Childhood Salivary Gland Tumors Treatment (PDQ®)–Health Professional Version
Salivary Gland Tumors
Salivary gland tumors are rare and account for 0.5% of all malignancies in children and adolescents. After rhabdomyosarcoma, they are the most common tumor in the head and neck.[1,2] Salivary gland tumors may occur after radiation therapy and chemotherapy are given for the treatment of primary leukemia or solid tumors.[3,4]
Most salivary gland neoplasms arise in the parotid gland.[5-10] About 15% of these tumors arise in the submandibular glands or in the minor salivary glands under the tongue and jaw. These tumors are most frequently benign but may be malignant, especially in young children.
Histology and Molecular Features
The most common malignant salivary gland tumor in children is mucoepidermoid carcinoma, followed by acinic cell carcinoma and adenoid cystic carcinoma. Less common malignancies include rhabdomyosarcoma, adenocarcinoma, and undifferentiated carcinoma.[1,8,10,12-14] Mucoepidermoid carcinoma is usually low or intermediate grade, although high-grade tumors do occur. Mammary analogue secretory carcinoma (MASC) of the salivary gland is a newly described pathological entity that has been seen in children.[Level of evidence C1] In one review, it was estimated that 12% of MASC cases occurred in the pediatric population.[16,17]
In a series of pediatric patients with salivary gland tumors, immunohistochemical and molecular profiling showed similarities to those tumors observed in adults. In one study, 12 of 12 tumors were positive for CRTC1::MAML2 fusion transcripts. This reflects the common chromosome translocation t(11;19)(q21;p13) that is seen in adults with salivary gland tumors. MASC is characterized by an ETV6::NTRK3 fusion.
The 5-year overall survival (OS) rate for salivary gland tumors in the pediatric age group is approximately 95%. A review of the Surveillance, Epidemiology, and End Results Program database identified 284 patients younger than 20 years with tumors of the parotid gland.[Level of evidence C1] The OS rate was 96% at 5 years, 95% at 10 years, and 83% at 20 years. Adolescents had higher mortality rates (7.1%) than children younger than 15 years (1.6%; P = .23).
A retrospective, multi-institutional survey identified 103 patients younger than 18 years with parotid gland cancer; mucoepidermoid carcinoma was the most common histology (71 patients).[Level of evidence C1] The authors did not report if patients underwent previous therapies; however, they mentioned that 12 of 103 patients had a history of lymphoma. The 10-year relapse-free survival (RFS) rate for the entire group was 91%. Presence of intraparotid lymph node metastasis (LNM) was associated with significantly worse event-free survival and OS, as was history of previous therapy for lymphoma. The 10-year RFS rate was 91% for patients without intraparotid LNM and 37% for patients with intraparotid LNM.
Mucoepidermoid carcinoma is the most common type of treatment-related salivary gland tumor. With standard therapy, the 5-year survival rate is about 95% for patients with this tumor.[14,24,25]
A retrospective review identified 57 pediatric patients (aged <18 years) (4.6%) and 1,192 adult patients (95.4%) with acinic cell carcinoma. Clinical LNMs were rare in children (n < 10) and adults (n = 88; 7.4%). Occult LNMs were uncommon in pediatric patients (n < 5) and adult patients (n = 41; 4.6%). The 3-year OS rate was 97.8% for pediatric patients. Adult patients with LNMs had worse 3-year OS rates than those without LNMs (66.0% vs. 96.3%; P < .001).
Treatment of Childhood Salivary Gland Tumors
The European Cooperative Study Group for Pediatric Rare Tumors within the PARTNER project (Paediatric Rare Tumours Network - European Registry) has published consensus guidelines for the diagnosis and treatment of childhood salivary gland tumors.
Treatment options for childhood salivary gland tumors include the following:
Radical surgical removal is the treatment of choice for salivary gland tumors whenever possible, with additional use of radiation therapy for high-grade tumors or tumors that have invasive characteristics such as LNM, positive surgical margins, extracapsular extension, or perineural extension.[21,28,29]; [Level of evidence C1] Parotid gland tumors are removed with the aid of neurological monitoring to prevent damage to the facial nerve.
