Point of Care - Triage and Treatment for Cervical Pre-cancer (POC)

POINT of CARE - Providing an Innovative New Triage and Treatment Strategy for Cervical Cancer Screening Efficiency

This study evaluates a modified two-probe thermal ablation protocol using the IRIS™ device and retrospectively assesses an AI-based Automated Visual Evaluation (AVE) triage algorithm among HPV-positive women in El Salvador. The primary objective is to estimate 1-year cure rates of CIN2+ following treatment. A secondary objective is to evaluate the diagnostic performance of AVE compared with histopathology.

Study Overview

• Status: Recruiting
• Conditions: Cervical Intraepithelial Neoplasia; Human Papillomavirus Infection; Cervical Precancer
• Intervention / Treatment: Device: IRIS™ Thermal Ablation Device

Detailed Description

In the past decade, several portable thermal ablation (TA) devices have been developed to treat cervical precancer in low-resource settings. Current data shows that portable TA is safe and effective, but questions remain regarding the optimal treatment protocol. The purpose of this trial is to validate a portable TA device equipped with an endocervical probe that could improve the effectiveness of treatment, and to evaluate a Automated Visual Evaluation (AVE), a novel, AI-based imaging triage strategy designed to more accurately identify women at highest risk. This will be done using IRIS™ (Liger Medical, Lehi, UT), an FDA-approved (K202915) device that combines a digital colposcope and thermal ablator. Study aims will be 1) To clinically validate the modified IRISTM probes by estimating the cure rates of CIN2+ one year after treatment, and 2) To perform a retrospective validation of the AVE algorithm on IRISTM images using histopathologic disease status as ground truth.

The first aim will be a prospective, single-arm, interventional cohort study. The second aim will be a retrospective diagnostic performance and decision modeling study evaluating how AVE-based triage might have altered treatment decisions, using histopathologic diagnosis as the reference standard. The study will enroll 5,000 women who have tested HPV+ in the El Salvador national program but have not yet received treatment. Inclusion criteria will be women, aged 30-49, non-pregnant (determined by a urine pregnancy test), HPV+ positive per MOH records, and willingness to have colposcopy and biopsies. Exclusion criteria will be plans to become pregnant during the study, history of a LEEP or ablation procedure in the past 5 years, history of total hysterectomy (verified by medical record or pelvic evaluation), history of cervical cancer, and inability or unwillingness to provide a permanent and reliable address, and/or informed consent. Eligibility criteria will be same for both aims, except that women who are ineligible for ablation treatment will be eligible for Objective 2 if the SCJ is visible and other eligibility criteria are met.

An anticipated 6,250 HPV+ women will be invited to the study, and about 80% (n=5,000) are expected to agree to participate over the course of 30 months (167 per month). During the first visit, consented participants will undergo a provider-collected HPV genotyping test, visual assessment for treatment (VAT), capture of digital images with the IRISTM device for AVE, colposcopy, biopsy, and endocervical curettage (ECC). Women eligible for ablation during VAT (approximately 85%, or 4,250 participants) will receive thermal ablation using a two-probe protocol with IRIS™. Pain during treatment will be evaluated using the Baker-Wong scale. Women deemed ineligible will be referred for standard of care. Based on prior data, an estimated 10% of treated women (n = 425) will have biopsy-confirmed CIN2+ at baseline. These participants will be asked to return in one year for follow-up which will include HPV genotyping, colposcopy, biopsy, and endocervical curettage (ECC) to assess for persistent disease. Accounting for an expected 15% loss to follow-up, endpoint data will be available for approximately 362 women under Aim 1. All captured cervical images-including those from women ineligible for TA-may be included in the AVE analysis for Aim 2. Additionally, a subsample of 200 women will return at 6 weeks post-treatment to monitor for potential side effects. A separate subsample of 50 women diagnosed with CIN2+ at baseline will return at 4-6 months for colposcopy, biopsy, and ECC, to further evaluate the safety of the two-probe treatment protocol.

