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Immunological tolerance of low-risk HPV in recurrent respiratory papillomatosis.

  • Ivancic, R1
  • Iqbal, H2
  • deSilva, B2
  • Pan, Q3
  • Matrka, L2
  • 1 College of Medicine, The Ohio State University, OH, USA.
  • 2 Department of Otolaryngology-Head and Neck Surgery, The Ohio State University Wexner Medical Center, Columbus, OH.
  • 3 Case Comprehensive Cancer Center, Cleveland, OH.
Published Article
Clinical & Experimental Immunology
Wiley (Blackwell Publishing)
Publication Date
Oct 19, 2019
DOI: 10.1111/cei.13387
PMID: 31628850


Recurrent respiratory papillomatosis (RRP) is characterized by benign exophytic lesions of the respiratory tract caused by the human papillomavirus (HPV), in particular low-risk HPV6 and HPV11. Aggressiveness varies greatly among patients. Surgical excision is the current standard of care for RRP, with adjuvant therapy used when surgery cannot control disease recurrence. Numerous adjuvant therapies have been used to control RRP with some success, but none are curative. Current literature supports a polarization of the adaptive immune response to a T helper type 2 (Th2)-like or T regulatory phenotype, driven by a complex interplay between innate immunity, adaptive immunity and HPV6/11 proteins. Additionally, certain immunogenetic polymorphisms can predispose individuals to an HPV6/11-tolerant microenvironment. As a result, immunomodulatory efforts are being made to restore the host immune system to a more balanced T cell phenotype and clear viral infection. Literature has shown exciting evidence for the role of HPV vaccination with Gardasil or Gardasil-9 as both primary prevention, by decreasing incidence through childhood vaccinations, and secondary prevention, by treating active RRP disease. Multi-institution randomized clinical trials are needed to better assess their efficacy as treatment for active disease. Interestingly, a DNA vaccine has recently shown in-vitro success in generating a more robust CD8+ T cell response. Furthermore, clinical trials for programmed death 1 (PD-1) inhibitors are under investigation for RRP management. Molecular insights into RRP, in particular the interplay between RRP and the immune system, are needed to advance our understanding of this disease and may lead to the identification of immunomodulatory agents to better manage RRP. © 2019 British Society for Immunology.

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