- • Thyroid cancer incidence (1998−2017) in Cypriot 0–19-year-olds among world’s highest.
- • Increasing temporal trends affect males and females of the 15−19-year age group.
- • Females 3.5 times more often affected; papillary carcinoma was the dominant type.
- • There was almost 4-fold increase in metastatic cases, but 100 % survival.
- • Thyroid cancer after previous cancer therapy did not contribute to increasing rate.
Paediatric and adolescent thyroid cancer incidence rates are increasing in many countries. We determined incidence rates, temporal trends and survival from thyroid cancer diagnosed in childhood and adolescence in Cyprus during 1998−2017.
Patients aged 0–19 years, diagnosed with thyroid cancer in the Pediatric Oncology Registry of Cyprus were included. Crude incidence rates, age standardized rates, time trends and overall survival were analysed. Annual rates and temporal trends were calculated using Microsoft Excel 2016 and Joinpoint regression analysis.
Eighty-one cases (76.5 % female, 23.5 % male) were identified. The crude rates (per 100,000 persons) were for both sexes 2.00 (95 % CI 1.61, 2.49), females 3.15 (95 % CI 2.45, 4.03) and males 0.92 (95 % CI 0.58, 1.44). The annual percentage changes of crude and standardised rates were 7.5 % (p < 0.05) and 7.6 % (p < 0.05). The annual percentage changes of crude rates were for females 5.1 % (p = 0.1), males 8.4 % (p < 0.05) and 15−19-year-olds 7.6 % (p < 0.05). The female to male rate ratio was 3.42 (95 % CI 2.06, 5.74). Papillary thyroid carcinoma represented 86.4 % of all cases. There was only one case after previous cancer therapy. The rate ratio of 2nd (2008−2017) to 1st (1998−2007) periods for metastatic (regional) stages was 3.76 (95 % CI 1.74, 8.31). Survival until 2018 was 100 %.
This population-based study demonstrated that thyroid cancer incidence rates in 0–19-year-olds in Cyprus was among the world’s highest. Increasing trends mainly affected males and females aged 15−19 years with papillary thyroid carcinoma, the dominant type. Cases after previous cancer therapy didn’t contribute to increasing rates. The increase of metastatic cases suggests a true increase of thyroid cancer rather than overdiagnosis. Although prognosis is excellent with 100 % survival, the rising incidence rate is unexplained, indicating the need to identify causes.
Thyroid cancer (TC) develops more commonly in adults, but also in children and adolescents. Over the last decades the incidence of TC has been significantly increasing worldwide [ ]. This pattern was also documented for paediatric and adolescent thyroid cancer (PATC) [ , ]. Although rare, it is the most common endocrine tumor in the 0–19-year age group [ ]. It represents 0.5 %–1.5 % of all cancers in the 0–19 age group [ , ] and 1.8 % of all TCs occurring at any age [ ]. In the paediatric population it is more frequent in the group aged 15−19 years, in females [ ] and 10 times more frequent in adolescents than in younger children [ ].
Differentiated thyroid carcinoma (DTC) is the predominant type, with IR (incidence rate) 0.02 to 0.3 per 100,000 children [ ]. The DTC includes papillary thyroid carcinoma (PTC, 85 %–95 % of cases), follicular carcinoma (5 %–10 %), both more frequent in 15−19-year-olds [ , ], and Hürthle cell carcinoma [ ]. Medullary carcinoma (MTC, 10 % of cases) is more frequent in the 0–4 age group [ ] and anaplastic carcinoma (1 %) [ ] is rare.
In childhood and adolescence, TC presents with more advanced stage, but overall better long term outcome [ , ] than in adults. It is usually painless, multifocal, with local metastases at the neck lymph nodes with up to 25 % of the cases presenting with pulmonary metastasis [ ].
The aetiology of PATC is not well understood and has been associated with environmental, genetic, hormonal and nutritional factors. Exposure to low dose diagnostic radiation, radiotherapy for benign conditions, radiotherapy and chemotherapy for malignant diseases inducing second cancers [ ], atomic bomb explosions in Japan [ ] and the Chernobyl nuclear accident in 1986 [ , ] highlight the role of environmental factors. Radioisotope ingestion may have a greater role in children than external irradiation [ , , ]. Autoimmune diseases [ , ] and nutritional iodine deficiency are also implicated in PTC.
DNA alterations observed in hereditary and de novo PATC may be different than in adulthood [ , ]. The genes involved in PATC include RET, NTRK, BRAF, RAS and DICER1 [ , ]. PATC can occur in individuals affected by cancer predisposition syndromes (CPS) [ , ].
The increasing temporal trends in TC incidence in adults was also found for PATC by Vaccarella et al. who suggested that overdiagnosis could have a major role in children and adolescents as well as in adults [ ]. While in a number of countries a significantly increasing IR of PATC has been documented [ , , , ], this is not a universal finding [ , ]. It also remains unclear whether any apparent rises are due to increased detection or true increase of PATC (at least in some populations). Incidence studies in less well examined regions would be of considerable value.
In Cyprus, in a study of people of all ages, during 1998–2008, Cooter et al. demonstrated rapid increases in TC rates, particularly in women [ ]. However, the epidemiology of PATC has not been investigated in detail previously in Cyprus. The purpose of this study was to determine the IRs, temporal trends and survival of TC in the 0–19-age group in Cyprus by conducting a novel population-based study for the 20-year period 1998−2017.