Adoption and implementation of affordable cancer technologies in El Salvador: identifying implementation strategies for successful cervical cancer prevention in resource-limited settings

Abstract

As part of the Affordable Cancer Technology (ACT) program, our team developed and tested a portable thermal ablation (TA) cervical precancer treatment. This research helped support subsequent implementation of the technology in El Salvador. Here we review successful implementation strategies deployed during the process and point to challenges and implications for other low and middle-income countries (LMICs). We utilize the Exploration, Preparation, Implementation and Sustainment (EPIS) framework to guide the discussion and identify associated implementation strategies utilized during each phase. Significant strategies were the development and maintenance of multi-actor partnerships and accessing new funding to introduce innovations to the country. In this case, planning for implementation began prior to the decision to adopt TA. The case of El Salvador highlights the need for such pragmatic approaches to shorten the time between scientific research and clinical practice in LMICs. The impact of these efforts has been significant: El Salvador has gone from one of the countries with the lowest cervical cancer screening rates in the region to one that can potentially meet elimination targets in the coming decades. This experience can serve as a blueprint for cervical cancer control efforts in other LMICs.

Background

Disparities in the global cancer burden are projected to increase over the next few decades.^1,2 While high-income settings have successfully reduced cancer rates, incidence and mortality in low-and-middle income countries (LMICs) are expected to increase by as much as 142% and 146%, respectively, by 2050.³ The consequences of these inequities are multidimensional, from immeasurable human cost to economic stagnation.^4,5 It is essential to find solutions that can reduce the global cancer burden and close gaps between wealthy and developing countries. A significant roadblock is the time lag between clinical research and the implementation of successful findings. An often-cited figure is that it takes an average of 17 years for scientific findings to make the transition to clinical practice.⁶ Data from LMICs indicates that even 10 years after regulatory approval, clinical interventions only reach 4–37% of targeted countries.⁶ The National Cancer Institute (NCI) Affordable Cancer Technologies (ACT) program is an opportunity to reduce the delay between research and practice in LMICs by encouraging the development of innovations that are designed, at the outset, to overcome implementation challenges. Here, we review the successful introduction of a novel cervical cancer control technology developed as part of the ACT program into El Salvador’s public health system and describe key strategies that facilitated this process. These experiences provide a learning opportunity for implementation of healthcare innovations in other LMICs.

Cervical cancer is one of the most unequally distributed cancers around the world with 90% of the global disease burden concentrated in LMICs.¹ Access to effective prevention is inadequate: global coverage for human papillomavirus (HPV) vaccination is only 12%⁷ and 67% of women between 20 and 70 years of age around the world have never been screened, with high-income countries accounting for 84% of screening coverage.⁸ These disparities led the World Health Organization (WHO) to launch an initiative to eliminate this disease through a triple strategy of vaccination, screening, and treatment.⁹ The potential for elimination has created significant momentum, reflected in 19 out of 41 ACT projects between 2019 and 2024 focused on cervical and HPV-related cancers. As evidence of the effectiveness of these innovations accumulates, the next urgent challenge is ensuring that they are adopted by public health systems so that they can reach intended end-users.

The field of implementation science (IS) focuses on developing and evaluating solutions to facilitate this transition.¹⁰ There is a growing literature that applies IS principles to cancer control in LMICs.^11,12 A central area of interest involves identifying and testing implementation strategies, defined as “methods or techniques used to enhance the adoption, implementation, and sustainability of a clinical program or practice”.¹³ Commonly used implementation strategies have been summarized in well-known compilations.^14,15 However, evidence of the use of implementation strategies in LMICs is inconsistent.¹⁶ Recent efforts have brought an IS perspective to cervical cancer research in LMICs,^17–19 but some of these instances may not be systematically identified or reported because they occur outside of research contexts or because investigators are not familiar with IS as an academic discipline.²⁰ Nevertheless, it is essential to build a pragmatic, contextually-informed knowledge base that reflects the experiences of public health systems as they successfully implement innovations.^21,22 In El Salvador, our multi-disciplinary team was able to leverage research conducted as part of the ACT program to support the Ministry of Health’s (MoH) implementation of a cervical precancer treatment at the national level. We identify strategies that were deployed during this process and point to practical and ethical considerations in planning and implementing innovations in LMICs.

