Periodic Reporting for period 3 - ELEVATE (Early detection of cervical cancer in hard-to-reach populations of women through portable and point-of-care HPV testing)
Reporting period: 2022-01-01 to 2023-06-30
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 the sexually transmittable Human Papillomavirus (HPV), is the fourth most prevalent cancer among women worldwide, even though it is detectable and preventable in pre-malignant stages through screening and early treatment. However, cervical cancer screening is often a time consuming and stressful event that requires a gynaecological examination. As a result, it is not adapted to women who are hard to reach due to social, geographical or other contextual barriers. A more accessible test, based on self-sampling, could increase cervical cancer screening in low-income or isolated populations, but also among women in general who for a variety of reasons do not attend regular screenings.
The ELEVATE consortium aims at developing a user-friendly portable, point-of-care HPV self-testing device that yields rapid, easy-to-understand results, and does not require any electrical outlets or specialized health personnel. The test will detect and identify both the human papilloma virus and cancer biomarker proteins to obtain a more complete and specific view on the risk of developing cervical cancer, so that a clear follow-up path can immediately be defined.
The new HPV self-testing tool will be piloted among hard-to-reach populations in a variety of countries (Belgium, Brazil, Ecuador and Portugal): by using a community-based participatory approach the study will test the user acceptability and the cost-effectiveness of the new screening tool. Ultimately, all acquired knowledge allows for optimised screening initiatives that will enhance participation among hard-to-reach women, and will feed into further refinement of national health strategies for cancer prevention in Latin-America and Europe.
Cervical cancer, caused by the sexually transmittable Human Papillomavirus (HPV), is the fourth most prevalent cancer among women worldwide, even though it is detectable and preventable in pre-malignant stages through screening and early treatment. However, cervical cancer screening is often a time consuming and stressful event that requires a gynaecological examination. As a result, it is not adapted to women who are hard to reach due to social, geographical or other contextual barriers. A more accessible test, based on self-sampling, could increase cervical cancer screening in low-income or isolated populations, but also among women in general who for a variety of reasons do not attend regular screenings.
The ELEVATE consortium aims at developing a user-friendly portable, point-of-care HPV self-testing device that yields rapid, easy-to-understand results, and does not require any electrical outlets or specialized health personnel. The test will detect and identify both the human papilloma virus and cancer biomarker proteins to obtain a more complete and specific view on the risk of developing cervical cancer, so that a clear follow-up path can immediately be defined.
The new HPV self-testing tool will be piloted among hard-to-reach populations in a variety of countries (Belgium, Brazil, Ecuador and Portugal): by using a community-based participatory approach the study will test the user acceptability and the cost-effectiveness of the new screening tool. Ultimately, all acquired knowledge allows for optimised screening initiatives that will enhance participation among hard-to-reach women, and will feed into further refinement of national health strategies for cancer prevention in Latin-America and Europe.
Work performed by the Public Health Team:
During this reporting period, an acceptability study was implemented in various countries in order to compare the uptake of a pap smear after an educational session with the acceptance of taking a self-sample, among women in hard-to-reach communities. Data collection for the acceptability study is finalized in Belgium and Ecuador and ongoing in Portugal. The team in Brazil will reach out to communities once ethical approval is obtained. Additionally, for the economic analysis, the costing framework and templates were finalized to capture the cost of standard care and the implementation of acceptability study. Also a Markov model was developed to perform the cost-effectiveness analysis in all four countries during period 4. The model was tested with data from Ecuador for calibration.
During this reporting period, a protocol is being developed for a hospital-based pilot study to allow us to compare the results of the new screening tool with standard tests in Belgium and Ecuador. Once the manufacturing process of the cartridges is up and running, we will roll-out this validation with the new screening device. Results of both studies will form the basis for the final cost-effectiveness analysis of our new screening strategy.
Work performed by the screening device Development Team:
During this reporting period, sample collection was finalized in Belgium and Brazil. A total of 987 samples (Belgium, Brazil, Ecuador, Portugal) have been collected and analysed. The samples were used for the development and validation of 1) the HPV DNA detection test), 2) the protein detection test, and 3) the genetic and proteomic sensor. Furthermore, Cobas 4800 (Roche) and NGS (Ion Torrent Platform, Thermo Fisher) were performed, identifying HPV genotypes as well as the most conserved regions on the HPV DNA of the 14 high-risk HPV types of interest. In addition, samples were analyzed with the comparative Anyplex™ II HPV High Risk Detection test in order to compare with and validate the results of NGS analysis.
