Networks

The Global Alliance for Chronic Diseases (GACD) is a collection of the world’s biggest public research funding agencies.

The alliance coordinates and supports research activities that address the prevention and treatment of NCDs or chronic non-communicable diseases, on a global scale. NCDs account for 60% of deaths globally. Our multi-country, multi-disciplinary research focuses in particular on the needs of low- and middle-income countries (LMICs), where 80% of deaths from chronic diseases occur. We also focus on research with vulnerable populations of more developed countries.

www.gacd.org

The CBIG-SCREEN project is a collaborative European-wide effort to tackle inequalities in cervical cancer screening.

Healthcare inequality is at the heart of CBIG-SCREEN’s effort to provide vulnerable subpopulations with functioning access to cervical cancers screening and thus improve health outcomes and reduce associated healthcare and societal costs. The vulnerable subpopulations CBIG-SCREEN will focus on are women of low socioeconomic status, women living with HIV or other sexually transmitted diseases (STDs), incarcerated women, sex workers and migrants who may not have had access to cancer screening in their country of origin but find it difficult to navigate health care systems in their new homes.

The CBIG-SCREEN project is coordinated by the French National Institute for health and medical research (Inserm) and brings together public health experts, epidemiologists, regional cancer institutes, a pan-European umbrella organisation of national and regional cancer societies, a non-governmental institution that promotes gender equity in public health, and the WHO specialised agency for cancer research, IARC.

www.cbig-screen.eu

Cervical cancer is the fourth most common cancer in women, and the hard-to-reach populations in many countries are at a higher risk of developing the disease. Preventive screening programmes and vaccination against human papillomavirus (HPV) result in reduced cancer incidence and mortality.

The EU-funded ELEVATE project is conducting studies to identify hard-to-reach women in Belgium, Brazil, Ecuador and Portugal in order to remove barriers to their early screening and design strategies to make it more accessible. A multidisciplinary team of experts from Europe and the Community of Latin American and Caribbean States are carrying out the fundamental and technological research to develop an efficient and marketable test for the detection of high-risk HPV infections in those populations. The goal is to design a portable test compatible with self-sampling, generating rapid and easy-to-understand results.

elevate-hp.com

Cervical cancer (CC) kills a 250,000 people annually, frequently affecting young women, and requires persistent infection with high-risk Human Papillomavirus (hrHPV) for its development. It is preventable, by HPV vaccination and the implementation of population screening programmes, and it is curable if detected and treated early. Despite overwhelming evidence that detection of viral nucleic acids (HPV testing) in cervical cellular samples allows earlier detection of CC as compared to cytology (Pap smear), it is feared that its use as a stand-alone test in CC screening would be responsible for over-diagnosis and over-treatment.

HPV OncoPredict is an innovative diagnostic device (IVD) capable of detecting all oncogenic hrHPV genotypes frequently causing cervical infection as well as allowing to accurate identification those 10% of infected women who are truly at risk of developing cervical cancer. With the use of novel viral biomarkers, HPV OncoPredict, starting from a single self- or clinician-collected cellular sample, will enable women to undergo both primary cervical screening and, if HPV-positive, subsequent triage. HPV OncoPredict will allow HPV testing to reliably replace Pap smears in cervical cancer prevention, as recently recommended by European guidelines, being based on a disruptive technology ahead of any competitor’s product and supported by key opinion leaders.

The HPV testing market is huge (€315 M) with around 100 million tests performed each year. The consortium formed by GeneFirst and Hiantis, both highly innovative companies with patented technologies, has the capacity to bring HPV OncoPredict to success. HPV OncoPredict will not only shape the manner in which we stratify women at risk of developing cervical cancer, but also provide an accurate and cost effective test of disease to benefit patients. More importantly, it will feed into how healthcare systems implement screening strategies to benefit patient pathways.

genefirst.com

Screening for cervical cancer is a globally recommended public-health policy. To date, limited screening programmes have been implemented, providing suboptimal protection for women at high risk. Development of risk-stratified screening is a priority, as cervical cancer is on the rise in many countries. The EU-funded RISCC project will develop a risk-based screening approach, taking into account history, human papillomavirus (HPV) vaccination status and other relevant risk factors. Risk profiles from screening history will be created using joint data from several large European HPV screening trials. Risk profiles based on vaccination status will be created for cohorts with varying screening and vaccination coverage, using data from community vaccination trials. Finally, RISCC will build open source applications using risk-based screening algorithms to support implementation in real-life programmes.

www.riscc-h2020.eu

Overcoming barriers to human papillomavirus cancer screening
Global implementation of cancer screening can be hindered by differences in cultures and available resources between countries. The EU-funded CHILI project will address this challenge by determining the acceptability, feasibility and cost-effectiveness of the ELEVATE cervical cancer screening tool for women in low-income countries. This portable, battery-powered device comprises a human papillomavirus DNA test and a proteomic biomarkers detection sensor. Social scientists will investigate current screening practices and draw up a tailored strategy embedded in the current health system, while engineers will validate the self-testing device and adapt it for large-scale manufacturing at an affordable cost. Public health specialists and health economists will then evaluate the implementation of the screening tool to determine its suitability and cost-effectiveness.

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Overcoming barriers to human papillomavirus cancer screening
Global implementation of cancer screening can be hindered by differences in cultures and available resources between countries. The EU-funded CHILI project will address this challenge by determining the acceptability, feasibility and cost-effectiveness of the ELEVATE cervical cancer screening tool for women in low-income countries. This portable, battery-powered device comprises a human papillomavirus DNA test and a proteomic biomarkers detection sensor. Social scientists will investigate current screening

Increasing screening to reduce cancer deaths
Screening for cancer followed by early treatment reduces mortality from colorectal, breast and cervical cancer, currently causing 155 000 deaths annually in eastern Europe. Screening in these countries is often less organised, leading to a lack of data, low coverage and minority groups being reached insufficiently. EU-TOPIA-EAST will improve the screening by investigating and implementing roadmaps developed under the first EU-TOPIA project. It will consider the local health and social systems in Georgia, Montenegro and Romania. The implemented programmes will be monitored using key indicators and EU-TOPIA tools, and by sophisticated decision models to predict the long-term benefits and harm-benefit ratios. Other (middle-income) countries will be involved in workshops, to share their experiences in improving screening programmes.

eu-toia-east.org

Cervical cancer (CxCa) is caused by high risk types of the human papillomavirus (a.o. HPV16). Prophylactic HPV vaccination is not the standard of care in all European countries, and where approved it is not sufficiently adopted. Once infected, these vaccines no longer prevent premalignant lesions and CxCa, which can only be treated with surgery or radio-chemotherapy. However, this is not effective in recurrent/advanced CxCa. In underdeveloped countries, CxCa is often detected when it is too late for curative treatment. With an estimated global incidence of 500.000 new cases of CxCa and 274.000 deaths per year, the need for an effective therapy is extremely high. Targeted immunotherapy is an effective approach to induce a tumour-directed immune response. Previously, members of the IMMUNISA consortium have formulated ISA101, a cancer vaccine consisting of overlapping synthetic long peptides covering all epitopes of the HPV16 oncogenic proteins. ISA101 has shown promising Phase 1 clinical trial results in patients with advanced CxCa where it works synergistically with chemotherapy. IMMUNISA now proposes the multi-centre randomised Phase 2 CervISA-2 trial; a careful assessment of the efficacy of the proprietary ISA101b therapeutic vaccine in combination with chemotherapy for the treatment of CxCa, measured by a prolonged progression free survival. A multidisciplinary collaboration between leading clinical EU sites specialised in CxCa, a partner providing strategic and operational regulatory service and a cutting-edge biotech SME will enable the optimal implementation of the CervISA-2 trial, exploitation activities and overall project dissemination. This is pivotal to catapult further development of ISA101b as a commercial vaccine and push it towards clinical implementation as fast as possible. For ISA101b, IMMUNISA will provide, 1) clinical data on the efficacy, 2) a solid exploitation strategy and 3) the regulatory framework for efficient translation to clinical use.