All biopsy and ECC samples from the initial, one-year, and safety evaluation visits will be sent to the same private laboratory in San Salvador for analysis. All cervical biopsy specimens will be reviewed by an expert in gynecologic pathology after local analysis is complete. If findings of the two pathologists agree, the diagnosis will be accepted as truth. If there is a discrepancy, a third expert in gynecologic pathology will review the specimen. Significant discrepancy occurs when pathologists disagree by more than one level: e.g., the diagnosis from pathologist 1 is normal and the diagnosis from pathologist 2 is CIN2+. Consensus will be reached when two of the three pathologists agree on a diagnosis. For cases in which there is no consensus, all three pathologists will hold an adjudication meeting and arrive at a consensus diagnosis (i.e., agreement of 2/3 pathologists). Results from the QA process will be considered ground truth in final analysis.

For Aim 1, cure rates of CIN2+ for IRISTM modified 2-probe treatment will be estimated after one year. Of the 425 women with CIN2+ treated with the IRISTM modified 2-probe approach, it is anticipated that 85% will return for the one-year follow-up visit (n=362) to have HPV testing, colposcopy/biopsy and ECC. The 1-year cure rate, defined as histopathological diagnosis of <CIN2, one year after treatment with the IRISTM modified 2-probe approach will be estimated with a precision (half-width of 95% confidence interval) of 3.7% assuming a cure rate of85%. Women diagnosed with recurrent/untreated CIN2+ and those with suspected cancer on the 1-year biopsy will be referred to the local cancer hospital for standard of care treatment. For Aim 2, the Area Under the Curve - Receiver Operator Characteristic (AUC-ROC) displays a model's performance across various classification thresholds, plotting the true positive rate (sensitivity) against the false positive rate. This curve gives a complete picture of performance, not just for one cutoff point, but for all possible thresholds. It illustrates how the AVE algorithm changes in accuracy depending on where the cutoff point is - or what is considered "positive." With a sample size of 4,500 women, the AUC can be estimated with high precision. For an AUC in the range of 0.5 to 0.9, the expected half-width of the 95% confidence interval will be approximately 0.01 to 0.03, corresponding to an uncertainty of only 1%-3% around the point estimate. This level of precision will provide strong statistical confidence that the measured AUC is close to the true performance of the AVE algorithm in identifying cervical images most consistent with CIN2+.

• Study Type: Interventional
• Enrollment (Estimated): 5000
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Karla Alfaro, MD; Phone Number: +503 22838731; Email: kalfaro@basichealth.org

Study Locations

• El Salvador
  • San Salvador Department
    • San Salvador, San Salvador Department, El Salvador
      • Recruiting
      • Basic Health International
      • Contact: Leticia Lopez, MD; Phone Number: +503 22838731; Email: info@basichealth.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Women aged 30-49 years
• Non-pregnant (determined by urine pregnancy test)
• HPV-positive per Ministry of Health (MOH) records
• Willing to undergo colposcopy and biopsies
• Able and willing to provide informed consent

Exclusion Criteria:

• Plans to become pregnant during the study
• History of LEEP or cervical ablation procedure in the past 5 years
• History of total hysterectomy (verified by medical record or pelvic evaluation)
• History of cervical cancer
• Unable or unwilling to provide a permanent and reliable address
• Unable or unwilling to provide informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Two-Probe Thermal Ablation Using IRIS™; Participants eligible for ablation will undergo thermal ablation using the IRIS™ device with a modified two-probe protocol. The short endocervical probe will be positioned in the distal canal (just inside the cervical os) for 20 seconds at 100°C, followed by placement of the appropriate-sized flat ectocervical probe in overlapping applications of 20 seconds at 100°C until the entire squamocolumnar junction is treated.

