Skip Navigation


Annals of Oncology Advance Access originally published online on July 28, 2007
Annals of Oncology 2007 18(10):1716-1721; doi:10.1093/annonc/mdm278
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
18/10/1716    most recent
mdm278v1
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Gosepath, J.
Right arrow Articles by Mann, W. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gosepath, J.
Right arrow Articles by Mann, W. J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2007 European Society for Medical Oncology

epidemiology

Incidence of childhood cancer of the head and neck in Germany

J. Gosepath1,*, C. Spix2, B. Talebloo1, M. Blettner3 and W. J. Mann1

1 Department of Otolaryngology, Head and Neck Surgery, School of Medicine, University of Mainz, Mainz
2 German Childhood Cancer Registry at the Institute for Medical Biostatistics, Epidemiology and Informatics, University of Mainz, Mainz
3 Institute for Medical Biostatistics, Epidemiology and Informatics, University of Mainz, Mainz, Germany

* Correspondence to: Dr J. Gosepath, Universitaets-HNO-Klinik, Langenbeckstrasse 1, 55101 Mainz, Germany. Tel: +49-6131-177361; Fax: +49-6131-176637; E-mail: gosepath{at}hno.klinik.uni-mainz.de


   Abstract
Top
 Abstract
introduction
 material and methods
 results
 discussion
 conclusion
 Acknowledgements
 References
 
Background: Only very limited data are available in the literature on the incidence of childhood cancer of the head and neck worldwide.

Methods: Based on data obtained from the national German Childhood Cancer Registry, a total of 370 malignancies of the head and neck in children under the age of 15 (199 boys and 171 girls), which were reported to this institution between 1994 and 2003, were analysed in this study.

Results: The overall incidence of malignancies of specific sites of the head and neck in Germany is 4.48 per 100000 children. The most frequently observed entities, representing primary tumours, are soft tissue sarcomas (0.39/100000), lymphomas (0.09/100000) and thyroid carcinoma (0.07/100000). The most commonly affected organs are the thyroid (1.21/100000), orbita (0.91/100000), nasopharynx (0.66/100000), tonsils (0.43/100000) and paranasal sinuses (0.14/100000). Overall, boys are more frequently affected than girls; however, incidence increases in girls with age and exceeds that of boys in the age group between 10 and 14 years.

Conclusions: This is a first statistical evaluation detailing cumulative incidences of various histologic types of malignancies of the head and neck including age and gender distribution as well as organ-specific localization in children below the age of 15 in Germany.

Key words: epidemiology, head and neck cancer, children, histology, age distribution, German Childhood Cancer Registry


   introduction
Top
 Abstract
 introduction
material and methods
 results
 discussion
 conclusion
 Acknowledgements
 References
 
The aim of this study was to investigate the incidence, localization, age distribution and gender preferences of malignant head and neck tumours of various histologies in the paediatric population of Germany. To date no evaluation of this kind has been published, neither worldwide nor for Germany. This study reflects data on tumours in the head and neck area treated in paediatric oncology centres. It therefore excludes benign tumours (such as ganglioneuroma).

As a data base we used all cases reported to the German Childhood Cancer Registry (GCCR) between 1994 and 2003. The population-based GCCR has been in operation since 1980 and is based in Mainz, Germany. It covers all of Germany, is almost complete and fulfils the international criteria for a high-quality registry [1]. After the reunification of Germany in 1990 the new federal states were included in the registry. Between 1994 and 2003 the completeness of the data assessment reached levels above 95%. All children who were German residents and diagnosed with a malignant primary tumour of a specific site of the head and neck before their 15th birthday were included in our study.

This descriptive analysis was designed primarily to target the following objectives:

  • Which are the predominant malignant entities contributing to head and neck cancer in children?
  • Do certain tumours have a gender-specific incidence in the head and neck region in children?
  • Which age groups of children are predominantly affected?
  • Which organs are specifically affected by which tumours in which incidence?
The results of this assessment will be discussed in relation to existing data on malignancies of other age groups. This analysis should help to bring about a more realistic and evidence-based perception of the risk of dealing with a malignancy in various childhood pathologies. This could be helpful as a first step toward early detection of suspicious lesions and therefore have a potential impact on outcome and prognosis for this patient group.


   material and methods
Top
 Abstract
 introduction
 material and methods
results
 discussion
 conclusion
 Acknowledgements
 References
 
All data used for this study were acquired from the GCCR. The number of children under 15 living in Germany is fairly constant at about 13 million, and approximately 1800 cases of head and neck cancer. *Between 1980 and 2004 a total of 35367 malignancies in total were reported and assessed in children under the age of 15. This analysis is based on data gathered from primary tumours that were diagnosed between 1994 and 2003. Age and sex of all patients are known. All cases included in this study are defined in the International Classification of Childhood Cancer (ICCC) [2]. The malignancies were characterized in detail regarding their morphology, topography and organ manifestation using the International Classification of Diseases for Oncology (ICD-O-2) code, as published by the Word Health Organization in 1990 [3]. This dual classification includes a code for localization and a second one for histology of a neoplastic lesion.

