Inflammatory marker testing in primary care in the year before Hodgkin lymphoma diagnosis: a UK population-based case–control study in patients aged ≤50 years

BACKGROUND: Proinflammatory conditions are associated with increased risk of Hodgkin lymphoma, although the neoplastic process per se often induces an inflammatory response. AIM: To examine pre-diagnostic inflammatory marker test use to identify changes that may define a ‘diagnostic window’ for potential earlier diagnosis. DESIGN AND SETTING: This was a matched case–control study in UK primary care using Clinical Practice Research Datalink data (2002–2016). METHOD: Primary care inflammatory marker test use and related findings were analysed in 839 Hodgkin lymphoma patients and 5035 controls in the year pre-diagnosis. Poisson regression models were used to calculate monthly testing rates to examine changes over time in test use. Longitudinal trends in test results and the presence/absence of ‘red-flag’ symptoms were examined. RESULTS: In patients with Hodgkin lymphoma, 70.8% (594/839) had an inflammatory marker test in the year pre-diagnosis versus 16.2% (816/5035) of controls (odds ratio 13.7, 95% CI = 11.4 to 16.5, P<0.001). The rate of inflammatory marker testing and mean levels of certain inflammatory marker results increased progressively during the year pre-diagnosis in Hodgkin lymphoma patients while remaining stable in controls. Among patients with Hodgkin lymphoma with a pre-diagnostic test, two-thirds (69.5%, 413/594) had an abnormal result and, among these, 42.6% (176/413) had no other ‘red-flag’ presenting symptom/sign. CONCLUSION: Increases in inflammatory marker requests and abnormal results occur in many patients with Hodgkin lymphoma several months pre-diagnosis, suggesting this period should be excluded in aetiological studies examining inflammation in Hodgkin lymphoma development, and that a diagnostic time window of appreciable length exists in many patients with Hodgkin lymphoma, many of whom have no other red-flag features.