DNA METHYLATION ANALYSIS TO PREDICT REGRESSION OF HIGH-GRADE ANAL INTRAEPITHELIAL NEOPLASIA IN HIV+ MEN (MARINE): AN UPDATE OF AN ONGOING COHORT STUDY
Background and Aims:
Anal high-grade squamous intraepithelial lesions (HSIL), are highly prevalent in men who have sex with men living with HIV (MSMLWH). Around 30% of lesions regress within 1 year, but current histopathological assessment is unable to distinguish between HSIL likely to regress and HSIL likely to persist or progress to cancer. This study aims to assess if host cell DNA methylation markers can predict regression of anal high-grade squamous intraepithelial lesions (HSIL), thus determining the need for immediate treatment or active surveillance. This could reduce overtreatment and the associated anal and psycho-sexual morbidity.
Methods:
This is an ongoing active surveillance cohort study in five centres located in Amsterdam, the Netherlands, in 200 MSMLWH diagnosed with HSIL. Participants will not be treated, but closely monitored during 24 months of follow-up with 6 monthly visits including cytology, and high-resolution anoscopy with biopsies. The primary study endpoint is histopathological regression of each baseline HSIL lesion at the end of the study. Regression proportions in lesions with low versus high methylation levels (ASCL1, ZNF582), other biomarkers (HPV genotype, HPV-E4, p16INK4A, Ki-67) and immunological markers at baseline will be compared.
Results:
To date, 189 participants have been enrolled, and recruitment is ongoing. Of these, 127 have completed the 6-month follow-up visit, 81 have completed the 12-month visit, 51 have completed the 18-month visit, and 32 have completed the study. Biomarker results are not available yet.
Conclusions:
DNA methylation markers are a promising tool to stratify HSIL by cancer risk and guide clinical management. Clinical validation is ongoing.
