title: E6 and E7 oncogene expression by human papilloma virus (HPV) and the aggressive behavior of recurrent laryngeal papillomatosis (RLP).
abstract: Recurrent laryngeal papillomatosis (RLP), a chronic disease associated with human papilloma virus (HPV), requires serial surgical procedures for debulking, resulting in debilitating long-term dysphonia, laryngeal scarring, and rarely malignant degeneration. Human papilloma virus 11 tumors have been widely accepted as more aggressive than HPV 6 tumors; however, the clinical course has been difficult to predict at disease onset, and the biologic mediators of proliferation have not been well characterized. A retrospective case review of 43 patients (4 months to 10 years at diagnosis) was performed on children treated for recurrent laryngeal papillomatosis. Patient charts were reviewed for demographic information, age at RLP diagnosis, approximate frequency of surgical intervention, and absolute number of surgical procedures performed. Human papilloma virus subtyping was performed. Expression analysis of the HPV-encoded E6 and E7 oncogenes was performed by reverse-transcriptase polymerase chain reaction. Fourteen patients had subtype 11 (33%) and 29 patients had subtype 6 (67%). As expected, HPV 11 patients showed a more aggressive clinical course than HPV 6 patients. However, 38% of patients with subtype 6 (11 patients) followed a clinical course that mirrored the more severe subtype 11 patients. These patients expressed the disease at a younger age (P < 0.0002) and showed higher levels of E6 and E7 oncogenes compared to the patients with the more indolent course. Although HPV subtype and early onset of RLP are well characterized prognostic factors, our study documents the significance of E6 and E7 oncogene expression as potential biologic mediators of proliferation and thereby clinical behavior.
authors.affiliation: Department of Pathology, Children's Healthcare of Atlanta, 1405 Clifton Rd, Atlanta, GA 30322, USA.
authors.forename: Bahig M
authors.initials: BM
authors.lastname: Shehata
authors.forename: Kristen J
authors.initials: KJ
authors.lastname: Otto
authors.forename: Steven E
authors.initials: SE
authors.lastname: Sobol
authors.forename: Christina A
authors.initials: CA
authors.lastname: Stockwell
authors.forename: Cora
authors.initials: C
authors.lastname: Foulks
authors.forename: Wayne
authors.initials: W
authors.lastname: Lancaster
authors.forename: Lucie
authors.initials: L
authors.lastname: Gregoire
authors.forename: Charles E
authors.initials: CE
authors.lastname: Hill
mesh_terms: D052685:Alphapapillomavirus / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D015967:Gene Expression Regulation, Viral; D006801:Humans; D007223:Infant; D007822:Laryngeal Neoplasms / Q000473:pathology / Q000601:surgery / Q000821:virology*; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000821:virology; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D010212:Papilloma / Q000473:pathology / Q000601:surgery / Q000821:virology*; D050725:Papillomavirus E7 Proteins / Q000235:genetics*; D030361:Papillomavirus Infections / Q000821:virology*; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D004279:DNA, Viral; C469553:E6 protein, Human papillomavirus type 11; C118860:E6 protein, Human papillomavirus type 6; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins