Single-tube four-target lateral flow assay detects human papillomavirus types associated with majority of cervical cancers.

Isothermal nucleic acid amplification methods have many advantages for use at the point of care. However, there is a lack of multiplexed isothermal amplification tests to detect multiple targets in a single reaction, which would be valuable for many diseases, such as infection with high-risk human papillomavirus (hrHPV). In this study, we developed a multiplexed loop-mediated isothermal amplification (LAMP) reaction to detect the three most common hrHPV types that cause cervical cancer (HPV16, HPV18, and HPV45) and a cellular control for sample adequacy. First, we characterized the assay limit of detection (LOD) in a real-time reaction with fluorescence readout; after 30 min of amplification the LOD was 100, 10, and 10 copies/reaction of HPV16, HPV18, and HPV45, respectively, and 0.1 ng/reaction of human genomic DNA (gDNA). Next, we implemented the assay on lateral flow strips, and the LOD was maintained for HPV16 and HPV18, but increased to 100 copies/reaction for HPV45 and to 1 ng/reaction for gDNA. Lastly, we used the LAMP test to evaluate total nucleic acid extracted from 38 clinical samples; compared to qPCR, the LAMP test had 89% sensitivity and 95% specificity. When integrated with sample preparation, this multiplexed LAMP assay could be useful for point-of-care testing.

The cost-effectiveness of human papillomavirus self-collection among cervical cancer screening non-attenders in El Salvador.

Cervical cancer screening with human papillomavirus (HPV) DNA testing has been incorporated into El Salvador's national guidelines. The feasibility of home-based HPV self-collection among women who do not attend screening at the clinic (i.e., non-attenders) has been demonstrated, but cost-effectiveness has not been evaluated. Using cost and compliance data from El Salvador, we informed a mathematical microsimulation model of HPV infection and cervical carcinogenesis to conduct a cost-effectiveness analysis from the societal perspective. We estimated the reduction in cervical cancer risk, lifetime cost per woman (2017 US$), life expectancy, and incremental cost-effectiveness ratio (ICER, 2017 US$ per year of life saved [YLS]) of a program with home-based self-collection of HPV (facilitated by health promoters) for the 18% of women reluctant to screen at the clinic. The model was calibrated to epidemiologic data from El Salvador. We evaluated health and economic outcomes of the self-collection intervention for women aged 30 to 59 years, alone and in concert with clinic-based HPV provider-collection. Home-based self-collection of HPV was projected to reduce population cervical cancer risk by 14% and cost $1210 per YLS compared to no screening. An integrated program reaching 99% coverage with both provider- and home-based self-collection of HPV reduced cancer risk by 74% (compared to no screening), and cost $1210 per YLS compared to provider-collection alone. Self-collection facilitated by health promoters is a cost-effective strategy for increasing screening uptake in El Salvador.

Evaluation of two alternative ablation treatments for cervical pre-cancer against standard gas-based cryotherapy: a randomized non-inferiority study.

INTRODUCTION: Gas-based cryotherapy is the conventional ablative treatment for cervical pre-cancer in low-income settings, but the use of gas poses significant challenges. We compared the depth of necrosis induced by gas-based cryotherapy with two gas-free alternatives: cryotherapy using CryoPen,and thermoablation. METHODS: We conducted a five-arm randomized non-inferiority trial: double-freeze carbon dioxide (CO2) cryotherapy (referent), single-freeze CO2 cryotherapy, double-freeze CryoPen, single-freeze CryoPen, and thermoablation. Subjects were 130 women scheduled for hysterectomy for indications other than cervical pathology, and thus with healthy cervical tissue available for histological evaluation of depth of necrosis post-surgery. The null hypothesis was rejected (ie, conclude non-inferiority) if the upper bound of the 90% confidence interval (90% CI) for the difference in mean depth of necrosis (referent minus each experimental method) was <1.14 mm. Patient pain during treatment was reported on a scale of 0 (no pain) to 10 (worst pain). RESULTS: A total of 133 patients were enrolled in the study. The slides from three women were deemed unreadable. One patient was excluded because her hysterectomy was postponed for reasons unrelated to the study, and two patients were excluded because treatment application did not follow the established protocol. For the remaining 127 women, mean depth of necrosis for double-freeze CO2 (referent) was 6.0±1.6 mm. Differences between this and other methods were: single-freeze CO2 = 0.4 mm (90% CI -0.4 to 1.2 mm), double-freeze CryoPen= 0.7 mm (90% CI 0.04 to 1.4 mm), single-freeze CryoPen= 0.5 mm (90% CI -0.2 to 1.2 mm), and thermoablation = 2.6 mm (90% CI 2.0 to 3.1 mm). Mean pain levels were 2.2±1.0 (double-freeze CO2 cryotherapy), 1.8±0.8 (single-freeze CO2 cryotherapy), 2.5±1.4 (double-freeze CryoPen), 2.6±1.4 (single-freeze CryoPen), and 4.1±2.3 (thermoablation). DISCUSSION: Compared with the referent, non-inferiority could not be concluded for other methods. Mean pain scores were low for all treatments. Depth of necrosis is a surrogate for treatment efficacy, but a randomized clinical trial is necessary to establish true cure rates.