With regard to the sensor development, the major achievements in this reporting period were the elucidation of optimal protocols for the simultaneous solid-phase amplification and electrochemical detection of the 14 high-risk genotypes and the beta-globin housekeeping gene, using the new electrode array designed for the simultaneous detection of these high-risk genotypes together with the Ki67 and p16 proteomic markers.
During this reporting period, the focus was also on the final design of the cartridge and development of laboratory specification of the point-of-care tools. Since the testing of several functionalities of the first proposed cartridge layout showed that there was a significant risk of uncertainty with respect to reliability, a major redesign was performed which led to a simplified design. Concerning the tool, by the end of this period, an ELEVATE specific engineering prototype device has been constructed and rigorously tested. Construction of two further units for laboratory testing and later clinical use has been started. Two standalone benchtop multichannel potentiostats have also been constructed. The results thus far are promising.
During this reporting period, an acceptability study was implemented in various countries in order to compare the uptake of a pap smear after an educational session with the acceptance of taking a self-sample, among women in hard-to-reach communities. Data collection for the acceptability study is finalized in Belgium and Ecuador and ongoing in Portugal. The team in Brazil will reach out to communities once ethical approval is obtained. Additionally, for the economic analysis, the costing framework and templates were finalized to capture the cost of standard care and the implementation of acceptability study. Also a Markov model was developed to perform the cost-effectiveness analysis in all four countries during period 4. The model was tested with data from Ecuador for calibration.
During this reporting period, a protocol is being developed for a hospital-based pilot study to allow us to compare the results of the new screening tool with standard tests in Belgium and Ecuador. Once the manufacturing process of the cartridges is up and running, we will roll-out this validation with the new screening device. Results of both studies will form the basis for the final cost-effectiveness analysis of our new screening strategy.
Work performed by the screening device Development Team:
During this reporting period, sample collection was finalized in Belgium and Brazil. A total of 987 samples (Belgium, Brazil, Ecuador, Portugal) have been collected and analysed. The samples were used for the development and validation of 1) the HPV DNA detection test), 2) the protein detection test, and 3) the genetic and proteomic sensor. Furthermore, Cobas 4800 (Roche) and NGS (Ion Torrent Platform, Thermo Fisher) were performed, identifying HPV genotypes as well as the most conserved regions on the HPV DNA of the 14 high-risk HPV types of interest. In addition, samples were analyzed with the comparative Anyplex™ II HPV High Risk Detection test in order to compare with and validate the results of NGS analysis.
With regard to the sensor development, the major achievements in this reporting period were the elucidation of optimal protocols for the simultaneous solid-phase amplification and electrochemical detection of the 14 high-risk genotypes and the beta-globin housekeeping gene, using the new electrode array designed for the simultaneous detection of these high-risk genotypes together with the Ki67 and p16 proteomic markers.
During this reporting period, the focus was also on the final design of the cartridge and development of laboratory specification of the point-of-care tools. Since the testing of several functionalities of the first proposed cartridge layout showed that there was a significant risk of uncertainty with respect to reliability, a major redesign was performed which led to a simplified design. Concerning the tool, by the end of this period, an ELEVATE specific engineering prototype device has been constructed and rigorously tested. Construction of two further units for laboratory testing and later clinical use has been started. Two standalone benchtop multichannel potentiostats have also been constructed. The results thus far are promising.
The ELEVATE project expects to empower women to be screened and envisions an alternative for current standard practice, an alternative in which mobile health units can measure the self-obtained samples at or close to women’s homes and are able to provide immediate and clear personal feedback on the risk of cervical cancer and which actions best to take.
The impact of the ELEVATE project is not limited to countries involved in the study, as development of a common methodology to reach hard-to-reach populations is targeted. The conclusions of the project could hence be a first step towards a worldwide strategy for screening diverse hard-to-reach populations. This would play an important role in reaching the critical point where screening helps decrease in a similar extent the worldwide incidence and mortality of cervical cancer.
The impact of the ELEVATE project is not limited to countries involved in the study, as development of a common methodology to reach hard-to-reach populations is targeted. The conclusions of the project could hence be a first step towards a worldwide strategy for screening diverse hard-to-reach populations. This would play an important role in reaching the critical point where screening helps decrease in a similar extent the worldwide incidence and mortality of cervical cancer.