Epstein-Barr virus may contribute to the pathogenesis of adult-onset recurrent respiratory papillomatosis: A preliminary study

Clin Otolaryngol. 2021 Mar;46(2):373-379. doi: 10.1111/coa.13681. Epub 2020 Dec 30.

Abstract

Objective: Human papillomavirus (HPV) causes adult-onset recurrent respiratory papillomatosis (AORRP), but AORPP prevalence is much lower than HPV prevalence. Thus, HPV infection is necessary, but not sufficient, to cause AORRP and other factors likely contribute to its pathogenesis. The present study aimed to investigate whether co-infection with herpetic viruses may contribute to the pathogenesis of AORRP.

Design: Prospective case-control study conducted from January 2018 to November 2019.

Settings: Tertiary referral centre.

Participants: Eighteen consecutive patients with AORRP and 18 adults with healthy laryngeal mucosa (control group) undergoing surgery.

Main outcome measures: Cytomegalovirus, Epstein-Barr virus (EBV), herpes simplex viruses 1 and 2, human herpesvirus 6, varicella zoster virus and HPV (including genotyping) were detected in biopsies of papilloma or healthy mucosa using real-time polymerase chain reaction and reverse line blot. Dysplasia and Ki67 levels were determined in papilloma specimens.

Results: EBV was present in 6 (33.3%) AORRP patients and no control patients (P = .019). Presence was not dependent on tobacco exposure (P = .413) or HPV genotype or concentration (P > .999). EBV presence was strongly related to increased cell proliferation (P = .005) and number of previous surgeries (P = .039), but not dysplasia (P > .999). Human herpesvirus 6 was found in 3 (16.7%) AORRP biopsies, with one false positive. No other herpetic virus was found.

Conclusions: Unlike other herpetic viruses, EBV seems to interact with HPV, enhancing cell proliferation and contributing to the pathogenesis and progression of AORRP. Further research is required to elucidate specific interactions and their role in the pathogenesis of AORRP.

Keywords: Epstein-Barr Virus Infections; Larynx Neoplasms; Papillomatosis; Papillomavirus Infections; Respiratory Tract Infections; Risk Factors.

MeSH terms

  • Biopsy
  • Case-Control Studies
  • Female
  • Humans
  • Laryngoscopy
  • Male
  • Middle Aged
  • Papillomavirus Infections / virology*
  • Prospective Studies
  • Recurrence
  • Respiratory Tract Infections / virology*
  • Risk Factors
  • Sensitivity and Specificity

Supplementary concepts

  • Recurrent respiratory papillomatosis