Respiratory Papillomatosis (RP) is a rare disease characterized by the growth of benign tumors, or papillomas, in the respiratory tract, most commonly in the larynx. These growths are caused by infection with human papillomavirus (HPV), particularly HPV types 6 and 11. RP can occur at any age and is classified into juvenile-onset and adult-onset forms, with juvenile cases often presenting more aggressively.
Clinically, RP manifests as hoarseness, voice changes, stridor, and airway obstruction in severe cases. Though benign, papillomas can recur frequently, requiring multiple interventions to maintain airway patency and preserve vocal function. Rarely, malignant transformation may occur, especially with co-infection with high-risk HPV types.
The condition poses significant challenges due to its chronic, recurrent nature, impact on quality of life, and the need for repeated surgical management. Recent advances in microlaryngeal surgery, laser therapy, and adjuvant medical treatments aim to reduce recurrence and improve patient outcomes.
Epidemiology
Before the introduction of the quadrivalent HPV vaccine in 2006, the incidence of recurrent respiratory papillomatosis (RRP) in the United States was estimated at 4 per 100,000 for juvenile-onset RRP (JORRP) and 2 per 100,000 for adult-onset RRP (AORRP). Although the overall incidence of RRP is declining, it remains the most common benign laryngeal tumor in children, accounting for approximately 15,000 surgical procedures annually, with an estimated cost of $100 million.
Internationally, the prevalence of RRP in the United Kingdom was reported as 1.42 per 100,000. In Australia, a nationwide HPV vaccination program began in 2007, initially targeting females aged 12–26 and later expanding to all students aged 12-13 years (girls in 2007, boys in 2013). Following this initiative, HPV prevalence in women aged 18-24 dropped from 22.7% in 2005 to 1.1% in 2015, and the incidence of JORRP declined to 0.022 per 100,000 by 2016.
Anatomy
Pathophysiology
Respiratory Papillomatosis is caused by infection of the respiratory epithelium with human papillomavirus (HPV), primarily types 6 and 11, which are considered low-risk HPV types. The virus infects basal epithelial cells of the respiratory tract, most commonly the larynx, and integrates its DNA into host cells, leading to abnormal epithelial proliferation.
Once infected, HPV expresses viral proteins E6 and E7, which interfere with host tumor suppressor pathways (p53 and Rb). This results in cell cycle dysregulation, allowing infected epithelial cells to proliferate uncontrollably, forming exophytic, wart-like lesions (papillomas). The lesions are typically benign, but their growth can obstruct the airway or impair vocal function.
The disease often follows a chronic and recurrent course, as the virus can evade host immune surveillance. Juvenile-onset RP is usually acquired during birth from maternal genital HPV infection, whereas adult-onset RP is often linked to sexual transmission or latent reactivation.
Additional factors influencing severity and recurrence include viral load, immune response, and anatomical site involvement, with the larynx being most affected. Rarely, malignant transformation can occur, particularly in cases co-infected with high-risk HPV types or after long-standing disease.
Etiology
Recurrent respiratory papillomatosis (RRP) is caused by human papillomavirus (HPV), most commonly HPV types 6 and 11, though HPV-16 and HPV-18 are occasionally detected in affected tissues. HPV is the most prevalent sexually transmitted infection in the United States, with up to 75% of women acquiring genital HPV at some point in their lives. Among mothers of children with juvenile-onset RRP (JORRP), 30–60% have genital HPV, compared with only 5% of mothers of unaffected children. Research using questionnaires from affected children or their parents, conducted via the RRP Foundation, identified three major risk factors for JORRP: being the firstborn, vaginal delivery, and maternal age under 20 years. These risk factors are specific to JORRP and do not appear to influence adult-onset RRP (AORRP), indicating that adult cases likely do not arise from reactivation of latent childhood infection. The exact route of HPV transmission in AORRP remains unclear, although sexual transmission is considered a probable mechanism.
Genetics
Prognostic Factors
Children with recurrent respiratory papillomatosis (RRP) often experience remission after several years, possibly linked to puberty, though many undergo over 20 surgeries. Younger patients with HPV-11 and older adults with HPV-6 have more severe courses, while adult disease is generally milder. Diagnosis is often delayed by about a year due to the need for direct laryngoscopy. Juvenile-onset RRP (JORRP) typically requires an average of 4.4 surgeries per year, with lifetime procedures exceeding 20, significantly impacting quality of life and school attendance. Tracheostomy is needed in 10–15% of children, usually under age 2, though many can later be decannulated. Adults rarely need tracheostomy, but frequent surgeries are common. Malignant transformation to squamous cell carcinoma occurs in 3–5%, with poor prognosis and rare cure.
Clinical History
Age group
Juvenile-Onset (JORRP): Usually <12 years, often 2–6 years, more aggressive, acquired during vaginal delivery.
Adult-Onset (AORRP): Typically 20-40 years, milder course, likely sexually transmitted.
Physical Examination
Voice Changes: Hoarseness, weak cry, or progressive dysphonia is often the earliest sign.
Respiratory Signs: Stridor, dyspnea, or wheezing may be present, especially in children with airway obstruction.
Inspection (Laryngoscopy/Endoscopy):
Multiple exophytic, wart-like lesions (papillomas) on the larynx, particularly the true vocal cords.
Lesions may extend to the trachea, bronchi, or rarely the lungs.
Airway Assessment: Evaluate for airway compromise, especially in juvenile-onset cases.
General Exam: Usually unremarkable unless chronic hypoxia or secondary infections develop.
Age group
Associated comorbidity
Associated activity
Acuity of presentation
Juvenile-Onset RP (JORRP):
Usually gradual onset of symptoms.
Commonly presents with hoarseness, weak cry, or progressive stridor.
Can become acute if papillomas cause airway obstruction.
Adult-Onset RP (AORRP):
Typically has a slower, insidious onset.
Presents mainly with voice changes; airway compromise is rare.
Differential Diagnoses
Vocal Cord Nodules or Polyps
Laryngeal Cysts
Laryngeal Granulomas
Laryngeal Malignancy
Subglottic Stenosis
Croup or Laryngotracheobronchitis
Vocal Fold Hemorrhage
Fungal or Bacterial Laryngeal Infections
Laboratory Studies
Imaging Studies
Procedures
Histologic Findings
Staging
Treatment Paradigm
Surgical Management (Mainstay):
Microlaryngoscopic surgery is the primary approach to remove papillomas while preserving vocal function.
Techniques include cold instruments, microdebriders, or COâ‚‚ laser excision.
Surgery is often repeated due to high recurrence, especially in juvenile-onset cases.
Adjuvant Medical Therapy (for recurrent or aggressive disease):
Cidofovir (intralesional antiviral injections)
Bevacizumab (anti-VEGF therapy)
Interferon-alpha (less commonly used)
Airway Management:
Urgent intervention if papillomas cause significant airway obstruction.
Tracheostomy may be required in severe or refractory cases, though avoided if possible.
Preventive Measures:
HPV vaccination (quadrivalent or nonavalent) reduces incidence of juvenile-onset RP.
Management is primarily surgical, with adjuvant therapies reserved for rapidly recurrent, extensive, or high-risk cases.
Reduce exposure to tobacco smoke, dust, and chemical fumes, which can irritate the airway and worsen symptoms.
Good Air Quality:
Ensure well-ventilated living spaces and consider air purifiers in areas with high pollution or allergens.
Voice Hygiene:
Minimize vocal strain and practice proper voice techniques, especially in children with JORRP.
Infection Control:
Limit exposure to respiratory infections, which can aggravate papilloma growth.
Vaccination:
HPV vaccination reduces the risk of new lesions and disease progression, particularly in children and young adults.
Role of Dietary supplements in treating respiratory papillomatosis
Indole-3-Carbinol (I3-C)
Indole-3-carbinol (I3-C) and its derivative diindolylmethane (Indolplex) are naturally occurring compounds in cruciferous vegetables. I3-C influences estradiol metabolism, promoting the formation of 2-hydroxylated metabolites, which may contribute to slowing papilloma growth. Anecdotal evidence suggests that consuming cabbage juice or a diet high in vegetables such as cabbage, cauliflower, broccoli, and Brussels sprouts may be beneficial. Clinical studies report that about one-third of patients achieve complete remission, while another one-third show partial improvement with I3-C supplementation.
Effectiveness of Antiviral agents in treating respiratory papillomatosis
Cidofovir
Cidofovir is an antiviral agent currently approved for the treatment of CMV retinitis in patients with AIDS. It is the first drug in the class of acyclic phosphonate nucleotide analogs. Within infected cells, cidofovir and similar nucleotide analogs inhibit viral DNA polymerase, which is essential for replication of viral DNA and RNA. Since HPV is the causative agent of RRP, targeting the virus provides a potential therapeutic approach.
Treatment of RRP usually involves multiple surgical procedures due to the recurrent nature of the disease. Microdebridement of laryngeal lesions is now often preferred over traditional laser therapy. During anesthesia induction, special attention must be given to maintaining the already-compromised airway, and the surgical team should be ready to perform an emergency tracheostomy if needed.
A survey of anesthesiologists on preferred techniques for RRP laser procedures reported the following approaches:
Laser-safe endotracheal tube: 46%
Jet ventilation: 26%
Apneic technique: 16%
Spontaneous ventilation: 12%
Surgical treatment is sometimes combined with intralesional medications aimed at reducing recurrence. Cidofovir has largely replaced interferon as it has proven effective in a significant number of patients.
Historically, COâ‚‚ laser was favored for papilloma removal due to its precise cutting, good hemostasis, and minimal thermal damage to surrounding tissue. However, many centers now prefer microdebridement with angled oscillating blades (incorporating suction and irrigation) or pulsed dye laser. These newer techniques offer advantages such as shorter operative times, outpatient feasibility, reduced risk to personnel, lower likelihood of airway burns, and possibly lower recurrence rates. For newly diagnosed RRP, airway evaluation may be required as frequently as every 2-4 weeks.
Photodynamic therapy has shown promise in small trials for slowing papilloma growth. In this approach, hematoporphyrins, which selectively accumulate in neoplastic cells, are used as photosensitizers. Dihematoporphyrin ether (DHE) is usually administered 2-3 days before surgery, and activation is achieved via argon laser delivered through a laryngoscope or bronchoscope.
Because surgical manipulation can aerosolize HPV, staff must use protective eyewear and particulate barrier masks or face shields during procedures to minimize viral exposure.
Administer 5x 10^11 particle units subcutaneously in the form of 4 doses over 12 weeks
For Initial dose (dose 1): on day 1
For dose 2: It should be administered 2 weeks after initial dose
For dose 3: It should be administered 6 weeks after initial dose
For dose 4: It should be administered 12 weeks after initial dose Dosing Considerations
Debulk the visible papilloma surgically to determine minimum remaining illness.
If there is a visible papilloma, remove it before the third and fourth dosages to ensure that there is little disease left over after therapy.
Respiratory Papillomatosis (RP) is a rare disease characterized by the growth of benign tumors, or papillomas, in the respiratory tract, most commonly in the larynx. These growths are caused by infection with human papillomavirus (HPV), particularly HPV types 6 and 11. RP can occur at any age and is classified into juvenile-onset and adult-onset forms, with juvenile cases often presenting more aggressively.
Clinically, RP manifests as hoarseness, voice changes, stridor, and airway obstruction in severe cases. Though benign, papillomas can recur frequently, requiring multiple interventions to maintain airway patency and preserve vocal function. Rarely, malignant transformation may occur, especially with co-infection with high-risk HPV types.
The condition poses significant challenges due to its chronic, recurrent nature, impact on quality of life, and the need for repeated surgical management. Recent advances in microlaryngeal surgery, laser therapy, and adjuvant medical treatments aim to reduce recurrence and improve patient outcomes.
Before the introduction of the quadrivalent HPV vaccine in 2006, the incidence of recurrent respiratory papillomatosis (RRP) in the United States was estimated at 4 per 100,000 for juvenile-onset RRP (JORRP) and 2 per 100,000 for adult-onset RRP (AORRP). Although the overall incidence of RRP is declining, it remains the most common benign laryngeal tumor in children, accounting for approximately 15,000 surgical procedures annually, with an estimated cost of $100 million.
