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

Study Overview
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Brief Summary
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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.

Detailed Description
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The aim of this study is to compare the effectiveness and efficiency of immediate colposcopy (IC), repeat conventional cytology at 6 and 12 months (RC) and HPV triage (HPV) (QIAGEN-The digene HPV Test®) for the clinical management of women with ASC-US insured in healthcare management organizations (HMO) within the Colombian health security system. This study randomized 2,661 20-69 years old women with ASC-US, insured in HMOs in Medellin-Colombia to 3 arms: IC, RC and HPV. All women are scheduled for a visit at 2 years after recruitment that includes HPV-test/cytology and colposcopy either if HPV+ (RLU>=1) or abnormal cytology (>=ASC-US). This colposcopy is performed by a trained colposcopist and women are followed-up according to a well-defined algorithm. The fewer high-grade cervical neoplasia (CIN2+) rate at the end of following will determine the most effective arm. The most efficiency arm will be which reach the major effective with the minimum resource (cytologies, colposcopies and histologies) consumed. The resource consumed is being retrieved from the HMOs. This study also pretends to evaluate the acceptability of the HPV testing. This study will allow us to know if within the Colombian health security system, the HPV test will remain superior to repeating cytology and/or to immediate colposcopy as it has been demonstrated in randomized controlled trials carried out in outside settings.

Official Title
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Evaluation of Strategies for Optimal Clinical Management of Women With Atypical Squamous Cells of Undetermined Significance (ASC-US)

Conditions
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Cervical Abnormalities, Cervical Intraepithelial Neoplasia Grade 2/3, Cervical Cancer

Intervention / Treatment
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* Device: HPV test
* Procedure: COLPOSCOPY
* Device: cytology


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ASC-US cytology, living in metropolitan area of Medellin Exclusion Criteria: Previous abnormal cytology

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 69 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HPV test<br>Women with ASC-US cytology are HPV tested and those HPV positive are refer to Colposcopy | Device: HPV test<br>* QIAGEN - The Digene HPV test®<br>* Other names: High risk HPV test;Procedure: COLPOSCOPY<br>* Colposcopy routine health services<br>|
| Active Comparator: COLPOSCOPY<br>Women with ASC-US cytology are immediately refer to colposcopy | Procedure: COLPOSCOPY<br>* Colposcopy routine health services<br>|
| Active Comparator: CYTOLOGY<br>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<br>* Colposcopy routine health services<br>Device: cytology<br>* Cytology routine health services<br>* Other names: cervical cytology;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative Number of Participants Diagnosed by a Panel of External Experts With Cervical Intraepithelial Neoplasia Grade 2 or Higher (CIN2+): Reviewed CIN2+ | Cumulative Cervical Intraepithelial Neoplasia Grade 2 or higher (CIN2+) diagnosed by a panel of external experts obtained after histological review of biopsies emitted by the community pathologists. Biopsies obtained during the two years of follow-up and the exit visit were reviewed by a panel of two external experts and a final result was adjudicated to each participant based on the panel of experts and the community of pathologists. This outcome is used for the effectiveness analysis of the three strategies. | 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+ | Cervical Intraepithelial Neoplasia Grade 2 or higher (CIN2+) diagnosed by a panel of external experts after reviewing biopsies collected at the exit visit, two years after the enrolment. This outcome is an estimate of the remaining disease that was not detected by the strategies during the 2 years of follow-up. The outcome was obtained after the review of all the biopsies taken during the exit visit. Biopsies were taken using a standardized research protocol to ensure the completeness of the remaining disease. Basically, all women attending the exit visit were tested with HPV testing and Pap and referred to colposcopy if any HPV positive or abnormal cytology. The colposcopy was performed by a researcher of the study team who took up to two biopsies from the observed lesion plus one or two at random if none lesion was observed. All biopsies were reviewed by the external panel. This outcome is used for the efficiency analysis of the three strategies. | Exit visit (two years after the enrolment) | 
| Number of Clinical Records (Cytologies, Colposcopies, and Histologies): Health Care Utilization | The outcome is defined as the number of cytologies, colposcopies, and histologies routinely performed during the two years of follow-up. Records were identified in databases or manually searched from clinical records. This outcome will be used for the analysis of the efficiency of the three strategies. | Two years since the enrolment to before the exit visit (i.e., excluding clinical records collected at the exit visit) | 
| Self-esteem | Self-esteem corresponds to the self-assessment of a positive or negative evaluation toward oneself. This outcome was measured using the Rosenberg Scale through 10 Likert-type questions with scores varying between 1 and 4 (1=strongly agree, 2=agree, 3=disagree, 4=strongly disagree). Total values range between 10 and 40 where lower scores suggest lower self-esteem. This outcome was measured at the enrollment visit, between two weeks and two months after receiving the triage result, and after one year of receiving the triage result. | Two years between the enrolment and the exit visit | 
| Trait Anxiety | Trait anxiety refers to the sustainable tendency to experience negative emotions (such as fears, worries, and anxiety) in various situations. This outcome was measured using the Spielberger State-Trait-Anxiety Inventory (STAI) through 20 Likert-type questions with scores varying between 0 and 3 (0=not at all, 1=somewhat, 2=moderately, 3=very much). Total values range between 0 and 60 where higher scores suggest higher levels of anxiety. This outcome was measured at the enrollment visit, between two weeks and two months after receiving the triage result, and after one year of receiving the triage result. | Two years between the enrolment and the exit visit | 
| State Anxiety | State anxiety refers to the transitory tendency to experience negative emotions (such as fears, worries, and anxiety). This outcome was measured using the Spielberger State-Trait-Anxiety Inventory (STAI) through 20 Likert-type questions with scores varying between 0 and 3 (0=not at all, 1=somewhat, 2=moderately, 3=very much). Total values range between 0 and 60 where higher scores suggest higher levels of anxiety. This outcome was measured at the enrollment visit, between two weeks and two months after receiving the triage result, and after one year of receiving the triage result. | Two years between the enrolment and the exit visit | 
| Concerns About Fertility, Cancer, and Gynecological Health | This outcome was measured using the HPV Impact Profile (HIP) scale through the following five domains: concerns about cancer and loss of fertility; emotional impact (depression and anxiety); self-image; interaction with the medical staff (pain or discomfort during the visit); and impact upon the life and its control. The response to each domain was measured on a scale from 0 to 10 (0=not at all, 1-3=a little, 4-6=somewhat, 7-9=a great deal, 10=extremely) and was then transformed to a scale from 0 to 100. A total score was calculated by adding all the items. Values <40 indicate no or little impact, between 40 and 70 moderate impact, and >70 indicate high psychosocial impact. This outcome was measured at the enrollment visit, between two weeks and two months after receiving the triage result, and after one year of receiving the triage result. | Two years between the enrolment and the exit visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Human Papillomavirus, cervical cancer, health services research, Colombia, Cervical Intraepithelial Neoplasia