Pilot Study of Markers for High-grade Anal Dysplasia in a Southern Cohort From the Women's Interagency Human Immunodeficiency Virus Study

Abstract

Background: Anal cancer rates have increased, particularly in human immunodeficiency virus (HIV)-infected (HIV+) women. We assessed factors associated with anal precancer in HIV+ and at-risk HIV-negative women from the Atlanta Women's Interagency HIV Study cohort.

Methods: All participants underwent high-resolution anoscopy and anal cytology and had anal and cervical samples collected. Specimens were tested for 37 human papillomavirus (HPV) types and for FAM19A4 and microRNA124-2 promoter methylation. Binary logistic regression and multivariate analysis were conducted with histologic anal high-grade squamous intraepithelial lesion (A-HSIL) as the dependent variable.

Results: Seventy-five women were enrolled: 52 (69%) were HIV+ with three-fourths having undetectable viral load; 64 (86%) were black; mean age was 49 ± 8 years. Forty-nine (65%) anal cytology samples were abnormal, and 38 (51%) of anal samples were positive for at least 1 of 13 high-risk HPV (hrHPV) types. Thirteen (18%) anal biopsies identified A-HSIL. Hypermethylation of FAM19A4 and/or microRNA124-2 was found in 69 (95%) anal samples and 19 (26%) cervical samples. In multivariate analyses, the odds of having A-HSIL were >6 times higher in women with anal hrHPV (adjusted odds ratio [aOR], 6.08 [95% confidence interval {CI}, 1.27-29.18], P = .02) and with positive cervical methylation (aOR, 6.49 [95% CI, 1.66-25.35], P = .007), but not significantly higher in women with positive anal methylation.

Conclusions: Anal hrHPV and promoter hypermethylation in the cervix show promise as biomarkers for anal cancer screening in HIV+ and at-risk HIV-negative women. Greater understanding of gene silencing by promoter hypermethylation in anal carcinogenesis is needed.

Keywords: HIV; anal cancer; high-grade squamous intraepithelial lesion (HSIL); methylation; women.

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Figures

Figure 1.

Study schema (N = 75 unless otherwise noted). Abbreviations: h/o, history of; HPV, human papillomavirus.