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Nasopharyngeal carcinoma arises in the lining of the nasal cavity and pharynx, and it accounts for about one-third of all cancers of the upper airways in children.[1,2] Nasopharyngeal carcinoma is rare in children younger than 10 years but increases in incidence to 0.5 cases per 1 million per year in children aged 10 to 14 years and 1.3 cases per million per year in children aged 15 to 19 years.[3,4,5,6] The incidence of nasopharyngeal carcinoma is characterized by racial and geographic variations, with an endemic distribution among well-defined ethnic groups, such as inhabitants of some areas in North Africa and the Mediterranean basin, and, particularly, Southeast Asia. In the United States, the incidence of nasopharyngeal carcinoma is higher in Black children and adolescents compared with White children and adolescents.[4,5] References: Nasopharyngeal carcinoma is strongly associated with Epstein-Barr virus (EBV) infection. In addition to the serological evidence of infection in more than 98% of patients, EBV DNA is present as a monoclonal episome in the nasopharyngeal carcinoma cells, and tumor cells can have EBV antigens on their cell surface.[1] The circulating levels of EBV DNA and serologic documentation of EBV infection may aid in the diagnosis.[2] Specific HLA subtypes, such as the HLA A2Bsin2 haplotype, are associated with a higher risk of nasopharyngeal carcinoma.[3] References: Three histologic subtypes of nasopharyngeal carcinoma are recognized by the World Health Organization (WHO): Children with nasopharyngeal carcinoma are more likely to have WHO type II or type III disease.[1,2] References: Signs and symptoms of nasopharyngeal carcinoma include the following:[1,2] Given the rich lymphatic drainage of the nasopharynx, bilateral cervical lymphadenopathy is often the first sign of disease. The tumor spreads locally to adjacent areas of the oropharynx and may invade the skull base, resulting in cranial nerve palsy or difficulty with movements of the jaw (trismus). Distant metastatic sites may include the bones, lungs, and liver. References: Diagnostic tests will determine the extent of the primary tumor and the presence of metastases. Visualization of the nasopharynx by an otolaryngologist using nasal endoscopy and magnetic resonance imaging of the head and neck can be used to determine the extent of the primary tumor. A diagnosis can be made from a biopsy of the primary tumor or enlarged lymph nodes of the neck. Nasopharyngeal carcinomas must be distinguished from all other cancers that can present with enlarged lymph nodes and from other types of cancer in the head and neck area. Thus, diseases such as thyroid cancer, rhabdomyosarcoma, non-Hodgkin lymphoma including Burkitt lymphoma, and Hodgkin lymphoma must be considered, as well as benign conditions such as nasal angiofibroma, which usually presents with epistaxis in adolescent males, infectious lymphadenitis, and Rosai-Dorfman disease. Evaluation of the chest and abdomen by computed tomography (CT) and bone scan is performed to determine whether there is metastatic disease. Fluorine F 18-fludeoxyglucose positron emission tomography (PET)–CT may also be helpful in the evaluation of potential metastatic lesions.[1] References: Four tertiary academic medical centers in China studied 30 patients (25 male and 5 female) with pathologically confirmed nasopharyngeal carcinoma who were younger than 20 years.[1] Nasopharyngeal primary tumors with paired blood samples were collected and sequenced using whole-exome sequencing. Several genes such as SHOC1 (formerly known as C9orf84) (20%), ZFHX4 (16.7%), ZC3H6 (16.7%), and RBM38 (16.7%) were frequently mutated in nasopharyngeal carcinoma. Copy number analysis revealed highly recurring gain/amplification of the HLA class II genes at 6p21.32 (63.3%) and losses of TOLLIP at 11p15.5 (20%). Recurrent NUTM1 (16.7%) fusion variants were found for the first time in nasopharyngeal carcinoma. The gene fusions included NUTM1::PAIP2B, NUTM1::TFDP2, and NUTM1::CUL2. The study also showed that 8 of 30 patients (26.7%) with nasopharyngeal carcinoma carried germline pathogenic and/or likely pathogenic variants in known cancer predisposition genes. In another analysis, homozygous deletion of the CDKN2A locus on 9p21.3 was confirmed in 7 of 15 nasopharyngeal carcinoma specimens (46.7%) and in 3 of 5 cell lines/patient-derived xenografts (60%). CCND1 amplification was found in 3 of 20 nasopharyngeal tumors (15%).