Malignant transformation of recurrent respiratory papillomatosis associated with integrated human papillomavirus type 11 DNA and mutation of p53

Peter L. Rady, Vicki J. Schnadig, Raymond L. Weiss, Thomas K. Hughes, Stephen K. Tyring

Research output: Contribution to journalArticle

98 Citations (Scopus)

Abstract

Recurrent respiratory papillomatosis (RRP), usually confined to the nasopharynx, trachea, and larynx, occasionally can progress to extensive bronchopulmonary disease. Most cases of bronchopulmonary and laryngeal papillomatosis are cytologically benign and do not undergo malignant transformation; however, squamous cell carcinoma (SCC) can arise in RRP in the absence of known risk factors such as radiation and smoking. In this study, the authors investigated molecular genetic alterations occurring in a case of metastasizing SCC that arose in long-standing bronchopulmonary papillomatosis. Genomic DNA from tracheal papillomata, tracheobronchial papillomata, SCC of the lung, and a lymph node metastasis was extracted. The physical state of the human papillomavirus type 11 (HPV-11) DNA was investigated by two-dimensional gel electrophoresis. Molecular genetic alterations of the host genome were studied by direct sequencing of polymerase chain reaction-amplified gene fragments and restriction fragment length polymorphism (RFLP) analysis. Episomal and integrated forms of HPV-11 sequences were detected in histologically benign tumors, but only the integrated form of the viral DNA could be found in malignant tissue samples. Molecular genetic studies revealed that an allelic loss of the interferon-β gene (IFNβ-1) and an endogenous type of mutation of the p53 antioncogene were found only in the malignant lesions. Mutations were not observed in the ras, neu, or multiple tumor suppressor (MTS1/p16) genes in any specimens. The authors' data indicated that the p53 genetic mutation was associated with integration of HPV-11 in histologically malignant lesions. This association may promote a progressive genetic instability that can lead to the development and clonal expansion of malignant lesions in RRP.

Original languageEnglish (US)
Pages (from-to)735-740
Number of pages6
JournalLaryngoscope
Volume108
Issue number5
DOIs
StatePublished - May 1998

Fingerprint

Human papillomavirus 11
Papilloma
p16 Genes
Molecular Biology
Squamous Cell Carcinoma
Mutation
DNA
Nasopharynx
Loss of Heterozygosity
Viral DNA
Electrophoresis, Gel, Two-Dimensional
Larynx
Trachea
Tumor Suppressor Genes
Restriction Fragment Length Polymorphisms
Interferons
Genes
Neoplasms
Lymph Nodes
Smoking

ASJC Scopus subject areas

  • Otorhinolaryngology

Cite this

Malignant transformation of recurrent respiratory papillomatosis associated with integrated human papillomavirus type 11 DNA and mutation of p53. / Rady, Peter L.; Schnadig, Vicki J.; Weiss, Raymond L.; Hughes, Thomas K.; Tyring, Stephen K.

In: Laryngoscope, Vol. 108, No. 5, 05.1998, p. 735-740.

Research output: Contribution to journalArticle

Rady, Peter L. ; Schnadig, Vicki J. ; Weiss, Raymond L. ; Hughes, Thomas K. ; Tyring, Stephen K. / Malignant transformation of recurrent respiratory papillomatosis associated with integrated human papillomavirus type 11 DNA and mutation of p53. In: Laryngoscope. 1998 ; Vol. 108, No. 5. pp. 735-740.
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