96 I KENYA NATIONAL CANCER SCREENING GUIDELINES
CHILDHOOD CANCERS: SCREENING AND EARLY DETECTION
BURDEN OF CHILDHOOD CANCERS
There are about 3000 new cases of childhood cancer diagnosed in
Kenya every year
According to World Health Organization (WHO), a child is defined to be 19 years or younger. Globally, the annual incidence of cancer in children is estimated at 300,000 cases (GLOBOCAN, 2018). Low- and middle-income countries (LMICs) account for 84% of childhood cancers (Ian Magrath, 2013). The cure rate of childhood cancer in high in- come countries is >80%, compared to <10% in LMICs (IARC, 2016).
In Kenya, GLOBOCAN estimated that 3,272 new cancer cases were diagnosed in 2018 (Figure 1)
FIGURE 7: Estimated number of all childhood cancer cases in Kenya
RISK FACTORS FOR CHILDHOOD CANCERS
The causes for most childhood cancers are unknown; However, a few environmental and infectious agents have been implicated
Genetic factors, environmental factors such as exposure to ionising radiation and chemicals have been implicated in the causation of childhood cancers, but there is insufficient data to make conclusive associations (PAHO, 201S). Infectious agents have also been linked to certain cancers; for example, Epstein Barr Virus (EBV) with Burkitt’s lymphoma, Hodgkin’s lymphoma and nasopharyngeal carcinoma, Human Immunodeficiency Virus (HIV) with Kaposi’s sarcoma and malaria with Burkitt’s lym- phoma, Human Papilloma Virus (HPV) with head & neck cancers and Hepatitis B Virus (HBV) with hepatocellular carcinoma (PAHO, 201S).
Diagram 2: Risk factors associated with childhood cancer
RATIONALE FOR SCREENING
Screening for childhood cancers is recommended mainly for hered- itary retinoblastoma, certain genetic syndromes and in childhood cancer survivors
The majority of childhood cancers are not amenable to screening, apart from ret- inoblastoma (RB) and other rarer heritable conditions. Furthermore, unlike some adult cancers, childhood cancers are not associated with lifestyle. The emphasis therefore, in childhood cancers is early detection as there is high potential for cure.
WHO SHOULD BE SCREENED?
Screening is recommended for the following groups:
|•||Children with a family history of genetic cancers like RB, which may|
|•||Children with a history of RB – should be screened for RB in the|
|other eye and for other related cancers|
|•||Childhood cancer survivors – should be regularly screened for|
|secondary cancers due to their exposure to chemotherapy and|
|•||Children with some familial genetic syndromes associated with|
|cancers, such as shown below:|
RETINOBLASTOMA SCREENING AND GENETIC COUNSELLING
Retinoblastoma (RB) is a hereditary disease and is the most common cancer of the
eye affecting children less than 5 years of age. In Kenya, it accounts for 4.8% of all
childhood cancers and is estimated to have an incidence of 1 in 17,000 live births
(Nyamori & Kimani, 2011).
Bilateral RB, found in 40% of cases, is caused by an inherited or a new germline mu- tation in the RB1 gene (OMIM 180200). Positive family history of RB is reported in
10% to 15% of all RB patients.
RATIONALE FOR SCREENING FOR RB
It has been noted that in countries with comprehensive screening and early detec-
tion programs, cure rates of over 90% have been achieved.
Children with a family history of retinoblastoma have a higher risk for retinoblas- toma and require surveillance. Early diagnosis, when tumours are small, maximizes survival and vision outcomes and reduces the need for chemotherapy, enucleation, and radiotherapy. Because retinoblastoma tumours may develop over time during early childhood, serial evaluations are beneficial in detecting tumours early and thus preserving vision.
A child who has RB should have genetic testing to determine their susceptibility of developing RB in the other eye or developing related cancers. It is recommended that for children who test positive for RB gene, family members such as siblings and offspring should also be tested.
Genetic testing has been shown to improve risk prediction for patients and family members as well as prevent overutilization of clinical screening tests.
WHO SHOULD BE SCREENED?
A patient “at risk” is defined as a person with a family history of retinoblastoma in a
parent, sibling, or first- or second-degree relative.
At-risk family members found to carry the same RB1 mutation as the proband (pa-
tient with RB who is the starting point for genetic testing) benefit from early and
intensive screening for RB.
WHEN & HOW OFTEN TO SCREEN
Genetic testing should be done for at-risk family members.
• Children with a known RB1 mutation should have an eye examination every
3 to 6 weeks until age 1 year, and then every 3 months until age 3 years, and
then every 6 months until age 6 years. This examination should be carried out by
an ophthalmologist and requires examination under anaesthesia (EUA).
• Those who test negative for a familial RB1 mutation do not require
Screening where genetic testing is not available:
• Positive family history where the parent is proband – the child should be screened at birth (or soonest afterwards) then every month for 3 months, then 3-4 monthly up to 3 years.
• Siblings of children with RB should be screened at birth then after one month then 3-monthly for one year. If they are still clear of disease then screening can be stopped.
Diagram 3: Flow diagram on RB screening in the absence of genetic testing
SCREENING TESTS TO BE DONE
• Molecular genetic testing of the RB1 gene: Comprehensive genetic counselling
must be done prior.