The following sites were selected as relevant: tongue, gum, floor of mouth, palate, mouth, parotid, submandibular gland, tonsils, oropharynx, nasopharynx, hypopharynx, pharynx, Waldeyer's ring, nasal cavity, middle ear, maxillary sinus, sphenoid sinus, accessory sinus, glottis, trachea, orbita and thyroid gland. Skin tumours (ICCC XId,e), central nervous system tumours (ICCC III) and retinoblastoma (ICCC V) were excluded specifically.

Based on this selection, 370 tumours registered in the GCCR 1994–2003 for children aged below 15 were identified as malignant neoplasms of the head and neck (199 boys and 171 girls). These 370 tumours identified for the study belonged to the ICCC classes specified as lymphomas (IIa–c), nervous system tumours (IV), chondrosarcomas (VIIIb), soft tissue sarcomas except for Kaposi's sarcoma (IXa,b,d,e), non-gonadal germ cell tumours (Xb), thyroid and nasopharyngeal carcinomas (XIb,c) and other carcinomas (XIf). In the years 1994–2003, 5078 cases below 15 years of age with these malignant diseases were observed by the GCCR in Germany overall. The 370 cases from the preselected head and neck localizations are 7.3% of these.

Another 1035 tumours out of these 5078 were either not clearly attributed to be primarily originating from the head and neck region or not from a specific region in the head and neck area and were therefore not included. The remaining 3673 cases were definitely not located in the head and neck region.

Only primary tumours were included, not metastatic disease or second primaries. All incidences given in this study refer to the period between 1994 and 2003 and are presented as cases per 100000 children in Germany. Incidences are presented by the age groups relevant in paediatrics (<1, 1–<4, 5–<9, and 9–<14) and are summed up as cumulative incidences, giving an estimate of the risk of a newborn developing the respective tumour before its 15th birthday. To be able to compare incidences of various topographic regions or age groups, we used age standardization by the world standard. This is specifically of interest for entities that are age-dependent.


   results
Top
 Abstract
 introduction
 material and methods
 results
discussion
 conclusion
 Acknowledgements
 References
 
Analysis of the data yielded the following for malignant tumours of the head and neck in children in Germany. Table 1 gives the incidence rates and cumulative incidence of all head and neck tumours, by age and sex. Table 2 summarizes the incidences of the observed histologies in all 370 tumours diagnosed as head and neck cancer between 1994 and 2003 by ICCC classes. Interestingly, looking at incidences of malignancies in boys and girls, boys are affected more frequently up until the age of 9; however, the incidence in girls rises with age and outweighs that of boys in the group of 10- to 14-year-old children (Figure 1).


View this table:
[in this window]
[in a new window]

  		Table 1. Incidences of all primary malignant tumours with a specific localization in the head and neck area diagnosed in children in Germany between 1994 and 2003 (n = 370)

 

View this table:
[in this window]
[in a new window]

  		Table 2. Primary paediatric tumours in Germany, 1994–2003, with a specific localization in the head and neck area by tumour classes based on ICCC [2] (n = 370)

 

Figure 1
View larger version (31K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Figure 1. Sex-specific cumulative incidences of primary malignant tumours of the head and neck in different age groups in children in Germany, 1994–2003 (n = 370).

 
Following the ICD-O-2 codes, all 370 tumours could be exactly classified as to their topographic and organ-specific manifestation in the head and neck region (Table 3). Combining these data with the morphology classification of the ICD-O-2 as summed up in the ICCC, we also calculated the organ-specific frequencies of various histologies within the 370 tumours (Table 4).


