HPV Strain Predicts Severity of Juvenile-Onset Recurrent Respiratory Papillomatosis with Implications for Disease Screening

Abstract

Juvenile-onset recurrent respiratory papillomatosis (JoRRP) is the most common benign neoplasm of the larynx in children, presenting with significant variation in clinical course and potential for progression to malignancy. Since JoRRP is driven by human papillomavirus (HPV), we evaluated viral factors in a prospective cohort to identify predictive factors of disease severity. Twenty children with JoRRP undergoing routine debridement of papillomas were recruited and followed for ≥1 year. Demographical features, clinical severity scores, and surgeries over time were tabulated. Biopsies were used to establish a tissue bank and primary cell cultures for HPV6 vs. HPV11 genotyping and evaluation of viral gene expression. We found that patients with HPV11+ disease had an earlier age at disease onset, higher frequency of surgeries, increased number of lifetime surgeries, and were more likely to progress to malignancy. However, the amplitude of viral E6/E7 gene expression did not account for increased disease severity in HPV11+ patients. Determination of HPV strain is not routinely performed in the standard of care for JoRRP patients; we demonstrate the utility and feasibility of HPV genotyping using RNA-ISH for screening of HPV11+ disease as a biomarker for disease severity and progression in JoRRP patients.

A Novel In Vivo Model of Laryngeal Papillomavirus-Associated Disease Using Mus musculus Papillomavirus

“…Models of low-risk HPV-associated diseases, including RRP, are limited [ 41 ]. Current preclinical models of RRP are limited to in vitro organotypic raft culture and xenografts, which are typically used at early passages to study short-term viral and host gene expression [ 42 , 43 , 44 , 45 ]. In the sole reported experimental infection of an animal larynx with an animal papillomavirus, canine oral papillomavirus (COPV) was injected into the supraglottic laryngeal tissues of canines [ 46 ].…”

Association between human papillomavirus particle production and the severity of recurrent respiratory papillomatosis

“…This study also focused on HPV involvement. The HPV frequency is reportedly more than 80% based on recent papers on RRP [4][5][6] , but a few reports demonstrated an HPV involvement of approximately 60% 1,2 . Reports also exist where clinical diagnosis has been made without examining whether or not HPV is involved [7][8][9] .…”

Single cell transcriptomic analysis of HPV16-infected epithelium identifies a keratinocyte subpopulation implicated in cancer

“…mRNA expression was detected using the RNAscope® 2.0 Assay (Advanced Cell Diagnostics, Inc., Hayward, CA, USA) 72 . Selected probes for human tissue are detailed in Supplementary Data 1 .…”