Childhood Laryngeal Tumors Treatment (PDQ®)–Health Professional Version

Childhood Laryngeal Cancer

Histology

Tumors of the larynx are rare. The most common benign tumor is subglottic hemangioma.[1] Malignant tumors, which are especially rare, may be associated with benign tumors such as polyps and papillomas.[2,3] A review of Surveillance, Epidemiology, and End Results (SEER) Program data from 1973 to 2016 identified 23 pediatric patients with laryngeal malignancies. Sixteen of the patients had squamous cell carcinoma. The other identified histologies included small cell carcinoma, mucoepidermoid carcinoma, myxosarcoma, embryonal rhabdomyosarcoma, and synovial sarcoma.[4]

Clinical Presentation

These tumors may present with the following:

  • Hoarseness.
  • Difficulty swallowing.
  • Stridor.
  • Enlargement of the lymph nodes of the neck.

Treatment of Childhood Laryngeal Cancer

Squamous cell carcinoma of the larynx in children is managed by surgery and radiation therapy, as in adults with carcinoma at this site.[4,5] Outcomes of pediatric patients with squamous cell carcinoma of the larynx are similar to those reported for adult patients.[4] Laser surgery may be the initial treatment used for these lesions. For more information about the treatment of laryngeal cancer in adults, see Laryngeal Cancer Treatment.

Treatment Options Under Clinical Evaluation for Childhood Laryngeal Cancer

Information about National Cancer Institute (NCI)–supported clinical trials can be found on the NCI website. For information about clinical trials sponsored by other organizations, see the ClinicalTrials.gov website.

References
  1. Bitar MA, Moukarbel RV, Zalzal GH: Management of congenital subglottic hemangioma: trends and success over the past 17 years. Otolaryngol Head Neck Surg 132 (2): 226-31, 2005. [PUBMED Abstract]
  2. McGuirt WF, Little JP: Laryngeal cancer in children and adolescents. Otolaryngol Clin North Am 30 (2): 207-14, 1997. [PUBMED Abstract]
  3. Bauman NM, Smith RJ: Recurrent respiratory papillomatosis. Pediatr Clin North Am 43 (6): 1385-401, 1996. [PUBMED Abstract]
  4. Forsyth AM, Camilon PR, Tracy L, et al.: Pediatric laryngeal tumors and demographics, management, and survival in laryngeal squamous cell carcinoma. Int J Pediatr Otorhinolaryngol 140: 110507, 2021. [PUBMED Abstract]
  5. Siddiqui F, Sarin R, Agarwal JP, et al.: Squamous carcinoma of the larynx and hypopharynx in children: a distinct clinical entity? Med Pediatr Oncol 40 (5): 322-4, 2003. [PUBMED Abstract]

Special Considerations for the Treatment of Children With Cancer

Cancer in children and adolescents is rare, although the overall incidence has slowly increased since 1975.[1] Children and adolescents with cancer should be referred to medical centers that have a multidisciplinary team of cancer specialists with experience treating the cancers that occur during childhood and adolescence. This multidisciplinary team approach incorporates the skills of the following pediatric specialists and others to ensure that children receive treatment, supportive care, and rehabilitation to achieve optimal survival and quality of life:

  • Primary care physicians.
  • Pediatric surgeons.
  • Pathologists.
  • Pediatric radiation oncologists.
  • Pediatric medical oncologists and hematologists.
  • Ophthalmologists.
  • Rehabilitation specialists.
  • Pediatric oncology nurses.
  • Social workers.
  • Child-life professionals.
  • Psychologists.
  • Nutritionists.

For specific information about supportive care for children and adolescents with cancer, see the summaries on Supportive and Palliative Care.

The American Academy of Pediatrics has outlined guidelines for pediatric cancer centers and their role in the treatment of children and adolescents with cancer.[2] At these centers, clinical trials are available for most types of cancer that occur in children and adolescents, and the opportunity to participate is offered to most patients and their families. Clinical trials for children and adolescents diagnosed with cancer are generally designed to compare potentially better therapy with current standard therapy. Other types of clinical trials test novel therapies when there is no standard therapy for a cancer diagnosis. Most of the progress in identifying curative therapies for childhood cancers has been achieved through clinical trials. Information about ongoing clinical trials is available from the NCI website.

Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2020, childhood cancer mortality decreased by more than 50%.[3-5] Childhood and adolescent cancer survivors require close monitoring because side effects of cancer therapy may persist or develop months or years after treatment. For information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors, see Late Effects of Treatment for Childhood Cancer.

Childhood cancer is a rare disease, with about 15,000 cases diagnosed annually in the United States in individuals younger than 20 years.[6] The U.S. Rare Diseases Act of 2002 defines a rare disease as one that affects populations smaller than 200,000 people in the United States. Therefore, all pediatric cancers are considered rare.

The designation of a rare tumor is not uniform among pediatric and adult groups. In adults, rare cancers are defined as those with an annual incidence of fewer than six cases per 100,000 people. They account for up to 24% of all cancers diagnosed in the European Union and about 20% of all cancers diagnosed in the United States.[7,8] In children and adolescents, the designation of a rare tumor is not uniform among international groups, as follows:

  • A consensus effort between the European Union Joint Action on Rare Cancers and the European Cooperative Study Group for Rare Pediatric Cancers estimated that 11% of all cancers in patients younger than 20 years could be categorized as very rare. This consensus group defined very rare cancers as those with annual incidences of fewer than two cases per 1 million people. However, three additional histologies (thyroid carcinoma, melanoma, and testicular cancer) with incidences of more than two cases per 1 million people were also included in the very rare group due to a lack of knowledge and expertise in the management of these tumors.[9]
  • The Children's Oncology Group defines rare pediatric cancers as those listed in the International Classification of Childhood Cancer subgroup XI, which includes thyroid cancers, melanomas and nonmelanoma skin cancers, and multiple types of carcinomas (e.g., adrenocortical carcinomas, nasopharyngeal carcinomas, and most adult-type carcinomas such as breast cancers and colorectal cancers).[10] These diagnoses account for about 5% of the cancers diagnosed in children aged 0 to 14 years and about 27% of the cancers diagnosed in adolescents aged 15 to 19 years.[4]

    Most cancers in subgroup XI are either melanomas or thyroid cancers, with other cancer types accounting for only 2% of the cancers diagnosed in children aged 0 to 14 years and 9.3% of the cancers diagnosed in adolescents aged 15 to 19 years.

These rare cancers are extremely challenging to study because of the relatively few patients with any individual diagnosis, the predominance of rare cancers in the adolescent population, and the small number of clinical trials for adolescents with rare cancers.

Information about these tumors may also be found in sources relevant to adults with cancer, such as Laryngeal Cancer Treatment.

References
  1. Smith MA, Seibel NL, Altekruse SF, et al.: Outcomes for children and adolescents with cancer: challenges for the twenty-first century. J Clin Oncol 28 (15): 2625-34, 2010. [PUBMED Abstract]
  2. American Academy of Pediatrics: Standards for pediatric cancer centers. Pediatrics 134 (2): 410-4, 2014. Also available online. Last accessed August 23, 2024.
  3. Smith MA, Altekruse SF, Adamson PC, et al.: Declining childhood and adolescent cancer mortality. Cancer 120 (16): 2497-506, 2014. [PUBMED Abstract]
  4. National Cancer Institute: NCCR*Explorer: An interactive website for NCCR cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed August 23, 2024.
  5. Surveillance Research Program, National Cancer Institute: SEER*Explorer: An interactive website for SEER cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed September 5, 2024.
  6. Ward E, DeSantis C, Robbins A, et al.: Childhood and adolescent cancer statistics, 2014. CA Cancer J Clin 64 (2): 83-103, 2014 Mar-Apr. [PUBMED Abstract]
  7. Gatta G, Capocaccia R, Botta L, et al.: Burden and centralised treatment in Europe of rare tumours: results of RARECAREnet-a population-based study. Lancet Oncol 18 (8): 1022-1039, 2017. [PUBMED Abstract]
  8. DeSantis CE, Kramer JL, Jemal A: The burden of rare cancers in the United States. CA Cancer J Clin 67 (4): 261-272, 2017. [PUBMED Abstract]
  9. Ferrari A, Brecht IB, Gatta G, et al.: Defining and listing very rare cancers of paediatric age: consensus of the Joint Action on Rare Cancers in cooperation with the European Cooperative Study Group for Pediatric Rare Tumors. Eur J Cancer 110: 120-126, 2019. [PUBMED Abstract]
  10. Pappo AS, Krailo M, Chen Z, et al.: Infrequent tumor initiative of the Children's Oncology Group: initial lessons learned and their impact on future plans. J Clin Oncol 28 (33): 5011-6, 2010. [PUBMED Abstract]