Opening the World Cancer Congress in Paris in November 2016, President François Hollande insisted that women should be at the heart of cancer control, “because they are victims of inequality in access to prevention, treatment and screening in every country in the world.”

Breast, ovarian and cervical cancers are a major public health problem world-wide. Each year, approximately 2.5 million women are diagnosed with one of these cancers, and 900,000 women die from them, mainly in low- and middle-income countries.

The CONCORD programme for global surveillance of cancer survival reported striking differences in survival from these three cancers. Population-based cancer survival is a key measure of the overall effectiveness of health systems in dealing with cancer, from early diagnosis to comprehensive investigation and optimal treatment. I will exploit the CONCORD data base, as follows:

• Access primary medical records in selected high- and low-income countries to collect more detailed data on stage at diagnosis, staging investigations, morphology, grade, prognostic bio-markers and treatment, for the most recent year during 2010-2014 for which data are available
• Analyse the distributions of stage and treatment (“patterns of care”)
• Estimate 1- and 5-year survival trends by stage, histological group and/or molecular subtype
• Quantify inequalities in survival as the number of premature deaths that would be avoidable if survival in a given country (region) were equal to that in a neighbouring country with higher survival.

This ground-breaking work will show that it is possible (a) to collect high-quality, complete clinical information at population level even in low- and middle-income countries; (b) to explain the striking inequalities in women’s cancer survival world-wide, and (c) to summarise these inequalities in a single number (avoidable deaths) as a powerful tool that motivates policymakers to reduce inequalities in survival.

The goal of the DIADEPH project is to develop a “Business Proposition Package” that could enable our group to eventually bring a new non-invasive gynaecological device to market. The device holds promise to reduce the number of biopsies that are currently carried out to rule out cervical cancer, thus mitigating the pain, anxiety, and financial costs that the shortcomings of the diagnosis pathway brings today on patients, their families, and our society.

Every year, more than half-a-million women are diagnosed with cervical cancer: for half of them, the diagnosis is a death sentence. This terrible disease often affects young lives: in Europe, it represents the 2nd most common form of cancer among women aged 15-44. The diagnostic evaluation starts if, during a periodical screening, the patient is found positive to high-risk Human Papilloma Virus. The patient is then primarily referred to colposcopy to look for possible signs of cervical intraepithelial neoplasia (CIN). Unfortunately, this exam leaves much to be desired: even for high grade leasions (CIN3), colposcopy gives a false negative in almost one case in three.

To address the shortcomings of colposcopy, we propose a new transvaginal probe that obtains two independent neoplasia indicators: (1) a high-resolution 3D subsurface image, and (2) a quantitative assessment of its mechanical properties. The data are collected during a procedure that does not generate discomfort and is expected to provide a better diagnosis in a few minutes.

We already developed a prototype for dermatological analysis, and tested it on volunteers; with this grant, we will convert the current form factor to enable transvaginal measurements. Supported by a team of physicists, engineers, medical doctors, and business developers, we will analyze the business opportunity and align all the stakeholders that are needed to go from a proof-of-concept to a market-ready product.

