title: Risk Factors for Dysplasia in Recurrent Respiratory Papillomatosis in an Adult and Pediatric Population.
abstract: OBJECTIVE
  Recurrent respiratory papillomatosis (RRP) is classically described as a benign neoplasm of the larynx caused by the low-risk human papillomavirus (HPV) viral subtypes. Nevertheless, transformation to dysplasia and invasive carcinoma can occur. We aimed to assess the prevalence of dysplasia and carcinoma-ex-papilloma in both adult-onset and juvenile-onset RRP and identify patient risk factors for this dysplastic transformation.
  
  
  METHODS
  Ten-year retrospective chart review of a tertiary otolaryngology referral center. Patients with papilloma were identified from a review of a pathology database and clinical records. Patient demographics, pathologic data, and treatment history, including use of cidofovir as an adjunctive therapy for papilloma, were extracted from electronic medical records.
  
  
  RESULTS
  One hundred fifty-nine RRP patients were identified, 96 adult-onset (AORRP) and 63 juvenile-onset (JORRP) cases. Of this cohort, 139 (87%) had only benign papilloma as a pathologic diagnosis. In the AORRP cohort, 10 patients (10%) were diagnosed with dysplasia or carcinoma in situ in addition to papilloma, and 5 patients (5%) had malignant transformation to invasive carcinoma-ex-papilloma. There was a significantly higher age of disease onset for those with dysplasia or carcinoma versus those without dysplasia or carcinoma (56 vs 45 years old; P = .0005). Of the 63 JORRP patients, there were no cases of dysplasia but 3 (5%) cases of invasive carcinoma-ex-papilloma, all involving pulmonary disease. The JORRP patients with carcinoma-ex-papilloma had a younger average disease onset (2 vs 6 years old; P = .009) and a higher rate of tracheal involvement than those without carcinoma. Gender, smoking history, number of operations, or use of cidofovir showed no association with the development of dysplasia or carcinoma-ex-papillomatosis in either the AORRP or JORRP population.
  
  
  CONCLUSIONS
  In a large series of RRP, age of disease onset is the strongest predictor of dysplastic transformation in the adult and pediatric population. Carcinoma-ex-papillomatosis was uniformly associated with pulmonary disease in the JORRP population in this series. No other demographic or behavioral factors, including adjunctive therapy with cidofovir, were statistically associated with dysplasia or carcinoma-ex-papilloma.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland, USA Department of Otolaryngology, Ufuk University, Ankara.
authors.forename: Selmin
authors.initials: S
authors.lastname: Karatayli-Ozgursoy
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland, USA Departments of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
authors.forename: Justin Avery
authors.initials: JA
authors.lastname: Bishop
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Hillel
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
authors.forename: Lee
authors.initials: L
authors.lastname: Akst
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland, USA selminkrt@hotmail.com.
authors.forename: Simon R A
authors.initials: SR
authors.lastname: Best
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000627:therapeutic use; D002277:Carcinoma / Q000473:pathology*; D002471:Cell Transformation, Neoplastic; D002648:Child; D002675:Child, Preschool; D000077404:Cidofovir; D003596:Cytosine / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use; D030361:Papillomavirus Infections / Q000188:drug therapy / Q000473:pathology*; D012141:Respiratory Tract Infections / Q000188:drug therapy / Q000473:pathology*; D012142:Respiratory Tract Neoplasms / Q000473:pathology*; D012189:Retrospective Studies; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; D003596:Cytosine; D000077404:Cidofovir
keywords: HPV; carcinoma ex-papilloma; dysplasia; laryngeal papillomatosis; larynx; low-risk HPV; papilloma; recurrent respiratory papillomatosis