Risk of subsequent primary oral cancer in a cohort of 69,460 5-year survivors of childhood and adolescent cancer in Europe: the PanCareSurFup study

Abstract

Background Survivors of childhood cancer are at risk of subsequent primary malignant neoplasms (SPNs), but the risk for rarer types of SPNs, such as oral cancer, is uncertain. Previous studies included few oral SPNs, hence large-scale cohorts are required to identify groups at risks. Methods The PanCareSurFup cohort includes 69,460 5-year survivors of childhood cancer across Europe. Risks of oral SPNs were defined by standardised incidence ratios (SIRs), absolute excess risks and cumulative incidence. Results One hundred and forty-five oral SPNs (64 salivary gland, 38 tongue, 20 pharynx, 2 lip, and 21 other) were ascertained among 143 survivors. Survivors were at 5-fold risk of an oral SPN (95% CI: 4.4–5.6). Survivors of leukaemia were at greatest risk (SIR = 19.2; 95% CI: 14.6–25.2) followed by bone sarcoma (SIR = 6.4, 95% CI: 3.7–11.0), Hodgkin lymphoma (SIR = 6.2, 95% CI: 3.9–9.9) and soft-tissue sarcoma (SIR = 5.0, 95% CI: 3.0–8.5). Survivors treated with radiotherapy were at 33-fold risk of salivary gland SPNs (95% CI: 25.3–44.5), particularly Hodgkin lymphoma (SIR = 66.2, 95% CI: 43.6–100.5) and leukaemia (SIR = 50.5, 95% CI: 36.1–70.7) survivors. Survivors treated with chemotherapy had a substantially increased risk of a tongue SPN (SIR = 15.9, 95% CI: 10.6–23.7). Conclusions Previous radiotherapy increases the risk of salivary gland SPNs considerably, while chemotherapy increases the risk of tongue SPNs substantially. Awareness of these risks among both health-care professionals and survivors could play a crucial role in detecting oral SPNs early.

Late Complications in Long-Term Childhood Cancer Survivors: What the Oral Health Professional Needs to Know

“…These malignancies may develop years after pediatric cancer treatment. A large European study investigating oral cancer risk in almost 70,000 long-term CCS reported an overall 5-fold increased risk of developing oral cancer as compared to the general population [15]. Hodgkin lymphoma and leukemia survivors treated with head and neck radiotherapy were at a 33-fold increased risk of developing salivary gland tumors, whereas CCS treated with chemotherapy had a substantially increased risk of tongue cancer (RR = 5.6, 95% CI: 1.0-31.2) [15].…”

“…A large European study investigating oral cancer risk in almost 70,000 long-term CCS reported an overall 5-fold increased risk of developing oral cancer as compared to the general population [15]. Hodgkin lymphoma and leukemia survivors treated with head and neck radiotherapy were at a 33-fold increased risk of developing salivary gland tumors, whereas CCS treated with chemotherapy had a substantially increased risk of tongue cancer (RR = 5.6, 95% CI: 1.0-31.2) [15]. A large study among recipients of allogeneic HCT found that young age at transplantation, total body radiation, and (a history of) cGVHD contributed to an increased risk of oral squamous cell carcinoma [87].…”

“…Screening should not be limited to the oral cavity, but should include inspection of the facial skin, as well as inspection and palpation of lymph nodes, salivary glands, and the thyroid gland for enlargement and nodules. Given the increased risk of various cancers, smoking and excessive alcohol use should be discouraged [15,92].…”

“…Tooth development, salivary gland function, craniofacial growth, and temporomandibular joint function might be disturbed and lead to decreased oral health and oral health-related quality of life [12,13]. Furthermore, CCS are at risk for developing subsequent malignancies, which may manifest in or near the oral cavity [14,15].…”