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

• Published in: Cancer epidemiology, biomarkers & prevention biomarkers & prevention, 2009-07, Vol.18 (7), p.1986-1992
• Main Authors: SALIT, Irving E, TINMOUTH, Jill, CHONG, Sylvia, RABOUD, Janet, DIONG, Christina, DESHENG SU, SANO, Marie, LYTWYN, Alice, CHAPMAN, William, MAHONY, James
• Format: Article
• Language: English
• Subjects: AIDS-Related Opportunistic Infections - complications; AIDS-Related Opportunistic Infections - virology; Alphapapillomavirus - genetics; Alphapapillomavirus - pathogenicity; Anal cancer; Anus Neoplasms - complications; Anus Neoplasms - epidemiology; Anus Neoplasms - pathology; Anus Neoplasms - virology; Biological and medical sciences; Carcinoma in Situ - complications; Carcinoma in Situ - epidemiology; Carcinoma in Situ - pathology; Carcinoma in Situ - virology; DNA, Viral - analysis; E6 transcripts; Genes, p16; Genotype; HIV; HIV Seropositivity - complications; HIV Seropositivity - epidemiology; HIV Seropositivity - pathology; HIV Seropositivity - virology; Homosexuality, Male; HPV DNA; Human viral diseases; Humans; Infectious diseases; Male; Medical sciences; Oncogene Proteins, Viral - genetics; p16; Papillomavirus Infections - complications; Papillomavirus Infections - epidemiology; Papillomavirus Infections - pathology; Papillomavirus Infections - virology; Repressor Proteins - genetics; Risk Factors; Tumors; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral Load
• ISSN: 1055-9965; 1538-7755
• DOI: 10.1158/1055-9965.EPI-08-1141

Background: 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. Methods: 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. Results: 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. Conclusions: 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. (Cancer Epidemiol Biomarkers Prev 2009;18(7):1986–92)