Effects of Maintenance on Quality of Performance of Cryotherapy Devices for Treatment of Precancerous Cervical Lesions.

OBJECTIVE: The aim of the study was to evaluate the impact of maintenance on performance of cryosurgical equipment used in El Salvador primary health clinics. MATERIALS AND METHODS: Nine gynecological cryotherapy devices used in El Salvador were bench tested against a new machine of the same make and model. The devices were run for five successive double-freeze cycles. The El Salvador machines then received maintenance by a specialized engineer and another double-freeze cycle was performed. Temperature at the device probe tip was recorded throughout each cycle and ballistic gelatin was used as the tissue analogue to measure freeze ball dimensions achieved by the devices. Outcome measures were mean lowest-sustained temperatures and freeze ball mean weight, depth, and diameter. Paired and unpaired t tests were used to compare results premaintenance versus postmaintenance and postmaintenance versus the reference, respectively. RESULTS: Premaintenance versus postmaintenance freeze ball dimensions were significantly different (mean differences in weight = 2.31 g, p = .01; depth = 2.29 mm, p = .03; diameter = 3.51 mm, p = .02). However, postmaintenance dimensions were not significantly different than those of the reference (weight = 7.44 g vs. 8.39 g, p = .07; depth = 10.71 vs. 11.24 mm, p = .1; diameter = 31.38 mm vs. 32.05 mm, p = .3). Postmaintenance, minimum, and lowest-sustained temperatures were within the recommended clinical range. CONCLUSIONS: Specialized maintenance was necessary for heavily used cryotherapy devices to perform adequately, highlighting the challenges of gas-based cryotherapy in low- and middle-income countries.

Scale-Up of an Human Papillomavirus Testing Implementation Program in El Salvador.

OBJECTIVE: The Cervical Cancer Prevention in El Salvador is a demonstration project to introduce a lower-cost human papillomavirus (HPV)-DNA test into a public sector project. Started in October 2012, The Cervical Cancer Prevention in El Salvador consists of 3 phases and will ultimately screen 30,000 women. Results of phase 2 of the project are presented. The objective of this project was to compare colposcopy and noncolposcopy-based management for HPV-positive women. MATERIAL AND METHODS: In phase 2, a total of 8,050 women, aged 30 to 49 years, were screened; 6,761 provided both self- and provider-collected specimens and 1,289 provided only provider-testing specimens. HPV results from self-collected specimens were not used in clinical management decisions. Women with provider-collected HPV-positive results were treated based on the strategy assigned to their community; the strategy was colposcopy management (CM) or screen-and-treat (ST) management if they were cryotherapy eligible or colposcopy if not eligible. Outcomes were assessed 6 months after screening. RESULTS: Overall, 489 (12.3%) of 3,963 women receiving CM and 465 (11.4%) of 4,087 women receiving ST tested HPV positive. In the CM cohort, 216 (44.2%) of 489 completed their intervention (203 treated, 11 diagnosed negative, 2 pregnant). In the ST cohort, 411 (88.4%) of 465 completed their intervention (407 treated, 2 diagnosed negative, 1 pregnant). Overall agreement between HPV test results from self-collected and provider-collected specimens was 93.7%, with a κ value of 0.70 (95% CI = 0.68-0.73). CONCLUSIONS: Human papillomavirus testing with ST management resulted in an approximately twice completion rate compared with CM management. Agreement between self- and provider-based sampling was good and might be used to extend screening to women in areas that are more difficult to reach.