Theoretical Framework

IS relies on theories, models and frameworks (TMFs) to contextualize studies and guide implementation of evidence-based practices (EBPs). TMFs are necessarily simplistic depictions, but helpful in imposing a systematic structure to complex and dynamic processes. Here we utilize the Exploration, Preparation, Implementation and Sustainment (EPIS) framework to describe the adoption and implementation of a new cervical precancer treatment (i.e., the EBP) in El Salvador.²³ Although an implementation process may not exactly reflect the linear structure or all components of EPIS, this is one of the most widely used TMFs.²⁴ EPIS describes the implementation process from the early exploratory phases to sustained use of the innovation. Additionally, it accounts for contextual factors, the relationships between them, and characteristics of the EBP itself (Fig. 1).

Fig. 1.

Exploration, Preparation, Implementation and Sustainment (EPIS) Framework²⁴

The Evidence-Based Practice (EBP)

In healthcare, an EBP (aka innovation, interventions, etc.) can refer to a treatment, program, or care protocol. Here, the EBP consisted of a novel therapy for cervical precancer embedded in El Salvador’s screening program. There are two types of cervical precancer treatment: excisional procedures and ablation methods. Since the former require specialized equipment and staff, the most widely used option in low-resource settings has been gas-based cryotherapy, a form of ablation that is affordable and simple to use. However, the ongoing need for gas and associated procurement and transportation challenges are well-recognized barriers.^25–27 At the start of the ACT project, our team partnered with a small company that had developed a gas-free cryotherapy machine (CryoPen^®, CryoPen Inc., Southlake, TX).²⁸ At the same time, there was renewed interest in thermal ablation (TA), a heat-based technique used for decades in the United Kingdom.^29–31 The original TA device is bulky and requires electricity, which makes it suboptimal for low-resource settings. We collaborated with the manufacturer to develop a handheld version suitable for LMICs (C3 cold coagulator, WISAP Medical GmbH, Brunnhtal, Germany) (Fig. 2). The device, now commercially available, is lightweight (<2lb), has a simple user interface, and operates with electricity or a rechargeable battery. A three-arm non-inferiority trial in El Salvador, Colombia, and China compared cure rates at one-year post-treatment between gas-based cryotherapy, CryoPen^®, and TA (NCT02814448, see Conzuelo Rodriguez et al in this series). Results of the trial are under review for publication.

Fig. 2.

LMIC-adapted TA device (C3, WISAP Medical Technology GmbH, Brunnnthal, Germany). There are at least two other commercially available portable TA devices manufactured by different companies.

In the EPIS framework, determinants of implementation associated with the EBP are called innovation factors. Here, these include the features of trialed devices which were designed to fit local needs (e.g., gas-free, portable treatments) and manufacturer characteristics. For example, the company that developed the CryoPen^® shut down,³² ending any attempts at implementation. On the other hand, the TA manufacturer is a well-established medical device company that now markets the model globally. Other innovation factors are discussed throughout the following sections.

Finally, it is important to mention that TA was introduced into an existing program (itself a multi-component EBP)^33,34 which originated some of the strategies described here (Table 1). A decade ago, cervical cancer incidence and mortality rates in El Salvador were 18.5 and 9.4 per 100,000 women (age-standardized), respectively.³⁵ Screening coverage was estimated at 19–47%^36,37 and only 44% of women with precancer completed treatment.³⁷ In 2011, a pharmaceutical company launched a donation program of low-cost HPV tests (careHPV, Qiagen, Gaithersburg, MD). Our team approached the MoH to take advantage of this opportunity through a collaborative demonstration initiative. The resulting three-phase project compared a screen-and-treat algorithm with conventional cytology and colposcopy. Findings demonstrated that 90.4% of women completed screen-and-treat procedures compared to 48.1% in the cytology group.^38,39 A scale-up to 18,000 women resulted in adherence rates of 75%.⁴⁰ As a result, the MoH adopted a national screen-and-treat program which currently screens 100,000 women annually. While there are challenges to ensure sustainability, recent estimates have reduced cervical cancer incidence and mortality rates to 15.2 and 8.4 per 100,000 women (age-standardized), respectively.⁴¹

Table 1.

