Cervical Cancer Screening With Human Papillomavirus Testing

Cervical Cancer Clinical Trial

— ESTAMPA  

Official title:

Multicentric Study of Cervical Cancer Screening and Triage With Human Papillomavirus (HPV) Testing

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01881659
• Other study ID #: IEC 12-27
• Status: Active, not recruiting
• Start date: May 2013
• Est. completion date: December 31, 2023

Study information

• Verified date: March 2023
• Source: International Agency for Research on Cancer
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 50000
• Est. completion date: December 31, 2023
• Est. primary completion date: August 30, 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 30 Years to 64 Years

Eligibility

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)

Related Conditions & MeSH terms

• Cervical Cancer
• CIN2
• CIN3
• Uterine Cervical Neoplasms

Intervention

Other:
• HPV screening
Women who signed informed consent will be screened with HPV testing.

Locations

Country	Name	City	State
Argentina	Hopsital de Clinicas	Buenos Aires
Argentina	Insituto Malbran - Hospital Posadas	Buenos Aires
Bolivia	Universidad San Francisco Xavier de Chuquisaca	Sucre
Colombia	National Cancer Institute of Colombia	Bogota
Colombia	Universidad de Antioquia	Medellin
Costa Rica	Social Security Institute of Costa Rica	San Jose
Honduras	Universidad Nacional Autonoma de Honduras	Tegucigalpa
Mexico	Instituto Nacional de Salud Publica de Mexico	Cuernavaca	Morelos
Paraguay	Instituto de Investigaciones en Ciencias de la Salud, Universidad Nacional de Asuncion	Asuncion
Paraguay	Laboratorio Central de Salud Publica	Asuncion
Peru	Hospital Santa Rosa	Lima
Uruguay	Comision Honoraria de Lucha contra el Cancer	Montevideo

Sponsors (1)

Lead Sponsor	Collaborator
International Agency for Research on Cancer

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with histologically confirmed cervical intraepithelial neoplasia grade 3 or cancer (CIN3+), including CIN2 positive for p16, on reviewed histology	There will be two HPV screening rounds. Women who test negative for HPV at initial screening will finish their participation. HPV positive women will be: 1) referred to colposcopy, 2) invited for a second HPV screening round if not yet treated, and 3) referred to final colposcopy if HPV positive at second screening. Clinical management will be based on local histology.; Histology specimens will be externally reviewed by one highly experience international pathologist. If the local and external results are the same, this will become the final histology. If there is disagreement, the specimen will be sent to a third pathologist (be blinded to previous readings). The final diagnosis will then be that agreed by two pathologists (local and either external or both external). Remaining discrepancies will be solved by adjudication at a multi-headed microscope. Worst histology on review will be used to define outcome measures.	Detected after initial HPV screening or at second screening round 18 months since entry
Secondary	Number of participants with histologically confirmed CIN2, CIN3 or cancer (CIN2+) on reviewed histology	There will be two HPV screening rounds. Women who test negative for HPV at initial screening will finish their participation. HPV positive women will be: 1) referred to colposcopy, 2) invited for a second HPV screening round if not yet treated, and 3) referred to final colposcopy if HPV positive at second screening. Clinical management will be based on local histology.; Histology specimens will be externally reviewed by one highly experience international pathologist. If the local and external results are the same, this will become the final histology. If there is disagreement, the specimen will be sent to a third pathologist (be blinded to previous readings). The final diagnosis will then be that agreed by two pathologists (local and either external or both external). Remaining discrepancies will be solved by adjudication at a multi-headed microscope. Worst histology on review will be used to define outcome measures.	Detected after initial HPV screening or at second screening round 18 months since entry