Pilot study of markers for high-grade anal dysplasia in a southern cohort from the Women's Interagency HIV Study (WIHS)

Abstract

Background: Anal cancer rates have increased in HIV+ women. Factors associated with anal cancer precursor high-grade squamous intraepithelial lesions (HSIL) in HIV+ and at-risk-HIV- women were assessed. Methods: HIV+ and HIV- women from the Atlanta WIHS cohort were enrolled in a cross-sectional pilot study. All anal (AS) and cervical (CS) swab samples were analyzed for HPV-genotyping (Linear-Array® HPV-Genotyping Test, LA-HPVGT) and FAM19A4 and microRNA-124-2 promoter methylation. All women underwent high resolution anoscopy with biopsy of suspicious lesions and anal cytology (AC) collection. Logistic regression was conducted with anal HSIL histology (A-HSIL) as the dependent variable. Results: 75 women were enrolled: 52(69%) were HIV+ with 3/4 having undetectable viral load, 64(86%) Black, with mean age 49. 44(59%) AC samples were ASCUS/+hrHPV or higher, 38(51%) of all AS were +hrHPV by LA-HPVGT.13 anal biopsies were confirmed A-HSIL. 69(95%) AS and 19(26%) CS tested positive for hypermethylation, respectively. A-HSIL model included ASCUS/+hrHPV or greater on AC and cervical hypermethylation as covariates (Table 1). AS hypermethylation was not associated with A-HSIL. Conclusions: Our results suggest AC with hrHPV testing and/or cervical gene promoter hypermethylation measurements as promising non-invasive screening strategies for A-HSIL in both HIV+ and HIV- women. Lack of association between AS hypermethylation and A-HSIL may reflect characteristics of the anal milieu and warrants further investigation.