Anal Intraepithelial Neoplasia (AIN) and HPV in HIV+ Males: A VAMC Report
JP Reynolds, HX Bui, NM Patil, S Samaan, AG Smulian, DM Moore, VL Skeen, J Robertson. Veterans Affairs Medical Center, Cincinnati, OH; U of Cincinnati
Background: HIV patients have higher risk of AIN and anal cancer. Anal cytologic screening on liquid based prep (LBP), automated PCR-based detection of up to 13 types of high risk HPV DNA (hrHPV) to detect HPV, and high resolution anoscopy (HRA) are used. Here we report the efficacy of hrHPV on LBP vs detection of viral cytopathic effect (CPE) in cytology and histology. IHC for P16, p53, p63 and Ki67, adjunctive markers for HPV and diagnosis of HSIL, are studied.
Design: 262 screening anal LBPs from HIV+ men (2005-2007) were assessed by the Bethesda criteria. PCR based hrHPV DNA testing (ARUP labs) was done on 70 LBPs with ASCUS or higher. 34 HRA-guided biopsies were performed; 27 biopsies with sufficient tissue for additional slides were stained with IHC for p16 (BD Pharmagen 1:500), p53, p63 and Ki67 (Dako 1:100, 1:50, 1:200). Two pathologists independently reviewed the cyto- and histopathology. Any discordance was addressed by a joint review of HRA findings and clinical information. ROC curves and areas were generated for each IHC stain.
Results: 262 LBPs analyzed, 87 abnormal: 24 (28%) ASCUS, 42 (48%) LSIL, and 21 (24%) HSIL. HRA guided anal biopsy histology with IHC: 2 (7%) normal, 11 (41%) LSIL, 12 (44%) HSIL, 2 (7%) SCCIS. Tables 1 and 2 summarize the performance of tests.
IHC for HSIL detection with optimal cutoff values
70 hrHPV tests: 49(70%) positive, 4 (6%) negative, 17 (24%) equivocal with scant cellularity.
PCR and LBP performance
Conclusions: HrHPV testing has high sensitivity, but is limited by low specificity. High prevalence of latent HPV infection HIV+ males limits hrHPV from being a stand alone screening test. Cytology improves the specificity of finding AIN due to direct identification of CPE. HRA guided biopsies are needed for direct visualization and accurate sampling of the lesion. Based on the ROC area under the curves, p16 and Ki67 had the best diagnostic value for identifying HSIL; p53 and p63 were not useful. Using these three tests together will optimize the detection of HSIL and facilitate appropriate management. IHC for P16 and Ki67 could be helpful in discordant cases. Further studies are warranted to confirm our findings.
Tuesday, March 10, 2009 2:30 PM
Platform Session: Section F, Tuesday Afternoon