Validation of a Lab-free Low-cost Screening Test for Prevention of Cervical Cancer

NCT06815939 | Recruiting

• 1 other identifier: 4R44CA247137
• Study Type: interventional
• Target: 10,000
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to validate Automated Visual Evaluation (AVE), specifically the CINFinder version developed by DL Analytics, a point-of-care screening and triage diagnostic tool for cervical cancer based on the assessment of digital images through artificial intelligence. Several teams around the world have developed versions of AVE as a triage technology but none as a screening tool.

Conditions

Cervical Intraepithelial Neoplasia; Human Papillomavirus (HPV); Uterine Cervical Neoplasms; Cervical Cancers

Keywords

Human Papillomavirus; Cervical Cancer; Screening; Neoplasms; Precancerous Conditions; Uterine Diseases; Uterine Cervical Diseases; Genital Diseases, Female; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms

Outcome Measures

Primary Outcomes (2)

• Sensitivity

  Proportion of true CIN2+ positive cases based on biopsy, detected by AVE compared to VIA.

  12 months, non-randomized

• Positive Predictive Value (PPV)

  Proportion of participants with AVE positive tests that have cervical precancer based on biopsy compared to those with positive VIA positive tests

  12 months, non-randomized

Study Arms (1)

Experimental

EXPERIMENTAL

Women eligible for HPV screening based on El Salvador's national guidelines will receive careHPV, VIA, and AVE (active comparator). Screen-positive women by HPV, VIA or AVE referred to colposcopy clinic and 5% of screen-negative women (negative on HPV, VIA, and AVE). Cervical cancer triage and diagnostic tests among screen- positive women and screen negative women. Biopsy-confirmed positive will receive necessary treatment by local standard of care.

Diagnostic Test: HPV Test; Device: EVA System; Procedure: Visual Inspection with Acetic Acid (VIA); Diagnostic Test: Automated Visual Evaluation (AVE); Other: Image Capture with Mobile Phone; Diagnostic Test: Pregnancy test; Diagnostic Test: ScreenFire HPV test; Procedure: Colposcopy with biopsy; Procedure: Thermal Ablation; Procedure: Loop electrosurgical excision procedure (LEEP)

Interventions

HPV Test DIAGNOSTIC_TEST

The careHPV (QIAGEN, Gaithersburg, MD) test was developed in a public-private partnership specifically for use in low-resource settings. It is a simplified, robust, and affordable HPV test that does not distinguish specific HPV types; rather, it gives a positive result if any of 14 hrHPV types is present in the specimen. Electricity is necessary to run the test, but it does not need running water or air conditioning. In order to be most cost effective, the samples must be run with a full plate of 96 samples. Results take 3-4 hours to complete.

Experimental

EVA System DEVICE

Digital colposcope

Experimental

Visual Inspection with Acetic Acid (VIA) PROCEDURE

unaided visual inspection with acetic acid

Experimental

Automated Visual Evaluation (AVE) DIAGNOSTIC_TEST

Digital diagnostic classification, quality classifier using captured images from EVA System

Also known as: CINFinder

Experimental

Image Capture with Mobile Phone OTHER

Compare performance of AVE installed on a mobile phone vs. on the EVA System

Experimental

Pregnancy test DIAGNOSTIC_TEST

Urine based pregnancy test

Experimental

ScreenFire HPV test DIAGNOSTIC_TEST

ScreenFire HPV test (Atila BioSystems, Inc, Mountain View, CA) uses isothermal amplification to detect 13 high risk (hr)HPV types directly from clinical samples in approximately one hour. The test can be run on any real-time PCR machine and gives separate results for hrHPV types 16 and 18, as well as a pooled positive result for 13 other hrHPV types. The human cellular gene beta-globin is used as an internal control to measure sample adequacy. ScreenFire can be self-collected and does not require batching. AmpFire® obtained CE-mark in 2017.

