Clinical trial NCT01881659: Cervical Cancer Screening With Human Papillomavirus Testing
Official title: Multicentric Study of Cervical Cancer Screening and Triage With Human Papillomavirus (HPV) Testing
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: CIN3
CIN2
Cervical Cancer
Keywords: cervical cancer
cancer prevention
cervical screening
HPV testing
triage techniques
Lead sponsor: International Agency for Research on Cancer
Sponsor class: OTHER
First posted: 2013-06-19
Enrollment: 50000
Sex: FEMALE
Minimum age (years): 30
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
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.

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.

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)

Primary outcomes:
measure: Number of participants with histologically confirmed cervical intraepithelial neoplasia grade 3 or cancer (CIN3+), including CIN2 positive for p16, on reviewed histology
timeFrame: Detected after initial HPV screening or at second screening round 18 months since entry
Secondary outcomes:
measure: Number of participants with histologically confirmed CIN2, CIN3 or cancer (CIN2+) on reviewed histology
timeFrame: Detected after initial HPV screening or at second screening round 18 months since entry
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
facility: Hopsital de Clinicas
city: Buenos Aires
country: Argentina
facility: Insituto Malbran - Hospital Posadas
city: Sucre
country: Bolivia
facility: Universidad San Francisco Xavier de Chuquisaca
city: Bogota
country: Colombia
facility: National Cancer Institute of Colombia
city: Medellin
country: Colombia
facility: Universidad de Antioquia
city: San Jose
country: Costa Rica
facility: Social Security Institute of Costa Rica
city: Tegucigalpa
country: Honduras
facility: Universidad Nacional Autonoma de Honduras
city: Cuernavaca
country: Mexico
facility: Instituto Nacional de Salud Publica de Mexico
state: Morelos
city: Asuncion
country: Paraguay
facility: Instituto de Investigaciones en Ciencias de la Salud, Universidad Nacional de Asuncion
city: Asuncion
country: Paraguay
facility: Laboratorio Central de Salud Publica
city: Lima
country: Peru
facility: Hospital Santa Rosa
city: Montevideo
country: Uruguay
facility: Comision Honoraria de Lucha contra el Cancer
Study officials:
affiliation: International Agency for Research on Cancer (IARC)
name: Rolando Herrero, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.