P10.10 T-cells in the anal mucosa of men with high-grade squamous intraepithelial lesions

Abstract

Introduction: Anal mucosal cellular immune responses and their role in controlling human papilloma virus (HPV)-induced precancerous lesions have not been previously studied. Methods: The Study of the Prevention of Anal Cancer (SPANC) is a longitudinal natural history study of anal HPV infection in men ≥35 years who have sex with men. 26 participants with anal high-grade squamous intraepithelial lesions (HSIL) had 44 anal biopsies. Lymphoid aggregates were detected by inspection of haematoxylin & eosin-stained sections. Additional sections were immunofluorescently stained to enumerate stromal and intra-epithelial CD4+ and CD8+ T-cell counts. Whole slide imaging of full tissue architecture (x600) was used. Student's t-test of log10-transformed T-cell density was used to compare means; a generalized, linear model was used to determine factors associated with total T-cell density (biopsy-based analysis with intra-subject adjustment). Results: Of 26 men (mean age 53 years, SD 10.5), 7 (27%) were HIV-infected. Seventeen (68%) had concurrent anal HPV16 detected. Of 44 biopsies, 26 (59%) revealed HSIL. Twenty-four (55%) had lymphoid aggregates localised in the stroma adjacent to the epithelium. Lymphoid aggregate presence was associated with higher CD4+ T-cell density (mean 192 vs. 69 cells/mm2, P< 0.001), but not higher CD8+ T-cell density (106 vs. 62 cells/mm2, P=0.077). A biopsy with HSIL was significantly associated with higher total T-cell density (OR 11.80, 95%CI 1.51 - 92.08, P=0.02), as was having anal HPV16 detected (OR 14.08, 95%CI 1.15 - 172.71, P=0.04). Conclusion: CD4+ T-cell enriched lymphoid aggregates in the anal mucosa were associated with anal HSIL and HPV16.