging tools. Research is still at the pre-clinical stage but together, these results could lead to earlier treatment and more precise surgery.
“Early diagnosis of pancreatic cancer has a major positive impact on outcomes,” says SaveMe project coordinator Louis Shenkman from Tel-Aviv University. This is because pancreatic tumours can only be removed successfully by surgery when they are small. At later stages, they spread to essential organs such as the liver and no longer respond to chemotherapy or radiotherapy.
SaveMe’s nanoparticles work by recognising the unique chemical signature of pancreatic tumours. The project team built a core nanoparticle, to which they attached molecules attracted to receptor proteins found only on the surface of pancreatic tumours.
Shenkman predicts that with this “decorating” manufacturing method, it could be possible to custom-build nanoparticles. Different patients have different receptors and it could be possible to attach tracking molecules tailored to a single patient. And if tumour cells mutate or grow, the nanoparticles could be adjusted to match each new type of tumour, he says.
If the technology reaches the stage of successful patient trials, the diagnostic system developed by SaveMe could also be used for other tumours. It would be especially useful for research into cancers that are currently difficult to diagnose, he adds. The nanoparticles use only biodegradable materials, so would be eliminated from the body after use.
As well as testing a new, personalised approach to detecting cancer, the team used their nanoparticle design to prove that two methods of shutting down pancreatic cancer cells could work in principle. The first method delivers small interfering RNA (siRNA - a version of one of the basic components of genes) into the tumour cells to switch off genes essential to their machinery. The second delivers antibodies to block the enzymes the cells produce for chemical reactions they need in order to function.
These concepts are attractive for researching an alternative to surgery because they would target only tumour cells, wherever they are, leaving the surrounding tissue unharmed. In contrast, surgery for pancreatic cancer is very complex and must be carried out before any tumour cells spread.
Adding to research knowledge
SaveMe’s researchers tested many different methods of making nanoparticles and different surface molecules to find the right nanoparticle composition for pancreatic cancer. In doing so, they created standardised methods of making each of these nanoparticle types that can be used to track and reproduce their results efficiently.
This generated extensive new data on how to synthesise different types of nanoparticles. These data are now available on the project website. Project members have also published over 30 articles on the project’s results in specialist journals and more are in the pipeline.
Computer modelling was another research tool advanced by the project. From existing software and research, the team created programs to predict tumour growth, blood flow and delivery rates of nanoparticles to the tumours. The final programs can apply to other bio-nanoparticles, assisting research in other projects.
Shenkman concludes: “We have developed an interesting platform for treating solid cancer … It is valid for any gene therapy that could use siRNA to deliver therapy into cells.”
“EU support for this project helped foster basic research in this field. This was a unique opportunity for different specialities to interact in a very effective manner.”
A new snow-gun prototype and nozzle design developed during the EcoArtiSnow project uses 15% less energy, produces 8% more snow, and makes much less noise. The project partners developed this system to ensure wider take-up of artificial snow-making, which is of vital and growing importance to winter tourist destinations in Europe and around the world. The prototype was tested in the Italian Alps, and the technology is today promising.
The project was coordinated by Mike Blicker of the Fraunhofer Gesellschaft. Blicker’s team built on the know-how of DemacLenko, the world leader in snow-making equipment, to develop analytical models of the snow-making process. The models focused in particular on the nozzles where water and compressed air are combined and ice crystals are nucleated. Of particular research interest were the nozzle geometry and the correlated particle sizes, to ensure that a high-quality snow cover could be produced for less energy over a broad range of ambient temperatures and humidity.
However, the main contributor to energy consumption and noise levels is the air blower, which the team of Profactor GmbH analysed and optimised, together with the project partners, to reduce noise emission and energy use substantially.
“As a result of our research, we have managed to reduce energy consumption by between 15-25% depending on the ambient temperature and humidity levels,” explains Blicker. “We have also reduced noise emissions by some 5dB, especially in the higher frequencies that are most troublesome to the human ear, making the machines 25% quieter. Taken together, this means that snow-making machines can be used more energy efficiently, in a wider range of situations and closer to human and wildlife habitats – which represents a successful step forward for this sector.”
Warmer winters with less snow can disrupt tourism and reduce the length of the tourist season, and this at a time when demand for skiing holidays is rising. This poses a serious economic problem for mountain communities, where winter sports may be the main source of income and employment.
For many years, snow-making equipment has been used to ensure that the ski slopes can operate. Indeed in some regions, such as the South Tyrol, some 90% of ski-slopes are now covered using artificial snow. However, there are barriers to the wider take-up of this technology, as Blicker explains: “Standard snow-making blowers and guns use a lot of expensive energy and are very noisy. These factors have prevented some ski facilities from using them where ski slopes are too close to residential areas and noise levels are too high.”
Where ski slopes are close to nature reserves and protected habitats, there are also strict environmental restrictions on noise levels. “For this reason, there was a demand for more efficient, quieter snow-making equipment which could be deployed in sensitive locations and ensure that high-quality snow is produced – leading to clear economic benefits for local communities,” says Blicker.
The project partners included the Fraunhofer Institute in Germany and Profactor GmbH from Austria, as well as the most important supply chain members and customers of DemacLenko Srl. The EcoArtiSnow prototype demonstration event in the 2013/2014 winter season is now being followed by wider field testing of improved machines.
