CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

281 IMMUNE GENE EXPRESSION IN ANAL DYSPLASTIC LESIONS BY HIV STATUS AND ABLATION OUTCOMES Nikhil Shamapant , Yuxin Liu, Michael Gaisa, Russell McBride, Keith M. Sigel Icahn School of Medicine at Mt Sinai, New York, NY, USA Background: The incidence of anal squamous cell carcinoma (SCCA) is 50-fold higher in HIV-infected persons and is a leading cause of morbidity among HIV patients. Anal high-grade squamous intraepithelial lesions (HSIL) are the precursors to SCCA. There has been limited study on the interactions between HIV infection, the immune microenvironment of HSIL and their natural history. In this study we compared immune gene expression profiles in HSIL lesions by HIV status and identified genes associated with post-ablation recurrence. Methods: From the Mount Sinai anal cancer screening programwe identified 44 persons (24 HIV+ and 20 uninfected persons) with HSIL and 4 with benign anal mucosal tissue as controls. All HSIL lesions were treated with electrocautery ablation and reassessed within 12 months for recurrence or regression. A targeted gene expression assay (Nanostring) was performed on the initial lesions consisting of 730 genes (including both an immuno-oncology panel and HIV and HPV related genes). After normalization we identified differentially expressed genes by HIV status and HSIL treatment outcome. All significance tests (q-values) were corrected for multiple testing. Results: There was no difference in age by HIV status or lesional outcomes after treatment (median age 46 years); the cohort was largely men who have sex with men (93%). HIV+ subjects were virally suppressed in 71% of the cases, with a median CD4 count of 749 per mm3. We identified a single gene (CCL27) that was expressed significantly more in HIV-infected than in uninfected patients (Fold change=38.6; q=1.1E-4). CCL27 is a cutaneous cytokine associated with the attraction of T-cells to squamous epithelium during inflammatory responses. In contrast, we found 27 genes (Table 1) with significant differential expression between cured and recurrent lesions. Genes associated with recurrence were involved with T cell proliferation, localization and antigen presentation. Conclusion: We found a significant overlap in the genes involved in host immune response, with only one gene with differential expression in HSIL lesions by HIV status. In contrast, 27 genes were associated with recurrent lesions. These findings may be useful for risk stratification of lesions. Further studies will expand on these findings by localizing the tissue compartments and cells expressing these gene products.

Poster Abstracts

282 HPV GENOTYPING IN 1,088 ANAL HSIL CASES: EXPECTED AND UNEXPECTED RESULTS Michael Gaisa , Keith M. Sigel, Yuxin Liu Icahn School of Medicine at Mt Sinai, New York, NY, USA

Background: High-grade squamous intraepithelial lesions (HSIL), the anal cancer precursors, are caused by high-risk human papillomavirus (hrHPV). HrHPV-negative HSILs occur occasionally in clinical practice and constitute an unexpected departure from that rule leading to diagnostic and therapeutic challenges. Using 1,088 simultaneously collected anal swab and histologic HSIL specimens, we aimed to determine the distribution of hrHPV types associated with anal HSIL and to further evaluate hrHPV-negative cases using tissue HPV genotyping. Methods: Anal swab and high-resolution anoscopy-guided biopsy were performed contemporaneously. Anal swabs were used for cytological diagnosis as well as Cobas® HPV DNA testing for HPV16, 18, and 12 other hrHPV types (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68). Cobas®-negative HSIL biopsy specimens were tested for HPV DNA using real-time PCR. Results: 1,088 anal swabs were collected from 742 patients (median age 46 years, range 20-76) with biopsy-proven HSIL. Most subjects were HIV-infected (94%), 91%were men who have sex with men and 9%women. Cytological diagnoses were unsatisfactory (5%), benign (12%), ASCUS (36%), LSIL (34%), ASC-H (5%), and HSIL (8%). Cobas® HPV cotesting revealed that 4% of swabs were negative for hrHPV, 55% positive for HPV16/18, and 41% positive for other hrHPV types. HPV16/18-positivity correlated with a higher degree of cytological abnormalities (p<0.001). Significantly more HPV16/18-positive subjects had ≥3 concurrent HSILs compared with subjects who either tested positive for non-16/18 or negative for hrHPV types (p<0.001). There was no significant difference regarding age, gender, smoking history, HIV status, CD4+ T cell count, and HIV-1 viral load between hrHPV groups. Among Cobas®-negative HSIL cases, PCR detected hrHPV types in 65% of biopsy specimens, half of which were not included in the Cobas® HPV assay (HPV53, 67, 69, 73, and 82). Conclusion: We assessed the performance of cytological and hrHPV cotesting in anal swab samples from a large cohort of patients with biopsy-proven anal HSIL. HPV16/18-positivity was associated with a greater number of concurrent HSILs presumably explaining the improved performance of anal cytology in these patients. HPV-negative HSILs were primarily caused by rare hrHPV types not included in routine screens; these outliers must be interpreted with caution and warrant further investigation.

CROI 2019 102

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