Triage Strategies in Cervical Cancer Prevention

Study Overview
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Brief Summary
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While there is broad consensus that HR-HPV detection is the best available primary screening test, there is no agreement about the most efficient and reliable triage procedure for HR-HPV positive women. Transient HR-HPV infections are very common, and the vast majority of these infections spontaneously regress after a year or two. Only a small fraction of cases will lead to persistent infection responsible for cervical neoplasia. The FRIDA Study is a large, population-based study that was designed to evaluate the performance and cost-effectiveness of different triage strategies for hrHPV-positive women in Mexico.

Detailed Description
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The target population is over <100,000 women aged 30 to 64 years who attend the Cervical Cancer Screening Program in 100 health centers in the state of Tlaxcala, Mexico. All women will be evaluated to determine hrHPV infection using the Cobas® 4800 HPV test. Triage strategies will be performed as reflex tests in all hrHPV-positive participants: HPV-16/18/45 genotyping, detection of the E6 oncoprotein of HPV-16/18, cytology, and immunocytochemistry using p16INK4a/Ki67. Women with at least one positive triage test will be referred for colposcopy evaluation, where a minimum of four biopsies and an endocervical sample are systematically collected. Histological confirmation will be performed by a standardized panel of pathologists.

Official Title
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Molecular Triage in Cervical Cancer Prevention: The Tlaxcala Study

Conditions
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Cervical Cancer, Intraepithelial Neoplasia

Intervention / Treatment
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* Other: HPV screening and triage tests


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women aged 30 to 64 Residents of the municipalities included in Sanitary Jurisdiction No. 1 of Tlaxcala. Exclusion Criteria: Pregnant or hysterectomized women Legally disabled women unable to give verbal informed consent required by the study protocol Women who do not wish to participate in the present study

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Women aged 30-64 years old<br>Women aged 30 to 64 years who attend the Cervical Cancer Screening Program in 100 health centers in the state of Tlaxcala, Mexico | Other: HPV screening and triage tests<br>* All cervical and/or vaginal specimens are tested for hrHPV using the Cobas® 4800 HPV test. Triage testing will be performed on all participants with a positive HR-HPV test declared consent at recruitment visit: HPV16/18 genotyping, Cobas® 4800 HPV test, HPV16/18/45 genotyping, BD OnclarityTM HPV Assay, OncoE6 Cervical Test, Liquid based cytology with Papanicolaou stain and p16INK4a/ Ki-67 immunostain.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Histologically confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+) | All women will be colposcopically evaluated in order to rule out any clinically evident invasive cancer. In cases of invasive cancer, patients will be referred to onco-gynecology services immediately. Before biopsy collection, endocervical sampling is performed using an Endocervex Brush®. A minimum of four biopsies are collected, at least one per quadrant, from the more suspicious area on cervical transformation zone. Histological evaluation of all samples (biopsies and/or endocervical curettage samples) will be evaluated for final diagnosis and confirmation of CIN2+ cases by two pathologists according to Mexico's Cervical Cancer Screening Programme's guidelines. An external expert-pathologist, will resolve discrepancies and render a final decision. | 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HPV testing, Triage, Mexico, Cervical cancer screening