• At community level, the healthcare provider should enquire about family
history of RB; if positive then refer for examination for children less than
2 years old.
Early detection/early diagnosis of childhood cancer results in better treat- ment outcomes.
EARLY DETECTION/ DIAGNOSIS OF CHILDHOOD CANCERS
Early detection of childhood cancers through early diagnosis results in better treatment outcomes. This depends on recognition, mainly at the community level where enhanced awareness regarding childhood cancers by parents and community health workers is important (Njuguna, 2016).
Every contact of a healthcare provider (HCP) with a child should provide an opportunity for comprehensive evaluation for possible signs and symptoms of cancer. It is important for the HCP to understand that cancer in children may present with non-specific signs and symptoms. When a child is examined and these signs and symptoms are found, cancer must be suspected and action taken accordingly to prevent late diagnosis.
COMMON SYMPTOMS AND SIGNS OF CHILDHOOD CANCER
Most of the signs and symptoms of childhood cancer are non-specific and require health care providers to have a high index of suspicion
The following are common symptoms and signs of childhood cancer:
• Continued, unexplained weight loss
• Recurrent or persistent fevers of unknown origin
• Constant tiredness or noticeable paleness
• Development of excessive bruising, bleeding, or rash
• Increased swelling or persistent pain in bones, joints,
back, or legs
• Lump or mass, especially in the abdomen, neck,
chest, pelvis, or armpits
• Rapidly growing mass on the jaw
• A mass in the abdomen with or without bloody urine
• Headaches, often with early morning vomiting
Diagram 4: Plausible signs and symptoms of childhood cancers
EARLY DIAGNOSIS AT VARIOUS HEALTHCARE LEVELS
Early detection of childhood cancers requires a high index of suspicion and appropriate
referral systems to avoid late presentation and worse outcomes. Figure 4 represents the
referral system for such patients but early referral to the comprehensive cancer centres
is also recommended when the cancer diagnosis is highly likely in order to avoid delays
and loss to follow up of patients.
The following are the roles of healthcare providers at each level of care:
1. Community level:
CHWs to mobilize parents or guardians of children with above symptoms to visit the nearest health facility.
2. Level 2 & 3 (Primary healthcare facility) – Dispensary & health centre
• Evaluate the child using the Childhood Cancer Assessment Tool for
early detection of cancer (see Figure 6)
• Generate comprehensive referral document and refer appropriately to
higher levels of care
3. Level 4 – Sub-county/County Hospital
• Comprehensive physical examination and identification of plausible
• Basic lab investigations such as TBC and PBF, UEC, LFTs
• Imaging tests such as ultrasound and x-ray
• Supportive care such as blood transfusions; treatment of infections,
palliative care and pain management
• Generate comprehensive referral documentation to a childhood
comprehensive cancer care center.
4. Comprehensive Cancer Care Centre (Level 5 and 6)
• All the activities done at lower levels of care above
• Management of cancer cases
THE IMCI (INTEGRATED MANAGEMENT OF CHILDHOOD ILLNESSES) APPROACH FOR ASSESSING A CHILD FOR POSSIBLE CANCER: Child- hood Cancer Assessment tool
The diagram below is suitable to guide HCPs at all levels to diagnose childhood cancers early. They should classify the child’s health status through the given colour coding sys- tem, and take the corresponding required actions:
• RED – Urgent treatment and referral
• YELLOW – Outpatient treatment and advice
• GREEN – Advice on treatment and home care
Diagram7: Childhood cancer assessment tool
HCPs need to have a high index of suspicion for early detection of childhood cancers through an integrated approach.
Bowman J, Mafwiri M, Luthert P, et al. Outcome of Retinoblastoma in East Africa. Pedi- atric Blood Cancer 2008; 50: 160- 162 (lower rates of cure in LMIC)
GLOBOCAN 2018 Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for
36 cancers in 185 countries. CA Cancer J Clin. 2018 Sep 12. doi: 10.3322/caac.21492.
Harif M, Traore F, Hessissen L, et al. Challenges for paediatric oncology in Africa. Lancet
Oncol 2013; 14:279-81
MacCarthy A, Birch J.M, Draper G. J et al. Retinoblastoma: treatment and survival in
Great Britain 1963 to 2002. British Journal of Ophthalmology2009; vol. 93, no. 1, pp.
38-39. (High cure rates in High Income countries)
Njuguna F., Martijn H., Langat S. et al. Factors Influencing Time to Diagnosis and Treat- ment among Pediatric Oncology Patients in Kenya. Pediatric Hematology and Oncol- ogy 2016; 33:186-99
Nyamori J, Kimani K, Njuguna M et al. The incidence and distribution of retinoblastoma in Kenya. Br J Ophthalmol 2011; doi:10.1136/bjophthalmol-2011-300739 (RB incidenc- es in Kenya)
Steliarova-Foucher E, Colombet M, Ries LAG, Hesseling P, Moreno F, Shin HY, Stiller CA, editors (2017). International Incidence of Childhood Cancer, Volume III (electronic version). Lyon, France: International Agency for Research on Cancer. Available from: http://iicc.iarc.fr/results/, accessed [25/07/2018].
World Health Organization. 2014. Early Diagnosis of Childhood Cancer. Washington, DC: PAHO.