Periodic Reporting for period 4 - ELEVATE (Early detection of cervical cancer in hard-to-reach populations of women through portable and point-of-care HPV testing)
Período documentado: 2023-07-01 hasta 2024-12-31
ELEVATE: EarLy dEtection of cerVical cAncer in hard-to-reach populations of women through portable and point-of-care HPV TEsting
Cervical cancer, caused by HPV, is the fourth most common cancer among women globally, despite being preventable through screening and early treatment. Traditional methods, like Pap smears, require gynecological exams, which can be inaccessible due to social, geographic, or financial barriers, leading to low screening rates and higher mortality in underserved populations.
ELEVATE aims to increase screening participation through education, self-sampling and decentralized testing, focusing on developing an innovative, portable HPV self-testing device that provides on-the-spot results. The project also evaluates the cost-effectiveness of combining community-based education with self-sampling.
Research shows that integrating self-sampling into community-based education boosts participation, while standalone awareness campaigns have limited impact on uptake. Cost-effectiveness analyses confirm that decentralized screening reduces cancer deaths, particularly in low-coverage areas.
The ELEVATE team is developing a point-of-care HPV self-testing device that delivers rapid, easy-to-interpret results, enhancing risk assessment and providing immediate follow-up guidance. This technology has the potential to shift cervical cancer screening from centralized settings to community or home-based solutions, removing barriers to access.
ELEVATE's findings support policy adaptations in Latin America and Europe, promoting decentralized screening and improving access to healthcare for underserved populations.
Cervical cancer, caused by HPV, is the fourth most common cancer among women globally, despite being preventable through screening and early treatment. Traditional methods, like Pap smears, require gynecological exams, which can be inaccessible due to social, geographic, or financial barriers, leading to low screening rates and higher mortality in underserved populations.
ELEVATE aims to increase screening participation through education, self-sampling and decentralized testing, focusing on developing an innovative, portable HPV self-testing device that provides on-the-spot results. The project also evaluates the cost-effectiveness of combining community-based education with self-sampling.
Research shows that integrating self-sampling into community-based education boosts participation, while standalone awareness campaigns have limited impact on uptake. Cost-effectiveness analyses confirm that decentralized screening reduces cancer deaths, particularly in low-coverage areas.
The ELEVATE team is developing a point-of-care HPV self-testing device that delivers rapid, easy-to-interpret results, enhancing risk assessment and providing immediate follow-up guidance. This technology has the potential to shift cervical cancer screening from centralized settings to community or home-based solutions, removing barriers to access.
ELEVATE's findings support policy adaptations in Latin America and Europe, promoting decentralized screening and improving access to healthcare for underserved populations.
1. Understanding the Challenges
Through extensive public health research, the team identified the primary obstacles preventing women from participating in routine screening. FGDs and interviews with hard-to-reach women and stakeholders revealed that factors such as limited understanding, shame, and logistical difficulties significantly impacted screening rates. Acceptability studies, which included educational sessions supported by newly developed materials, showed high acceptance of self-sampling among hard-to-reach women, with a 90% uptake rate. Cost-effectiveness analyses further demonstrated how screening programs, including education and self-sampling, can reduce cervical cancer deaths, particularly in low-coverage communities.
2. Advancing HPV DNA Testing
The ELEVATE consortium established a biobank of nearly 1,000 samples from women with and without cervical lesions. E6 and E7 genes were sequenced using Next-Generation Sequencing (NGS) to assess the performance and accuracy of various HPV tests. The research revealed that variations in HPV genetic structures could explain the discordant results observed among certain commercial tests. These findings open avenues for improving diagnostic tests and reducing false negatives: the NGS analysis identified well-conserved regions of the HPV genomes, which could serve as potential target areas for more reliable HPV detection.
3. Developing a Portable Diagnostic Tool
One of the project’s most groundbreaking goals was the creation of an innovative point-of-care screening test. This involved designing a sensor to capture target molecules like HPV DNA and proteomic biomarkers, integrated into a custom micro-fluidic cartridge for detection. To ensure accessibility, the consortium also developed a read-out device that translates the detected biomarkers into an interpretable health outcome.
The sensor integrates Ki67 and P16 biomarkers, commonly used in diagnostics, but faced challenges related to antibody stability and inconsistent cross-linking to the sensor's gold substrate, which affect detection reliability. Nevertheless, protein detection was feasible, yet not a clinically relevant levels.
A breakthrough was achieved with the detection of 14 high-risk HPV types, utilizing specific primers that showed 100% correlation with the Anyplex HR HPV DNA test for 162 samples. The sensor's electrochemical detection allows for simultaneous amplification of HPV DNA from a single sample, streamlining the testing process and reducing assay time.
A disposable microfluidic cartridge was developed for the sensor, enabling self-sample introduction for genomic and proteomic analysis. The cartridge's design features microchannels, integrated blisters with liquid reagents, and waste chambers to prevent interference.
The portable read-out tool automates microfluidic sample handling and electrochemical measurements, delivering results within 1 to 2 hours. The compact device weighs 12 kg and uses a 64-channel potentiostat for simultaneous readings, reducing processing time. The tool underwent extensive testing to ensure reliability and long-term stability.
Despite promising results, early validation with real samples showed variability in sensor performance, prompting further testing to identify sources of inconsistency, such as electrode conditions, reagent stability, and procedural issues. Addressing these challenges is crucial for improving the sensor's and cartridges’ overall performance.