Introducing a High-Risk HPV DNA Test Into a Public Sector Screening Program in El Salvador.

OBJECTIVE: In a primary human papillomavirus (HPV) screening program, we compared the 6-month follow-up among colposcopy and noncolposcopy-based management strategies for screen-positive women. MATERIALS AND METHODS: Women aged 30 to 49 years were screened with HPV DNA tests using both self-collection and provider collection of samples. Women testing positive received either (1) colposcopy management (CM) consisting of colposcopy and management per local guidelines or (2) screen-and-treat (ST) management using visual inspection with acetic acid to determine cryotherapy eligibility, with eligible women undergoing immediate cryotherapy. One thousand women were recruited in each cohort. Of these, 368 (18.4%) of 2000 women were recruited using a more intensive outreach strategy. Demographics, HPV positivity, and treatment compliance were compared across recruitment and management strategies. RESULTS: More women in the ST cohort received treatment within 6 months compared with those in the CM cohort (117/119 [98.3%] vs 64/93 [68.8%]; p < .001). Women recruited through more intensive outreach were more likely to be HPV positive, lived in urban areas, were more educated, and had higher numbers of lifetime sexual partners and fewer children. CONCLUSIONS: Women in the CM arm were less likely to complete care than women in the ST arm. Targeted outreach to underscreened women successfully identified women with higher prevalence of HPV and possibly higher disease burden.

The comparative and cost-effectiveness of HPV-based cervical cancer screening algorithms in El Salvador.

Cervical cancer is the leading cause of cancer death among women in El Salvador. Utilizing data from the Cervical Cancer Prevention in El Salvador (CAPE) demonstration project, we assessed the health and economic impact of HPV-based screening and two different algorithms for the management of women who test HPV-positive, relative to existing Pap-based screening. We calibrated a mathematical model of cervical cancer to epidemiologic data from El Salvador and compared three screening algorithms for women aged 30-65 years: (i) HPV screening every 5 years followed by referral to colposcopy for HPV-positive women (Colposcopy Management [CM]); (ii) HPV screening every 5 years followed by treatment with cryotherapy for eligible HPV-positive women (Screen and Treat [ST]); and (iii) Pap screening every 2 years followed by referral to colposcopy for Pap-positive women (Pap). Potential harms and complications associated with overtreatment were not assessed. Under base case assumptions of 65% screening coverage, HPV-based screening was more effective than Pap, reducing cancer risk by ∼ 60% (Pap: 50%). ST was the least costly strategy, and cost $2,040 per year of life saved. ST remained the most attractive strategy as visit compliance, costs, coverage, and test performance were varied. We conclude that a screen-and-treat algorithm within an HPV-based screening program is very cost-effective in El Salvador, with a cost-effectiveness ratio below per capita GDP.

Factors affecting attendance to cervical cancer screening among women in the Paracentral Region of El Salvador: a nested study within the CAPE HPV screening program.

BACKGROUND: Cervical cancer is the third most commonly occurring cancer among women and the fourth leading cause of cancer-related deaths in women worldwide, with more than 85 % of these cases occurring in developing countries. These global disparities reflect the differences in cervical cancer screening rates between high-income and medium- and low-income countries. At 19 %, El Salvador has the lowest reported screening coverage of all Latin American countries. The purpose of this study is to identify factors affecting public sector HPV DNA-based cervical cancer screening participation in El Salvador. METHODS: This study was nested within a public sector screening program where health promoters used door-to-door outreach to recruit women aged 30-49 years to attend educational sessions about HPV screening. A subgroup of these participants was chosen randomly and questioned about demographic factors, healthcare utilization, previous cervical cancer screening, and HPV knowledge. Women then scheduled screening appointments at their public health clinics. Screening participants were adherent if they attended their scheduled appointment or rescheduled and were screened within 6 months. The association between non-adherence and demographic variables, medical history, history of cancer, sexual history, birth control methods, and screening barriers was assessed using Chi-square tests of significance and logistic regression. RESULTS: All women (n = 409) enrolled in the study scheduled HPV screening appointments, and 88 % attended. Non-adherence was associated with a higher number of lifetime partners and being under-screened-defined as not having participated in cervical cancer screening within the previous 3 years (p = 0.03 and p = 0.04, respectively); 22.8 % of participants in this study were under-screened. CONCLUSIONS: Adherence to cervical cancer screening after educational sessions was higher than expected, in part due to interactions with the community-based health promoters as well as the educational session itself. More effective recruitment methods targeted toward under-screened women are required.