Childhood Laryngeal Papillomatosis

General Information

Recurrent respiratory papillomatosis is the most common benign laryngeal tumor in children, and it is associated with human papillomavirus (HPV) infection, most commonly HPV-6 and HPV-11.[1,2] The presence of HPV-11 appears to correlate with a more aggressive clinical course than does the presence of HPV-6.[3] An Australian survey of pediatric otorhinolaryngologists documented a decline in the incidence of laryngeal papillomatosis after the introduction of HPV vaccinations for adolescent girls and young women aged 12 to 26 years.[4] In another study of patients younger than 18 years with laryngeal papillomatosis, the incidence decreased from 165 cases in children born between 2004 and 2005 to 36 cases in children born between 2012 and 2013. The authors of the study attribute the decline in incidence to the widespread use of the HPV vaccine, which was released in 2006.[5]

These tumors can cause hoarseness because of their association with wart-like nodules on the vocal cords, and they may rarely extend into the lung, producing significant morbidity.[6] Malignant degeneration may occur, with development of laryngeal carcinoma and squamous cell lung cancer, generally reported at rates of 2% to 10% in the pediatric population.[7]

A multi-institutional registry study identified children with juvenile-onset recurrent respiratory papillomatosis from 23 states between January 2015 and August 2020.[8] Of the 215 children with juvenile-onset recurrent respiratory papillomatosis, 88.8% were delivered vaginally. Among 190 mothers, the median age at the time of delivery was 22 years. Of 114 mothers (60.0%) who were age-eligible for the HPV vaccination, 16 (14.0%) were vaccinated, 1 (0.9%) of whom was vaccinated before delivery. Of 162 tested biopsy specimens, 157 (96.9%) had detectable HPV. All 157 specimens had a vaccine-preventable HPV type.

Treatment of Childhood Laryngeal Papillomatosis

Primary treatment for papillomatosis is surgical ablation with laser vaporization.[9] Frequent recurrences are common. Lung involvement, although rare, can occur.[6]

Evidence (surgery):

  1. A single-institution retrospective analysis evaluated 121 children with respiratory papillomatosis. The age at initial operation was 4.3 years (±2.9 years), and 47.9% of patients (58 of 121) experienced a recurrence and underwent surgical treatment after the age of 14 years.[10]
    • At follow-up, 5% of the patients (6 of 121) had died, 41.3% of the patients (50 of 121) had been recurrence free for 5 years or longer (cured group), and 53.7% of the patients (65 of 121) experienced a recurrence in the previous 5 years (recurrent group).
    • There were no significant differences in sex, age at initial operation, or adjuvant therapy between the cured and recurrent groups of patients.
    • In the recurrent group, there was a higher incidence of overall operation frequency, aggressive disease, tracheal dissemination of papilloma, and HPV infection.

If a patient requires more than four surgical procedures per year, other interventions may be necessary, including the following:

  • Interferon therapy.[11]
  • Immunotherapy with HspE7, a recombinant fusion protein that has shown activity in other HPV-related diseases. A pilot study suggested a marked increase in the amount of time between surgeries.[12]
  • Laser therapy combined with intralesional bevacizumab.[13]

The effectiveness of intralesional cidofovir has not been conclusively demonstrated.[14] Intralesional bevacizumab has also been used in some patients. In a pilot study, ten patients with severe respiratory papillomatosis received intralesional bevacizumab. With this treatment, the number of surgical procedures per year decreased and quality-of-life scores improved.[15]

The role of checkpoint inhibitors, such as PD-1 inhibitors, is currently being investigated.[16] Reports (with small numbers of patients) have documented that in selected cases, the administration of a quadrivalent HPV vaccine can be associated with a complete remission and an increase in the intersurgical interval.[17,18] In contrast, other reports have not documented a therapeutic effect of the quadrivalent HPV vaccine.[19]