ELEVATE's impact has been driven by strong collaboration, engaging hard-to-reach communities while partnering with local healthcare providers and stakeholders. The project's work underscores the importance of interdisciplinary cooperation and technological innovation in addressing global health challenges. Findings have been widely disseminated through scientific publications, conference presentations, and various (social) media platforms to reach a broader audience. On October 18, 2024, the UCuenca team presented ELEVATE results during Ecuador’s National Assembly, contributing to the development of a cervical cancer prevention law that was passed later that month. The project’s website (https://elevate-hpv.com/(se abrirá en una nueva ventana)) remains a key resource for ongoing updates.
Through extensive public health research, the team identified the primary obstacles preventing women from participating in routine screening. FGDs and interviews with hard-to-reach women and stakeholders revealed that factors such as limited understanding, shame, and logistical difficulties significantly impacted screening rates. Acceptability studies, which included educational sessions supported by newly developed materials, showed high acceptance of self-sampling among hard-to-reach women, with a 90% uptake rate. Cost-effectiveness analyses further demonstrated how screening programs, including education and self-sampling, can reduce cervical cancer deaths, particularly in low-coverage communities.
2. Advancing HPV DNA Testing
The ELEVATE consortium established a biobank of nearly 1,000 samples from women with and without cervical lesions. E6 and E7 genes were sequenced using Next-Generation Sequencing (NGS) to assess the performance and accuracy of various HPV tests. The research revealed that variations in HPV genetic structures could explain the discordant results observed among certain commercial tests. These findings open avenues for improving diagnostic tests and reducing false negatives: the NGS analysis identified well-conserved regions of the HPV genomes, which could serve as potential target areas for more reliable HPV detection.
3. Developing a Portable Diagnostic Tool
One of the project’s most groundbreaking goals was the creation of an innovative point-of-care screening test. This involved designing a sensor to capture target molecules like HPV DNA and proteomic biomarkers, integrated into a custom micro-fluidic cartridge for detection. To ensure accessibility, the consortium also developed a read-out device that translates the detected biomarkers into an interpretable health outcome.
The sensor integrates Ki67 and P16 biomarkers, commonly used in diagnostics, but faced challenges related to antibody stability and inconsistent cross-linking to the sensor's gold substrate, which affect detection reliability. Nevertheless, protein detection was feasible, yet not a clinically relevant levels.
A breakthrough was achieved with the detection of 14 high-risk HPV types, utilizing specific primers that showed 100% correlation with the Anyplex HR HPV DNA test for 162 samples. The sensor's electrochemical detection allows for simultaneous amplification of HPV DNA from a single sample, streamlining the testing process and reducing assay time.
A disposable microfluidic cartridge was developed for the sensor, enabling self-sample introduction for genomic and proteomic analysis. The cartridge's design features microchannels, integrated blisters with liquid reagents, and waste chambers to prevent interference.
The portable read-out tool automates microfluidic sample handling and electrochemical measurements, delivering results within 1 to 2 hours. The compact device weighs 12 kg and uses a 64-channel potentiostat for simultaneous readings, reducing processing time. The tool underwent extensive testing to ensure reliability and long-term stability.
Despite promising results, early validation with real samples showed variability in sensor performance, prompting further testing to identify sources of inconsistency, such as electrode conditions, reagent stability, and procedural issues. Addressing these challenges is crucial for improving the sensor's and cartridges’ overall performance.
ELEVATE's impact has been driven by strong collaboration, engaging hard-to-reach communities while partnering with local healthcare providers and stakeholders. The project's work underscores the importance of interdisciplinary cooperation and technological innovation in addressing global health challenges. Findings have been widely disseminated through scientific publications, conference presentations, and various (social) media platforms to reach a broader audience. On October 18, 2024, the UCuenca team presented ELEVATE results during Ecuador’s National Assembly, contributing to the development of a cervical cancer prevention law that was passed later that month. The project’s website (https://elevate-hpv.com/(se abrirá en una nueva ventana)) remains a key resource for ongoing updates.
Over the past six years, the ELEVATE consortium has made significant progress in improving cervical cancer screening for hard-to-reach populations. Through formative research, interventions, and technological advancements, we’ve provided valuable insights to guide policymakers in enhancing accessibility. While standalone awareness sessions had limited impact on uptake, integrating self-sampling in community-based settings drastically increased participation. Cost-effectiveness analyses demonstrated that combining education and self-sampling can optimize screening programs, especially in low-coverage areas, while reducing healthcare system burden and empowering women with easy-to-use kits. Additionally, health literacy initiatives ensured women understood the importance of HPV screening and prevention.
ELEVATE also advanced a novel point-of-care screening test using a portable electrochemical sensor designed to detect 14 high-risk HPV types and biomarkers. Although initial validation showed variability, ongoing improvements are enhancing reliability. Once validated, this rapid test could increase uptake by offering immediate, personalized risk assessments at the point of testing, addressing logistical and psychological barriers.
ELEVATE’s broader impact extends globally, providing a model for engaging underserved populations and informing policies aimed at eliminating cervical cancer as a public health problem. If adopted, this approach could reduce cervical cancer incidence and mortality worldwide, ensuring equitable access to screening services.
ELEVATE also advanced a novel point-of-care screening test using a portable electrochemical sensor designed to detect 14 high-risk HPV types and biomarkers. Although initial validation showed variability, ongoing improvements are enhancing reliability. Once validated, this rapid test could increase uptake by offering immediate, personalized risk assessments at the point of testing, addressing logistical and psychological barriers.
ELEVATE’s broader impact extends globally, providing a model for engaging underserved populations and informing policies aimed at eliminating cervical cancer as a public health problem. If adopted, this approach could reduce cervical cancer incidence and mortality worldwide, ensuring equitable access to screening services.