Evaluation of a low-cost liquid-based Pap test in rural El Salvador: a split-sample study.

OBJECTIVE: We sought to test the diagnostic efficacy of a low-cost, liquid-based cervical cytology that could be implemented in low-resource settings. MATERIALS AND METHODS: A prospective, split-sample Pap study was performed in 595 women attending a cervical cancer screening clinic in rural El Salvador. Collected cervical samples were used to make a conventional Pap (cell sample directly to glass slide), whereas residual material was used to make the liquid-based sample using the ClearPrep method. Selected samples were tested from the residual sample of the liquid-based collection for the presence of high-risk Human papillomaviruses. RESULTS: Of 595 patients, 570 were interpreted with the same diagnosis between the 2 methods (95.8% agreement). There were comparable numbers of unsatisfactory cases; however, ClearPrep significantly increased detection of low-grade squamous intraepithelial lesions and decreased the diagnoses of atypical squamous cells of undetermined significance. ClearPrep identified an equivalent number of high-grade squamous intraepithelial lesion cases as the conventional Pap. High-risk human papillomavirus was identified in all cases of high-grade squamous intraepithelial lesion, adenocarcinoma in situ, and cancer as well as in 78% of low-grade squamous intraepithelial lesions out of the residual fluid of the ClearPrep vials. CONCLUSIONS: The low-cost ClearPrep Pap test demonstrated equivalent detection of squamous intraepithelial lesions when compared with the conventional Pap smear and demonstrated the potential for ancillary molecular testing. The test seems a viable option for implementation in low-resource settings.

Gynecologic infection rates after ablation treatment for cervical intraepithelial neoplasia grade 2 and higher (CIN2+): Secondary analysis of a non-inferiority randomized trial.

Although concerns have been raised regarding potential infection and morbidity in women undergoing ablation treatment for cervical precancer in low- and middle-income countries (LMIC), there is extremely limited data to substantiate this claim. This is a secondary analysis of a randomized non-inferiority trial (id: NCT03084081) that compares the efficacy and safety of three ablation treatments for biopsy-confirmed cervical intraepithelial neoplasia grade 2 or higher (CIN2+): CO2 gas-based cryotherapy, non-gas cryotherapy, and thermal ablation (TA). Here, we present findings regarding the incidence of sexually transmitted infections (STI) and vaginitis post-treatment. Samples were collected at enrollment and again at 6 weeks post-treatment and assessed for STIs (Chlamydia trachomatis (CT), Neisseria gonorrhea (NG), and Trichomonas vaginalis (TV)) and vaginitis (Bacterial vaginosis (BV) and/or Candida albicans (Candida)). This analysis reflects 864 women with baseline and 6-week follow-up data. None of the ablative treatments put women at increased risk for STIs (CT, NG, TV) or vaginitis (BV, Candida). While most women adhered to post-treatment recommendations (97%) and no difference by treatment arm was observed, the incidence of STIs at follow-up in women that did not adhere with a given recommendation was higher compared to their adherent counterparts. The incidence of gynecologic infection did not increase with any of the ablation treatments from baseline to the six-week follow-up. Non-gas cryotherapy and TA emerge as safe alternatives to gas-based cryotherapy with respect to gynecologic infection rates.

Cervical Cancer Prevention in El Salvador: Gains to Date and Challenges for the Future.

Cervical cancer is preventable through vaccination, early detection, and the treatment of pre-cancerous lesions. However, global inequalities mean that the disease remains a leading cause of cancer death around the world, with over 80% of new cases and 90% of deaths occurring in low- and middle-income countries (LMICs). In El Salvador, joint efforts between the Ministry of Health (MoH) and the non-profit organization Basic Health International (BHI) have been in place since 2008, with the goal of reducing the country's disease burden. While the World Health Organization's (WHO) call to action to eliminate cervical cancer provided worldwide momentum to implement new public health initiatives, the COVID-19 pandemic disrupted ongoing programs and jeopardized plans for the future. The purpose of this manuscript is to describe the progress that El Salvador has achieved in improving cervical cancer prevention, the impact of the pandemic on current strategies, and potential solutions that can help the country meet the WHO's strategic targets by 2030 to accelerate the elimination of cervical cancer.

Safety and Acceptability of Three Ablation Treatments for High-Grade Cervical Precancer: Early Data From a Randomized Noninferiority Clinical Trial.

PURPOSE: This ongoing trial is comparing the efficacy and safety of three ablation treatments for cervical intraepithelial neoplasia grade 2 or higher. Here, we present early data regarding pain, side effects, and acceptability of CO2 gas-based cryotherapy (CO2), nongas cryotherapy, and thermal ablation (TA). Efficacy results are expected to become available in late 2023. MATERIALS AND METHODS: This noninferiority randomized trial is taking place in El Salvador, China, and Colombia. Patients are 1,152 eligible women with biopsy-confirmed cervical intraepithelial neoplasia grade 2 or higher who will receive one of three ablation treatments. Pain is measured before, during, and after treatment with a visual analog scale (1-10). Side effects and acceptability are assessed at 6 weeks. RESULTS: To date, 1,024 of 1,152 (89%) women were randomly assigned to treatment. The median pain level was higher during TA (4, IQR = 4) than CO2 (2, IQR = 4) or nongas cryotherapy (2, IQR = 4) (P < .01, range: 0-10). The most common post-treatment symptom was watery discharge, reported by 97.9% of women, and it lasted longer in the CO2 group than the other two treatments (in days, median [IQR]: CO2 = 20[20], nongas cryotherapy = 15[10], TA = 18[15], P < .01). Bleeding was reported more frequently in women treated with TA (27.6%) than CO2 (17.5) or nongas cryotherapy (18.7%) (P < .01). The majority of patients reported being very satisfied with the treatment they received at 6 weeks (91%) and again at 12 months post-treatment (97%). CONCLUSION: Despite differences in pain and side effects across ablation treatments, all were safe and highly acceptable to patients. In addition to efficacy, considerations such as cost and portability may be more significant in choosing a treatment method.

Image Quality Classification for Automated Visual Evaluation of Cervical Precancer.

Image quality control is a critical element in the process of data collection and cleaning. Both manual and automated analyses alike are adversely impacted by bad quality data. There are several factors that can degrade image quality and, correspondingly, there are many approaches to mitigate their negative impact. In this paper, we address image quality control toward our goal of improving the performance of automated visual evaluation (AVE) for cervical precancer screening. Specifically, we report efforts made toward classifying images into four quality categories ("unusable", "unsatisfactory", "limited", and "evaluable") and improving the quality classification performance by automatically identifying mislabeled and overly ambiguous images. The proposed new deep learning ensemble framework is an integration of several networks that consists of three main components: cervix detection, mislabel identification, and quality classification. We evaluated our method using a large dataset that comprises 87,420 images obtained from 14,183 patients through several cervical cancer studies conducted by different providers using different imaging devices in different geographic regions worldwide. The proposed ensemble approach achieved higher performance than the baseline approaches.

Multi-site clinical validation of Isothermal Amplification based SARS-COV-2 detection assays using different sampling strategies.

BACKGROUND: Isothermal amplification-based tests were developed as rapid, low-cost, and simple alternatives to real-time reverse transcriptase-polymerase chain reaction (RT-PCR) tests for SARS-COV-2 detection. METHODS: Clinical performance of two isothermal amplification-based tests (Atila Biosystems iAMP COVID-19 detection test and OptiGene COVID-19 Direct Plus RT-LAMP test) was compared to clinical RT-PCR assays using different sampling strategies. A total of 1378 participants were tested across four study sites. RESULTS: Compared to standard of care RT-PCR testing, the overall sensitivity and specificity of the Atila iAMP test for detection of SARS-CoV-2 were 76.2% and 94.9%, respectively, and increased to 88.8% and 89.5%, respectively, after exclusion of an outlier study site. Sensitivity varied based on the anatomic collected site. Sensitivity for nasopharyngeal was 65.4% (range across study sites:52.8%-79.8%), mid-turbinate 88.2%, saliva 55.1% (range across study sites:42.9%-77.8%) and anterior nares 66.7% (range across study sites:63.6%-76.5%). The specificity for these anatomic collection sites ranged from 96.7% to 100%. Sensitivity improved in symptomatic patients (overall 82.7%) and those with a higher viral load (overall 92.4% for ct≤25). Sensitivity and specificity of the OptiGene Direct Plus RT-LAMP test, conducted at a single study-site, were 25.5% and 100%, respectively. CONCLUSIONS: The Atila iAMP COVID test with mid-turbinate sampling is a rapid, low-cost assay for detecting SARS-COV-2, especially in symptomatic patients and those with a high viral load, and could be used to reduce the risk of SARS-COV-2 transmission in clinical settings. Variation of performance between study sites highlights the need for site-specific clinical validation of these assays before clinical adoption.

Multisite Clinical Validation of Isothermal Amplification-Based SARS-CoV-2 Detection Assays Using Different Sampling Strategies.

Isothermal amplification-based tests have been introduced as rapid, low-cost, and simple alternatives to real-time reverse transcriptase PCR (RT-PCR) tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection. The clinical performance of two isothermal amplification-based tests (Atila Biosystems iAMP coronavirus disease of 2019 [COVID-19] detection test and OptiGene COVID-19 direct plus RT-loop-mediated isothermal amplification [LAMP] test) was compared with that of clinical RT-PCR assays using different sampling strategies. A total of 1,378 participants were tested across 4 study sites. Compared with standard of care RT-PCR testing, the overall sensitivity and specificity of the Atila iAMP test for detection of SARS-CoV-2 were 76.2% and 94.9%, respectively, and increased to 88.8% and 89.5%, respectively, after exclusion of an outlier study site. Sensitivity varied based on the anatomic site from which the sample was collected. Sensitivity for nasopharyngeal sampling was 65.4% (range across study sites, 52.8% to 79.8%), for midturbinate was 88.2%, for saliva was 55.1% (range across study sites, 42.9% to 77.8%), and for anterior nares was 66.7% (range across study sites, 63.6% to 76.5%). The specificity for these anatomic collection sites ranged from 96.7% to 100%. Sensitivity improved in symptomatic patients (overall, 82.7%) and those with a higher viral load (overall, 92.4% for cycle threshold [CT] of ≤25). Sensitivity and specificity of the OptiGene direct plus RT-LAMP test, which was conducted at a single study site, were 25.5% and 100%, respectively. The Atila iAMP COVID test with midturbinate sampling is a rapid, low-cost assay for detecting SARS-CoV-2, especially in symptomatic patients and those with a high viral load, and could be used to reduce the risk of SARS-CoV-2 transmission in clinical settings. Variation of performance between study sites highlights the need for site-specific clinical validation of these assays before clinical adoption. IMPORTANCE Numerous SARS-CoV-2 detection assays have been developed and introduced into the market under emergency use authorizations (EUAs). EUAs are granted primarily based on small studies of analytic sensitivity and specificity with limited clinical validations. A thorough clinical performance evaluation of SARS-CoV-2 assays is important to understand the strengths, limitations, and specific applications of these assays. In this first large-scale multicentric study, we evaluated the clinical performance and operational characteristics of two isothermal amplification-based SARS-CoV-2 tests, namely, (i) iAMP COVID-19 detection test (Atila BioSystems, USA) and (ii) COVID-19 direct plus RT-LAMP test (OptiGene Ltd., UK), compared with those of clinical RT-PCR tests using different sampling strategies (i.e., nasopharyngeal, self-sampled anterior nares, self-sampled midturbinate, and saliva). An important specific use for these isothermal amplification-based, rapid, low-cost, and easy-to-perform SARS-CoV-2 assays is to allow for a safer return to preventive clinical encounters, such as cancer screening, particularly in low- and middle-income countries that have low SARS-CoV-2 vaccination rates.