[2] Whole-genome sequencing of nasopharyngeal carcinoma revealed that TP53 was the most significantly mutated gene (n = 10), followed by TRAF3, NFKBIA, AEBP1, and NLRC5. All of these genes have been reported to regulate nuclear factor kappa B.[3] In addition, significant somatic aberrations detected in HLA-A and NLRC5 suggest the impairment of antigen presentation, while PTEN mutations may activate the PI3K pathway. This study found four coding genes that were significantly mutated, namely PLIN4, MUC21, SLC35G5, and ERVW-1. References: Tumor staging is performed using the tumor-node-metastasis (TNM) classification system of the American Joint Committee on Cancer (AJCC).[1,2] The AJCC has designated staging by TNM classification to define nasopharyngeal carcinoma.[3] More than 90% of children and adolescents with nasopharyngeal carcinoma present with advanced disease (stage III/IV or T3/T4).[4,5] Population-based studies have reported that patients younger than 20 years had a higher incidence of advanced-stage disease than did adult patients.[6,7] However, less than 10% of children and adolescents with nasopharyngeal carcinoma presented with distant metastases at diagnosis.[4,5,8] References: The overall survival of children and adolescents with nasopharyngeal carcinoma has improved over the last four decades; with state-of-the-art multimodal treatment, 5-year survival rates exceed 80%.[1,2,3,4,5,6,7,8] After controlling for stage, children with nasopharyngeal carcinoma have significantly better outcomes than adults.[1,7] However, the intensive use of chemotherapy and radiation therapy results in significant acute and long-term morbidities, including subsequent neoplasms.[1,2,3,6] References: Cancer in children and adolescents is rare, although the overall incidence has been slowly increasing since 1975.[1] Referral to medical centers with multidisciplinary teams of cancer specialists experienced in treating cancers that occur in childhood and adolescence should be considered. This multidisciplinary team approach incorporates the skills of the following health care professionals and others to ensure that children receive treatment, supportive care, and rehabilitation that will achieve optimal survival and quality of life: For 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 pediatric patients with cancer.[2] At these pediatric cancer 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. Most of the progress made in identifying curative therapy 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%.[3,4,5] 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. 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] Also, the designation of a pediatric rare tumor is not uniform among international groups, as follows: Most cancers in subgroup XI are either melanomas or thyroid cancers, with other cancer types accounting for only 2% of the cancers in children aged 0 to 14 years and 9.3% of the cancers in adolescents aged 15 to 19 years. These rare cancers are extremely challenging to study because of the low number of patients with any individual diagnosis, the predominance of rare cancers in the adolescent population, and the lack 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 Nasopharyngeal Cancer Treatment. References: The European Cooperative Study Group for Pediatric Rare Tumors within the PARTNER project (Paediatric Rare Tumours Network–European Registry) have published comprehensive recommendations for the diagnosis and treatment of nasopharyngeal carcinoma in children and adolescents.