In a report of two patients with aggressive recurrent respiratory papillomatosis, treatment with systemic bevacizumab produced good results with minimal toxicity.[20] In another report of seven children who were treated with bevacizumab, continued responses were noted and subsequent surgical debridement was avoided in most patients. Of the seven patients, five have not required surgical debridement after initiation of bevacizumab. Four of these five patients had previously required between four to ten debridements per year. Follow-up for these patients was between 8 months and 3.5 years. No serious adverse events were reported.[21] In a study of 24 patients with recurrent respiratory papillomatosis, 15 had pediatric-onset disease. Patients were treated with systemic bevacizumab (7.5–10 mg/kg) every 3 to 4 weeks. All patients had a reduction in the number and size of lesions after three doses, excluding one patient who was lost to follow-up. Voice outcomes were improved in 87.5% of patients, as measured by Voice Handicap Index-30 (VHI) or pediatric VHI. No grade 3 Common Terminology Criteria for Adverse Events were reported. However, follow-up was limited to a maximum of 14 months after initiation of therapy and 10 months after discontinuation of bevacizumab.[22]

Treatment Options Under Clinical Evaluation for Childhood Laryngeal Papillomatosis

Information about National Cancer Institute (NCI)–supported clinical trials can be found on the NCI website. For information about clinical trials sponsored by other organizations, see the ClinicalTrials.gov website.

References
  1. Kashima HK, Mounts P, Shah K: Recurrent respiratory papillomatosis. Obstet Gynecol Clin North Am 23 (3): 699-706, 1996. [PUBMED Abstract]
  2. Derkay CS, Wiatrak B: Recurrent respiratory papillomatosis: a review. Laryngoscope 118 (7): 1236-47, 2008. [PUBMED Abstract]
  3. Maloney EM, Unger ER, Tucker RA, et al.: Longitudinal measures of human papillomavirus 6 and 11 viral loads and antibody response in children with recurrent respiratory papillomatosis. Arch Otolaryngol Head Neck Surg 132 (7): 711-5, 2006. [PUBMED Abstract]
  4. Novakovic D, Cheng ATL, Zurynski Y, et al.: A Prospective Study of the Incidence of Juvenile-Onset Recurrent Respiratory Papillomatosis After Implementation of a National HPV Vaccination Program. J Infect Dis 217 (2): 208-212, 2018. [PUBMED Abstract]
  5. Meites E, Stone L, Amiling R, et al.: Significant Declines in Juvenile-onset Recurrent Respiratory Papillomatosis Following Human Papillomavirus (HPV) Vaccine Introduction in the United States. Clin Infect Dis 73 (5): 885-890, 2021. [PUBMED Abstract]
  6. Gélinas JF, Manoukian J, Côté A: Lung involvement in juvenile onset recurrent respiratory papillomatosis: a systematic review of the literature. Int J Pediatr Otorhinolaryngol 72 (4): 433-52, 2008. [PUBMED Abstract]
  7. Karatayli-Ozgursoy S, Bishop JA, Hillel A, et al.: Risk Factors for Dysplasia in Recurrent Respiratory Papillomatosis in an Adult and Pediatric Population. Ann Otol Rhinol Laryngol 125 (3): 235-41, 2016. [PUBMED Abstract]
  8. Amiling R, Meites E, Querec TD, et al.: Juvenile-Onset Recurrent Respiratory Papillomatosis in the United States, Epidemiology and HPV Types-2015-2020. J Pediatric Infect Dis Soc 10 (7): 774-781, 2021. [PUBMED Abstract]
  9. Andrus JG, Shapshay SM: Contemporary management of laryngeal papilloma in adults and children. Otolaryngol Clin North Am 39 (1): 135-58, 2006. [PUBMED Abstract]
  10. Xiao Y, Zhang X, Ma L, et al.: Long-term outcomes of juvenile-onset recurrent respiratory papillomatosis. Clin Otolaryngol 46 (1): 161-167, 2021. [PUBMED Abstract]
  11. Avidano MA, Singleton GT: Adjuvant drug strategies in the treatment of recurrent respiratory papillomatosis. Otolaryngol Head Neck Surg 112 (2): 197-202, 1995. [PUBMED Abstract]
  12. Derkay CS, Smith RJ, McClay J, et al.: HspE7 treatment of pediatric recurrent respiratory papillomatosis: final results of an open-label trial. Ann Otol Rhinol Laryngol 114 (9): 730-7, 2005. [PUBMED Abstract]
  13. Sidell DR, Nassar M, Cotton RT, et al.: High-dose sublesional bevacizumab (avastin) for pediatric recurrent respiratory papillomatosis. Ann Otol Rhinol Laryngol 123 (3): 214-21, 2014. [PUBMED Abstract]
  14. Chadha NK, James A: Adjuvant antiviral therapy for recurrent respiratory papillomatosis. Cochrane Database Syst Rev 12: CD005053, 2012. [PUBMED Abstract]
  15. Rogers DJ, Ojha S, Maurer R, et al.: Use of adjuvant intralesional bevacizumab for aggressive respiratory papillomatosis in children. JAMA Otolaryngol Head Neck Surg 139 (5): 496-501, 2013. [PUBMED Abstract]
  16. Ivancic R, Iqbal H, deSilva B, et al.: Current and future management of recurrent respiratory papillomatosis. Laryngoscope Investig Otolaryngol 3 (1): 22-34, 2018. [PUBMED Abstract]
  17. Young DL, Moore MM, Halstead LA: The use of the quadrivalent human papillomavirus vaccine (gardasil) as adjuvant therapy in the treatment of recurrent respiratory papilloma. J Voice 29 (2): 223-9, 2015. [PUBMED Abstract]
  18. Mészner Z, Jankovics I, Nagy A, et al.: Recurrent laryngeal papillomatosis with oesophageal involvement in a 2 year old boy: successful treatment with the quadrivalent human papillomatosis vaccine. Int J Pediatr Otorhinolaryngol 79 (2): 262-6, 2015. [PUBMED Abstract]
  19. Katsuta T, Miyaji Y, Offit PA, et al.: Treatment With Quadrivalent Human Papillomavirus Vaccine for Juvenile-Onset Recurrent Respiratory Papillomatosis: Case Report and Review of the Literature. J Pediatric Infect Dis Soc 6 (4): 380-385, 2017. [PUBMED Abstract]
  20. Carnevale C, Ferrán-De la Cierva L, Til-Pérez G, et al.: Safe use of systemic bevacizumab for respiratory recurrent papillomatosis in two children. Laryngoscope 129 (4): 1001-1004, 2019. [PUBMED Abstract]
  21. Ruiz R, Balamuth N, Javia LR, et al.: Systemic Bevacizumab Treatment for Recurrent Respiratory Papillomatosis: Long-Term Follow-Up. Laryngoscope 132 (10): 2071-2075, 2022. [PUBMED Abstract]
  22. Zhao X, Wang J, Chen Q, et al.: Systemic bevacizumab for treatment of recurrent respiratory papillomatosis. Eur Arch Otorhinolaryngol 281 (4): 1865-1875, 2024. [PUBMED Abstract]

Latest Updates to This Summary (08/28/2024)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

This summary was comprehensively reviewed.

This summary is written and maintained by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® Cancer Information for Health Professionals pages.

About This PDQ Summary

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of childhood laryngeal cancer and papillomatosis. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.

Reviewers and Updates

This summary is reviewed regularly and updated as necessary by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

Board members review recently published articles each month to determine whether an article should:

  • be discussed at a meeting,
  • be cited with text, or
  • replace or update an existing article that is already cited.

Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.

The lead reviewers for Childhood Laryngeal Tumors Treatment are:

  • Denise Adams, MD (Children's Hospital Boston)
  • Karen J. Marcus, MD, FACR (Dana-Farber of Boston Children's Cancer Center and Blood Disorders Harvard Medical School)
  • William H. Meyer, MD
  • Paul A. Meyers, MD (Memorial Sloan-Kettering Cancer Center)
  • Thomas A. Olson, MD (Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta - Egleston Campus)
  • Alberto S. Pappo, MD (St. Jude Children's Research Hospital)
  • Arthur Kim Ritchey, MD (Children's Hospital of Pittsburgh of UPMC)
  • Carlos Rodriguez-Galindo, MD (St. Jude Children's Research Hospital)
  • Stephen J. Shochat, MD (St. Jude Children's Research Hospital)

Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.

Levels of Evidence

Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Pediatric Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

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The preferred citation for this PDQ summary is:

PDQ® Pediatric Treatment Editorial Board. PDQ Childhood Laryngeal Tumors Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/head-and-neck/hp/child/laryngeal-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 29337477]

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