MEsHH · DNA MEthylation for HPV-related disease among women living with HIV
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2018-09-05 → 2020-09-04
- EU contribution
- €158,122
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
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Results in brief
DNA MEthylation for HPV-related disease among women living with HIV
Women living with human immunodeficiency virus (WLHIV) have an increased risk of cervical cancer and precancer. The majority of WLHIV live in low- and middle-income countries where access to cervical cancer screening, and treatment of precancerous cervical lesions is limited. Cervical cancer screening strategies have previously shown variable sensitivity (visual inspection methods) or low specificity (HPV-DNA based tests) for the detection of cervical precancer among WLHIV. Novel strategies are required to more effectively screen WLHIV with or without an effective triage strategy without resulting in unnecessary referrals. The precise diagnostic accuracy of various cervical cancer screening strategies in WLHIV remains uncertain and varies widely across studies. The aim of the MEsHH study was to evaluate novel cervical cancer screening strategies, including DNA methylation assays compared to other existing cervical cancer screening methods, including visual inspection, cervical cytology and HPV DNA for detection of cervical precancer among a cohort of WLHIV in Sub-Saharan Africa. Secondary objectives were to gain an understanding on how HIV disease progression (measured using ART status and CD4+ count) impacts the diagnostic accuracy of cervical cancer screening strategies.
Data: CORDIS, © European Union
Project objective
Background: The current screening methods for cervical cancer screening among women living with HIV (WLHIV) have previously shown high sensitivity but poor specificity for the detection of high-grade cervical intraepithelial neoplasia (CIN2+), resulting in over-referral for colposcopy and overtreatment of cervical lesions that may have low potential for progression to cancer. Methylation changes of human genes or HPV DNA have been reported early in carcinogenesis but their validation for predicting CIN among WLHIV is lacking. Objectives: Among 1238 WLHIV enrolled in Burkina Faso (BF; n=615) and South Africa (SA; n=623), the MesHH study aims to evaluate the performance of the DNA methylation of human genes (CADM1, MAL, MiR and EPB41L3) and HPV (HPV16/18/31/33) for the detection of prevalent and incident CIN2+ compared to, or in combination with, other screening methods (visual inspection using acetic acid [VIA] or Lugol’s iodine [VILI], cytology and HPV DNA) and to evaluate the capacity of the DNA methylation markers to distinguish cervical lesion progression, persistence or regression at 16 months follow-up. Methods: The study will use endocervical swabs with matching histological data collected as part of a prospective study evaluating cervical cancer screening strategies among WLHIV in BF and SA. The DNA methylation assays for human genes (CADM1, MAL, MiR, EPB41L3) and HPV (HPV16/18/31/33) will be performed using pyrosequencing assays. Sensitivity, specificity, positive and negative predictive values for the detection of CIN2+ will be estimated for the various DNA methylation markers, as stand-alone or multiplex tests. Relevance: Multiplex DNA methylation assays including a combination of human genes and HPV virus may have potential as primary screening for CIN2+ among WLHIV. DNA methylation assays also have the potential to be performed using the same clinician- or self-collected sample used for cytology or HPV testing, thereby increasing screening coverage.
Original text from CORDIS.
Participants
- FUNDACIO INSTITUT D'INVESTIGACIO BIOMEDICA DE BELLVITGE · L'Hospitalet De LlobregatCoordinatorSpain
Links
Data: CORDIS, © European Union