Internationally, the prevalence of RRP in the United Kingdom was reported as 1.42 per 100,000. In Australia, a nationwide HPV vaccination program began in 2007, initially targeting females aged 12–26 and later expanding to all students aged 12-13 years (girls in 2007, boys in 2013). Following this initiative, HPV prevalence in women aged 18-24 dropped from 22.7% in 2005 to 1.1% in 2015, and the incidence of JORRP declined to 0.022 per 100,000 by 2016.
Respiratory Papillomatosis is caused by infection of the respiratory epithelium with human papillomavirus (HPV), primarily types 6 and 11, which are considered low-risk HPV types. The virus infects basal epithelial cells of the respiratory tract, most commonly the larynx, and integrates its DNA into host cells, leading to abnormal epithelial proliferation.
Once infected, HPV expresses viral proteins E6 and E7, which interfere with host tumor suppressor pathways (p53 and Rb). This results in cell cycle dysregulation, allowing infected epithelial cells to proliferate uncontrollably, forming exophytic, wart-like lesions (papillomas). The lesions are typically benign, but their growth can obstruct the airway or impair vocal function.
The disease often follows a chronic and recurrent course, as the virus can evade host immune surveillance. Juvenile-onset RP is usually acquired during birth from maternal genital HPV infection, whereas adult-onset RP is often linked to sexual transmission or latent reactivation.
Additional factors influencing severity and recurrence include viral load, immune response, and anatomical site involvement, with the larynx being most affected. Rarely, malignant transformation can occur, particularly in cases co-infected with high-risk HPV types or after long-standing disease.
Recurrent respiratory papillomatosis (RRP) is caused by human papillomavirus (HPV), most commonly HPV types 6 and 11, though HPV-16 and HPV-18 are occasionally detected in affected tissues. HPV is the most prevalent sexually transmitted infection in the United States, with up to 75% of women acquiring genital HPV at some point in their lives. Among mothers of children with juvenile-onset RRP (JORRP), 30–60% have genital HPV, compared with only 5% of mothers of unaffected children. Research using questionnaires from affected children or their parents, conducted via the RRP Foundation, identified three major risk factors for JORRP: being the firstborn, vaginal delivery, and maternal age under 20 years. These risk factors are specific to JORRP and do not appear to influence adult-onset RRP (AORRP), indicating that adult cases likely do not arise from reactivation of latent childhood infection. The exact route of HPV transmission in AORRP remains unclear, although sexual transmission is considered a probable mechanism.
Children with recurrent respiratory papillomatosis (RRP) often experience remission after several years, possibly linked to puberty, though many undergo over 20 surgeries. Younger patients with HPV-11 and older adults with HPV-6 have more severe courses, while adult disease is generally milder. Diagnosis is often delayed by about a year due to the need for direct laryngoscopy. Juvenile-onset RRP (JORRP) typically requires an average of 4.4 surgeries per year, with lifetime procedures exceeding 20, significantly impacting quality of life and school attendance. Tracheostomy is needed in 10–15% of children, usually under age 2, though many can later be decannulated. Adults rarely need tracheostomy, but frequent surgeries are common. Malignant transformation to squamous cell carcinoma occurs in 3–5%, with poor prognosis and rare cure.
Age group
Juvenile-Onset (JORRP): Usually <12 years, often 2–6 years, more aggressive, acquired during vaginal delivery.
Adult-Onset (AORRP): Typically 20-40 years, milder course, likely sexually transmitted.
Voice Changes: Hoarseness, weak cry, or progressive dysphonia is often the earliest sign.
Respiratory Signs: Stridor, dyspnea, or wheezing may be present, especially in children with airway obstruction.
Inspection (Laryngoscopy/Endoscopy):
Multiple exophytic, wart-like lesions (papillomas) on the larynx, particularly the true vocal cords.
Lesions may extend to the trachea, bronchi, or rarely the lungs.
Airway Assessment: Evaluate for airway compromise, especially in juvenile-onset cases.
General Exam: Usually unremarkable unless chronic hypoxia or secondary infections develop.
