Cervical cancer is a major public health problem, with annually more than 500.000 women worldwide diagnosed with this disease. The Prevention and Screening Innovation Project toward Elimination of Cervical Cancer (PRESCRIP-TEC) contributes to effective and innovative cervical cancer screening, including direct treatment for women in resource-poor or hard-to-reach settings in the world.
PRESCRIP-TEC conducts implementation research in four countries over three continents: Bangladesh and India in Asia, Uganda in Africa, and Slovakia in Eastern Europe. We will improve existing screening protocols in the four countries. In this research universities, cancer institutes and non-governmental organisations from these countries collaborate with the University Medical Center Groningen and the Female Cancer Foundation in the Netherlands.
We will improve interactive information with communities via traditional media, mobile devices and social media. At this moment, in most hard-to-reach areas women are approached through radio, face-to-face meetings, flyers, posters, etc. This results in limited uptake of cervical cancer screening in many populations.
All over the world, the use of mobile devices, social media, and modern communication technology is spreading quickly. Also women with limited health literacy or limited internet access, are using the technology more and more. PRESCRIP-TEC will investigate to which extent the range of social mobilisation options can be expanded for prevention and screening of cervical cancer.
Better testing for HPV
Nearly all cervical cancers are caused by infection with the Human Papilloma Virus (HPV). The Word Health Organisation recommends HPV testing as the primary screening intervention.
We will offer client-friendly HPV self-tests at home. Women do not have to travel to a clinic for gynaecological examination, to know if they have a HPV infection. Only those women who are HPV positive will be invited for further investigation.
In India, Bangladesh and Uganda HPV positive women will undergo a Visual Inspection of the cervix with Acetic acid (VIA) in mobile clinics or primary healthcare facilities, to diagnose any precancerous lesions, which need treatment.
We will use an artificial intelligence decision support systems (AI-DSS) in gynaecological examination. The use of artificial intelligence built into mobile devices offers high quality diagnosis in resource-poor settings. Inter-observer variation in VIA will be reduced.
We will offer to women who need treatment for precancerous lesions direct treatment in the location where the VIA is performed. This reduces travel time and therefore drop-out of women in the process.
We will analyse the uptake of cervical cancer screening offered. Will improved communication lead to higher attendance? Will convenient HPV testing at home lead to higher acceptance? Will AI-DSS lead to better diagnosis?
We will perform a cost-effectiveness analysis and a produce a business case for the global introduction of hrHPV testing as routine screening for cervical cancer. We will show the advantage of point-of-delivery testing and the benefits of self-testing for cancer in the post-COVID era, which reduces pressure on the health system. This research, therefore will be a major contribution in supporting the global WHO strategy for elimination of cervical cancer.
More information about Project Overview
Cancer of the cervix of the uterus is a global health challenge: worldwide numbers are increasing, although cervical cancer is largely preventable through vaccination and screening programmes. In 2018 approximately 570,000 women were diagnosed with cervical cancer worldwide, and 311,000 died of the disease, of whom 90% in low- and middle-income countries (LMICs). This number is higher than the registered number of deaths due to Corona Virus Infectious Disease (COVID 19) in the period January – May 2020. In high-income countries (HICs) the infection rate is lower, but women from vulnerable communities are mostly affected.
Primary prevention: Primary prevention of cervical cancer consists of vaccination for high risk Human Papilloma Virus (hrHPV). This virus is responsible for over 90% of cervical cancers and vaccination significantly reduces the incidence of HPV infection and premalignant lesions. Over the last ten years, most high income countries have started vaccination programmes but coverage is not optimal. The HPV vaccination is slowly being introduced in low- and middle-income countries. This project will provide information to at least 450,000 people about vaccination, but will not engage in vaccination programmes.
Screening and secondary prevention: The occurrence of premalignant lesions and invasive cervical cancer is almost exclusively dependent on a persistent hrHPV infection. Tests determining presence of hrHPV have become the first line screening tool for cervical cancer in the Netherlands and few other Western countries, even before Pap-smear or VIA test. hrHPV infection often does not lead to cervical cancer. Depending on the age of the woman and other risk factors like HIV-co-infection, around 80% women with HPV-infection will clear the virus and not develop precancerous changes. When women are HPV-positive, additional testing (Pap-smear or VIA) is needed to detect precancerous lesions and select women for treatment.
