Screening for HIV-associated anal cancer: correlation of HPV genotypes, p16, and E6 transcripts with anal pathology.
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.
Salit
Irving E
IE
University Health Network, Toronto General Hospital, Toronto, Ontario, Canada. irving.salit@uhn.on.ca
Tinmouth
Jill
J
Chong
Sylvia
S
Raboud
Janet
J
Diong
Christina
C
Su
DeSheng
D
Sano
Marie
M
Lytwyn
Alice
A
Chapman
William
W
Mahony
James
J
D017088:AIDS-Related Opportunistic Infections / Q000150:complications / Q000821:virology; D052685:Alphapapillomavirus / Q000235:genetics* / Q000472:pathogenicity; D001005:Anus Neoplasms / Q000150:complications / Q000453:epidemiology* / Q000473:pathology / Q000821:virology; D002278:Carcinoma in Situ / Q000150:complications / Q000453:epidemiology* / Q000473:pathology / Q000821:virology; D004279:DNA, Viral / Q000032:analysis; D019942:Genes, p16; D005838:Genotype; D006679:HIV Seropositivity / Q000150:complications / Q000453:epidemiology / Q000473:pathology / Q000821:virology*; D018451:Homosexuality, Male; D006801:Humans; D008297:Male; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D030361:Papillomavirus Infections / Q000150:complications / Q000453:epidemiology / Q000473:pathology / Q000821:virology; D012097:Repressor Proteins / Q000235:genetics*; D012307:Risk Factors; D019562:Viral Load
D004279:DNA, Viral; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins