Laryngeal Papillomatosis

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Laryngeal Papillomatosis

• Recurrent respiratory papillomatosis (RRP) is a
  disease of viral origin associated with exophytic
  lesions of the airway.

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Laryngeal Papillomatosis
The HPV is a small DNA-containing Nonenveloped
icosahedral (20-sided) capsid virus
100 different HPV types
Typically HPV types 6 and 11
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Epidemiology

• Childhood (lt12) or Adulthood (20-40).
• About 4 per 100.000 children
• About 2 per 100.000 adults
• HPV 6 and 11 most common in cervical condylomata.

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Epidemiology

• Childhood
• firstborn
• teenage mother (10-25 HPV cervical swabs)
• vaginal delivery
• ?Others factors
• Insufficient evidence to support CS
• Adult - ?oral-genital route

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Histology

• Finger-like projections of nonkeratinized
  stratified squamous epithelium with core of
  highly vascularized connective tissue stroma.
• Ciliated and squamous epithelium junctions

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Clinical

• Dysphonia
• Airway obstruction
• Examination
• Voice
• Flexible laryngoscopy
• Staging?

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Management aims

• Reduce tumor burden
• Decrease the spread of disease
• Create safe and patent airway
• Improve voice quality
• Prolong interval between surgery

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Surgery

• Debulking
• Cold steel
• Laser (CO2, KTP, Argon)
• Microdebrider
• shorter operating time
• less pain
• less expense
• ?less scarring than CO2 laser.

Ant. Commissure
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Prognosis

• HPV11 worse than HPV6
• Children
• Mean 20 procedures over lifetime (4 p.a.)
• Younger (lt4yr) worse disease
• Remission at adolescence
• Adults
• 50 require gt5 procedures
• 30 remission after age 40yr
• Latent disease
• ?smoking ?reflux

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Tracheostomy

• 14 children, 4 adults
• Severe disease
• Distal spread (lungs)
• Cause or effect?
• Avoid if at all possible
• If unavoidable attempt early decannulation

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Progression

• Extralaryngeal spread
• 13 to 30 of children
• 16 of adults
• Oral cavity, trachea, and bronchi
• 12 of children distal tracheal spread
• 7 pulmonary dissemination
• Common thread use of jet ventilation

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Adjuvant therapy

• 20 patients
• gt4 surgical procedures per year
• Extensive disease
• Distal spread of disease
• Rapid regrowth with airway compromise.

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Cidofovir

• (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)
  cytosine
• Van Cutsem in 1995
• Severe disease only
• 5.0 mg/mL intralesional (1-2ml, monthly for 6
  months)
• Improve airway
• Reduce frequency of surgery
• Animal studies
• nephrotoxicity and carcinogenesis

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a-Interferon

• Blocks viral replication of RNA and DNA cell
  less susceptible to viral penetration
• Haglund in 1981
• Subcutaneous injection (repeated)
• Side effects
• fever, nausea, vomiting, malaise, renal and
  hepatic dysfunction, growth retardation and
  spastic diplegia

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Indole-3-carbinol

• Inhibits growth via effect on oestrogen
  metabolism (oestrogen increases HPV gene
  expression)
• cruciferous vegetables
• cabbage,broccoli, and cauliflower.
• 200-400 mg/d adults
• 1/3 complete
• 1/3 partial
• 1/3 no response

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Photodynamic therapy

• Sensitiser and Laser (argon)
• Up to 50 reduction
• Late recurrence
• Photosensitivity fro up to 12 weeks after
• Inconclusive

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Others

• Heat shock protein E7 (from BCG mycobacterium)
• Subcutaneous injection-monthly
• Reduced growth rate
• Ribavirin
• Acyclovir
• Cox-2 inhibitors
• Intralesion Mumps vaccine
• Retinoids (?synergise interferon)
• Under investigation

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Future

• Pathophysiology
• Vascular endothelial growth factor
• HPV effect on apoptosis
• Cell mediators (IL-2)
• Genetics
• host genes that govern susceptibility to RRP
• Vaccines for HPV

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Conclusion

• Incurable
• Regular contact with patients
• Minimise adverse effects
• RRP Task Force initiate multicenter studies
• Self help groups
• www.rrpwebsite.org
• www.rrpf.org

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