Juvenile-Onset RP (JORRP):
Usually gradual onset of symptoms.
Commonly presents with hoarseness, weak cry, or progressive stridor.
Can become acute if papillomas cause airway obstruction.
Adult-Onset RP (AORRP):
Typically has a slower, insidious onset.
Presents mainly with voice changes; airway compromise is rare.
Vocal Cord Nodules or Polyps
Laryngeal Cysts
Laryngeal Granulomas
Laryngeal Malignancy
Subglottic Stenosis
Croup or Laryngotracheobronchitis
Vocal Fold Hemorrhage
Fungal or Bacterial Laryngeal Infections
Surgical Management (Mainstay):
Microlaryngoscopic surgery is the primary approach to remove papillomas while preserving vocal function.
Techniques include cold instruments, microdebriders, or COâ‚‚ laser excision.
Surgery is often repeated due to high recurrence, especially in juvenile-onset cases.
Adjuvant Medical Therapy (for recurrent or aggressive disease):
Cidofovir (intralesional antiviral injections)
Bevacizumab (anti-VEGF therapy)
Interferon-alpha (less commonly used)
Airway Management:
Urgent intervention if papillomas cause significant airway obstruction.
Tracheostomy may be required in severe or refractory cases, though avoided if possible.
Preventive Measures:
HPV vaccination (quadrivalent or nonavalent) reduces incidence of juvenile-onset RP.
Management is primarily surgical, with adjuvant therapies reserved for rapidly recurrent, extensive, or high-risk cases.
Pulmonary Medicine
Avoidance of Respiratory Irritants:
Reduce exposure to tobacco smoke, dust, and chemical fumes, which can irritate the airway and worsen symptoms.
Good Air Quality:
Ensure well-ventilated living spaces and consider air purifiers in areas with high pollution or allergens.
Voice Hygiene:
Minimize vocal strain and practice proper voice techniques, especially in children with JORRP.
Infection Control:
Limit exposure to respiratory infections, which can aggravate papilloma growth.
Vaccination:
HPV vaccination reduces the risk of new lesions and disease progression, particularly in children and young adults.
Pulmonary Medicine
Indole-3-Carbinol (I3-C)
Indole-3-carbinol (I3-C) and its derivative diindolylmethane (Indolplex) are naturally occurring compounds in cruciferous vegetables. I3-C influences estradiol metabolism, promoting the formation of 2-hydroxylated metabolites, which may contribute to slowing papilloma growth. Anecdotal evidence suggests that consuming cabbage juice or a diet high in vegetables such as cabbage, cauliflower, broccoli, and Brussels sprouts may be beneficial. Clinical studies report that about one-third of patients achieve complete remission, while another one-third show partial improvement with I3-C supplementation.
Pulmonary Medicine
Cidofovir
Cidofovir is an antiviral agent currently approved for the treatment of CMV retinitis in patients with AIDS. It is the first drug in the class of acyclic phosphonate nucleotide analogs. Within infected cells, cidofovir and similar nucleotide analogs inhibit viral DNA polymerase, which is essential for replication of viral DNA and RNA. Since HPV is the causative agent of RRP, targeting the virus provides a potential therapeutic approach.
Intervention with procedure
Treatment of RRP usually involves multiple surgical procedures due to the recurrent nature of the disease. Microdebridement of laryngeal lesions is now often preferred over traditional laser therapy. During anesthesia induction, special attention must be given to maintaining the already-compromised airway, and the surgical team should be ready to perform an emergency tracheostomy if needed.
A survey of anesthesiologists on preferred techniques for RRP laser procedures reported the following approaches:
Laser-safe endotracheal tube: 46%
Jet ventilation: 26%
Apneic technique: 16%
Spontaneous ventilation: 12%
Surgical treatment is sometimes combined with intralesional medications aimed at reducing recurrence. Cidofovir has largely replaced interferon as it has proven effective in a significant number of patients.
Historically, COâ‚‚ laser was favored for papilloma removal due to its precise cutting, good hemostasis, and minimal thermal damage to surrounding tissue. However, many centers now prefer microdebridement with angled oscillating blades (incorporating suction and irrigation) or pulsed dye laser. These newer techniques offer advantages such as shorter operative times, outpatient feasibility, reduced risk to personnel, lower likelihood of airway burns, and possibly lower recurrence rates. For newly diagnosed RRP, airway evaluation may be required as frequently as every 2-4 weeks.
Photodynamic therapy has shown promise in small trials for slowing papilloma growth. In this approach, hematoporphyrins, which selectively accumulate in neoplastic cells, are used as photosensitizers. Dihematoporphyrin ether (DHE) is usually administered 2-3 days before surgery, and activation is achieved via argon laser delivered through a laryngoscope or bronchoscope.
Because surgical manipulation can aerosolize HPV, staff must use protective eyewear and particulate barrier masks or face shields during procedures to minimize viral exposure.
Pulmonary Medicine
Phases of management
Initial Assessment and Diagnosis:
History & Physical Examination: Evaluate voice changes, stridor, and airway compromise.
Endoscopic Evaluation: Direct laryngoscopy or bronchoscopy to visualize lesions and assess extent.
Imaging (if needed): CT or MRI for subglottic, tracheal, or pulmonary involvement.
Surgical Management (Primary Treatment):
Techniques:
Microdebridement (preferred in many centers)
COâ‚‚ laser or pulsed dye laser
Frequency: Repeat procedures often required due to recurrence, especially in juvenile-onset cases.
Adjuvant Therapy (for aggressive or recurrent disease):
Respiratory Papillomatosis (RP) is a rare disease characterized by the growth of benign tumors, or papillomas, in the respiratory tract, most commonly in the larynx. These growths are caused by infection with human papillomavirus (HPV), particularly HPV types 6 and 11. RP can occur at any age and is classified into juvenile-onset and adult-onset forms, with juvenile cases often presenting more aggressively.
Clinically, RP manifests as hoarseness, voice changes, stridor, and airway obstruction in severe cases. Though benign, papillomas can recur frequently, requiring multiple interventions to maintain airway patency and preserve vocal function. Rarely, malignant transformation may occur, especially with co-infection with high-risk HPV types.
The condition poses significant challenges due to its chronic, recurrent nature, impact on quality of life, and the need for repeated surgical management. Recent advances in microlaryngeal surgery, laser therapy, and adjuvant medical treatments aim to reduce recurrence and improve patient outcomes.
Before the introduction of the quadrivalent HPV vaccine in 2006, the incidence of recurrent respiratory papillomatosis (RRP) in the United States was estimated at 4 per 100,000 for juvenile-onset RRP (JORRP) and 2 per 100,000 for adult-onset RRP (AORRP). Although the overall incidence of RRP is declining, it remains the most common benign laryngeal tumor in children, accounting for approximately 15,000 surgical procedures annually, with an estimated cost of $100 million.
Internationally, the prevalence of RRP in the United Kingdom was reported as 1.42 per 100,000. In Australia, a nationwide HPV vaccination program began in 2007, initially targeting females aged 12–26 and later expanding to all students aged 12-13 years (girls in 2007, boys in 2013). Following this initiative, HPV prevalence in women aged 18-24 dropped from 22.7% in 2005 to 1.1% in 2015, and the incidence of JORRP declined to 0.022 per 100,000 by 2016.
Respiratory Papillomatosis is caused by infection of the respiratory epithelium with human papillomavirus (HPV), primarily types 6 and 11, which are considered low-risk HPV types. The virus infects basal epithelial cells of the respiratory tract, most commonly the larynx, and integrates its DNA into host cells, leading to abnormal epithelial proliferation.
Once infected, HPV expresses viral proteins E6 and E7, which interfere with host tumor suppressor pathways (p53 and Rb). This results in cell cycle dysregulation, allowing infected epithelial cells to proliferate uncontrollably, forming exophytic, wart-like lesions (papillomas). The lesions are typically benign, but their growth can obstruct the airway or impair vocal function.
The disease often follows a chronic and recurrent course, as the virus can evade host immune surveillance. Juvenile-onset RP is usually acquired during birth from maternal genital HPV infection, whereas adult-onset RP is often linked to sexual transmission or latent reactivation.