Prototype snow-gun testing and snow quality evaluation
© Fraunhofer IGB, Boris Linke
Analysing spray behaviour and noise emissions of a snow gun
© Fraunhofer IGB, Boris Linke
“Current HPC platforms consume such a huge amount of energy that the further successful development and use of such systems will strongly depend on optimization towards energy efficiency” – Prof. Vincent Hueveline, Exa2Green Coordinator
Identifying the hidden potential
The future advances in HPC technology will keep leading to significant increase in energy consumption. Having recognized that the focus in energy-efficiency development lies in the hardware design, the main objective of the Exa2green project was to investigate the so far unexplored potential to reduce energy use on the level of algorithmic design and software engineering.
The project followed three main lines of activities:
Software and hardware for green supercomputing
As a result, Exa2green developed software and hardware instruments for high resolution power monitoring. The software tool that allows tracing and analyzing the power and energy consumption of parallel scientific applications will bring benefit to scientists and technicians – they will be able to identify the sources of power inefficiency and optimize the application code. Additionally, the project team has designed a low-cost and accurate measurement device called ArduPower. This internal power meter can be used to examine the energy consumption of scientific applications of HPC infrastructures. Furthermore, Exa2green has created very precise models for characterization and time-energy-power prediction of several elementary computational kernels. Finally, the team members have also optimized the weather forecast software COSMO-ART. By identifying the energy-consumptive components, they were able to tailor the model to be more energy-efficient. It can now perform higher-resolution forecasts over longer periods, while being eco-friendly.
Bringing the know-how to the market
After three years of intense work, the FET project Exa2Green achieved remarkable results. In 2015 the scientists from IBM Zurich Research Laboratory of Exa2green received a Gordon Bell Prize, a highly prestigious award recognizing outstanding development in HPC technology. The outcome of the project opens the door for further development in HPC in an energy-smart manner. Translating this technology into products for the market will be the next step – indeed, the team considers continuing in that direction with a spin-off project for the ArduPower device.
This FET Proactive project, funded under the initiative "Minimising energy consumption of computing to the limit", ran from November 2011 till October 2015, and was coordinated by the University of Heidelberg.
In Europe, 25 000 women die from cervical cancer every year. Most European countries have implemented programmes to vaccinate against the causal virus, the human papillomavirus (HPV), as well as Pap smear screening (cytology testing) to detect the early signs of cervical cancer. “However, vaccination and cytology testing are not enough. Vaccination and screening programmes need to improve further because no woman should die of cervical cancer,” says PreHdict’s project coordinator, Johannes Berkhof.
PreHdict collected extensive data on HPV-related disease, including incidences of HPV infections and disease, effectiveness of vaccination, performance of novel screening methods, screening practice, life style and demographics. The results were used to determine the prerequisites and strategies for effective HPV vaccination and testing in Europe, and to predict their likely impact on cervical screening programmes.
HPV-testing a priority for prevention
The early prevention of cervical cancer involves HPV vaccination, Papanicolaou (Pap) smear testing (cytology testing), and HPV screening. “Most countries in Europe have implemented HPV vaccination and Pap smear programmes, with varying degrees of success,” says Berkhof. The incidences of cervical cancer are therefore higher in some countries than in others. Many health care systems in Europe are also considering the implementation of HPV testing.
In the PreHdict project, medical researchers pooled clinical trial data across Europe. “This enabled us to demonstrate that HPV DNA testing is more sensitive than cytology testing (Pap smears). HPV-based screening provides up to 70% more protection against invasive cervical cancers compared with cytology screening,” reports Berkhof.
HPV vaccination helps prevent infection with the HPV types that cause most cervical cancers. Many countries have delivered HPV vaccination through a school-based programme. But even when girls have been vaccinated, it is still important for them to undergo screening at various intervals because the vaccination does not protect against all genotypes of HPV.
The Pap test screens for cervical intraepithelial neoplasia (CIN), which are abnormal cells that may develop into cancer. However, the Pap test is only 50-75% effective in detecting CIN Grade 2/3. “On its own, cytology testing for CIN is not optimal for screening women for the early signs of cervical cancer,” explains Berkhof. Simulation modelling by PreHdict researchers indicates that the addition of HPV testing to cervical cancer prevention programmes can reduce the incidence of cervical cancer by about 20%.
Room for improvement in screening programmes
As a result of the evidence-based data generated through PreHdict, several countries in Europe have integrated HPV testing into their cervical cancer prevention programmes. For example, Italy, the Netherlands and Sweden are currently implementing HPV-screening, as are the USA and Australia.
Health care systems can find it challenging to bolster vaccination and screening programmes. “Even if a health care system implements a vaccination programme, people can still refuse vaccination. For example, the uptake of HPV-vaccination is below 10% in Romania,” explains Berkhof.
Countries also need sufficient numbers of gynaecologists and laboratory technicians. And in addition to high-quality cytology and HPV-testing, as well as an infrastructure of laboratories and protocols, local organisations must proactively call women to attend testing at optimal intervals.
A willingness to be tested is also important, but some women are reluctant to undergo cervical smears. “Self-sampling is effective and can increase the screening uptake, but has not yet been implemented in Europe,” emphasises Berkhof.
PreHdict contributed to the body of evidence about optimal cervical cancer prevention and led to positive changes within some European countries. However, the battle against cervical cancer is far from over. The EU is continuing its fight against the disease by investing in a follow-on project, CoheaHr, which compares health service interventions to identify the most effective ways to further prevent HPV-related cancer.