Human papillomaviruses (HPVs) cause a range of serious diseases, with particular regard to cervical cancer, most anal cancers and half of head and neck cancers, and the need for new and effective antiviral therapies is of paramount importance. Important advancements regarding the HPV infection, throughout the infected epithelium, have been recently made. However, a full mechanistic understanding of how stochastic and dynamical properties of the HPV gene network interact with the cellular circuitry that controls proliferation/differentiation and cell-to-cell communication affects responses at the single cell and tissue level during infection is lacking. A better understanding of these aspects is critical to understand viral persistence, cancer progression, and to develop novel strategies for antiviral therapies. Mathematical models, developed under rigorous mathematical and biological assumptions, can be of great help in generating optimal solutions to these problems. STEPV project aims at improving the current available frameworks for stochastic tissue-level mathematical modeling, by tackling their limitations and specialize them in the context of HPVs, as well as to improve clinical/biological discoveries about HPVs infection. The specific goals are: (1) development of novel spatio-temporal modeling frameworks in order to describe HPVs gene expression and its connection with the phenotype control; (2) use of the developed models to understand the phenotype regulation by oncoproteins, understand viral persistence and propose novel antiviral strategies. By achieving these goals, STEPV will provide, for the first time, innovative modeling frameworks in the field of the computational systems biology applied to the context of HPVs infection, allowing quantitative and noninvasive tools to deeply investigate still elusive mechanisms, regarding HPVs infection, as well as investigate inaccessible or poorly understood clinical/biological scenarios.

Since decades the bulk of cancer research focusses on the genetic and molecular level. To complement this knowledge, I will focus on the collective behaviour of cancer cells in cell clusters and in the extracellular matrix (ECM). Conventional cancer research tackles issues like genetic changes, signalling pathways or intracellular mechanisms, I want to answer the question: When is a cancer cell jammed or when can it overcome the yield stress to actively “flow” in a dense microenvironment (ME)? I have brought forward the basic idea within the concept of Physics of Cancer that changes in a cancer cell’s material properties determine its metastatic potential. As follows I propose the next breakthrough by determining a predictive phase diagram for unjamming transitions of cancer cells. Cancer cell jamming is quantified by cell speed as a measure of the motile forces and by cellular shape to account for the interplay between cell contractility and adhesion. Our self-propelled Voronoi model (SPV) will explain whether a cell is jammed by its neighbours or the ECM, overcoming the limitations of existing theories which only apply to specific environments. Building on my leadership in cell biomechanics and the exclusive access to two types of carcinomas (mamma, cervix), I will introduce highly innovative bionic modulators of intracellular mechanics and develop live cancer cell tracking in biopsies as a ground-breaking alternative to vital imaging. While these approaches are perfect to prove that unjamming transitions are key to tumour progression, I will investigate to what extent fluid, i.e. unjammed, tissue behaviour can be detected by magnetic resonance imaging elastography (MRE) as an individual predictive marker for metastasis. Moreover the results may guide surgeons when concerning the local spreading of cancer and thus greatly empower surgery in tumour therapies.

Recent evidence demonstrates that cancer is overtaking cardiovascular disease as the number one cause of mortality in Europe. This is largely due to the lack of preventative measures for common (e.g. breast) or highly fatal (e.g. ovarian) human cancers. Most cancers are multifactorial in origin. The core hypothesis of this research programme is that the extremely high risk of BRCA1/2 germline mutation carriers to develop breast and ovarian cancer is a net consequence of cell-autonomous (direct effect of BRCA mutation in cells at risk) and cell non-autonomous (produced in distant organs and affecting organs at risk) factors which both trigger epigenetic, cancer-initiating effects.

The project’s aims are centered around the principles of systems medicine and built on a large cohort of BRCA mutation carriers and controls who will be offered newly established cancer screening programmes. We will uncover how ‘cell non-autonomous’ factors work, provide detail on the epigenetic changes in at-risk tissues and investigate whether these changes are mechanistically linked to cancer, study whether we can neutralise this process and measure success in the organs at risk, and ideally in easy to access samples such as blood, buccal and cervical cells.

In my Department for Women’s Cancer we have assembled a powerful interdisciplinary team including computational biologists, functionalists, immunologists and clinician scientists linked to leading patient advocacy groups which is extremely well placed to lead this pioneering project to develop the fundamental understanding of cancer development in women with BRCA mutations. To reset the epigenome, re-establishing normal cell identity and consequently reducing cancer risk without the need for surgery and being able to monitor the efficacy using multicellular epigenetic outcome predictors will be a major scientific and medical breakthrough and possibly applicable to other chronic diseases.