Secondary prevention programmes were initiated decades ago in high-income countries, even before the relation between HPV infection and cervical cancer was known, and have led to a dramatic decrease in the incidence of cervical cancer. Secondary prevention for cervical cancer without hrHPV testing includes several strategies. In settings where pathology laboratory facilities are available, screening with Pap smear, collected through gynaecological examination, is recommended. Presence of dysplasia (precancerous cells) is an indication for a colposcopy, where the cervix is examined visually with a magnifying lens and biopsies can be taken for histological analysis. If indicated, lesions are treated with local electrosurgical excision.
In LMICs laboratory facilities are limited and screening is performed using visual inspection with acetic acid (VIA). During gynaecological examination, acetic acid is applied to the cervix and under direct visual inspection the cervix is screened for aceto-white lesions, indicating presence of precancerous cells. In the same visit (one stop-shop) women are treated with cryotherapy or thermal ablation, techniques that destroy the precancerous cells of the cervix through respectively freezing or heating.
The diagnostic accuracy of both colposcopy and VIA are dependent on the skills of the health care worker, especially for VIA sensitivity and specificity reported varies across studies. Manipal Academy of Higher Education in India has proven that adding artificial intelligence to VIA improves diagnostic accuracy (an accuracy of 97.94%, a sensitivity of 99.05% and specificity of 97.16%. ). Artificial intelligence is a Decision Support System and can support the individual judgement of observers, reduce the interobserver variability and provides highly sensitive results. This means that screening can be done by nurses or midwives without extensive training in VIA.
Bottlenecks for increasing coverage of cervical cancer screening programmes
Several publications analysed factors for success of cervical cancer screening programmes. The factors can be distinguished in client-related factors and health systems factors.
Factors related to clients can be categorised as in the table below. In general, the factors mentioned below are more prevalent in people with lower levels of education, low health literacy and lower socio-economic status.
Table 1 Client-related factors influencing uptake (modified and adapted from SAGE)
|Contextual influences(historic, socio-cultural, environmental, health systems, political factors)||Communication and media environmentInfluential leaders, lobbiesHistorical factorsReligion, cultureGender issuesPoliticsGeographical barriersPerceptions of technology|
|Individuals and groups||Personal and family experience with cancerBeliefs and attitudes with regard to screening and preventionKnowledge and awarenessTrust in health system and providersPerceived benefits of early treatmentSocial norms in community|
|Specific issues related to cervical cancer screening||Attitudes toward gynaecological examinationAttitudes towards privacy, or involvement of male providersCosts (also indirect costs of travel etc.)Health systems factors (waiting, returning for screening)|
From literature, the following health system factors can be identified as in the table below.
Table 2 Health system factors for cervical cancer screening
|Building block||Health System Factors|
|Human resources||Insufficient or lack of staff, i.e. gynaecologists, trained nurses or midwives, pathologists, laboratory staff. There is a high turn-over of staff.|
|Medicines and supplies||No hrHPV tests available, supplies for cryotherapy or thermal ablation only via commercial suppliers.Not enough sterilisation equipment. Lack of maintenance and repair. Limited number of distributors in LMICs.|
|Infrastructure||No suitable private examination rooms at primary healthcare level. Health system overburdened with curative care.|
|Finance||Vertical approach toward community-based programmes, most focus on financing curative care.|
|Monitoring and Evaluation||Inadequate paper patient files and reporting, no system of reminding defaulting patients.|
|Governance||No guidelines, or insufficient implementation of guidelinesNo functional National Screening Programme.|
|Service delivery||No user-friendly services, opportunistic screening instead of pro-active screening Inadequate privacy or confidentiality.|
The project will address both health systems- and client-related factors in order to improve the coverage (Availability Accessibility Acceptability Quality) of cervical cancer screening.
The overall objective of PRESCRIP-TEC is to build on and upscale existing screening programmes with women-friendly and cost-effective tools and test whether and why they are effective in increasing participation in cervical cancer screening in Europe and in Low- and Middle-Income Countries in accessible, affordable and equitable ways.
The purpose of this project is to study and to address the barriers and facilitators of providing state-of-the-art community-based screening, treatment and follow-up programme for cervical cancer in selected settings in Bangladesh, India, Uganda and Slovak Republic. The research project measures coverage and uptake in relation to availability, accessibility, acceptability, quality and cost-effectiveness, and options for scaling up. The implementation research will focus on best ways to increase participation and compliance in cervical cancer screening (on the beneficiaries’ side) and improve implementation fidelity (on the providers’ side).
More information about Communication
National screening programmes and country-specific information
In all high income countries and in many low and middle income countries national screening programmes have been introduced, however coverage of screening by eligible women is low. In the Netherlands, for example, 61% of eligible women participate in the screening programme. When opportunistic screening (offered when gynaecological examination is performed for another reason) is included, the total of 72% of women is reached. In Central and Eastern Europe coverage is less than 50% and below 10% in LMICs.
Table National programmes for cervical cancer screening
|Country||Year of publication||Primary screening test||Target group (age)||Target screening coverage||Target treatment lesions||Revision of protocol|
|India||2017||VIA or cytology||35-63||not||not||NA|
NA= not applicable
Most LMICs have not yet integrated the cervical cancer screening in the standard package of health care services, because of different health system challenges, e.g. lack of human resources (gynaecologists, pathologists, nurses and midwives), lack of equipment (colposcopes, cryo-therapeutic equipment), lack of suitable examination rooms in primary healthcare facilities. Often, screening activities are opportunistic (when a woman comes for another reason to a health facility) and direct treatment for women with precancerous lesions is not available in a single visit.
Client-related factors, such as complacency concerning threats of cancer, lack of understanding due to low health literacy, lack of financial resources to travel and lack of time are contributing factors. Moreover, because of the gynaecological examination involved, there are religious and cultural barriers that prevent women to come to clinics for examination.
In HIC, screening does not cover all at-risk populations. Especially women at high risk, for example migrants, asylum seekers, women from minority groups and commercial sex workers, have low participation in national screening programmes, halting national coverage at 60-70%. Sometimes, it is because they are not registered and not invited, but also client-related factors (health literacy, culture, religion) play a role, especially when coming from other cultural backgrounds.
The countries selected for this implementation project – Bangladesh, India, Uganda and Slovakia – differ not only in geographical location, but also in terms of population size and density, health worker force, cervical cancer burden and implementation of a national strategy for the prevention of cervical cancer. The table below illustrates the estimated incidence and mortality per 100,000 women for each country participating in this research. Uganda has a much higher hrHPV infection rate than other countries, also caused by higher incidence of the HIV co-infection.
Table Mortality due to cervical cancer
|Country||Incidence(all new case per year)||Age-standardizedincidence(per 100,000 women)||Mortality(per year)||Age-standardizedmortality(per 100,000 women)|
The table below illustrates the differences in terms of total population and current coverage of the cervical cancer screening programmes. Women above the age of 15 years are considered to be at risk to develop cervical cancer. The WHO recommends targeting women between the age of 30 and 49 years old to be screened for cervical cancer, in order to have a significant impact. The different target groups shown below are derived from the national strategies of each country.
Table Screening for cervical cancer in target countries
|Country||Total population (million)||Women >15 yrs. (million)||Target group (years)||Screening coverage (both programmes and opportunistic screening)|
Community mobilisation through communication activities
The project consortium will conceptualise, design and implement per country a communication plan, focusing on community mobilisation. Those country plans will build on existing community mobilisation activities and communication platforms, like for example Friendship in Bangladesh or URDT in Uganda. Previous experiences for UNICEF and other organisations will be used in the design.
Our model for community mobilisation will be consisting of four elements: situation analysis, information provision, engagement and advocacy and support to community groups.