EPIS phases and associated strategies, activities, and challenges

EPIS Phases	Strategies	Activities
Exploration	Assess existing evidence	Reviewed literature, collected primary data
	Developing multi-actor partnerships	Approached stakeholders, leveraged existing networks
	Accessing new funding	Sought research and donation funding
Preparation	Designing clinical research with implementation in mind	Incorporated implementation-related assessments early on
	Learning field visits	Visited other sites to learn from experts
	Creating adaptable training materials	Developed videos, manuals, and quick treatment guides
	Maintaining partnerships	Created opportunities for regular interaction; conducted research activities that benefitted site
	Identifying and preparing champions	Found champions in stable, middle-management MoH roles
	Engaging decision-makers	Focused on local priorities, presented contextual information and results
Implementation	Providing technical advice	Shared clinical and academic expertise (e.g., grant writing)
	Creation of a dedicated joint team	Assigned specific roles and tasks, shared accountability
	“Train the trainers” approach	Trained 10 MoH providers to then train 70 physicians and 70 nurses
	Challenges	Potential strategies/activities
Sustainment	Equipment distribution and maintenance	Leverage networks to engage industry partners, collect and disseminate data on demand
	Need for ongoing provider training	Refresher courses, “audit and feedback”
	Patient-level barriers	Facilitate/eliminate travel (e.g., vouchers, point-of-care TA treatment), education/outreach
	Fully transferring ownership to MoH	Build local capacity, develop plan for gradually stepping back

Inner and outer context of the EBP

EPIS describes the “inner context” as the organization where an EBP will be implemented. Features of the inner context that shape implementation include organizational leadership, internal policies, and characteristics of individual implementers (e.g., providers in the system). In El Salvador, the healthcare system is regulated by the Ministry of Health (MoH), which is also responsible for providing services free of cost. . Other providers within the single-payer national health system (Sistema Integrado de Salud) serve specific populations (i.e., salaried workers, military personnel), while private providers offer more diverse services but are unaffordable for many. The central level at the MoH is responsible for administration and policy-setting, while primary care services are overseen by a network of regional offices (SIBASI, or the Basic Integrated Health System). The screen-and-treat program is led by the MoH Cancer Unit. Screening and ablation treatment are offered under SIBASI-managed clinics. Other related services (e.g., excisional treatments, oncology, radiology) are provided at the hospital level..

“Outer context” refers to aspects of the environment that influence the implementation process but are external to the organization. For many LMICs, international agencies and aid organizations are critical elements of the outer context. In this case, two initiatives by the WHO must be acknowledged: the 2018 call to action to eliminate cervical cancer,⁴² which has spurred research and implementation efforts to meet elimination targets, and the inclusion of TA in WHO cervical precancer treatment guidelines in 2019.⁴³ As further described, these and other elements of the outer context (i.e., funding agencies, industry partners, etc.) have been an important backdrop for El Salvador’s implementation efforts.

Bridging factors

The updated EPIS framework highlights bridging factors as ties or processes that connect the inner and outer contexts.²⁴ While the overlap between this construct and implementation strategies is not yet clear, there is growing interest in this area.^44,45 In El Salvador, bridging factors have been crucial to the adoption of various innovations. Among these is the partnership between the MoH and Basic Health International (BHI), a non-profit organization that has operated in the country for over a decade. Starting with medical missions, BHI now serves in a technical advisory role. Although US-based, BHI has a strong presence in El Salvador with a multi-disciplinary team that has evolved as needs have changed. Strengthening local capacity has included extensive trainings, expanded research roles, and addition of specialized personnel. Through ongoing joint initiatives (i.e., research projects, workshops, conferences, trainings), BHI has been able to connect the MoH with outer context actors that have collaborated in implementation efforts.

