Intralesional immunological tolerance and immune checkpoint expression in HPV mediated recurrent respiratory papillomatosis

Recurrent respiratory papillomatosis (RRP) is a rare neoplastic disorder of the upper airway caused by HPV types 6 and 11. While latent HPV infection of the upper airway is detectable in 1-5% of healthy individuals, the incidence of RRP is less than 0,005%. A shift of the T-cell repertoire towards TH2-/ Treg cells and decreased antiviral IFN-γ producing Th1 and cytotoxic CD8 T cells is related to HPV tolerance. Immune checkpoint (ICB) therapies directed against programmed cell death protein 1 (PD-1) and cytotoxic lymphocyte antigen 4 (CTLA-4) are indispensable treatment options in cancer therapy due to their efficacy and low toxicity. PD-1 and PD-L1 overexpression was observed in RRP tissue while no data regarding CTLA-4 expression is yet available. In a cohort of 7 cases of juvenile and 42 cases of adult onset RRP treated at our department, three patients (6,25%) were affected by extra laryngeal manifestation and in over 20% of cases histopathological analysis revealed at least low-grade dysplasia. While the median number of surgeries in the adult-onset group was three, juvenile onset RRP cases underwent a median number of 10 procedures highlighting the need for further investigation of alternative therapies including ICBs.

Publication History

Article published online:
12 May 2023