Screening for HIV-Associated Anal Cancer: Correlation of HPV Genotypes, p16, and E6 Transcripts with Anal Pathology
- Irving E. Salit1,2,
- Jill Tinmouth2,3,
- Sylvia Chong4,
- Janet Raboud1,2,
- Christina Diong1,
- DeSheng Su1,
- Marie Sano1,
- Alice Lytwyn4,
- William Chapman1,2 and
- James Mahony4
- 1University Health Network, Toronto General Hospital; 2University of Toronto; 3Sunnybrook Medical Centre, Toronto, Ontario, Canada; 4Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
- Requests for reprints:
Irving E. Salit, Toronto General Hospital, 200 Elizabeth Street, Eaton 13N-215, Toronto, Ontario, Canada M5G 2C4. Phone: 416-340-3697; Fax: 415-340-3357. E-mail: irving.salit{at}uhn.on.ca
Abstract
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/mm3 (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)
Footnotes
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Grant support: Ontario HIV Treatment Network (grant ROGB184), the Canadian Cancer Society (grant 18164), and Canadian Cancer Etiology Research Network, and Ontario HIV Treatment Network Career Scientist Award and the Toronto General and Western Hospital Foundation Skate the Dream Fund (J. Raboud).
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- Accepted April 30, 2009.
- Received December 8, 2008.
- Revision received April 27, 2009.