Experimental

Colposcopy with biopsy PROCEDURE

A colposcopic exam with biopsy entails visual magnification of the cervix and the removal of a small piece of cervical tissue. After the application of acetic acid 5% onto the cervix, a device called a colposcope allows the clinician to visually identify changes consistent with HPV. Areas of the cervix where lesions appear (or if not, randomly selected sections) are then biopsied (small piece of sample removed) and an endocervical curettage is performed (removing a small section from the inside of the cervix). Tissue specimens are then sent to the lab for pathology diagnosis.

Experimental

Thermal Ablation PROCEDURE

Thermal ablation is utilized to treat high-grade cervical precancer. First, a speculum is introduced into the vagina to identify the cervix. Acetic acid 5% is applied to the cervix for one minute and the cervix is observed to look for changes consistent with precancer. If the cervix is able to be fully evaluated and there are no signs of invasive cancer, the tip of the device is heated to 100ºC and applied directly to the cervix for 1-2 minutes, which ablates or destroys the abnormal cells.

Experimental

Loop electrosurgical excision procedure (LEEP) PROCEDURE

LEEP is utilized to remove abnormal tissue from the cervix. This may include tissue with precancerous cells (called cervical dysplasia) or cancerous cells. The loop is heated using electricity to remove the tissue. LEEP may also be called a loop excision or large loop excision of the transformation zone (LLETZ).

Experimental

Eligibility Criteria

• Age: 30 Years - 59 Years
• Gender Eligibility Details: Cisgender women
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Women between 30 and 59 years of age

You may not qualify if:

• Pregnancy at the time of colposcopy/biopsy
• Hysterectomy with surgically absent cervix
• HPV test in the last 5 years independently of negative or positive result
• Previous cervical cancer diagnosis or treatment in the last 5 years
• Lack of willingness or capacity to provide informed consent

Sponsors & Collaborators

• DL Analytics: lead
• Basic Health International, Inc.: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Ministerio de Salud

San Salvador, El Salvador

RECRUITING

Related Publications (9)

• Rao DW, Bayer CJ, Liu G, Chikandiwa A, Sharma M, Hathaway CL, Tan N, Mugo N, Barnabas RV. Modelling cervical cancer elimination using single-visit screening and treatment strategies in the context of high HIV prevalence: estimates for KwaZulu-Natal, South Africa. J Int AIDS Soc. 2022 Oct;25(10):e26021. doi: 10.1002/jia2.26021.

  PMID: 36225139 BACKGROUND

• Parham GP, Egemen D, Befano B, Mwanahamuntu MH, Rodriguez AC, Antani S, Chisele S, Munalula MK, Kaunga F, Musonda F, Malyangu E, Shibemba AL, de Sanjose S, Schiffman M, Sahasrabuddhe VV. Validation in Zambia of a cervical screening strategy including HPV genotyping and artificial intelligence (AI)-based automated visual evaluation. Infect Agent Cancer. 2023 Oct 16;18(1):61. doi: 10.1186/s13027-023-00536-5.

  PMID: 37845724 BACKGROUND

• Hull R, Mbele M, Makhafola T, Hicks C, Wang SM, Reis RM, Mehrotra R, Mkhize-Kwitshana Z, Kibiki G, Bates DO, Dlamini Z. Cervical cancer in low and middle-income countries. Oncol Lett. 2020 Sep;20(3):2058-2074. doi: 10.3892/ol.2020.11754. Epub 2020 Jun 19.

  PMID: 32782524 BACKGROUND

• Desai KT, Befano B, Xue Z, Kelly H, Campos NG, Egemen D, Gage JC, Rodriguez AC, Sahasrabuddhe V, Levitz D, Pearlman P, Jeronimo J, Antani S, Schiffman M, de Sanjose S. The development of "automated visual evaluation" for cervical cancer screening: The promise and challenges in adapting deep-learning for clinical testing: Interdisciplinary principles of automated visual evaluation in cervical screening. Int J Cancer. 2022 Mar 1;150(5):741-752. doi: 10.1002/ijc.33879. Epub 2021 Dec 6.

  PMID: 34800038 BACKGROUND

• Xue Z, Novetsky AP, Einstein MH, Marcus JZ, Befano B, Guo P, Demarco M, Wentzensen N, Long LR, Schiffman M, Antani S. A demonstration of automated visual evaluation of cervical images taken with a smartphone camera. Int J Cancer. 2020 Nov 1;147(9):2416-2423. doi: 10.1002/ijc.33029. Epub 2020 May 19.