EPIS Exploration Phase

The exploration phase of the EPIS framework involves evaluating needs, identifying solutions, and evaluating the potential fit of the new EBP in the local context. In El Salvador, challenges related to procurement and transportation of gas refills for cryotherapy were evident since the beginning of the program. Although there are 731 screening sites in the country, treatment is offered at far fewer locations (75 regional clinics). Gas shortages can cause treatment delays⁴⁶ and patients must travel to two different clinics to receive treatment. The MoH estimates that in 2023, almost 30% of women with HPV-positive results did not complete treatment (pers. comm.).

To fully understand the challenges associated with the treatment component, our team first assessed existing evidence. Previous studies provided data to understand barriers to screening and treatment.^{47,48, 49} We also conducted a review of cervical precancer treatments²⁷ and assessed cryotherapy machines in local treatment clinics. This revealed problems such as gas blockages, leaks, and lack of maintenance that prevented cryotherapy machines from reaching therapeutic temperatures.⁵⁰ A consensus emerged that a gas-free treatment was most suitable for this setting.

Once the need and potential solution were identified, it was important to develop partnerships that could contribute expertise or resources. The initial HPV screen-and-treat pilot project had brought together collaborators from multiple arenas, including MoH officials, the scientific community, the non-profit sector, and international agencies such as WHO and the Pan American Health Organization (PAHO). However, it was necessary to seek out new relationships with relevant expertise. For example, our team approached the manufacturer of the CryoPen^® at an academic conference and proposed a collaboration to develop an LMIC-adapted prototype. A “cold call” to another manufacturer led to the eventual development, trial, and commercialization of the TA device. In all cases, it was crucial to find points of convergence among researchers’ areas of expertise, local priorities, and the interests of key industry actors.

Since El Salvador did not have the resources to change the treatment component of the screen-and-treat strategy, an effort was launched to identify potential sources of funding. The ACT program represented an ideal opportunity to develop an alternative to cryotherapy. As global interest in TA grew, we obtained additional funding from private foundations to add a TA arm. This approach paralleled the earlier strategy of seeking diversified funding for HPV tests which resulted in the current national program.

Of note, in the EPIS framework, the end of the Exploration phase is the moment where the decision to adopt is made. However, implementation is a flexible process driven by both practical and scientific considerations.^51–53 Most TMFs have been developed in high-income countries and may need to be adapted in settings where healthcare needs are urgent and resources are limited.^54,55 Moreover, the decision to adopt typically rests on local actors and may be contingent on many contextual factors. Thus, our goal at this stage was to prepare the ground for potential adoption of TA.

EPIS Preparation Phase

In the preparation phase, it is critical to develop a plan that enables the intended use of the EBP considering barriers and facilitators. Thus, our clinical trial was designed to support rapid and flexible implementation if needed. While there is growing work on hybrid trial designs that combine effectiveness and implementation outcomes⁵⁶ these approaches are relatively new and not well-known outside of IS research.⁵⁷ Our trial did not follow a hybrid design, but research objectives included the evaluation of factors that might impact implementation. Thus, strategies utilized to prepare and plan for the introduction of TA into the public health system occurred concurrently with the research trial. For example, the research protocol was designed to include acceptability and cost-effectiveness assessments and the TA devices were designed for use in low-resource settings (i.e., simple operating system, rechargeable battery, portable). Company leadership worked with our team to receive input on design, troubleshoot technical issues, and facilitate regulatory documentation, an essential component of implementation efforts.

Another priority was providing high-quality training to healthcare workers. Clinician team members traveled to Scotland, where TA has long been part of routine healthcare, to learn optimal application technique. Insights from these visits were essential in finalizing device design and building a knowledge base that informed clinical practice. We also created a series of training materials in preparation for the trial. These included video demonstrations, step-by-step user manuals, and one-page treatment “quick guides”. These tools were later adapted for MoH workers once TA was adopted into the system.

