Optimal Strategy for the Management of ASCUS Cytology in Health Care Services of Medellin, Colombia

NCT02067468 | Completed Results

• 1 other identifier: 111545921657
• Study Type: interventional
• Target: 2,661
• Locations: 1 country
• Sites: 1

Brief Summary

Cervical cancer as well cervical preneoplastic abnormalities (CIN2+) are cause by human papillomavirus (HPV) infection. These abnormalities have been historically detected by cervical cytology, but recent evidence shows that HPV testing is superior to cytology to detect cervical lesions that eventually will progress to cancer. Despite evidence, conventional cytology (Pap) remains as a primary screening test in Colombia and HPV test is recommended as a triage test for women with atypical squamous cells of undetermined significance (ASC-US) in settings around the world. Women with ASC-US have low risk to CIN2+ but higher than healthy population, and therefore it is important to provide appropriate clinical management. However, there is no consensus of how to deal women with ASC-US and therefore there are still three strategies for this purpose: 1) immediate colposcopy, 2) repeat conventional cytology at 6 and 12 months and 3) HPV testing. The main objective of this study is to compare the effectiveness and the efficient among the strategies as well as to evaluate the acceptability of the HPV testing in a real-life setting.

Conditions

Cervical Abnormalities; Cervical Intraepithelial Neoplasia Grade 2/3; Cervical Cancer

Keywords

Human Papillomavirus; cervical cancer; health services research; Colombia; Cervical Intraepithelial Neoplasia

Outcome Measures

Primary Outcomes (1)

• Cumulative Number of Participants Diagnosed by the Community Pathologist With Cervical Intraepithelial Neoplasia Grade 2 or Higher (CIN2+): "Community-based CIN2+"

  Cumulative Cervical Intraepithelial Neoplasia Grade 2 or higher (CIN2+) diagnosed by the community pathologists during the two years of follow-up. The first community-based CIN2+ diagnosis was adjudicated to the participant (including the exit visit if none community-based CIN2+ during the two years of follow-up). This outcome is used for the effectiveness analysis of the three strategies.

  Two years since the enrolment to the exit visit (inclusive)

Secondary Outcomes (7)

• Cumulative Number of Participants Diagnosed by a Panel of External Experts With Cervical Intraepithelial Neoplasia Grade 2 or Higher (CIN2+): "Reviewed CIN2+"

  Two years since the enrolment to the exit visit (inclusive)

• Number of Participants Diagnosed by a Panel of External Experts With Cervical Intraepithelial Neoplasia Grade 2 or Higher (CIN2+) at the Exit Visit, Two Years After the Enrolment: "Exit-reviewed CIN2+"

  Exit visit (two years after the enrolment)

• Number of Clinical Records (Cytologies, Colposcopies, and Histologies): "Health Care Utilization"

  Two years since the enrolment to before the exit visit (i.e., excluding clinical records collected at the exit visit)

• Self-esteem

  Two years between the enrolment and the exit visit

• Trait Anxiety

  Two years between the enrolment and the exit visit

Study Arms (3)

HPV test

EXPERIMENTAL

Women with ASC-US cytology are HPV tested and those HPV positive are refer to Colposcopy

Device: HPV test; Procedure: COLPOSCOPY

COLPOSCOPY

ACTIVE COMPARATOR

Women with ASC-US cytology are immediately refer to colposcopy

Procedure: COLPOSCOPY

CYTOLOGY

ACTIVE COMPARATOR

Women with ASC-US Cytology are follow-up with cytology at 6 and/or 12 months and be referred to colposcopy if any of these cytologies is ASC-US or higher

Procedure: COLPOSCOPY; Device: cytology

Interventions

HPV test DEVICE

QIAGEN - The Digene HPV test®

Also known as: Human Papillomavirus test, DNA HPV test, High risk HPV test

HPV test

COLPOSCOPY PROCEDURE

Colposcopy routine health services

COLPOSCOPY; CYTOLOGY; HPV test

cytology DEVICE

Cytology routine health services

Also known as: Pap smear, Papanicolaou test, cervical cytology

CYTOLOGY

Eligibility Criteria

• Age: 20 Years - 69 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ASC-US cytology, living in metropolitan area of Medellin

You may not qualify if:

• Previous abnormal cytology

Sponsors & Collaborators

• Universidad de Antioquia: lead
• International Agency for Research on Cancer: collaborator
• Barts and the London School of Medicine and Dentistry: collaborator
• Instituto Colombiano para el Desarrollo de la Ciencia y la Tecnología (COLCIENCIAS): collaborator
• QIAGEN Gaithersburg, Inc: collaborator
• EPS SURA: collaborator
• EPS COMFAMA: collaborator
• EPS COMFENALCO: collaborator
• DINAMICA IPS: collaborator
• Laboratorio Clínico Escuela de Microbiología (Universidad de Antioquia): collaborator
• Metrosalud: collaborator

Study Sites (1)

Universidad de Antioquia

Medellín, Antioquia, Colombia

Location

Related Publications (27)

• Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010 Dec 15;127(12):2893-917. doi: 10.1002/ijc.25516.