View this table:
[in this window]
[in a new window]

  		Table 3. Primary paediatric tumours in Germany, 1994–2003, with a specific localization in the head and neck area by localizations based on ICD-O-2 (n = 370)

 

View this table:
[in this window]
[in a new window]

  		Table 4. Primary paediatric tumours in Germany, 1994–2003, with a specific localization in the head and neck area by morphology based on ICD-O-2, as summed up in the ICCC [2] (n = 370)

 

   discussion
Top
 Abstract
 introduction
 material and methods
 results
 discussion
conclusion
 Acknowledgements
 References
 
A search of the international literature reveals that so far there has not been a thorough work-up of the incidences of head and neck cancer for paediatric tumours like the one presented in this analysis on an international or national level. The data are difficult to compare to other existing overviews or statistics. The American statistics based on the Surveillance Epidemiology and End Results (SEER) study are of a different structure as they either assess incidences of tumours within the whole body (in children) or of the head and neck, but without any stratification for age groups [4]. One needs to be aware of the different selection criteria at the basis of this study and other publications when interpreting the results presented. We extracted 370 cases where we could clearly attribute histologically malignant disease, as classified by the ICCC, of children diagnosed with a primary tumour before their 15th birthday to a specific localization in the head and neck area. However, in 1035 further cases of lymphomas, nervous system tumours or soft tissue sarcomas, of all 5078 cases of paediatric cancer reported to the GCCR between 1993 and 2004, a localization (also) in the head and neck region was coded, but no specific part of the head, face or neck area was given, based on the ICD-O-2 coding. This is especially true for the numerous manifestations of lymphoma with widespread disease, where involvement of the head and neck region is often observed but not reported to the registry, as it is not with certainty identifiable as the primary tumour site. In an effort to exclude any vague or inaccurate data from our analysis we excluded all these cases, focusing on those 370 (7.3% of the total of 5078) undoubtedly representing primary malignomas of the head and neck.

Apart from these, another 56 cases below the age of 15 with second primary tumours were observed in the ICCC classes included. Of these, 16 were non-Hodgkin lymphoma (NHL) (IIb) and nine were thyroid carcinoma (XIb). More than half of these 56 cases were aged 10 years or older, though two were infants. Thirteen of these had a second primary tumour in the head and neck region, specifically the nine thyroid carcinomas; the other four were a non-Hodgkin lymphoma (IIb), a nasopharyngeal carcinoma and two other carcinomas (XIf). Most of these cases were aged 12 years or older; the youngest case was 6 years old.

There are, however, numerous reports on incidences of cancer in the literature that include or focus on the paediatric population: The Swiss Childhood Cancer Registry (SCCR) in its annual report for 2004 published incidences of malignancies in children, but not by localization [5]. Carcinomas of the nasopharynx or the thyroid, the only two tumours specific to the head and neck area, are included under ‘other diagnoses’ in this report. The Charles group from Pittsburgh published incidences of childhood cancer in the head and neck region based on data on 241 children in their book Pediatric Otolaryngology [6]. These incidences are not further analysed as to age- or sex-related characteristics. Other publications from the USA mostly relate to individual federal states and do not give specific data for head and neck cancer [7, 8] A 2003 study from Finland of oropharyngeal cancer looked at incidences in men and women between 1953 and 1999, but did not stratify for age [9]. Chokunonga et al. compared the incidences of cancer in the total population of Harare, Zimbabwe in the time period between 1993 and 1995 with that of the same population between 1990 and 1992 [10]. No further specifications of age groups or gender were given.

The frequencies of the most common childhood malignancies in the head and neck area in Germany based on the population of 370 boys and girls assessed by the GCCR are given in Tables 2 and 4. The most frequent entities will be discussed in detail below.

soft tissue sarcomas (cumulative incidence of 0.39 per 100000 children)
Analysing our data we found that soft tissue sarcomas are by far the most common malignancy of the head and neck in children, representing 147 of all 370 tumours. Interestingly, 76 of these (51.7%) are located in the orbita and another 21 (14.3%) in the nasopharynx. They contribute to 68.3% (28/41) of all sinunasal cancers in children, 39.7% of all investigated paediatric malignomas in the head and neck area. Of all soft tissue sarcomas found here, 70% are rhabdomyosarcomas (RMS), with a preponderance of the male gender of 1.2:1, which would be expected for soft tissue sarcomas independent of localization. It is known that 52% of all children diagnosed with RMS are under the age of 5 [11]. Looking at the whole body, RMS have an incidence of 0.5 per 100000 children and are the third most common solid tumour (excluding central nervous system tumours) after neuroblastoma and Wilms' tumour [11, 12]. In the USA 250 cases of RMS are diagnosed each year and 65% of the children thus diagnosed are under the age of 6 [13]. Interestingly, there seems to be a female predominance with regard to RMS in this population [14, 15].

