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E6/E7 mRNA Performance to Detect HSIL and Cost-effectiveness Analysis of This Screening Strategy in HIV + MSM (ELAVI-67)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03357991
Recruitment Status : Recruiting
First Posted : November 30, 2017
Last Update Posted : December 7, 2017
Institut d'Investigació Biomèdica de Bellvitge
Information provided by (Responsible Party):
Daniel Podzamczer Palter, Hospital Universitari de Bellvitge

Brief Summary:
This study evaluates the positive and negative predictive value of E6/E7 mRNA expression for anal HSIL and its capacity to predict incident HSIL in HIV + MSM. We also analyse the cost-effectiveness of this new screening strategy. It is an ambispective study with 355 participants and a follow-up period of 2 to 5 years.

Condition or disease
HPV - Anogenital Human Papilloma Virus Infection HSIL, High Grade Squamous Intraepithelial Lesions Anal Cancer Hiv

Detailed Description:

Introduction: Anal cancer incidence is increasing in HIV-infected men who have sex with men (MSM). There are still no standardized criteria for anal cancer screening. Anal cytology has not shown enough sensitivity and specificity in the selection of patients who need more invasive procedures, as high resolution anoscopy (HRA). Human Papillomavirus (HPV) E6 and E7 oncogenes deregulation is a crucial factor in neoplasic lesions progression.

Objectives: 1)To assess the negative and positive predictive value of E6/E7 mRNA expression for high-grade squamous intraepithelial lesions (HSIL) and its capacity to predict the incidence of new HSIL during the follow-up 2)To analyze the cost-effectiveness of E6/E7 as a new screening strategy for anal cancer compared with usual strategies (cytology and DNA detection).

Methodology: Ambispective longitudinal study. Participants: HIV MSM from the outpatients HIV and STD Unit of Bellvitge Hospital. We include patients visited within the usual outpatient practice since January 2015 with a cytology stored following the Hospital protocol, as well as patients collected prospectively since January 2017. This methodological approach will let to reduce the time of inclusion and maximize follow-up time. Sample size calculated: 355 participants. Follow-up period: 2 to 5 years. At each visit an anal smear for cytology, HPV DNA detection (by Linear Array and Hybrid Capture) and E6/E7 mRNA expression and a HRA with biopsy of suspicious areas of dysplasia will be performed. The analysis of cost-effectiveness will be made with a Markov model that projects long-term cost and effectiveness for both strategies, the E6/E7 and conventional cytology plus detection of High Risk HPV.

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Study Type : Observational [Patient Registry]
Estimated Enrollment : 355 participants
Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 2 Years
Official Title: Performance of E6/E7 mRNA to Detect Anal High-Grade Intraepithelial Lesions and Cost-effectiveness Analysis of a New Screening Strategy for Anal Cancer in HIV Positive Men Who Have Sex With Men
Actual Study Start Date : January 11, 2015
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : June 2020

Primary Outcome Measures :
  1. Determine the predictive value of HPV E6/E7 mRNA for the detection of HSIL and its ability to predict incident cases. [ Time Frame: 2-5 years ]
    Determination of HPV E6/E7 ARNm in anal samples of 355 HIV + MSM. Correlation of the detection of HPV E6/E7 ARNm with the diagnosis of HSIL in this patients performing anal cytology an HRA at the first visit and during the follow-up.

Secondary Outcome Measures :
  1. Cost-effectiveness analysis of an anal cancer screening strategy based on HPV E6/E7 mRNA analysis. [ Time Frame: 2-5 years ]
    Cost-effectiveness analysis of an anal cancer screening strategy based on the selection of candidates for HRA according to the expression of the E6 / E7 mRNA, compared to the usual strategy based on cytology and DNA HPV detection.

Biospecimen Retention:   Samples With DNA
  1. Detection of anal HPV

    • Hybrid Capture® 2 HPV DNA (QIAGEN Inc., Gaithersburg, Maryland; EE.UU): enzyme linked immunoabsorvent assay based on a sandwich hybridisation that allows a qualitative measure of DNA of 13 HPV.
    • Linear Array HPV Genotyping Test (Roche Molecular Systems Inc., Alameda, California, EE.UU): it detects a region within the HPV L1 that share 37 anogenital HPV genotypes.
    • Detection of E6/E7 VPH mRNA using APTIMA® HPV Test (Gen-Probe Inc., San Diego, California, EE.UU): it allows the qualitative detection of HPV E6/E7 mRNA from 14 high-risk HPVs.
  2. Anal cytology: processed with Thinprep Pap Test (Hologic, Marlborough, Massachusetts, USA). The swab is deposited into preserved liquid based cytology: PreservCyt Solution.
  3. HRA with biopsy of suspicious lesions

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Adult HIV-infected MSM visited in the HIV Unit of Bellvitge's University Hospital and underwent routine anal cancer screening.

Retrospective participants: patients attended between January 2015 and December 2016 and with part of the anal smear sample stored.

Prospective participants: patients who start anal cancer screening during the inclusion period.


Inclusion Criteria:

  • Men who have sex with men >= 18 years
  • HIV documented infection
  • Signature of the informed consent

Exclusion Criteria:

  • Previous diagnosis of anal cancer.
  • Treatment of anal intraepithelial lesions the 5 years before study inclusion.
  • Suspect infiltrating anal cancer, requiring exploration under anesthesia and surgical removal for histological confirmation.
  • History of diffuse ano-genital condylomatous disease the 5 years before study inclusion or presence at first visit.
  • Other factors that could prevent correct diagnosis and monitoring of the anal dysplastic lesions (test intolerance, proctological pathology that does not allow HRA, etc.).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03357991

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Contact: Ana C Silva Klug 0034932607667 ext 2859
Contact: Maria Saumoy Linares 0034932607667 ext 2887

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Hospital Universitary de bellvitge Recruiting
L'Hospitalet de Llobregat, Barcelona, Spain, 08907
Contact: Ana C Silva Klug    0034932607667 ext 2859   
Contact: Maria Saumoy Linares    0034932607667 ext 2887   
Principal Investigator: Daniel Podzamczer Palter         
Sponsors and Collaborators
Hospital Universitari de Bellvitge
Institut d'Investigació Biomèdica de Bellvitge
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Principal Investigator: Daniel Podzamczer Palter Hospital Universitari de Bellvitge

Additional Information:

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Responsible Party: Daniel Podzamczer Palter, PhD. Chief of the HIV and STD Unit (Infectious Disease Service), Hospital Universitari de Bellvitge Identifier: NCT03357991     History of Changes
Other Study ID Numbers: PR076/17
PI16/01056 ( Other Grant/Funding Number: Instituto de Salud Carlos III )
First Posted: November 30, 2017    Key Record Dates
Last Update Posted: December 7, 2017
Last Verified: December 2017

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Daniel Podzamczer Palter, Hospital Universitari de Bellvitge:
E6/E7 mRNA
anal cancer screening
men who have sex with men
cost-effectiveness analysis
High resolution anoscopy

Additional relevant MeSH terms:
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Anus Diseases
Virus Diseases
Anus Neoplasms
Squamous Intraepithelial Lesions of the Cervix
Papillomavirus Infections
Neoplasms, Squamous Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Uterine Cervical Dysplasia
Precancerous Conditions
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female
DNA Virus Infections
Tumor Virus Infections