Additional factors influencing severity and recurrence include viral load, immune response, and anatomical site involvement, with the larynx being most affected. Rarely, malignant transformation can occur, particularly in cases co-infected with high-risk HPV types or after long-standing disease.
Recurrent respiratory papillomatosis (RRP) is caused by human papillomavirus (HPV), most commonly HPV types 6 and 11, though HPV-16 and HPV-18 are occasionally detected in affected tissues. HPV is the most prevalent sexually transmitted infection in the United States, with up to 75% of women acquiring genital HPV at some point in their lives. Among mothers of children with juvenile-onset RRP (JORRP), 30–60% have genital HPV, compared with only 5% of mothers of unaffected children. Research using questionnaires from affected children or their parents, conducted via the RRP Foundation, identified three major risk factors for JORRP: being the firstborn, vaginal delivery, and maternal age under 20 years. These risk factors are specific to JORRP and do not appear to influence adult-onset RRP (AORRP), indicating that adult cases likely do not arise from reactivation of latent childhood infection. The exact route of HPV transmission in AORRP remains unclear, although sexual transmission is considered a probable mechanism.
Children with recurrent respiratory papillomatosis (RRP) often experience remission after several years, possibly linked to puberty, though many undergo over 20 surgeries. Younger patients with HPV-11 and older adults with HPV-6 have more severe courses, while adult disease is generally milder. Diagnosis is often delayed by about a year due to the need for direct laryngoscopy. Juvenile-onset RRP (JORRP) typically requires an average of 4.4 surgeries per year, with lifetime procedures exceeding 20, significantly impacting quality of life and school attendance. Tracheostomy is needed in 10–15% of children, usually under age 2, though many can later be decannulated. Adults rarely need tracheostomy, but frequent surgeries are common. Malignant transformation to squamous cell carcinoma occurs in 3–5%, with poor prognosis and rare cure.
Age group
Juvenile-Onset (JORRP): Usually <12 years, often 2–6 years, more aggressive, acquired during vaginal delivery.
Adult-Onset (AORRP): Typically 20-40 years, milder course, likely sexually transmitted.
Voice Changes: Hoarseness, weak cry, or progressive dysphonia is often the earliest sign.
Respiratory Signs: Stridor, dyspnea, or wheezing may be present, especially in children with airway obstruction.
Inspection (Laryngoscopy/Endoscopy):
Multiple exophytic, wart-like lesions (papillomas) on the larynx, particularly the true vocal cords.
Lesions may extend to the trachea, bronchi, or rarely the lungs.
Airway Assessment: Evaluate for airway compromise, especially in juvenile-onset cases.
General Exam: Usually unremarkable unless chronic hypoxia or secondary infections develop.
Juvenile-Onset RP (JORRP):
Usually gradual onset of symptoms.
Commonly presents with hoarseness, weak cry, or progressive stridor.
Can become acute if papillomas cause airway obstruction.
Adult-Onset RP (AORRP):
Typically has a slower, insidious onset.
Presents mainly with voice changes; airway compromise is rare.
Vocal Cord Nodules or Polyps
Laryngeal Cysts
Laryngeal Granulomas
Laryngeal Malignancy
Subglottic Stenosis
Croup or Laryngotracheobronchitis
Vocal Fold Hemorrhage
Fungal or Bacterial Laryngeal Infections
Surgical Management (Mainstay):
Microlaryngoscopic surgery is the primary approach to remove papillomas while preserving vocal function.
Techniques include cold instruments, microdebriders, or COâ‚‚ laser excision.
Surgery is often repeated due to high recurrence, especially in juvenile-onset cases.
Adjuvant Medical Therapy (for recurrent or aggressive disease):
Cidofovir (intralesional antiviral injections)
Bevacizumab (anti-VEGF therapy)
Interferon-alpha (less commonly used)
Airway Management:
Urgent intervention if papillomas cause significant airway obstruction.
Tracheostomy may be required in severe or refractory cases, though avoided if possible.
Preventive Measures:
HPV vaccination (quadrivalent or nonavalent) reduces incidence of juvenile-onset RP.