lymphomas and reticuloendothelial neoplasms (cumulative incidence of 0.09 per 100000 children)
According to our data non-Hodgkin lymphoma (excluding Burkitt's lymphoma), accounting for 16.2% of the 370 tumours, exceed in frequency Hodgkin's disease (HD), accounting for only 0.5%. This is different from the general manifestations, where HD is only slightly less frequent than NHL, and thus most likely reflects the coding conventions with respect to localization in the national treatment protocols. Moran and Ultmann [16] point out that lymphoma, especially HD, is rare under the age of 5 and mostly affects adolescents and adults. We found 50% of all NHL manifestations in the tonsils and 20% in the nasopharynx. Boys are diagnosed with NHL twice as often as girls and the incidence increases with age, as would be expected for NHL in general [11]. As stated earlier, we assume that the incidences reported here for lymphoma manifestations in the head and neck area are underestimated, as primarily widespread findings are common in this systemic disease and are thus not registered as head- or neck-specific. This is emphasized by a comparison to the numbers of Charles et al. [6], who report higher incidences for both diseases. Following our data, lymphomas primarily manifest in the tonsils are mostly other non-Hodgkin lymphomas, but Burkitt's lymphoma is found in 19% of these and has a male predisposition of 7.5:1, as expected.

thyroid carcinoma (cumulative incidence of 0 .07 per 100000 children)
Thyroid carcinomas represent 27.6% of all tumours included in this study. Of all reported cases, 67.3% were diagnosed in children between the ages of 10 and 15. Papillary carcinomas accounted for 53% of cases, while 21% were medullary and 13% were follicular carcinomas. Both Charles et al. and Young et al. [6, 13] reported slightly higher incidences as they included secondary tumours. Even in children under 15, a number of thyroid carcinomas are radiogenic after dosages of 18 to 45 gray, with over 90% being of the papillary type [17–19].

neuroblastoma and other sympathetic nervous system tumours (cumulative incidence of 0.02 per 100000 children)
Neuroblastomas are considered the most common solid extracranial neurogenic tumours of the head and neck in children and show a decreasing incidence with age. Although less so than for lymphomas, the coding of the localization for neuroblastoma might lead to some underestimation of their incidence in the head and neck region; however, most of those tumours potentially missed in this localization would be metastatic disease rather than primary tumours. We found 2% of the head and neck tumours to be neuroblastomas, mostly ganglioneuroblastomas. Nevertheless, Charles et al. found neuroblastoma in 5% of all paediatric head and neck tumours [6].

nasopharyngeal carcinoma (cumulative incidence of 0.01 per 100000 children)
With an overall incidence of 1–3% of all malignancies in children [17, 18, 21] and 6.2% of all 370 tumours investigated in the present study, nasopharyngeal carcinomas seem comparable to the 5% observed by the Charles group in Pittsburgh in their analysis reflecting their experience between 1965 and 1985 [6]. We saw a predominance of the male gender of 1.5:1 and a marked increase with age, with 96% of these tumours being found in children between 10 and 14 years of age. It is known that there is a geographic variation, with the highest incidence being in Asia and Africa and a causative coincidence with Epstein-Barr virus in many cases [20].

Among the far less frequent remaining entities in the GCCR data were chondrosarcomas and non-gonadal germ cell tumours. Of all the histological entities described, the most common localizations are thyroid, orbita, nasopharynx and tonsils, followed by the accessory sinuses.


   conclusion
Top
 Abstract
 introduction
 material and methods
 results
 discussion
 conclusion
Acknowledgements
 References
 
The data presented in this study are meant to give an overview concerning incidences of childhood cancer of the head and neck, to give a rationale for risk assessment when confronted with unclear masses in children presenting at otolaryngeal clinics and to facilitate a targeted work-up for these patients based on the incidences calculated. This could be helpful in an early and correct diagnosis, which—just as in any age group—is correlated with a chance for better treatment options and potentially associated with better prognosis.


   Acknowledgements
Top
 Abstract
 introduction
 material and methods
 results
 discussion
 conclusion
 Acknowledgements
References
 
This work was supported by the Stiftung Tumorforschung Kopf- Hals foundation, Wiesbaden, Germany.

This study was partly funded by Deutsche Krebshilfe eingetragener Verein (106259).

The funding agencies did not have a role in study design, data collection, analysis or interpretation or the writing or submission of this report.

Received for publication March 7, 2007. Revision received May 8, 2007. Accepted for publication May 9, 2007.