Throughout all EPIS phases, the importance of maintaining partnerships cannot be overestimated. To do this, our team created frequent opportunities for members of various constituencies to interact through regular calls, presentations, workshops, conferences, and site field visits. In addition, research activities such intensive follow-up of treated patients and pathology quality review represented benefits to the health system that served to build trust and strengthen relationships. Regular interactions also created opportunities to identify individuals who came to play essential roles as advocates for introduction of TA (“champions”). Political instability can result in frequent turnover of government personnel, but these changes tend to impact those at the top of organizational hierarchies while workers responsible for day-to-day operations remained in place. Key individuals in these positions have ensured that the cervical cancer program in El Salvador continues despite broad political changes.

A distinct aspect of building and maintaining relationships is engaging local leadership. Changes to a public health program ultimately require buy-in from those who make budgeting and programmatic decisions. Presentation of cost-effectiveness analyses^58,59 to government officials were crucial in the adoption of screen-and-treat. Thus, regular meetings between team members and MoH decision-makers during the trial focused on dissemination of the WHO TA guidelines, communication of emerging TA evidence, and sharing data on provider and patient experiences. These interactions facilitated the decision to include the treatment in the national program.

EPIS Implementation Phase

The implementation phase refers to introduction and utilization of the EBP in the target organization. As the trial approached its end, the MoH convened an expert committee to update its national cervical cancer guidelines, including endorsement of TA. Once the decision to adopt was made, the next step involved internal budgeting discussions to procure devices and roll-out the program. As with HPV testing, the MoH was able to access a new source of funding: a grant opportunity funded by PAHO, WHO, and Clinton Health Access Initiative. Ultimately, El Salvador received 70 TA devices in 2023. Our team supported the introduction of the new treatment through various strategies, such as providing technical support during the grant application, helping define an evidence-based TA protocol, and co-developing and executing a training plan for providers.

Another successful strategy was the creation of a dedicated joint team of local MoH members and MoH staff to lead training and monitor early implementation. The MoH managed logistics and timelines, while BHI brought clinical and practical experience acquired during the trial. This delineated specific roles and responsibilities, fostered transparency and accountability, and ultimately resulted in roll out of TA within 6 months of receiving the device donation. Finally, over the course of the trial, team members had acquired extensive experience with TA. This knowledge was essential to recreate a “train the trainers” model that had been first utilized during the introduction of the screen-and-treat program. The joint implementation team convened a team of 10 MoH physicians, who then went on to train and supervise their colleagues working around the country.

While data on the use of TA is limited, implementation is underway and appears successful. Records from the Oriental region indicate that out of 1,539 women who attended treatment in 2024, 336 (22%) underwent cryotherapy while 1002 (65%) received TA (the remaining were ineligible for ablation and referred to colposcopy). However, the percentage of women treated with each method varied across clinics from 10–43% for cryotherapy and 49–79% for TA (pers. comm.). Thus, further research is needed to understand determinants of adoption, long-term effectiveness, and other outcomes.

EPIS Sustainment Phase

Sustainability is an understudied aspect of implementation,^60,61 not least because it inherently requires extended periods of time to evaluate. The goal of this phase is to ensure that all processes are in place to ensure continued delivery of the EBP. At the time of writing, TA has been part of the HPV screen-and-treat program for approximately two years. The technology is now used alongside cryotherapy in treatment clinics and early data indicates high acceptability by providers and patients.⁶² However, we have also identified challenges that need to be addressed to ensure sustainability and which are likely to apply to other LMICs.