[1] Treatment of nasopharyngeal carcinoma is multimodal and includes the following: The following two modifications of this approach have been investigated: References: The outcome of patients with relapsed nasopharyngeal carcinoma is poor, and most patients present with distant metastases. However, long-term remissions can be achieved with conventional chemotherapy. In a retrospective review of 14 pediatric patients with relapsed nasopharyngeal carcinoma who were treated with varying chemotherapy regimens, the 3-year event-free survival rate was 34%, and the overall survival rate was 44%.[1] Given the unique pathogenesis of nasopharyngeal carcinoma, immunotherapy has been explored for patients with refractory disease, as follows: Treatment Options Under Clinical Evaluation for Childhood Nasopharyngeal Carcinoma 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: 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. Genomics of Childhood Nasopharyngeal Carcinoma Added text to state that the gene fusions found in one study of pediatric nasopharyngeal carcinoma included NUTM1::PAIP2B, NUTM1::TFDP2, and NUTM1::CUL2. Added text to state that in another analysis, homozygous deletion of the CDKN2A locus on 9p21.3 was confirmed in 7 of 15 nasopharyngeal carcinoma specimens and in 3 of 5 cell lines/patient-derived xenografts (cited Tsang et al. as reference 2). Also added text about a study that reported a comprehensive genomic analysis of nasopharyngeal carcinoma (cited Bruce et al. as reference 3). Treatment of Newly Diagnosed Childhood Nasopharyngeal Carcinoma Added text to state that the U.S. Food and Drug Administration approved the anti-PD-1 monoclonal antibody toripalimab-tpzi in combination with cisplatin and gemcitabine for first-line treatment of adults with metastatic or recurrent, locally advanced nasopharyngeal carcinoma. The approval was based on the results of a phase III placebo-controlled clinical trial. Patients received toripalimab or placebo in combination with gemcitabine plus cisplatin every 3 weeks for up to six cycles, followed by monotherapy with toripalimab or placebo. Patients randomly assigned to receive toripalimab had superior progression-free survival and overall survival (OS) (cited Mai et al. as reference 5). Added text to state that for adults with nasopharyngeal carcinoma, gemcitabine plus cisplatin is more effective than 5-fluorouracil (5-FU) plus cisplatin, both in the front-line setting and the recurrent setting (cited 2016 Zhang et al. and Liu et al. as references 6 and 7, respectively). Added text to state that the addition of gemcitabine plus cisplatin induction therapy improved OS, compared with chemoradiation therapy alone, for patients with locoregionally advanced nasopharyngeal carcinoma (cited 2019 Zhang et al. and 2022 Zhang et al. as references 8 and 9, respectively). Added Yao et al. as reference 13. Added text about the outcome results of a German Society of Pediatric Oncology and Hematology study that reviewed 45 patients enrolled on the NPC-2003 study and an additional 21 patients who were subsequently treated per the NPC-2003 protocol (cited Römer et al. as reference 14). 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. Purpose of This Summary This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of childhood nasopharyngeal cancer. 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: 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 Nasopharyngeal Cancer Treatment are: 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. Permission to Use This Summary PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as "NCI's PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary]." The preferred citation for this PDQ summary is: PDQ® Pediatric Treatment Editorial Board. PDQ Childhood Nasopharyngeal Cancer Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/head-and-neck/hp/child/nasopharyngeal-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 29320137] Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in Visuals Online, a collection of over 2,000 scientific images. Disclaimer Based on the strength of the available evidence, treatment options may be described as either "standard" or "under clinical evaluation." These classifications should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Managing Cancer Care page. Contact Us More information about contacting us or receiving help with the Cancer.gov website can be found on our Contact Us for Help page. Questions can also be submitted to Cancer.gov through the website's Email Us. Last Revised: 2023-12-15 This information does not replace the advice of a doctor. Healthwise, Incorporated disclaims any warranty or liability for your use of this information. 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Childhood Nasopharyngeal Cancer Treatment (PDQ®): Treatment - Health Professional Information [NCI]
Incidence
Risk Factors
Histology
Clinical Presentation
Diagnostic and Staging Evaluation
Genomics of Childhood Nasopharyngeal Carcinoma
Stage Information for Childhood Nasopharyngeal Carcinoma
Stage TNM Description T = primary tumor; N = regional lymph node; M = distant metastasis. a Reprinted with permission from AJCC: Nasopharynx. In: Amin MB, Edge SB, Greene FL, et al., eds.:AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 103–11. 0 Tis, N0, M0 Tis = Carcinomain situ. N0 = No regional lymph node metastasis. M0 = No distant metastasis. Stage TNM Description T = primary tumor; N = regional lymph node; M = distant metastasis. a Reprinted with permission from AJCC: Nasopharynx. In: Amin MB, Edge SB, Greene FL, et al., eds.:AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 103–11. I T1, N0, M0 T1 = Tumor confined to nasopharynx, or extension to oropharynx and/or nasal cavity without parapharyngeal involvement. N0 = No regional lymph node metastasis. M0 = No distant metastasis. Stage TNM Description T = primary tumor; N = regional lymph node; M = distant metastasis; EBV = Epstein-Barr virus. a Reprinted with permission from AJCC: Nasopharynx. In: Amin MB, Edge SB, Greene FL, et al., eds.:AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 103–11. II T0, Tis, T1, N1, M0 T0 = No tumor identified, but EBV-positive cervical node(s) involvement. Tis = Carcinomain situ. T1 = Tumor confined to nasopharynx, or extension to oropharynx and/or nasal cavity without parapharyngeal involvement. N1 = Unilateral metastasis in cervical lymph node(s) and/or unilateral or bilateral metastasis in retropharyngeal lymph node(s), ≤6 cm in greatest dimension, above the caudal border of cricoid cartilage. M0 = No distant metastasis. T2, N0, M0 T2 = Tumor with extension to parapharyngeal space, and/or adjacent soft tissue involvement (medial pterygoid, lateral pterygoid, prevertebral muscles). N0 = No regional lymph node metastasis. M0 = No distant metastasis. T2, N1, M0 T2 = Tumor with extension to parapharyngeal space, and/or adjacent soft tissue involvement (medial pterygoid, lateral pterygoid, prevertebral muscles). N1 = Unilateral metastasis in cervical lymph node(s) and/or unilateral or bilateral metastasis in retropharyngeal lymph node(s), ≤6 cm in greatest dimension, above the caudal border of cricoid cartilage. M0 = No distant metastasis. Stage TNM Description T = primary tumor; N = regional lymph node; M = distant metastasis; EBV = Epstein-Barr virus. a Reprinted with permission from AJCC: Nasopharynx. In: Amin MB, Edge SB, Greene FL, et al., eds.:AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 103–11. III T0, Tis, T1, N2, M0 T0 = No tumor identified, but EBV-positive cervical node(s) involvement. Tis = Carcinomain situ. T1 = Tumor confined to nasopharynx, or extension to oropharynx and/or nasal cavity without parapharyngeal involvement. N2 = Bilateral metastasis in cervical lymph node(s), ≤6 cm in greatest dimension, above the caudal border of cricoid cartilage. M0 = No distant metastasis. T2, N2, M0 T2 = Tumor with extension to parapharyngeal space, and/or adjacent soft tissue involvement (medial pterygoid, lateral pterygoid, prevertebral muscles). N2 = Bilateral metastasis in cervical lymph node(s), ≤6 cm in greatest dimension, above the caudal border of cricoid cartilage. M0 = No distant metastasis. T3, N0, M0 T3 = Tumor with infiltration of bony structures at skull base, cervical vertebra, pterygoid structures, and/or paranasal sinuses. N0 = No regional lymph node metastasis. M0 = No distant metastasis. T3, N1, M0 T3 = Tumor with infiltration of bony structures at skull base, cervical vertebra, pterygoid structures, and/or