Latent human papillomavirus infection is comparable in the larynx and trachea

Abstract

Recurrent respiratory papillomas are benign airway tumors caused by Human Papillomaviruses (HPVs) types 6 and 11. The disease is characterized by multiple recurrences of papillomas following surgical removal, caused by activation of latent HPV DNA. Most patients have laryngeal disease, while only a small subset has tracheal involvement. We have asked whether the lower frequency of tracheal papillomas was due to reduced prevalence of latent/subclinical tracheal HPV infection or reduced likelihood of activation to clinically apparent disease. A total of 121 biopsies of clinically normal laryngeal and tracheal tissues from 61 patients with laryngeal papillomas were analyzed for HPV DNA by polymerase chain reaction, confirmed by Southern blot hybridization. Patients were followed for 3-18 years (mean = 5.5 +/- 4.4), with only one developing subsequent tracheal disease. There was no significant difference in prevalence of latent HPV DNA between larynx and trachea, analyzing either those patients with a single biopsy or those with more than one biopsy of larynx, trachea, or both. There was also no significant difference between tracheal latency with HPV 6 and HPV 11. We conclude that HPV infects tracheal mucosa and is maintained as a latent infection in the trachea as efficiently as in the larynx. Therefore, we propose that the low frequency of tracheal disease reflects a lower frequency of HPV activation, and postulate that cellular factors that differ between the stratified squamous epithelium of the larynx and the ciliated pseudo-stratified columnar epithelium of the trachea contribute to this difference.

Management of Adult Recurrent Respiratory Papillomatosis with Oral Acyclovir Following Micro Laryngeal Surgery: A Case Series

“…It has been reported that low-risk (i.e., low malignant potential) HPV types 6 and 11 cause about 90% of cases of recurrent respiratory papillomatosis [1,4]. Their existence as latent infections in morphologically normal tissue of the airway and are believed to be the source of recurrent disease [10,11]. The association between the virus and the characteristic lesions of this disease was proven with electron microscopic studies and DNA analysis.…”

A Case of Multiple Squamous Cell Papillomas of the Trachea

“…This report proposed that the low frequency of tracheal disease reflects a lower frequency of activation. 5) Risk factors leading to virus activation in RRP have not been recognized; however, gastroesophageal reflux disease has been suggested as a possible factor. 10) Malignant degeneration into squamous cell carcinoma occurs in 3% to 5% of papilloma patients and more often in patients with a history of smoking or radiation therapy.…”

Constitutive Overexpression of the Oncogene Racl in the Airway of Recurrent Respiratory Papillomatosis Patients Is a Targetable Host-Susceptibility Factor

“…Hypothesizing that HPV infection activates the EGFR→Rac1→p38→COX-2 pathway, we compared primary biopsies from laryngeal papillomas, which have active HPV infection, to clinically normal biopsies from the same patient, which have either latent or no HPV infection (15). Western blot analysis of the EGFR confirmed increased expression is limited to papillomas of RRP patients ( Figure 1A).…”