One retrospective study compared proton therapy with conventional radiation therapy and found that proton therapy had a favorable acute toxicity and dosimetric profile. Another retrospective study used brachytherapy with iodine I 125 seeds to treat 24 children with mucoepidermoid carcinoma who had high-risk factors. Seeds were implanted within 4 weeks of surgical resection. With a median follow-up of 7.2 years, the disease-free survival and OS rates were 100%; no severe radiation-associated complications were reported.[Level of evidence C2]
Objective responses have been observed in all reported patients with recurrent NTRK fusion–positive MASC who were treated with entrectinib or larotrectinib.[32,33] Ten of 11 adolescent or adult patients with TRK fusion–positive salivary gland tumors who were treated with larotrectinib experienced partial or complete responses.
For more information, see Salivary Gland Cancer Treatment (Adult).
Treatment Options Under Clinical Evaluation for Childhood Salivary Gland Tumors
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.
The following is an example of a national and/or institutional clinical trial that is currently being conducted:
- APEC1621 (NCT03155620) (Pediatric MATCH: Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients with Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders): NCI-COG Pediatric Molecular Analysis for Therapeutic Choice (MATCH), referred to as Pediatric MATCH, will match targeted agents with specific molecular changes identified in a patient's tumor (refractory or recurrent). Children and adolescents aged 1 to 21 years are eligible for the trial.
Patients with tumors that have molecular variants addressed by open treatment arms in the trial may be enrolled in treatment on Pediatric MATCH. Additional information can be obtained on the NCI website and ClinicalTrials.gov website.
- Sultan I, Rodriguez-Galindo C, Al-Sharabati S, et al.: Salivary gland carcinomas in children and adolescents: a population-based study, with comparison to adult cases. Head Neck 33 (10): 1476-81, 2011. [PUBMED Abstract]
- Cesmebasi A, Gabriel A, Niku D, et al.: Pediatric head and neck tumors: an intra-demographic analysis using the SEER* database. Med Sci Monit 20: 2536-42, 2014. [PUBMED Abstract]
- Chowdhry AK, McHugh C, Fung C, et al.: Second primary head and neck cancer after Hodgkin lymphoma: a population-based study of 44,879 survivors of Hodgkin lymphoma. Cancer 121 (9): 1436-45, 2015. [PUBMED Abstract]
- Boukheris H, Stovall M, Gilbert ES, et al.: Risk of salivary gland cancer after childhood cancer: a report from the Childhood Cancer Survivor Study. Int J Radiat Oncol Biol Phys 85 (3): 776-83, 2013. [PUBMED Abstract]
- da Cruz Perez DE, Pires FR, Alves FA, et al.: Salivary gland tumors in children and adolescents: a clinicopathologic and immunohistochemical study of fifty-three cases. Int J Pediatr Otorhinolaryngol 68 (7): 895-902, 2004. [PUBMED Abstract]
- Muenscher A, Diegel T, Jaehne M, et al.: Benign and malignant salivary gland diseases in children A retrospective study of 549 cases from the Salivary Gland Registry, Hamburg. Auris Nasus Larynx 36 (3): 326-31, 2009. [PUBMED Abstract]
- Fu H, Wang J, Wang L, et al.: Pleomorphic adenoma of the salivary glands in children and adolescents. J Pediatr Surg 47 (4): 715-9, 2012. [PUBMED Abstract]
- Galer C, Santillan AA, Chelius D, et al.: Minor salivary gland malignancies in the pediatric population. Head Neck 34 (11): 1648-51, 2012. [PUBMED Abstract]
- Thariat J, Vedrine PO, Temam S, et al.: The role of radiation therapy in pediatric mucoepidermoid carcinomas of the salivary glands. J Pediatr 162 (4): 839-43, 2013. [PUBMED Abstract]
- Chiaravalli S, Guzzo M, Bisogno G, et al.: Salivary gland carcinomas in children and adolescents: the Italian TREP project experience. Pediatr Blood Cancer 61 (11): 1961-8, 2014. [PUBMED Abstract]
- Laikui L, Hongwei L, Hongbing J, et al.: Epithelial salivary gland tumors of children and adolescents in west China population: a clinicopathologic study of 79 cases. J Oral Pathol Med 37 (4): 201-5, 2008. [PUBMED Abstract]
- Rahbar R, Grimmer JF, Vargas SO, et al.: Mucoepidermoid carcinoma of the parotid gland in children: A 10-year experience. Arch Otolaryngol Head Neck Surg 132 (4): 375-80, 2006. [PUBMED Abstract]
- Kupferman ME, de la Garza GO, Santillan AA, et al.: Outcomes of pediatric patients with malignancies of the major salivary glands. Ann Surg Oncol 17 (12): 3301-7, 2010. [PUBMED Abstract]
- Aro K, Leivo I, Mäkitie A: Management of salivary gland malignancies in the pediatric population. Curr Opin Otolaryngol Head Neck Surg 22 (2): 116-20, 2014. [PUBMED Abstract]
- Simon CT, McHugh JB, Rabah R, et al.: Secretory Carcinoma in Children and Young Adults: A Case Series. Pediatr Dev Pathol 25 (2): 155-161, 2022 Mar-Apr. [PUBMED Abstract]
- Ngouajio AL, Drejet SM, Phillips DR, et al.: A systematic review including an additional pediatric case report: Pediatric cases of mammary analogue secretory carcinoma. Int J Pediatr Otorhinolaryngol 100: 187-193, 2017. [PUBMED Abstract]
- Khalele BA: Systematic review of mammary analog secretory carcinoma of salivary glands at 7 years after description. Head Neck 39 (6): 1243-1248, 2017. [PUBMED Abstract]
- Locati LD, Collini P, Imbimbo M, et al.: Immunohistochemical and molecular profile of salivary gland cancer in children. Pediatr Blood Cancer 64 (9): , 2017. [PUBMED Abstract]
- Techavichit P, Hicks MJ, López-Terrada DH, et al.: Mucoepidermoid Carcinoma in Children: A Single Institutional Experience. Pediatr Blood Cancer 63 (1): 27-31, 2016. [PUBMED Abstract]
- Skálová A, Vanecek T, Sima R, et al.: Mammary analogue secretory carcinoma of salivary glands, containing the ETV6-NTRK3 fusion gene: a hitherto undescribed salivary gland tumor entity. Am J Surg Pathol 34 (5): 599-608, 2010. [PUBMED Abstract]
- Rutt AL, Hawkshaw MJ, Lurie D, et al.: Salivary gland cancer in patients younger than 30 years. Ear Nose Throat J 90 (4): 174-84, 2011. [PUBMED Abstract]
- Allan BJ, Tashiro J, Diaz S, et al.: Malignant tumors of the parotid gland in children: incidence and outcomes. J Craniofac Surg 24 (5): 1660-4, 2013. [PUBMED Abstract]
- Seng D, Fang Q, Liu F, et al.: Intraparotid Lymph Node Metastasis Decreases Survival in Pediatric Patients With Parotid Cancer. J Oral Maxillofac Surg 78 (5): 852.e1-852.e6, 2020. [PUBMED Abstract]
- Verma J, Teh BS, Paulino AC: Characteristics and outcome of radiation and chemotherapy-related mucoepidermoid carcinoma of the salivary glands. Pediatr Blood Cancer 57 (7): 1137-41, 2011. [PUBMED Abstract]
- Védrine PO, Coffinet L, Temam S, et al.: Mucoepidermoid carcinoma of salivary glands in the pediatric age group: 18 clinical cases, including 11 second malignant neoplasms. Head Neck 28 (9): 827-33, 2006. [PUBMED Abstract]
- Dublin JC, Oliver JR, Tam MM, et al.: Nodal Metastases in Pediatric and Adult Acinic Cell Carcinoma of the Major Salivary Glands. Otolaryngol Head Neck Surg 167 (6): 941-951, 2022. [PUBMED Abstract]
- Surun A, Schneider DT, Ferrari A, et al.: Salivary gland carcinoma in children and adolescents: The EXPeRT/PARTNER diagnosis and treatment recommendations. Pediatr Blood Cancer 68 (Suppl 4): e29058, 2021. [PUBMED Abstract]
- Ryan JT, El-Naggar AK, Huh W, et al.: Primacy of surgery in the management of mucoepidermoid carcinoma in children. Head Neck 33 (12): 1769-73, 2011. [PUBMED Abstract]
- Morse E, Fujiwara RJT, Husain Z, et al.: Pediatric Salivary Cancer: Epidemiology, Treatment Trends, and Association of Treatment Modality with Survival. Otolaryngol Head Neck Surg 159 (3): 553-563, 2018. [PUBMED Abstract]
- Grant SR, Grosshans DR, Bilton SD, et al.: Proton versus conventional radiotherapy for pediatric salivary gland tumors: Acute toxicity and dosimetric characteristics. Radiother Oncol 116 (2): 309-15, 2015. [PUBMED Abstract]
- Mao MH, Zheng L, Wang XM, et al.: Surgery combined with postoperative (125) I seed brachytherapy for the treatment of mucoepidermoid carcinoma of the parotid gland in pediatric patients. Pediatr Blood Cancer 64 (1): 57-63, 2017. [PUBMED Abstract]
- Drilon A, Siena S, Ou SI, et al.: Safety and Antitumor Activity of the Multitargeted Pan-TRK, ROS1, and ALK Inhibitor Entrectinib: Combined Results from Two Phase I Trials (ALKA-372-001 and STARTRK-1). Cancer Discov 7 (4): 400-409, 2017. [PUBMED Abstract]
- Drilon A, Laetsch TW, Kummar S, et al.: Efficacy of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Children. N Engl J Med 378 (8): 731-739, 2018. [PUBMED Abstract]
Sialoblastoma is usually a benign tumor presenting in the neonatal period, but it has been reported to present as late as age 15 years. Sialoblastoma rarely metastasizes to the lungs, lymph nodes, or bones.