paranasal sinuses. N1 = Unilateral metastasis in cervical lymph node(s) and/or unilateral or bilateral metastasis in retropharyngeal lymph node(s), ≤6 cm in greatest dimension, above the caudal border of cricoid cartilage. M0 = No distant metastasis. T3, N2, M0 T3 = Tumor with infiltration of bony structures at skull base, cervical vertebra, pterygoid structures, and/or paranasal sinuses. N2 = Bilateral metastasis in cervical lymph node(s), ≤6 cm in greatest dimension, above the caudal border of cricoid cartilage. M0 = No distant metastasis. Stage TNM Description T = primary tumor; N = regional lymph node; M = distant metastasis; EBV = Epstein-Barr virus. a Reprinted with permission from AJCC: Nasopharynx. In: Amin MB, Edge SB, Greene FL, et al., eds.:AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 103–11. IVA T4, N0, M0 T4 = Tumor with intracranial extension, involvement of cranial nerves, hypopharynx, orbit, parotid gland, and/or extensive soft tissue infiltration beyond the lateral surface of the lateral pterygoid muscle. N0 = No regional lymph node metastasis. M0 = No distant metastasis. T4, N1, M0 T4 = Tumor with intracranial extension, involvement of cranial nerves, hypopharynx, orbit, parotid gland, and/or extensive soft tissue infiltration beyond the lateral surface of the lateral pterygoid muscle. N1 = Unilateral metastasis in cervical lymph node(s) and/or unilateral or bilateral metastasis in retropharyngeal lymph node(s), ≤6 cm in greatest dimension, above the caudal border of cricoid cartilage. M0 = No distant metastasis. T4, N2, M0 T4 = Tumor with intracranial extension, involvement of cranial nerves, hypopharynx, orbit, parotid gland, and/or extensive soft tissue infiltration beyond the lateral surface of the lateral pterygoid muscle. N2 = Bilateral metastasis in cervical lymph node(s), ≤6 cm in greatest dimension, above the caudal border of cricoid cartilage. M0 = No distant metastasis. Any T, N3, M0 TX = Primary tumor cannot be assessed. T0 = No tumor identified, but EBV-positive cervical node(s) involvement. Tis = Carcinomain situ. T1 = Tumor confined to nasopharynx, or extension to oropharynx and/or nasal cavity without parapharyngeal involvement. T2 = Tumor with extension to parapharyngeal space, and/or adjacent soft tissue involvement (medial pterygoid, lateral pterygoid, prevertebral muscles). T3 = Tumor with infiltration of bony structures at skull base, cervical vertebra, pterygoid structures, and/or paranasal sinuses. T4 = Tumor with intracranial extension, involvement of cranial nerves, hypopharynx, orbit, parotid gland, and/or extensive soft tissue infiltration beyond the lateral surface of the lateral pterygoid muscle. N3 = Unilateral or bilateral metastasis in cervical lymph node(s), >6 cm in greatest dimension, and/or extension below the caudal border of cricoid cartilage. M0 = No distant metastasis. IVB Any T, Any N, M1 Any T = See Stage IVA above. NX = Regional lymph nodes cannot be assessed. N0 = No regional lymph node metastasis. N1 = Unilateral metastasis in cervical lymph node(s) and/or unilateral or bilateral metastasis in retropharyngeal lymph node(s), ≤6 cm in greatest dimension, above the caudal border of cricoid cartilage. N2 = Bilateral metastasis in cervical lymph node(s), ≤6 cm in greatest dimension, above the caudal border of cricoid cartilage. N3 = Unilateral or bilateral metastasis in cervical lymph node(s), >6 cm in greatest dimension, and/or extension below the caudal border of cricoid cartilage. M1 = Distant metastasis. Prognosis
Special Considerations for the Treatment of Children With Cancer
Treatment of Newly Diagnosed Childhood Nasopharyngeal Carcinoma
Treatment of Relapsed or Refractory Childhood Nasopharyngeal Carcinoma
Latest Updates to This Summary (12 / 15 / 2023)
About This PDQ Summary
Our Health Library information does not replace the advice of a doctor. Please be advised that this information is made available to assist our patients to learn more about their health. Our providers may not see and/or treat all topics found herein.Childhood Nasopharyngeal Cancer Treatment (PDQ®): Treatment - Health Professional Information [NCI]