Figure 8 Community mobilisation model
At the beginning of the project, we will start in collaboration with the local teams in Bangladesh, India, Uganda and Slovakia to identify the key needs, social religious and cultural factors influencing uptake of cervical cancer screening, available information resources, etc. Objectives, key results, strategies and performance indicators will be set. This will result in a community mobilisation plan and manual.
To reach the target audiences, we apply a branded content approach that will help us to transmit values, emotions and behaviours: graphics, data visualisation diagrams, infographics GIFs, designs, blog posts, press releases, human interest stories, etc.
We will produce one informative video for each country. The videos will be adapted for the web, Instagram, Facebook, YouTube and Twitter. These videos can also be used in the presentations that the local implementers perform in the target countries.
We create a website that will have a specific section for each target country, that can be linked to the existing websites of organisation.
Table 11 Internet in four project countries
|Country||Total population||Internet users||Internet Penetration||Accessing from Smartphone||Accessing from Computer||Accessing from Tablet|
Internet penetration varies for the 4 countries. In Uganda and Bangladesh it is around 20%, in India it is about 50% and in Slovakia it reaches 80%. Even if in Uganda and Bangladesh the penetration seems low, in nearly each family there is a simple phone. Those phones are quickly being replaced with smartphones. People who have access to the internet, use mostly the smartphone to access, therefore the PRESCRIP-TEC website will be designed from a mobile first approach. The website will have an interactive agenda where local implementers and beneficiary women will be able to schedule their screening appointments and they will integrate with their personal agendas. The website will also have the functionality to send push notifications to smartphones for appointment reminders, etc.
The project will use social media to mobilise women to come for screening, offered close to their homes. We will select the type of social media to be used based on the situation analysis. Social media will also be used to influence other social actors around target women.
We will design, configure and optimise advertising campaigns in Facebook ads, Twitter ads and Google ads to be sure we reach a massive and targeted audience within the target groups. Considering the current social media advertising fares and average interaction of the users in Uganda, Bangladesh, India and Slovakia, we can estimate that, on average, with each 100 € invested on digital advertising, we can reach a targeted audience of approximately 90.000 people.
Besides social media, to reach the people who have mobile phones but not smartphones, we will also use SMS technology to raise awareness and encourage the women to participate in the screening sessions. The project aims to reach at least 90,000 women in eligible age groups.
Engagement and advocacy
In collaboration with local partners we create lobby and advocacy activities with local civil society, (e.g. religious leaders, women organisations, teachers, community leaders) to increase awareness and commitment to screening programmes, which will reinforce present mobilisation mechanisms. We will produce tailored advocacy plans and activities for community mobilisation for each specific context in each of the four countries.
Table 12 engagement in community mobilisation
|Adjust policies and practices to facilitate behaviour change||Policy makers, local authorities, and practitioners||Deliberative dialogues and debates at local level. Policy/implementation briefs|
|Change attitudes and opinions||Community groups and leaders (e.g. religious leaders, women organisations, schools, teachers, volunteers of local organisations, local staff), patients groups||Community dialogues, local media (theatre shows, radio, etc.), videos, infographics|
|Develop skills of local staff on advocacy development plans and tools||Local civil society||Training, hands-on support, presentations, workshops|
Support to community groups
During the three years of the project, we will offer technical assistance and support to local teams. We will also ensure that the necessary knowledge transfer takes place so that local teams have the know-how and tools to continue mobilising the community to encourage women to come for screening.
We will perform the following activities to support community groups:
- Training: The communication experts in the consortium will provide specific trainings in community management and social marketing to the local teams to reach the target audiences efficiently.
- Content curation: Support to the local teams in edition, curation, optimisation and dissemination of the contents generated by them.
- Support on community management: We will support the local implementers in updating and managing social media profiles.
- Promoted content: We will run advertising campaigns to promote the contents shared on social media to make sure they reach a massive and targeted audience.
- Printed materials: Design and implementation of printed materials in compliance with the communication plan: posters, flyers, roll up, POP material, brochures, etc.
- Events and presentations: Strategic expert advice and technical assistance in events organisation and layout and design of reports and presentations. We will create diagrams, infographics and other data visualisation tools to make the presentations. We will also support the local teams in events organisation.