The main treatment for patients with sialoblastoma is surgical resection. However, it has been suggested that neoadjuvant chemotherapy may be indicated as an alternative to mutilating surgery. Chemotherapy regimens with carboplatin, epirubicin, vincristine, etoposide, dactinomycin, doxorubicin, and ifosfamide have produced responses in two children with sialoblastoma.; [Level of evidence C3]
- Irace AL, Adil EA, Archer NM, et al.: Pediatric sialoblastoma: Evaluation and management. Int J Pediatr Otorhinolaryngol 87: 44-9, 2016. [PUBMED Abstract]
- Prigent M, Teissier N, Peuchmaur M, et al.: Sialoblastoma of salivary glands in children: chemotherapy should be discussed as an alternative to mutilating surgery. Int J Pediatr Otorhinolaryngol 74 (8): 942-5, 2010. [PUBMED Abstract]
- Scott JX, Krishnan S, Bourne AJ, et al.: Treatment of metastatic sialoblastoma with chemotherapy and surgery. Pediatr Blood Cancer 50 (1): 134-7, 2008. [PUBMED Abstract]
Special Considerations for the Treatment of Children With Cancer
Cancer in children and adolescents is rare, although the overall incidence has been slowly increasing since 1975. 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:
- Primary care physicians.
- Pediatric surgeons.
- Radiation oncologists.
- Pediatric medical oncologists/hematologists.
- Rehabilitation specialists.
- Pediatric nurse specialists.
- Social workers.
- Child-life professionals.
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. 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%.[3-5] 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. 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:
- 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 2 cases per 1 million people. However, three additional histologies (thyroid carcinoma, melanoma, and testicular cancer) with incidences of more than 2 cases per 1 million people were also included in the very rare group because there is a lack of knowledge and expertise in the management of these tumors.
- The Children's Oncology Group (COG) 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, colorectal cancers, etc.). 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.
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 Salivary Gland Cancer Treatment (Adult).
- 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]
- American Academy of Pediatrics: Standards for pediatric cancer centers. Pediatrics 134 (2): 410-4, 2014. Also available online. Last accessed May 19, 2023.
- Smith MA, Altekruse SF, Adamson PC, et al.: Declining childhood and adolescent cancer mortality. Cancer 120 (16): 2497-506, 2014. [PUBMED Abstract]
- National Cancer Institute: NCCR*Explorer: An interactive website for NCCR cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed May 19, 2023.
- Surveillance Research Program, National Cancer Institute: SEER*Explorer: An interactive website for SEER cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed February 13, 2023.
- 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]
- 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]
- 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]
- 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]
- 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]
Changes to This Summary (03/30/2023)
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.
Added text to state that a retrospective review identified 57 pediatric patients and 1,192 adult patients with acinic cell carcinoma. Clinical lymph node metastases (LNMs) were rare in children and adults. Occult LNMs were uncommon in pediatric patients and adult patients. The 3-year OS rate was 97.8% for pediatric patients. Adult patients with LNMs had worse 3-year OS rates than those without LNMs (cited Dublin et al. as reference 26).
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 salivary gland tumors. 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 Salivary Gland Tumors Treatment are:
- Denise Adams, MD (Children's Hospital Boston)
- Karen J. Marcus, MD, FACR (Dana-Farber Cancer Institute/Boston Children's Hospital)
- 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)
- D. Williams Parsons, MD, PhD (Texas Children's 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 Salivary Gland Tumors Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/head-and-neck/hp/child/salivary-gland-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 29337478]
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