  PMID: 32356305 BACKGROUND

• Ebrahimi N, Yousefi Z, Khosravi G, Malayeri FE, Golabi M, Askarzadeh M, Shams MH, Ghezelbash B, Eskandari N. Human papillomavirus vaccination in low- and middle-income countries: progression, barriers, and future prospective. Front Immunol. 2023 May 12;14:1150238. doi: 10.3389/fimmu.2023.1150238. eCollection 2023.

  PMID: 37261366 BACKGROUND

• Desai KT, Ajenifuja KO, Banjo A, Adepiti CA, Novetsky A, Sebag C, Einstein MH, Oyinloye T, Litwin TR, Horning M, Olanrewaju FO, Oripelaye MM, Afolabi E, Odujoko OO, Castle PE, Antani S, Wilson B, Hu L, Mehanian C, Demarco M, Gage JC, Xue Z, Long LR, Cheung L, Egemen D, Wentzensen N, Schiffman M. Design and feasibility of a novel program of cervical screening in Nigeria: self-sampled HPV testing paired with visual triage. Infect Agent Cancer. 2020 Oct 14;15:60. doi: 10.1186/s13027-020-00324-5. eCollection 2020.

  PMID: 33072178 BACKGROUND

• de Sanjose S, Perkins RB, Campos N, Inturrisi F, Egemen D, Befano B, Rodriguez AC, Jeronimo J, Cheung LC, Desai K, Han P, Novetsky AP, Ukwuani A, Marcus J, Ahmed SR, Wentzensen N, Kalpathy-Cramer J, Schiffman M; PAVE Study Group. Design of the HPV-automated visual evaluation (PAVE) study: Validating a novel cervical screening strategy. Elife. 2024 Jan 15;12:RP91469. doi: 10.7554/eLife.91469.

  PMID: 38224340 BACKGROUND

• Hu L, Bell D, Antani S, Xue Z, Yu K, Horning MP, Gachuhi N, Wilson B, Jaiswal MS, Befano B, Long LR, Herrero R, Einstein MH, Burk RD, Demarco M, Gage JC, Rodriguez AC, Wentzensen N, Schiffman M. An Observational Study of Deep Learning and Automated Evaluation of Cervical Images for Cancer Screening. J Natl Cancer Inst. 2019 Sep 1;111(9):923-932. doi: 10.1093/jnci/djy225.

  PMID: 30629194 BACKGROUND

MeSH Terms

Conditions

Uterine Cervical Dysplasia; Uterine Cervical Neoplasms; Neoplasms; Precancerous Conditions; Uterine Diseases; Uterine Cervical Diseases; Genital Diseases, Female; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site

Interventions

Human Papillomavirus DNA Tests; Watchful Waiting; Acetic Acid; Pregnancy Tests; Colposcopy; Biopsy; Transurethral Resection of Prostate

Condition Hierarchy (Ancestors)

Female Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Molecular Diagnostic Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Genetic Techniques; Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Quality of Health Care; Health Services Administration; Acetates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids; Diagnostic Techniques, Obstetrical and Gynecological; Endoscopy; Diagnostic Techniques, Surgical; Minimally Invasive Surgical Procedures; Surgical Procedures, Operative; Obstetric Surgical Procedures; Gynecologic Surgical Procedures; Urogenital Surgical Procedures; Cytodiagnosis; Cytological Techniques; Specimen Handling; Prostatectomy; Urologic Surgical Procedures, Male; Urologic Surgical Procedures

Study Officials

• Karla Alfaro, MD

  Basic Health International, Inc.

  PRINCIPAL INVESTIGATOR

• David Levitz, PhD

  DL Analytics

  PRINCIPAL INVESTIGATOR

Central Study Contacts

David Levitz, PhD

CONTACT

817-966-5600; levitz@dlanalytics.ai

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 21, 2025
• First Posted: February 10, 2025
• Study Start: February 12, 2025
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: January 29, 2026

Record last verified: 2026-01

Locations

EL (1)