Device: IRIS™ Thermal Ablation Device; Thermal ablation will be performed using the IRIS™ device with a modified two-probe protocol. The short endocervical probe will be positioned in the distal canal for 20 seconds at 100°C, followed by overlapping applications of the appropriate-sized flat ectocervical probe for 20 seconds at 100°C until the entire squamocolumnar junction is treated.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1-Year Cure Rate of CIN2+	Cure rate defined as histopathologic diagnosis of <CIN2 one year after treatment with the IRIS™ modified two-probe approach.	12 months after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic Performance of AVE Algorithm	Diagnostic performance of the AVE algorithm will be evaluated by comparing AVE image classifications ("normal," "indeterminate," or "severe") with histopathologic diagnosis as the reference standard. Performance will be quantified using the Area Under the Receiver Operating Characteristic Curve (AUC-ROC), which assesses the algorithm's ability to distinguish cervical intraepithelial neoplasia grade 2 or higher (CIN2+) from less severe findings across classification thresholds. AVE analysis will be conducted retrospectively and will not influence real-time clinical management decisions.	Baseline (initial visit cervical images compared with histopathology results)
Extreme Misclassification Rate of the AVE Algorithm	The proportion of extreme misclassifications by the AVE algorithm will be assessed. Extreme misclassification is defined as a two-class error (e.g., normal histopathology classified as severe by AVE). The algorithm will be evaluated to ensure extreme misclassification occurs in less than 5% of cases.	Baseline (initial visit cervical images compared with histopathology results)
Rate of Serious Side Effects Following Thermal Ablation	Serious side effects will include serious adverse events (SAEs), cervical stenosis (defined as inability to pass a cytobrush through the cervical os), or infection requiring intravenous antibiotics. These events will be assessed during the 6-week follow-up visit among a subset of participants treated with thermal ablation.	6 weeks after treatment
Persistence of CIN2+ at Early Safety Follow-Up	Among a subset of participants diagnosed with CIN2+ at the initial visit and treated with thermal ablation, follow-up evaluation at 4-6 months will assess for persistent disease using colposcopy, biopsy, and endocervical curettage.	4-6 months after treatment
Participant Acceptability of Thermal Ablation Treatment	Participant perceptions of treatment acceptability will be assessed using a brief questionnaire evaluating pain, comfort, perceived effectiveness, ease of treatment, and overall satisfaction. Pain will be measured using the Wong-Baker Faces Pain Rating Scale, a validated self-report pain assessment tool with scores ranging from 0 to 10, where 0 indicates "no pain" and 10 indicates "worst pain possible." Higher scores indicate greater pain and lower treatment acceptability.	Immediately after treatment

Collaborators and Investigators

• Sponsor: Basic Health International, Inc.
• Collaborators: The Cleveland Clinic; Medical College of Wisconsin; Liger Medical Llc
• Investigators: Principal Investigator: Karla Alfaro, MD, Basic Health International, Inc.; Principal Investigator: Rachel Masch, MD, Basic Health International, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2026
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): August 1, 2029

Study Registration Dates

• First Submitted: March 5, 2026
• First Submitted That Met QC Criteria: March 5, 2026
• First Posted (Actual): March 10, 2026

Study Record Updates

• Last Update Posted (Actual): March 11, 2026
• Last Update Submitted That Met QC Criteria: March 9, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Cervical Cancer
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Pathologic Processes; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Disease Attributes; Infections; Virus Diseases; Uterine Diseases; Genital Diseases, Female; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; DNA Virus Infections; Genital Neoplasms, Female; Precancerous Conditions; Uterine Cervical Diseases; Uterine Neoplasms; Tumor Virus Infections; Pathological Conditions, Signs and Symptoms; Uterine Cervical Neoplasms; Papillomavirus Infections; Uterine Cervical Dysplasia
• Other Study ID Numbers: 00005660; 5R01CA285369-02 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Cervical images, AVE analysis results, HPV genotype, and colposcopy and biopsy correlates may be shared with teams that are working on AVE development in order to optimize the technology. During the informed consent procedure, patients will have the opportunity to accept or decline having their cervical images captured and shared. Women who decline may still participate in the rest of the research. Shared data will be de-identified; that is, it will only contain participants' study ID code and no information that can personally identify them. De-identified data will be stored in an NCI repository such as the Clinical and Translational Data Commons or the Cancer research Data Commons.
• IPD Sharing Time Frame: All materials will be available after study analysis is finished. The data will be made available five years from the last date of access.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes