Major Human Leukocyte Antigen Expression in Respiratory Papillomatosis Clinical Specimens

Prior studies have reported low or absent major HLA class I expression on respiratory papilloma cells, conflicting with the recent clinical success of immunotherapy designed to activate HPV-specific T cells in patients with recurrent respiratory papillomatosis (RRP). We aimed to determine major human leukocyte antigen (HLA) class I expression on respiratory papilloma cells in untreated RRP clinical specimens using contemporary techniques.

Formalin-fixed, paraffin-embedded RRP sections were subjected to signal-amplified multispectral immunofluorescence using the OPAL system to determine major and minor HLA class I expression, and digitally scanned slides were analyzed using digital pathology software. Positive and negative controls were used to optimize primary antibody conditions.

All samples harbored major HLA class I expression on varying proportions of papilloma cells. Considering all samples, major HLA class I expression was observed on the majority (74%) of papilloma cells. Nearly all (98%) papilloma infiltrating immune cells were positive for major HLA class I expression, serving as an internal control for each stained sample. Major HLA class I negative papilloma cells were enriched in the apical, suprabasal layers compared to the basal layers of the papillomatous epithelium, suggesting an association with the epithelial cell differentiation state. Fewer papilloma cells inconsistently expressed the minor HLA class I HLA-E across the basal and suprabasal epithelial layers.

Papilloma cells express major HLA class I molecules. Using contemporary immunofluorescent techniques with signal amplification that likely provide improved sensitivity, these results clarify the major HLA class I expression status on papilloma cells in clinical specimens.

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