Clinical trial NCT03357991: E6/E7 mRNA Performance to Detect HSIL and Cost-effectiveness Analysis of This Screening Strategy in HIV + MSM
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
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: HPV - Anogenital Human Papilloma Virus Infection
HSIL, High Grade Squamous Intraepithelial Lesions
Anal Cancer
Hiv
Keywords: E6/E7 mRNA
anal cancer screening
men who have sex with men
cost-effectiveness analysis
High resolution anoscopy
Lead sponsor: Hospital Universitari de Bellvitge
Sponsor class: OTHER
Collaborators: name: Institut d'Investigació Biomèdica de Bellvitge
First posted: 2017-11-30
Enrollment: 355
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

Eligibility criteria: 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.).

Primary outcomes:
measure: Determine the predictive value of HPV E6/E7 mRNA for the detection of HSIL and its ability to predict incident cases.
timeFrame: 2-5 years
Secondary outcomes:
measure: Cost-effectiveness analysis of an anal cancer screening strategy based on HPV E6/E7 mRNA analysis.
timeFrame: 2-5 years
Other outcomes:
Locations:
city: L'Hospitalet de Llobregat
country: Spain
facility: Hospital Universitary de bellvitge
state: Barcelona
Study officials:
affiliation: Hospital Universitari de Bellvitge
name: Daniel Podzamczer Palter
role: PRINCIPAL_INVESTIGATOR
References: