Otolaryngeal system (ENT)

Laryngeal papillomatosis (LP)

Over-proliferation of benign squamous papillomas in the aerodigestive tract.

Over-proliferation of benign squamous papillomas in the aerodigestive tract.

  • Also known as recurrent respiratory papillomatosis (RRP)
  • M/C benign mesenchymal neoplasm of larynx in children
  • #2 M/C cause of childhood hoarseness.

The condition has a predilection to respiratory tract transition zones. The true vocal cords transition from pseudostratified epithelium to stratified squamous epithelium. Therefore, they are a common location for papilloma lesions to occur. Nevertheless, LP may be seen in other regions of the respiratory tract.


Human papilloma virus (HPV):

Small deoxyribonucleic acid (DNA) nonenveloped capsid virus of the Papovaviridae family, which has a predilection of infecting epithelial cells.
  • HPV 6 & 11 (also associated with condyloma lata), most related
  • HPV 16 & 18: Less common with low malignant potential

Juvenile-onset LP: Aggressive form

It has a higher chance to cause airway obstruction, spread to more than one site of the aerodigestive tract, recur faster, and lead to more frequent surgical interventions.

Adult-onset LP: Less aggressive

Mode of transmission is speculated to be oral sex.

Clinical features

  • Tachypnea, stridor, use of accessory muscles, speech, cry or change of stridor with position.


  • Malignant transformation to squamous cell carcinoma (1-4% cases and depends mostly on the HPV typing and is more common in adults)



Flexible fiberoptic nasopharyngoscope provides a precise preoperative diagnosis and the ability to rule out some differential diagnoses.
  • Pinkish to white “grape-like” projections that can be sessile/pedunculate with a visible central vascular core. It appears as a clear grape with visible seed.
  • Narrow-band imaging (NBI): Short wavelength blue light absorbed mostly by hemoglobin. Therefore, since laryngeal papilloma has a vascular core, it will be depicted as a soft tissue surrounding blue foci.

Computed tomography (CT) scan:

Due to the benign course of the disease, imaging modalities are normally not required yet CT scan can be useful in differential diagnosis

Tissue biopsy with HPV typing:

Definitive diagnosis of laryngeal papilloma.
  • Multiple proliferations of hyperplastic stratified squamous epithelium with a central fibrovascular core
  • Basal and parabasal cell hyperplasia in a perpendicular orientation with koilocytosis atypia

Differential diagnosis:

Malignant lesions can be easily differentiated with a biopsy of the lesion. Benign lesions, contrary to malignant lesions, are mostly differentiated with a detailed stroboscopic examination.
  • Malignant conditions:
    • Vocal cord leukoplakia
    • Squamous cell carcinoma
    • Verrucous carcinoma
  • Benign conditions:
    • Vocal cord granulomas
    • Vocal cord nodules
    • Polypoid corditis (Reinke edema)


Currently, there is no “cure” for LP. The standard of care consists of surgical removal of the papillomas with preservation of normal mucosa. LP is one of the most difficult benign histologic conditions to treat due to its high tendency to recur and spread to the adjacent respiratory tract.

Surgical management:

  • Suspension microlaryngoscopy with laser removal (gold standard)
    • CO2 laser (10,600 nm)/potassium titanium phosphate (KTP) laser (585-nm pulsed-dye laser) or an argon laser can be used.
  • Other modalities: Microdebriders, cold instruments, and phonomicrosurgery

Endoscopic management:

The operating room has been the standard of care until the emergence of the flexible laryngoscope, which has been improved with high-definition distal chip endoscopes. Nowadays, office-based laser surgery has helped with the control of the disease and decreased the need for general anesthesia.

Adjuvant management:

Criteria for implementing adjuvant therapy consists of more than 4 surgical procedures in 1 year, rapid regrowth of papilloma, airway compromise, and/or distal multisite spread of disease. Many of these adjuvant therapies are mostly off label use and have a wide range of responses to therapy.
  • Chemotherapy: ABC
    • α-interferon: Now replaced due high side-effects and emergence of cidofovir
    • Bevacizumab
    • Cidofovir: Intralesional injection of cidofovir is a prodrug that becomes incorporated into the DNA and leads to toxicity against the virus. RRP task force recommends the use of cidofovir for patients with extra-laryngeal spread or those with more than six surgeries per year
  • Photodynamic therapy
  • Indole-3 carbinol
  • Proton pump inhibitors: Controlling chronic exposure of gastric acid with proton pump inhibitors can help avoid metaplastic changes in the epithelium that could lead to the propagation of the papillomas

Preventive therapy:

  • Human papillomavirus 9-valent vaccine

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