Tuberculosis Preceding Lung Cancer: A Contemporary Meta-Analysis Revealing a Critical Gap in Post-2020 Evidence.

Abstract

<h4>Background</h4>Tuberculosis (TB) has long been suspected to contribute to lung carcinogenesis through chronic inflammation and immune dysregulation. However, contemporary controlled evidence quantifying this association remains limited. We aimed to systematically evaluate the relationship between prior TB and subsequent lung malignancy, using recent observational studies and complementary case reports.<h4>Methods</h4>A systematic review and random-effects meta-analysis were conducted, including controlled cohort and case-control studies published from 2020 onward. Adjusted effect estimates were converted to the logarithmic scale for pooling. Heterogeneity and small-study effects were assessed using standard meta-analytic techniques. Additionally, published case reports were descriptively analyzed to explore clinicopathological patterns.<h4>Results</h4>Across eligible studies, prior TB was consistently associated with an increased risk of subsequent lung cancer (LC). The pooled estimate demonstrated a statistically significant positive association, despite moderate heterogeneity. Larger nationwide cohorts contributed greater statistical weight, while smaller studies showed wider variability. Case reports revealed heterogeneous temporal patterns, including long-latency scar-associated carcinoma and concurrent inflammatory-malignant presentations.<h4>Conclusions</h4>Contemporary controlled evidence supports an association between prior tuberculosis and increased risk of subsequent lung malignancy. However, despite strong biological plausibility and the abundant literature on cancer-associated tuberculosis, modern longitudinal studies specifically evaluating tuberculosis as a preceding independent risk factor remain limited. The small number of eligible post-2020 investigations identified in this meta-analysis highlights a significant contemporary research gap and underlines the need for well-designed prospective studies to clarify causality and guide surveillance strategies in TB-exposed populations.