Inflammatory marker testing in primary care in the year before Hodgkin lymphoma diagnosis in patients aged 50 and under: A UK population-based case-control study

Abstract

Background: Pro-inflammatory conditions are associated with increased risk of Hodgkin Lymphoma (HL), 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: A matched case-control study set in UK primary care using Clinical Practice Research Datalink (CPRD) data (2002-2016). Method: Primary care inflammatory marker test use and related findings were analysed in 839 HL 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 patterns of test use. Longitudinal trends in test results and the presence/absence of ‘red-flag’ symptoms were examined. Results: 71% of HL patients had an inflammatory marker test in the year pre-diagnosis versus 16% of controls (Odds Ratio 13.7, 95%CI 11.4-16.5, p<0.001). The rate of inflammatory marker testing and mean levels of certain inflammatory marker results increased progressively during the year before HL diagnosis among cases while remaining stable in controls. Among HL patients with a pre-diagnostic test, two thirds (70%) had an abnormal result and among these, 43% had no other ‘red-flag’ presenting symptom/sign. Conclusion: Increases in inflammatory marker requests and abnormal results occur in many HL patients several months pre-diagnosis, suggesting this period should be excluded in aetiological studies examining inflammation in HL development, and that a diagnostic time window of appreciable length exists in many HL patients, many of whom have no other red-flag features.