Screening for HIV-associated anal cancer: correlation of HPV genotypes, p16, and E6 transcripts with anal pathology

Cancer Epidemiol Biomarkers Prev. 2009 Jul;18(7):1986-92. doi: 10.1158/1055-9965.EPI-08-1141. Epub 2009 Jun 30.

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/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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS-Related Opportunistic Infections / complications
  • AIDS-Related Opportunistic Infections / virology
  • Alphapapillomavirus / genetics*
  • Alphapapillomavirus / pathogenicity
  • Anus Neoplasms / complications
  • Anus Neoplasms / epidemiology*
  • Anus Neoplasms / pathology
  • Anus Neoplasms / virology
  • Carcinoma in Situ / complications
  • Carcinoma in Situ / epidemiology*
  • Carcinoma in Situ / pathology
  • Carcinoma in Situ / virology
  • DNA, Viral / analysis
  • Genes, p16*
  • Genotype
  • HIV Seropositivity / complications
  • HIV Seropositivity / epidemiology
  • HIV Seropositivity / pathology
  • HIV Seropositivity / virology*
  • Homosexuality, Male
  • Humans
  • Male
  • Oncogene Proteins, Viral / genetics*
  • Papillomavirus Infections / complications
  • Papillomavirus Infections / epidemiology
  • Papillomavirus Infections / pathology
  • Papillomavirus Infections / virology
  • Repressor Proteins / genetics*
  • Risk Factors
  • Viral Load

Substances

  • DNA, Viral
  • E6 protein, Human papillomavirus type 16
  • Oncogene Proteins, Viral
  • Repressor Proteins