Cervical Cancer Screening With Human Papillomavirus Testing

NCT ID: NCT01881659

Last Updated: 2023-03-14

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 50000 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2013-05-31
• Study Completion Date: 2023-12-31

Brief Summary

HPV testing for primary cervical cancer screening of women over 30 years of age is likely to become the standard of care in the near future in many areas of the world. Its high sensitivity can significantly improve the effectiveness of screening programs and its prolonged negative predictive value can allow extension of screening intervals. However, a single HPV test has low positive predictive value and can lead to unnecessary workup and over-treatment and generate unnecessary distress. This multi-centric study will screen 50,000 women with HPV testing and compare several triage approaches that can follow HPV testing in order to make an HPV-based screening programme efficient, affordable and sustainable.

Detailed Description

The study will be conducted in several Latin American countries. Currently, the study has started in one site in Colombia and soon another site in Mexico will start. In each participating center, women aged 30-64 years who are attending clinics for cervical screening will be invited to participate in the study. Women who agree to participate and sign the corresponding Institutional Review Board (IRB) approved consent forms will undergo a pelvic examination, and cervical cells for primary screening and triage will be collected. Recruitment specimens will be used for primary screening with an established HPV DNA test (Food and Drug Administration FDA approved). All women who are HPV-positive by the recruitment test will be referred for a standardized colposcopy examination for diagnosis. At the colposcopy visit, but before colposcopy is performed, a risk factor interview will be administered and participants will undergo visual inspection of the cervix with acetic acid (VIA) and collection of additional cervical cells and a blood specimen. The results of VIA will not be disclosed to the colposcopist. During colposcopy, the colposcopists will obtain (2-4) biopsies from any abnormally-appearing areas to ascertain neoplastic outcomes (CIN3+) and to direct treatment as required. All women who attend colposcopy will have a second round of HPV testing approximately 18 months after recruitment and those who are HPV-positive will be referred to colposcopy for final diagnosis. Data management and study supervision will be the responsibility of the International Agency for Research on Cancer (IARC) and the local Principal Investigators, most of whom are experienced HPV researchers.

The combined number of histologically-confirmed diagnoses of CIN3+, including CIN2 lesions positive for p16, (estimated n=500) will be the outcome of primary interest for evaluation of the performance of the various triage modalities. Our initial analyses will focus on comparisons of triage strategies that employ a single method: VIA, conventional/liquid-based cytology, HPV DNA genotyping, HPV RNA detection, detection of E6 proteins of high risk HPV types, or markers of HPV-induced cell-cycle alterations (e.g., p16, ki67, etc). To the extent possible, molecular testing for HPV triage will be carried out on the recruitment specimens to simulate a 'reflex testing' approach wherein screening and triage are done on the same specimen without additional visits. Subsequent analyses will consider various alternative strategies that employ more than one triage methodology; e.g., HPV DNA genotyping followed by cytology. The effectiveness and costs of each alternative strategy will be assessed under various scenarios of feasibility, cost, and effectiveness.

Conditions

CIN3; CIN2; Cervical Cancer

Study Design

• Observational Model Type: OTHER
• Study Time Perspective: PROSPECTIVE

Study Groups

Women attending cervical screening

Women aged 30-64 years who signed informed consent and comply with inclusion and exclusion criteria.

HPV screening

Intervention Type: OTHER

Women who signed informed consent will be screened with HPV testing.

Interventions

HPV screening

Women who signed informed consent will be screened with HPV testing.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Aged 30-64 years
• Mentally competent to be able to understand the consent form
• Able to communicate with study staff
• Physically able to have a pelvic exam

Exclusion Criteria

• Reporting no previous sexual activity
• History of cervical cancer
• Previous treatment for cervical pre-cancer in the last six months
• Hysterectomy
• Plans to move out of the study area in the next 12 months
• Screened for cervical cancer in the last 12 months (depending on local regulations)

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

International Agency for Research on Cancer

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Rolando Herrero, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

International Agency for Research on Cancer (IARC)

Locations

Hopsital de Clinicas

Buenos Aires, , Argentina

Insituto Malbran - Hospital Posadas

Buenos Aires, , Argentina

Universidad San Francisco Xavier de Chuquisaca

Sucre, , Bolivia

National Cancer Institute of Colombia

Bogotá, , Colombia

Universidad de Antioquia

Medellín, , Colombia

Social Security Institute of Costa Rica

San José, , Costa Rica

Universidad Nacional Autonoma de Honduras

Tegucigalpa, , Honduras

Instituto Nacional de Salud Publica de Mexico

Cuernavaca, Morelos, Mexico

Instituto de Investigaciones en Ciencias de la Salud, Universidad Nacional de Asuncion

Asunción, , Paraguay

Laboratorio Central de Salud Publica

Asunción, , Paraguay

Hospital Santa Rosa

Lima, , Peru

Comision Honoraria de Lucha contra el Cancer

Montevideo, , Uruguay

Countries

Argentina; Bolivia; Colombia; Costa Rica; Honduras; Mexico; Paraguay; Peru; Uruguay

References

Baena A, Picconi MA, Mendoza L, Ferrera A, Mesher D, Lineros J, Brizuela M, Mongelos P, Cabrera Y, Fellner MD, Zambrana O, Garcia L, Hernandez P, Bobadilla ML, Ramon M, Venegas G, Villagra V, Cruz A, Rodriguez G, Teran C, Calderon A, Wiesner C, Herrero R, Almonte M; ESTAMPA study group. Short-term repeat HPV testing for triaging HPV-positive women in cervical cancer screening. Br J Cancer. 2025 Oct 3. doi: 10.1038/s41416-025-03193-0. Online ahead of print.

Reference Type: DERIVED

PMID: 41044173 (View on PubMed)

Baena A, Mesher D, Salgado Y, Martinez S, Villalba GR, Amarilla ML, Salgado B, Flores B, Bellido-Fuentes Y, Alvarez-Larraondo M, Valls J, Lora O, Virreira-Prout G, Figueroa J, Turcios E, Soilan AM, Ortega M, Celis M, Gonzalez M, Venegas G, Teran C, Ferrera A, Mendoza L, Kasamatsu E, Murillo R, Wiesner C, Broutet N, Luciani S, Herrero R, Almonte M; ESTAMPA study group. Performance of visual inspection of the cervix with acetic acid (VIA) for triage of HPV screen-positive women: results from the ESTAMPA study. Int J Cancer. 2023 Apr 15;152(8):1581-1592. doi: 10.1002/ijc.34384. Epub 2022 Dec 7.

Reference Type: DERIVED

PMID: 36451311 (View on PubMed)

Almonte M, Murillo R, Sanchez GI, Gonzalez P, Ferrera A, Picconi MA, Wiesner C, Cruz-Valdez A, Lazcano-Ponce E, Jeronimo J, Ferreccio C, Kasamatsu E, Mendoza L, Rodriguez G, Calderon A, Venegas G, Villagra V, Tatti S, Fleider L, Teran C, Baena A, Hernandez ML, Rol ML, Lucas E, Barbier S, Ramirez AT, Arrossi S, Rodriguez MI, Gonzalez E, Celis M, Martinez S, Salgado Y, Ortega M, Beracochea AV, Perez N, Rodriguez de la Pena M, Ramon M, Hernandez-Nevarez P, Arboleda-Naranjo M, Cabrera Y, Salgado B, Garcia L, Retana MA, Colucci MC, Arias-Stella J, Bellido-Fuentes Y, Bobadilla ML, Olmedo G, Brito-Garcia I, Mendez-Herrera A, Cardinal L, Flores B, Penaranda J, Martinez-Better J, Soilan A, Figueroa J, Caserta B, Sosa C, Moreno A, Mural J, Doimi F, Gimenez D, Rodriguez H, Lora O, Luciani S, Broutet N, Darragh T, Herrero R. Multicentric study of cervical cancer screening with human papillomavirus testing and assessment of triage methods in Latin America: the ESTAMPA screening study protocol. BMJ Open. 2020 May 24;10(5):e035796. doi: 10.1136/bmjopen-2019-035796.

Reference Type: DERIVED

PMID: 32448795 (View on PubMed)

Robles C, Wiesner C, Martinez S, Salgado Y, Hernandez M, Lucas E, Lineros J, Romero P, Herrero R, Almonte M, Murillo R. Impact of operational factors on HPV positivity rates in an HPV-based screening study in Colombia. Int J Gynaecol Obstet. 2018 Oct;143(1):44-51. doi: 10.1002/ijgo.12574. Epub 2018 Jul 16.

Reference Type: DERIVED

PMID: 29944728 (View on PubMed)

Other Identifiers

IEC 12-27

Identifier Type: -

Identifier Source: org_study_id