  PMID: 21351269 BACKGROUND

• Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, Snijders PJ, Peto J, Meijer CJ, Munoz N. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999 Sep;189(1):12-9. doi: 10.1002/(SICI)1096-9896(199909)189:13.0.CO;2-F.

  PMID: 10451482 BACKGROUND

• ASCUS-LSIL Traige Study (ALTS) Group. Results of a randomized trial on the management of cytology interpretations of atypical squamous cells of undetermined significance. Am J Obstet Gynecol. 2003 Jun;188(6):1383-92. doi: 10.1067/mob.2003.457.

  PMID: 12824967 BACKGROUND

• Andres-Gamboa O, Chicaiza L, Garcia-Molina M, Diaz J, Gonzalez M, Murillo R, Ballesteros M, Sanchez R. Cost-effectiveness of conventional cytology and HPV DNA testing for cervical cancer screening in Colombia. Salud Publica Mex. 2008 Jul-Aug;50(4):276-85. doi: 10.1590/s0036-36342008000400005.

  PMID: 18670718 BACKGROUND

• Schiffman M, Adrianza ME. ASCUS-LSIL Triage Study. Design, methods and characteristics of trial participants. Acta Cytol. 2000 Sep-Oct;44(5):726-42. doi: 10.1159/000328554.

  PMID: 11015972 BACKGROUND

• Schiffman M, Solomon D. Findings to date from the ASCUS-LSIL Triage Study (ALTS). Arch Pathol Lab Med. 2003 Aug;127(8):946-9. doi: 10.5858/2003-127-946-FTDFTA.

  PMID: 12873166 BACKGROUND

• Arbyn M, Sasieni P, Meijer CJ, Clavel C, Koliopoulos G, Dillner J. Chapter 9: Clinical applications of HPV testing: a summary of meta-analyses. Vaccine. 2006 Aug 31;24 Suppl 3:S3/78-89. doi: 10.1016/j.vaccine.2006.05.117.

  PMID: 16950021 BACKGROUND

• Carozzi FM, Confortini M, Cecchini S, Bisanzi S, Cariaggi MP, Pontenani G, Raspollini MR, Sani C, Zappa M, Ciatto S. Triage with human papillomavirus testing of women with cytologic abnormalities prompting referral for colposcopy assessment. Cancer. 2005 Feb 25;105(1):2-7. doi: 10.1002/cncr.20736.

  PMID: 15593261 BACKGROUND

• Legood R, Gray A, Wolstenholme J, Moss S. Lifetime effects, costs, and cost effectiveness of testing for human papillomavirus to manage low grade cytological abnormalities: results of the NHS pilot studies. BMJ. 2006 Jan 14;332(7533):79-85. doi: 10.1136/bmj.38698.458866.7C. Epub 2006 Jan 6.

  PMID: 16399769 BACKGROUND

• Kulasingam SL, Kim JJ, Lawrence WF, Mandelblatt JS, Myers ER, Schiffman M, Solomon D, Goldie SJ; ALTS Group. Cost-effectiveness analysis based on the atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion Triage Study (ALTS). J Natl Cancer Inst. 2006 Jan 18;98(2):92-100. doi: 10.1093/jnci/djj009.

  PMID: 16418511 BACKGROUND

• Sheriff SK, Petry KU, Ikenberg H, Crouse G, Mazonson PD, Santas CC. An economic analysis of human papillomavirus triage for the management of women with atypical and abnormal Pap smear results in Germany. Eur J Health Econ. 2007 Jun;8(2):153-60. doi: 10.1007/s10198-007-0038-5. Epub 2007 Feb 17.

  PMID: 17308921 BACKGROUND

• Vanni T, Legood R, Franco EL, Villa LL, Luz PM, Schwartsmann G. Economic evaluation of strategies for managing women with equivocal cytological results in Brazil. Int J Cancer. 2011 Aug 1;129(3):671-9. doi: 10.1002/ijc.25708. Epub 2010 Nov 12.

  PMID: 20886598 BACKGROUND

• Dillner L, Kemetli L, Elfgren K, Bogdanovic G, Andersson P, Carlsten-Thor A, Andersson S, Persson E, Rylander E, Grillner L, Dillner J, Tornberg S. Randomized healthservices study of human papillomavirus-based management of low-grade cytological abnormalities. Int J Cancer. 2011 Jul 1;129(1):151-9. doi: 10.1002/ijc.25649. Epub 2010 Nov 9.

  PMID: 20824706 BACKGROUND

• Ostensson E, Froberg M, Hjerpe A, Zethraeus N, Andersson S. Economic analysis of human papillomavirus triage, repeat cytology, and immediate colposcopy in management of women with minor cytological abnormalities in Sweden. Acta Obstet Gynecol Scand. 2010 Oct;89(10):1316-25. doi: 10.3109/00016349.2010.512066.

  PMID: 20846064 BACKGROUND

• Inter-American-Development-Bank. Structured Pluralism: Toward an Innovative Model for the Reform of Health Systems in Latin America. Office of the Chief Economist. 1997;Working Paper 353.

  BACKGROUND

• Luce BR, Kramer JM, Goodman SN, Connor JT, Tunis S, Whicher D, Schwartz JS. Rethinking randomized clinical trials for comparative effectiveness research: the need for transformational change. Ann Intern Med. 2009 Aug 4;151(3):206-9. doi: 10.7326/0003-4819-151-3-200908040-00126. Epub 2009 Jun 30. No abstract available.

  PMID: 19567619 BACKGROUND

• Verdoodt F, Szarewski A, Halfon P, Cuschieri K, Arbyn M. Triage of women with minor abnormal cervical cytology: meta-analysis of the accuracy of an assay targeting messenger ribonucleic acid of 5 high-risk human papillomavirus types. Cancer Cytopathol. 2013 Dec;121(12):675-87. doi: 10.1002/cncy.21325. Epub 2013 Jul 23.

  PMID: 23881840 BACKGROUND

• Arbyn M, Ronco G, Anttila A, Meijer CJ, Poljak M, Ogilvie G, Koliopoulos G, Naucler P, Sankaranarayanan R, Peto J. Evidence regarding human papillomavirus testing in secondary prevention of cervical cancer. Vaccine. 2012 Nov 20;30 Suppl 5:F88-99. doi: 10.1016/j.vaccine.2012.06.095.

  PMID: 23199969 BACKGROUND

• Sorbye SW, Arbyn M, Fismen S, Gutteberg TJ, Mortensen ES. Triage of women with low-grade cervical lesions--HPV mRNA testing versus repeat cytology. PLoS One. 2011;6(8):e24083. doi: 10.1371/journal.pone.0024083. Epub 2011 Aug 30.

  PMID: 21918682 BACKGROUND

• Arbyn M, Martin-Hirsch P, Buntinx F, Van Ranst M, Paraskevaidis E, Dillner J. Triage of women with equivocal or low-grade cervical cytology results: a meta-analysis of the HPV test positivity rate. J Cell Mol Med. 2009 Apr;13(4):648-59. doi: 10.1111/j.1582-4934.2008.00631.x. Epub 2009 Jan 23.

  PMID: 19166485 BACKGROUND

• Cuzick J, Arbyn M, Sankaranarayanan R, Tsu V, Ronco G, Mayrand MH, Dillner J, Meijer CJ. Overview of human papillomavirus-based and other novel options for cervical cancer screening in developed and developing countries. Vaccine. 2008 Aug 19;26 Suppl 10:K29-41. doi: 10.1016/j.vaccine.2008.06.019.

  PMID: 18847555 BACKGROUND

• Dalla Palma P, Pojer A, Girlando S. HPV triage of women with atypical squamous cells of undetermined significance: a 3-year experience in an Italian organized programme. Cytopathology. 2005 Feb;16(1):22-6. doi: 10.1111/j.1365-2303.2004.00196.x.

  PMID: 15859311 BACKGROUND

• Instituto Nacional de C. Recomendaciones para el tratamiento de las pacientes con citologia reportada con células escamosas atipicas de significado indeterminado (ASC-US) en Colombia. Guias de practica clinica (No. 2). Bogota, Colombia: INC, 2007

  BACKGROUND

• Baena A, Agudelo MC, Posada G, Lopez C, Buitrago CA, Suescun D, Gomez LJ, Ochoa JC, Sasieni P, Almonte M, Herrero R, Sanchez GI. Efectividad de tres estrategias para el manejo clínico de la citología ASC-US en servicios rutinarios de salud de Medellín, Colombia: diseño y resultados de dos años de seguimiento del ensayo pragmático aleatorio ASCUS-COL (NCT02067468). Rev Colomb Cancerol 2017;21:49 - DOI: 10.1016/j.rccan.2017.02.012

  RESULT

• Baena A, Agudelo MC, Posada G, Lopez C, Buitrago CA, Suescun D, Gomez LJ, Ochoa JC, Sasieni P, Almonte M, Herrero R, Sanchez GI. EI triage con prueba de VPH de aIto riesgo y Ia citoIogía repetida son estrategias eficientes para eI manejo cIínico de mujeres con citoIogía ASC-US en servicios rutinarios de saIud de MedeIIín, CoIombia: resuItados finaIes deI ensayo pragmático aIeatorio ASCUS-COL. Rev Colomb Cancerol 2017;21:49-50 - DOI: 10.1016/j.rccan.2017.02.013

  RESULT

• Urrea Cosme Y, Cordoba Sanchez V, Sanchez GI, Baena A, Ruiz Osorio MA, Rodriguez Zabala D, Garces-Palacio IC. Health-related quality of life of women after HPV testing as triage strategy for an abnormal Pap smear: a nested randomized pragmatic trial in a middle-income country. Qual Life Res. 2020 Nov;29(11):2999-3008. doi: 10.1007/s11136-020-02563-w. Epub 2020 Jul 2.

  PMID: 32617889 DERIVED

• Henao AR, Gomez NEM, Gonzalez-Gomez D, Garces-Palacio IC. Validation of Spanish version of the human papilloma virus impact profile (HIP). Curr Med Res Opin. 2020 Apr;36(4):705-712. doi: 10.1080/03007995.2020.1729709. Epub 2020 Mar 6.

  PMID: 32049551 DERIVED

MeSH Terms

Conditions

Uterine Cervical Neoplasms; Uterine Cervical Dysplasia

Interventions

Human Papillomavirus DNA Tests; Colposcopy; Cytological Techniques; Papanicolaou Test

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Molecular Diagnostic Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Genetic Techniques; 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; Biopsy; Cytodiagnosis; Specimen Handling

Results Point of Contact

• Title: Dr Gloria I Sanchez
• Organization: Universidad de Antioquia

sanchezg@une.net.co

+57 (4) 219 6062

Study Officials

• Gloria I Sanchez, MSc, PhD

  Universidad de Antioquia

  PRINCIPAL INVESTIGATOR

• Armando Baena, MSc, PhD

  Universidad de Antioquia

  STUDY CHAIR

• Maria C Agudelo, MD

  Universidad de Antioquia

  STUDY CHAIR

• Alejandra Botero, MSc

  Universidad de Antioquia

  STUDY CHAIR

• Victor Florez, MSc

  Universidad de Antioquia

  STUDY CHAIR

• Calatina Villa, BSc

  Universidad de Antioquia

  STUDY CHAIR

• Astrid Bedoya, MSc

  Universidad de Antioquia

  STUDY CHAIR

• Guadalupe Posada, MD, Esp

  DINAMICA IPS

  STUDY CHAIR

• Carlos A Buitrago, MD, Esp

  EPS COMFENALCO

  STUDY CHAIR

• Juan C Ochoa, MD, Esp

  EPS COMFAMA

  STUDY CHAIR

• Luis J Gomez, MD, Esp

  DINAMICA IPS

  STUDY CHAIR

• Tatiana Ramirez, BSc

  Universidad de Antioquia

  STUDY CHAIR

• Maribel Almonte, MSc, PhD

  International Agency for Research on Cancer (IARC)

  STUDY CHAIR

• Rolando Herrero, MSc, PhD

  International Agency for Research on Cancer (IARC)

  STUDY CHAIR

• Peter Sasieni, MSc, PhD

  Centre for Cancer Prevention, Queen Mary University of London

  STUDY CHAIR

• Yessid Álvarez, Student

  Universidad de Antioquia

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: February 18, 2014
• First Posted: February 20, 2014
• Study Start: January 1, 2011
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: September 19, 2019
• Results First Posted: September 19, 2019

Record last verified: 2019-09

Locations

CO (1)