It is widely acknowledged that having an effective screening and treatment program is a crucial step toward ultimately reducing cervical cancer burden.10 Our analysis of data from the first systemic collection of indicators for cervical cancer screening and treatment showed that HPV tests in Nicaragua reached approximately 31.5% coverage of the target population of the three provinces analyzed in 2017. If replicated in subsequent years, this approach could reach 100% coverage within the 5-year screening interval specified in Nicaraguan guidelines for HPV testing.13 In order to achieve this coverage, MINSA would likely need to undertake a population-based outreach strategy rather than the opportunistic approach used here, and our data do not allow us to speculate on HPV test uptake under such a strategy. Although MINSA had substantial existing Pap infrastructure before HPV test introduction, it is unclear how HPV test coverage may compare to previous efforts because these indicators were not routinely monitored. While HPV test positivity varied by province, it was within the expected range for this region, including mirroring the U-shaped curve in HPV prevalence by age seen in other studies, with higher prevalence among younger and older women and a decline in middle age.14,15 The high percentage of self-collected HPV samples indicates a wide acceptance of this screening modality when it is offered as a primary outreach strategy. These programmatic successes were largely made possible by MINSA’s broad network of provincial and local health facilities extending dedicated resources and personnel time.
Although these successes in screening outreach and test performance are notable, the low overall triage and treatment percentages are of concern. Only half of the triage-positive women had documented treatment, and if the same triage-positive rates are applied for women lost at triage, the overall treatment percentage is just 27.8%substantially lower than the 90% goal set by WHO in its elimination targets.10 This estimate relies on several assumptions, including that women were truly lost in the triage step rather than receiving treatment elsewhere. In Guatemala and Honduras, where similar HPV testing strategies were implemented under the Scale-Up project, the percentages of triage-positive women treated between 2015 and 2018 were 84.7% and 58.8%, respectively;11 and estimated percentages of women treated, accounting for those lost in the triage step, were reduced to 71.2% and 30.2%, respectively. Findings from an HPV-based screening program in Argentina, where the screening algorithm uses Pap and colposcopy for triage, 85.2% of women with confirmed CIN2+ lesions were treated; this represents just 27.7% of women with an abnormal Pap in triage.16 Although limited, some of these findings are similar to Nicaragua’s and suggest that the Nicaraguan experience may point to challenges common to low-resource settings that will require specific interventions to retain women in the screening and treatment cascade.
Our analysis suggests that MINSA’s decision to triage most HPV-positive women with Pap rather than VIA is an important factor contributing to low triage and treatment percentages. Although data on time elapsed in the screening and treatment process were incomplete, available data show that while it took slightly more time for women to access VIA compared to having a Pap smear collected, the subsequent time to treatment was dramatically shorter because most women triaged with VIA received treatment the same day, whereas most women triaged with Pap had to wait for their results and receive treatment in a different appointment months later. Over 15% of women triaged with Pap never had a result recorded, likely because of the challenges presented by distance of and delay in cytology processing services. Even women with HSIL+ Pap results did not appear to be prioritized within the system for rapid follow-up, perhaps due to limited availability of more advanced treatment such as LEEP, although it is difficult to draw firm conclusions about this subgroup of women in the absence of histological confirmation of disease. Notably, over three times as many women who were triage-positive with VIA received treatment compared to those who were triage-positive with Pap. This is likely due, at least in part, to the multiple visits required for a complete Pap follow-up compared to VIA.
Evidence suggests that triaging with either Pap or VIA effectively nullifies the gain in sensitivity of testing with HPV for primary screening.17 Cost-effectiveness models suggest that a screen-and-treat approach, in which all HPV-positive women are treated and VIA is used only to determine treatment eligibility (rather than to triage women), would be the most effective and cost-effective strategy for Nicaragua18 and other countries in the region.19 Alternatively, emerging evidence indicates that machine learning algorithms , which are currently under evaluation, could dramatically improve the quality of the visual triage step using digital images of the cervix,20 enabling providers to better “see-and-treat” with less overtreatment than we currently observe in an “HPV test-and-treat” algorithm.
Although the Nicaraguan management algorithm mirrors WHO guidelines in calling for a one-year follow-up visit for women who were HPV positive but negative in the triage step, unfortunately our data set did not include this indicator. In another evaluation nested within the Scale-Up project, we analyzed one-year follow-up attendance among HPV positive, triage negative women in Honduras. In that context, just 3.6% of women returned spontaneously. Health care providers were able to recall an additional 71.3% of women using phone calls and other reminder contacts. 36% of women returning for a one-year follow up appointment remained HPV positive, underscoring the importance of this follow-up step.21 In Central America and elsewhere, health authorities may wish to consider these findings when designing their screening and treatment algorithms and delivering their screening programs.
Another finding was that women with clinician-collected samples were more likely to receive triage (although sampling modality was not associated with receiving treatment); our data do not provide insight into why these women had clinician-collected samples. While broad use of self-sampling is likely to be the most practical way for LMICs to screen 70% of their target populations in order to reach WHO elimination goals, it is important to consider additional programmatic implications of this approach. It may be that women who self-sample require more tailored outreach to encourage attendance at follow-up compared to women with provider-collected samples.
Our results also raise concerns about treatment modality in Nicaragua. According to MINSA and project field workers, cryotherapy was widely available in the provinces where HPV testing took place and stockouts of cryotherapy gas were rare, which is often not the case in low-resource settings.22 However, the lack of availability of advanced treatment modalities was clearly a challenge, particularly in Carazo and Chinandega where no women were reported to have received excision treatment although studies in other populations suggest that about 15% of women with precancerous lesions could benefit from it.23,24 Some women seek care in the private sector and records of their treatment may be lost to the public system.
Histological data and cancer registry data were not available for our evaluation; thus, it is beyond the scope of the current analysis to confirm diagnoses or estimate cure rates. Nevertheless, our data give us important insight into the state of treatment efforts in 2017. Other LMICs are also likely to face the challenge of limited capacity for treatment. Reports from other countries indicate that thermal ablation is an effective and practical alternative to cryotherapy that may enable countries to increase their ablative treatment capacity.25,26 WHO guidelines issued in 2019 support the use of thermal ablation in LMICs.27
Of note, in 2018 MINSA invested time and resources in finding and following up women who screened positive for HPV in previous years, including 2017. This effort led to additional women in the target provinces receiving treatment, for a total of 67.1% of HPV-positive, triage-positive women receiving treatment from 2015 to 2018,11 and suggests that there is potential for LMICs to address the problem of loss to follow-up within a longer timeframe, given sufficient resources and prioritization.
Our analysis was possible because of a concerted effort by MINSA to implement more robust data collection practices, enabling tracing of screen-positive women through triage and treatment, analysis of individual data, and periodic review of key consolidated indicators. Weakness in existing health information system (HIS) infrastructure is likely to present challenges in many LMICs as they work to eliminate cervical cancer. Examples of cervical cancer screening-related HIS improvements from Nicaragua,28 Argentina,29 and Malaysia30 provide practical models for countries seeking to ensure that their HIS enables them to effectively monitor treatment completion and overall screening program performance.