- Monitoring and reporting: We will provide technical assistance to make sure all the countries are able to effectively measure the impact of their communication activities (e.g. by using Google analytics, questions in exit interviews after screening) and have time based goals and evaluation mechanisms.
More information about HPV Testing
The figures below provide the protocol applied in the implementation research project. The figures show two alternatives for use with VIA and AI-DSS or use with PAP smear. These protocols show how steps in the screening process are taken in a logical sequence. The two alternative approaches are applied in their proper context. In low-resource settings where pathologists are only available in university laboratories, as explained in the introduction, VIA is the standard. In European settings PAP smear is the standard. In both protocols these tests will be preceded by a hrHPV test.
The project will work with governmental and non-governmental organisations within the local context of financing, clinical guidelines and regulations, and where necessary assist the responsible authorities to draft them. The project will apply– and, if necessary, further develop – the necessary procedures for protection of vulnerable women, for avoidance of stigmatisation (see inventory above),
The dotted lines in the figures below show where the project interacts with the existing systems for referral. In the Slovak Republic Pap smear and further steps are done by the primary healthcare gynaecologist and reimbursed by the health insurance.
Figure 2 Protocol for screening in LMICs
Figure 3 Protocol for screening in Slovak Republic
More information about Artificial intelligence
The AI-DSS for cervical cancer screening is a low-risk type of artificial intelligence. The images of cervix before and after application of acetic acid will be saved into the device storage. A diagnosis report is generated with these two images, random generated number and the final assessment.
In case of doubt, a second opinion can be sought – since this device provides images of cervix, it eliminates the need of the expert on site. (Calling the senior on the spot is not needed). The senior can be in remote location, while images is sent to him/her. This kind of remote evaluation is possible.
More information about Research
The project will apply a Comparative Effectiveness (CE) approach, in order to facilitate better informed and more evidence-based decisions by clinicians, clients, third-party payers, and policy makers.
We compare the effectiveness of cervical cancer screening and treatment of precancerous lesions under different circumstances and settings. In each country, we will work in at least two settings. This approach makes it possible to identify generalisable factors that work under all conditions. It reduces the risk of giving too much weight to specific local conditions, which may hamper or stimulate success of screening programmes. This is relevant for scaling up approaches. The CE provides essential information to improve outcomes in everyday clinical practice.
For this research we will work with an interdisciplinary faculty capable of designing and executing multimodal implementation and evaluation research. We will work with ready-to-roll field testing sites. Thus the project will create a research network across continents. At the project level, we will aggregate results to see the overall effects, and compare countries and sites, to assess specific success or fail factors.
The methodology of researching the comparative effectiveness and efficacy of the new processes is based on comparing the baseline to data collected after the introduction of the protocol.
Measuring conditions for scaling-up
Through applying the RE-AIM framework for assessment of scaling up interventions, the project will show its impact and feasibility. The indicators mentioned under the first five research questions (above) can be fitted into the RE-AIM framework, of
- Reach: uptake and coverage and contributing factors
- % of eligible women aware of cervical cancer and screening
- % of eligible women screened
- Scores on trust and cancer awareness
- Effectiveness: adherence to follow-up and referrals
- % of hrHPV women coming for VIA or Pap smear
- % of women receiving early treatment
- % of women referred for advanced care
- Adoption: implementation fidelity and stakeholders involvement
- % of health professionals implementing standard procedures
- Involvement of authorities in implementation of screening programme
- Implementation: implementation fidelity
- Scores in the SARA surveys
- Maintenance: commitment of governments, NGOs and funding agencies to continue the improved protocol.
- Adoption of improved national screening guidelines
PRESCRIP-TEC will show how conditions for scaling up can be met, and will deliver a concrete implementation plan for integrating cervical cancer screening in a package of Universal Health Coverage. This will be developed for broad dissemination across countries, contributing to the WHO strategy for elimination of cervical cancer.
Learn all the details about how PRESCRIP-TEC contributes to the elimination of cervical cancer in the following video.