Management is primarily surgical, with adjuvant therapies reserved for rapidly recurrent, extensive, or high-risk cases.
Pulmonary Medicine
Avoidance of Respiratory Irritants:
Reduce exposure to tobacco smoke, dust, and chemical fumes, which can irritate the airway and worsen symptoms.
Good Air Quality:
Ensure well-ventilated living spaces and consider air purifiers in areas with high pollution or allergens.
Voice Hygiene:
Minimize vocal strain and practice proper voice techniques, especially in children with JORRP.
Infection Control:
Limit exposure to respiratory infections, which can aggravate papilloma growth.
Vaccination:
HPV vaccination reduces the risk of new lesions and disease progression, particularly in children and young adults.
Pulmonary Medicine
Indole-3-Carbinol (I3-C)
Indole-3-carbinol (I3-C) and its derivative diindolylmethane (Indolplex) are naturally occurring compounds in cruciferous vegetables. I3-C influences estradiol metabolism, promoting the formation of 2-hydroxylated metabolites, which may contribute to slowing papilloma growth. Anecdotal evidence suggests that consuming cabbage juice or a diet high in vegetables such as cabbage, cauliflower, broccoli, and Brussels sprouts may be beneficial. Clinical studies report that about one-third of patients achieve complete remission, while another one-third show partial improvement with I3-C supplementation.
Pulmonary Medicine
Cidofovir
Cidofovir is an antiviral agent currently approved for the treatment of CMV retinitis in patients with AIDS. It is the first drug in the class of acyclic phosphonate nucleotide analogs. Within infected cells, cidofovir and similar nucleotide analogs inhibit viral DNA polymerase, which is essential for replication of viral DNA and RNA. Since HPV is the causative agent of RRP, targeting the virus provides a potential therapeutic approach.
Intervention with procedure
Treatment of RRP usually involves multiple surgical procedures due to the recurrent nature of the disease. Microdebridement of laryngeal lesions is now often preferred over traditional laser therapy. During anesthesia induction, special attention must be given to maintaining the already-compromised airway, and the surgical team should be ready to perform an emergency tracheostomy if needed.
A survey of anesthesiologists on preferred techniques for RRP laser procedures reported the following approaches:
Laser-safe endotracheal tube: 46%
Jet ventilation: 26%
Apneic technique: 16%
Spontaneous ventilation: 12%
Surgical treatment is sometimes combined with intralesional medications aimed at reducing recurrence. Cidofovir has largely replaced interferon as it has proven effective in a significant number of patients.
Historically, COâ‚‚ laser was favored for papilloma removal due to its precise cutting, good hemostasis, and minimal thermal damage to surrounding tissue. However, many centers now prefer microdebridement with angled oscillating blades (incorporating suction and irrigation) or pulsed dye laser. These newer techniques offer advantages such as shorter operative times, outpatient feasibility, reduced risk to personnel, lower likelihood of airway burns, and possibly lower recurrence rates. For newly diagnosed RRP, airway evaluation may be required as frequently as every 2-4 weeks.
Photodynamic therapy has shown promise in small trials for slowing papilloma growth. In this approach, hematoporphyrins, which selectively accumulate in neoplastic cells, are used as photosensitizers. Dihematoporphyrin ether (DHE) is usually administered 2-3 days before surgery, and activation is achieved via argon laser delivered through a laryngoscope or bronchoscope.
Because surgical manipulation can aerosolize HPV, staff must use protective eyewear and particulate barrier masks or face shields during procedures to minimize viral exposure.
Pulmonary Medicine
Phases of management
Initial Assessment and Diagnosis:
History & Physical Examination: Evaluate voice changes, stridor, and airway compromise.
Endoscopic Evaluation: Direct laryngoscopy or bronchoscopy to visualize lesions and assess extent.
Imaging (if needed): CT or MRI for subglottic, tracheal, or pulmonary involvement.
Surgical Management (Primary Treatment):
Techniques:
Microdebridement (preferred in many centers)
COâ‚‚ laser or pulsed dye laser
Frequency: Repeat procedures often required due to recurrence, especially in juvenile-onset cases.
Adjuvant Therapy (for aggressive or recurrent disease):
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