Screening for HIV-Associated Anal Cancer: Correlation of HPV Genotypes, p16, and E6 Transcripts with Anal Pathology

Abstract

HIV-positive men with a history of anal-receptive intercourse are at risk for anal cancer. We determined whether human papilloma virus (HPV) biomarkers were correlated with anal pathology in these men. HPV genotype was determined by PCR/line blot assay. Real-time PCR assays were done for viral load, E6 transcripts for HPV genotypes 16, 18, and 31, and p16 transcripts. The most common oncogenic HPV types were HPV 16 (38%), 18 (19%), 45 (22%), and 52 (19%). HPV types 16, 18, 31, 52, 59, and 68 were associated with high-grade histology. The number of HPV genotypes per anal swab was higher for anal intraepithelial neoplasia (AIN) 2/3 than for normal or AIN 1 histology [median, 5 types (interquartile range) (IQR), 3-7 versus 3.5 (IQR), 2-6; P = 0.0005]. HPV 16 viral load was also associated with AIN 2/3 histology. There was no difference in p16 or E6 transcripts between histologic grades. In the multivariable logistic regression model, HPV genotypes 16 [odds ratio, 2.58; 95% confidence interval (95% CI), 1.31-5.08; P = 0.006] and 31 (odds ratio, 4.74; 95% CI, 2.00-11.22; P = 0.0004), baseline CD4 count < 400 cells/mm(3) (odds ratio, 2.96; 95% CI, 1.46-5.99; P = 0.0025), and Acquired Immunodeficiency Syndrome (AIDS)-defining illness (odds ratio, 2.42; 95% CI, 1.22-4.82; P = 0.01) were associated with high-grade histology after adjusting for age. The presence of high-grade anal pathology (AIN 2/3) in HIV-positive men was associated with multiple HPV genotypes, HPV genotypes 16 and 31, and HPV 16 viral load.