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

• Conditions: HPV - Anogenital Human Papilloma Virus Infection; HSIL, High Grade Squamous Intraepithelial Lesions; Anal Cancer; Hiv

• Registration Number: NCT03357991
• Lead Sponsor: 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.

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.

Study Timeline

• Study Start: 2015-01-11
• Study First Submitted: 2017-11-24
• Study First Submitted QC: 2017-11-29
• Study First Posted: 2017-11-30
• Status Verified: 2017-12
• Last Update Submitted: 2017-12-05
• Last Update Posted: 2017-12-07
• Primary Completion: 2020-06
• Study Completion: 2020-06

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Male
• Target Recruitment: 355

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.).

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Determine the predictive value of HPV E6/E7 mRNA for the detection of HSIL and its ability to predict incident cases.	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

Name	Time	Method
Cost-effectiveness analysis of an anal cancer screening strategy based on HPV E6/E7 mRNA analysis.	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.

Trial Locations

Locations (1)

Hospital Universitary de bellvitge; 🇪🇸 L'Hospitalet de Llobregat, Barcelona, Spain