   References
Top
 Abstract
 introduction
 material and methods
 results
 discussion
 conclusion
 Acknowledgements
 References
 
1. Kaatsch P. German Childhood Cancer Registry and its favorable setting. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz (2004) 47(5):437–443.[CrossRef][Medline]

2. Kramarova E, Stiller CA. The International Classification of Childhood Cancer. Int J Cancer (1996) 68:759–765.[CrossRef][ISI][Medline]

3. Percy C, van Holten V, Muir C, eds. International Classification of Diseases for Oncology (1990) 2nd edn. Geneva: World Health Organization. ICD-O-2.

4. Surveillance Epidemiology and End Results. United States Cancer Statistics 2002: Incidence and Mortality Statistics on Cancer Incidence and Mortality from the CDC's National Program of Cancer Registries (NPCR) and the SEER Program. http://seer.cancer.gov/.

5. Swiss Childhood Cancer Registry. SCCR Annual Report 2004. http://www.kinderkrebsregister.ch/.

6. Charles D, Bluestone MD, Sylvan E, et al. Pediatric Otolaryngology (1990) 2nd edn. Philadelphia: W.B. Saunders.

7. Bandi P, Dranger E, Hampton JM, et al. Trends in childhood cancer incidence in Wisconsin, 1980–1999. Wisconsin Med J (2006) 105(7):30–37.

8. Thompson JA, Carozza SE, Zhu L. An evaluation of spatial and multivariate covariance among childhood cancer histotypes in Texas (United States). Cancer Causes Control (2007) 18(1):105–113.[CrossRef][ISI][Medline]

9. Tarvainen L, Suuronen R, Lindqvist C, et al. Is the incidence of oral and pharyngeal cancer increasing in Finland? An epidemiological study of 17,383 cases in 1953–1999. Oral Dis (2004) 10(3):167–172.[CrossRef][ISI][Medline]

10. Chokunonga E, Levy LM, Basset MT, et al. Cancer incidence in the African population of Harare, Zimbabwe: second results from the cancer registry 1993–1995. Int J Cancer (2000) 85(1):54–59.[CrossRef][ISI][Medline]

11. Kaatsch P, Spix C. Jahresbericht des Deutschen Kinderkrebsregisters 2005 (2006) Mainz: Johannes Gutenberg-University of Mainz.

12. Kramer S, Meadows AT, Jarett P, et al. Incidence of childhood cancer: experience of a decade in a population-based registry. J Natl Cancer Inst (1983) 70(1):49–55.[ISI][Medline]

13. Young JL, Ries LG, Silverberg E, et al. Cancer incidence, survival, and mortality for children younger than age 15 years. Cancer (1986) 58(Suppl 2):598–602.[CrossRef][Medline]

14. Wexler L, Helman L. Rhabdomyosarcoma and the undifferentiated sarcomas. In: Principles and Practice of Pediatric Oncology—Pizzo P, Poplack D, eds. (1997) 3rd edn. Philadelphia: Lippincott-Raven. 799–829.

15. Christ W, Gehan EA, Ragab AH, et al. The Third Intergroup Rhabdomyosarcoma Study. J Clin Oncol (1995) 13:610–630.[Abstract/Free Full Text]

16. Moran E, Ultmann J. Clinical features and course of Hodgkin's disease. Clin Haematol (1974) 3:91–93.[Medline]

17. Black P, Straaten A, Gutjahr P. Secondary thyroid carcinoma after treatment for childhood cancer. Med Pediatr Oncol (1998) 31(2):91–95.[CrossRef][ISI][Medline]

18. Greenspan FS, Forsham PH, eds. Basic and Clinical Endocrinology (1986) 2nd edn. New York: Los Altos. Appleton and Lange.

19. Morrof SV, Fuks JZ. Thyroid cancer following radiotherapy for Hodgkin's disease: a case report and review of the literature. Med Pediatr Oncol (1986) 14:216–220.[CrossRef][ISI][Medline]

20. Ingesoll L, Woo SY, Donaldson S, et al. Nasopharyngeal carcinoma in the young: a combined M.D. Anderson and Standford experience. Int J Radiat Oncol Biol Phys (1990) 19:881–887.[ISI][Medline]

21. Mertens R, Granzen B, Lassay L, et al. Nasopharyngeal carcinoma in childhood and adolescence. Cancer (1997) 80:951–959.[CrossRef][ISI][Medline]


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?



This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
18/10/1716    most recent
mdm278v1
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Gosepath, J.
Right arrow Articles by Mann, W. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gosepath, J.
Right arrow Articles by Mann, W. J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?