A major issue is the lack of regional distributors to replace parts or repair faulty machines. Although there are three TA companies that market the TA devices, the technology is still novel. To maintain scale-up, it will be necessary to integrate TA into global commercial networks. Researchers that collaborate with industry partners are well positioned to push for changes that will ultimately benefit both commercial entities and end-users. On the health system side, continued education is necessary to ensure treatment quality is maintained. Refresher training and “audit and feedback” sessions may help ensure long-term treatment effectiveness. Digital technologies such as telementoring also offer opportunities to address these gaps.^63,64 Moreover, implementation of TA in El Salvador has mostly focused on organization-level strategies (i.e., provider training, guideline dissemination), but patient-level barriers remain. At least 30% of screen-positive women do not attend the treatment visit. It is essential that future implementation strategies address HPV and cervical cancer awareness, transportation to clinics, and sociocultural issues (i.e., stigma, misconceptions about procedures, etc.). Our team is conducting ongoing research to explore solutions, such as single-visit screen-and-treat algorithms (R01CA266059, R01CA285369) and interventions to reduce HPV-related stigma (R01CA266059-S).

Finally, external partners have had a significant role in the implementation of TA in El Salvador, but ultimately it is an MoH initiative. In such cases, it is ideal to eventually transfer all -related activities to local actors. Currently, our team disseminates emerging evidence, collaborates in provider training, and serves as a liaison with device manufacturers to troubleshoot technical issues. While transferring ownership of all activities may not always be achievable in the short term, the goal should remain at the forefront of planned initiatives in similar cases. For example, our team may need to continue facilitating the repair of TA devices until a local distributor is established. On the other hand, the MoH’s political will has promoted self-sufficiency through strategies such as identification of internal champions to advocate for the program and models such as “train-the-trainer” that are inherently designed to cede leadership to the local organization..

Discussion

El Salvador is one of a few LMICs with a national HPV screen-and-treat program. The success of this initiative is the result of a decades-long effort between MoH officials, dedicated frontline staff, researchers, and international actors. The experience of introducing TA to El Salvador points to strategies, some previously reported in the IS literature,^14,15 that supported the implementation of this technology. Of particular significance are the development and maintenance of multi-actor collaborations. The partnership between the MoH and BHI as a bridging factor has been key in procuring research funding for high priority needs and facilitating relationships with the outer context (i.e., other researchers, industry partners), which have been pivotal to accelerate implementation efforts. To maintain such relationships, it is essential to create frequent opportunities for interaction among various constituencies (e.g., meetings, conferences, workshops, field visits), center research on local interests, and strengthen capacity of the local team to meet emerging needs.

Another successful strategy has been accessing diverse sources of funding. LMICs may not have the financial and human resources to develop, test, or introduce innovations to the communities that need them. Tapping into research, donations, or other types of grants can be an effective method to launch initiatives, gather data to presented to decision-makers, and supplement domestic investment. This is an area where research collaborators may act as bridging factors to link implementers in the inner context with external funding opportunities and application processes. It is also important to note that most strategies were deployed during the early exploration and planning stages. Although it may seem onerous in low-resource settings, extensive preparation ultimately saves time, effort, and financial costs.

In this case, planning for implementation occurred prior to a firm decision to adopt TA. This may be necessary in environments where there are limited resources and competing priorities. In such settings, pragmatic approaches such as adaptation of TMFs and interventions or hybrid study designs may be particularly appropriate to shorten the time between scientific research and clinical practice. These approaches are also inherently embedded in the local context and allow for a bi-directional flow of knowledge between researchers and local communities, avoiding “parachute research”^65,66 that has no applicability or utility to the site. Even if a local implementation project is not informed by IS, it is an opportunity to gather practice-based evidence,⁶⁷ which is often undervalued and underutilized.

The trial funded by the ACT program has led to the implementation of an innovative portable cervical precancer treatment in El Salvador. Other research-initiated interventions (e.g., HPV self-sampling,^48,68 a telehealth result delivery method⁶⁹) have either been adopted or are in consideration for inclusion in national guidelines. The impact of these efforts has been significant: El Salvador has gone from one of the countries with the lowest cervical cancer screening rates in the region to one that can potentially meet elimination targets in the coming decades.⁷⁰ Our hope is that reporting this experience will help others working in cervical cancer control in LMICs.