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Published on: March 11, 2014
HPV Strain Predicts Severity of Juvenile-Onset Recurrent Respiratory Papillomatosis with Implications for Disease
Mary C Bedard1, Alessandro de Alarcon2,3, Yann-Fuu Kou2
1Division of Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Insights
Human papillomavirus (HPV) type 11 in juvenile-onset recurrent respiratory papillomatosis (JoRRP) is linked to earlier onset, more surgeries, and higher malignancy risk. HPV genotyping can identify severe JoRRP cases for better management.
Area of Science:
- Pediatric Otolaryngology
- Viral Oncology
- Molecular Epidemiology
Background:
- Juvenile-onset recurrent respiratory papillomatosis (JoRRP) is the most common pediatric laryngeal neoplasm.
- JoRRP pathogenesis is primarily driven by human papillomavirus (HPV).
- Disease course and malignant potential of JoRRP vary significantly among patients.
Purpose of the Study:
- To identify predictive factors of JoRRP disease severity and progression.
- To evaluate the role of HPV genotyping in disease outcome.
- To assess the feasibility of HPV genotyping as a clinical biomarker.
Main Methods:
- Prospective cohort study of 20 children with JoRRP.
- Collection of demographic data, clinical severity scores, and surgical history.
- HPV6 vs. HPV11 genotyping and viral gene expression analysis using RNA-ISH on patient biopsies.
Main Results:
- Patients with HPV11+ JoRRP exhibited earlier disease onset and required more frequent and numerous lifetime surgeries.
- HPV11+ JoRRP cases demonstrated a higher likelihood of progressing to malignancy.
- Viral E6/E7 gene expression amplitude did not correlate with increased disease severity in HPV11+ patients.
Conclusions:
- HPV11 genotyping serves as a valuable biomarker for predicting JoRRP severity and malignant progression.
- RNA-ISH is a feasible method for HPV genotyping in JoRRP patients.
- Routine HPV strain determination can enhance the management of JoRRP.
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.
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