Cervical Cancer Screening with Human Papillomavirus Self-Sampling Among Transgender Men in El Salvador.

Purpose: Sexual and gender minority persons in low-income countries have very limited access to routine health services. This study evaluated the feasibility of using a self-sampled human papillomavirus (HPV) test to increase access to screening for cervical cancer among transgender men in El Salvador. Methods: We partnered with a local advocacy organization for recruitment. A total of 24 transgender men (men assigned female at birth) ages 19-55 were enrolled and provided consent. Questionnaires assessed sociodemographics, health and sexual histories, and knowledge about HPV and cervical cancer. Screening was performed with a self-sampled HPV test. Participants with a positive test were offered colposcopy and cryotherapy treatment, if appropriate. Those with a negative test were advised to return in 5 years for rescreening. Results: Out of 24 consenting participants, 23 (95.83%) agreed to conduct HPV self-sampling, and 22/23 (95.65%) expressed willingness to self-sample in the future. Among self-sampled individuals, 3/23 (13%) tested positive and accepted colposcopy and biopsy. Analyses of biopsied tissue revealed one case of cervical intraepithelial neoplasia grade 1. Conclusion: HPV self-sampling and subsequent procedures were accepted by the majority of participants. This screening method may be a viable alternative to cytology among transgender men in El Salvador.

Outcomes for Step-Wise Implementation of a Human Papillomavirus Testing-Based Cervical Screen-and-Treat Program in El Salvador.

PURPOSE: The Cervical Cancer Prevention in El Salvador (CAPE) project is a public-sector intervention introducing lower-cost human papillomavirus (HPV) testing in all four departments of the Paracentral region that screened a total of 28,015 women. After demonstrating success of an HPV screen-and-treat (S&T) algorithm over colposcopy management in the first two phases, the third phase scaled up the S&T strategy. We present results from phase III and evaluate S&T components across the entire project. METHODS: During phase III, 17,965 women age 30-59 years underwent HPV testing. HPV-positive women were asked to return and, if eligible, received gas-based cryotherapy. We compare loss to follow-up and time intervals between S&T steps across the three phases. RESULTS: There were no differences in HPV positivity across phases (phase I, 11.9%; phase II, 11.4%; phase III, 12.3%; P = .173). Although most HPV-positive women completed indicated follow-up procedures within 6 months in phases I (93.3%, 111 of 119) and II (92.3%, 429 of 465), this proportion declined to 74.9% (1,659 of 2,214; P < .001) in phase III. Mean days between testing and delivery of results to patients increased over program phases (phase I, 23.2 days; phase II, 46.7 days; phase III, 99.8 days; P < .001). CONCLUSION: A public-sector implementation of an HPV-based S&T algorithm was successfully scaled up in El Salvador, albeit with losses in efficiency. After CAPE, the Ministry of Health changed its screening guidelines and procured additional tests to expand the program.

The cost-effectiveness of implementing HPV testing for cervical cancer screening in El Salvador.

OBJECTIVE: To assess the cost-effectiveness of HPV-based screening and management algorithms for HPV-positive women in phase 2 of the Cervical Cancer Prevention in El Salvador (CAPE) demonstration, relative to the status quo of Pap-based screening. METHODS: Data from phase 2 of the CAPE demonstration (n=8000 women) were used to inform a mathematical model of HPV infection and cervical cancer. The model was used to project the lifetime health and economic outcomes of HPV testing every 5 years (age 30-65 years), with referral to colposcopy for HPV-positive women; HPV testing every 5 years (age 30-65 years), with immediate cryotherapy for eligible HPV-positive women; and Pap testing every 2 years (age 20-65 years), with referral to colposcopy for Pap-positive women. RESULTS: Despite slight decreases in the proportion of HPV-positive women who received treatment relative to phase 1, the health impact of screening in phase 2 remained stable, reducing cancer risk by 58.5%. As in phase 1, HPV testing followed by cryotherapy for eligible HPV-positive women remained the least costly and most effective strategy (US$490 per year of life saved). CONCLUSION: HPV-based screening followed by immediate cryotherapy in all eligible women would be very cost-effective in El Salvador.