Abstract Body

Background: We investigated anal inflammation, systemic T cell phenotype activation, and HPV-specific immunity in HIV HPV coinfected patients (pts) with and without HPV driven dysplasia and the association with HPV disease progression or clearance at anal site. Methodology: We enrolled HIV+ men who underwent anorectal swabs for HPV-PCR detection/genotyping (High Risk HR) and cytologic abnormalities (Bethesda 2001: Low and High Grade Squamous Intraepithelial Lesions, L-HSIL). A subgroup was re-examined at a 18 months follow-up (FU) visit. The following parameters were measured at baseline (BL) and associated with anorectal cytology at FU: TNFα/IFNγ mRNA at anal site by RT-PCR; CD4/CD8 T cell activation (CD25, CD25/HLADRII, CD45R0, CD38/CD45R0), maturation (CCR7/CD45RA) and cytokine production (IL2, IFNγ, TNFα, granzyme, perforine) following HPV (type 16) specific stimulation were measured by flow cytometry on PBMCs. Mann-Whitney and χ-square test were used. Results: 40 pts were studied. 27 pts had SIL (26 LSIL) at BL while 13 had normal cytology. No differences were found in immune parameters between the two groups (Fig). 29/40 pts underwent a FU visit. 21/29 were diagnosed HR HPV and LSIL at BL. At FU, 13/21 displayed persistence of LSIL (nonregressors, nR), 6/21 normalised cytology (regressors, R), 2/21 had inadequate results. At BL, R pts displayed higher naive CCR7+CD45RA+CD4+ T cells (6.45% IQR 1.9-7.6 vs 1.8% IQR 0.4-3.4, p=.05) and significantly higher activated CD45R0+CD8+(19.45% IQR 8.1-22.2 vs 7.2% IQR 3.7-15.7, p=.02) and CD38+CD45R0+CD8+ (10.8% IQR 7.6-17.6 vs 3.9% IQR 2.05-12.5, p=.03) compared to nRs. Interestingly, nRs were characterized by a significant increase in CD4/CD8 single-positive (CD4+IL2+, CD4+IFNγ+, CD8+TNFα+, CD8+IFNγ+), and double-positive (CD4+IL2+IFNγ+, CD8+TNFα+IFNγ+) cells upon HPV-specific stimulus (Fig), whereas no effect of HPV stimulation was displayed by R pts. At mucosal level, R pts tended to show higher anal TNFα (2.92% IQR 0.8-6.6 vs 0.53% IQR 0.19-2.8, p=.03) and IFNγ transcripts (2.81% IQR 1.2-9.1 vs 0.57% IQR 0.2-1.8, p=.08) compared to nR pts. Conclusions: In HIV/HPV pts, clinical regression of HPV-related anal SIL seems to correlate with heightened local inflammation, systemic T cell activation and expansion of naive lymphonode homing CCR7+ cells. These findings suggest efficacious immunity at the site of injury, that is not seen in patients with persistent dysplasia despite ex vivo reactivity to an HPV specific trigger.