Cervical Cancer Screening With Human Papillomavirus Testing (ESTAMPA)

This study is currently recruiting participants.
Verified June 2013 by International Agency for Research on Cancer
Sponsor:
Information provided by (Responsible Party):
International Agency for Research on Cancer
ClinicalTrials.gov Identifier:
NCT01881659
First received: June 17, 2013
Last updated: June 26, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention
CIN3
CIN2
Cervical Cancer
Other: HPV screening

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: Multicentric Study of Cervical Cancer Screening and Triage With Human Papillomavirus (HPV) Testing

Resource links provided by NLM:


Further study details as provided by International Agency for Research on Cancer:

Primary Outcome Measures:
  • Number of participants with histologically confirmed cervical intraepithelial neoplasia grade 3 or cancer (CIN3+) on reviewed histology [ Time Frame: Detected after initial HPV screening or at second screening round 18 months since entry ] [ Designated as safety issue: No ]

    There will be two HPV screening rounds. Women who test negative for HPV at initial screening will finish their participation, except a 2% random sample who will be followed as if HPV positive. 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.



Secondary Outcome Measures:
  • Number of participants with histologically confirmed CIN2, CIN3 or cancer (CIN2+) on reviewed histology [ Time Frame: Detected after initial HPV screening or at second screening round 18 months since entry ] [ Designated as safety issue: No ]

    There will be two HPV screening rounds. Women who test negative for HPV at initial screening will finish their participation, except a 2% random sample who will be followed as if HPV positive. 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.



Biospecimen Retention:   Samples With DNA

Three cervical samples will be collected at entry (one dry and two liquid-based). Sample retaining or discharge will depend on HPV test (done in first liquid sample) results. If HPV positive (and 2% of HPV negatives): 1) the dry sample will be used for the E6 protein strip test, 2) the first liquid sample remains will be used for liquid-based cytology and the p16/ki67 test and, 3) 10 aliquots from the second liquid sample will be stored. If HPV negative: 1) the dry sample will be stored for the E6 strip test until the end of the study. Testing will be done based on evidence towards usefulness in primary screening, 2) two aliquots from the first liquid sample will be stored and, 3) the second liquid sample will be discharged. At initial colposcopy, a cervical sample (6 aliquots) and a 10mL blood sample (serum, plasma and buffy-coat) will be collected and stored. All stored samples will be used for testing of triage techniques, either currently available or develop in the near future.


Estimated Enrollment: 50000
Study Start Date: June 2013
Estimated Study Completion Date: September 2018
Estimated Primary Completion Date: May 2018 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Women attending cervical screening
Women aged 30-64 years who signed informed consent and comply with inclusion and exclusion criteria.
Other: HPV screening
Women who signed informed consent will be screened with HPV testing.

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, at least 5,000 women ages 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, and a 2% sample of the HPV-negative women, 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 (CIN 3+) 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 CIN 3+ (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.

  Eligibility

Ages Eligible for Study:   30 Years to 64 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

This is a multicentric study to be carried out in countries across the Latin American region. At each site, a census of all women 28-64 years of age residents of the selected area will be done previously to the start of the study. All women will then be invited using different approaches to the local health centers where screening is to happen.

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)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01881659

Contacts
Contact: Rolando Herrero, MD, PhD +33472738683 herreror@iarc.fr
Contact: Maribel Almonte, PhD +33472738492 almontem@iarc.fr

Locations
Colombia
National Cancer Institute of Colombia Recruiting
Bogota, Colombia
Contact: Raul Murillo, MD    +5713341111 ext 4001    rmurillo@cancer.gov.co   
Contact: Carolina Wiesner, MD       cwiesner@cancer.gov.co   
Principal Investigator: Raul Murillo, MD         
Sub-Investigator: Carolina Wiesner, MD         
Mexico
Instituto Nacional de Salud Publica de Mexico Not yet recruiting
Cuernavaca, Morelos, Mexico
Contact: Aurelio Cruz, MD, PhD    +527773293020 ext 3108    acruz@insp.mx   
Principal Investigator: Aurelio Cruz, MD, PhD         
Sub-Investigator: Eduardo Lazcano Ponce, MD, PhD         
Sponsors and Collaborators
International Agency for Research on Cancer
Investigators
Principal Investigator: Rolando Herrero, MD, PhD International Agency for Research on Cancer (IARC)
  More Information

No publications provided

Responsible Party: International Agency for Research on Cancer
ClinicalTrials.gov Identifier: NCT01881659     History of Changes
Other Study ID Numbers: IEC 12-27
Study First Received: June 17, 2013
Last Updated: June 26, 2013
Health Authority: Colombia: Ministry of Health and Social Protection
Mexico: National Institute of Public Health, Health Secretariat

Keywords provided by International Agency for Research on Cancer:
cervical cancer
cancer prevention
cervical screening
HPV testing
triage techniques

Additional relevant MeSH terms:
Uterine Cervical Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female

ClinicalTrials.gov processed this record on April 15, 2014