Burden of tuberculosis among patients with cancer: a comprehensive systematic review and meta-analysis of global data

Abstract

Background

Patients with cancer are at a higher risk of tuberculosis (TB) infection because of the immunosuppressive effect of prolonged chemotherapy. This study determined the prevalence of TB and TB-related deaths among patients with cancer from a global perspective.

Methods

We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to conduct the current study. Extracted data from relevant articles were analyzed using Stata, version 17.0, software (StataCorp LP). The effect size estimate was computed using a random-effects model, considering a 95% confidence interval (CI). The I² statistic and Galbraith plot were used to confirm heterogeneity. A univariate meta-regression, sensitivity, and subgroup analyses were conducted to identify the source of heterogeneity. The Egger test and a funnel plot were used to check publication bias.

Results

In the 13 articles, of the 2 135 402 patients with malignancy, 31 073 had TB. The pooled estimate of TB was 3.69% (95% CI = 1.79% to 5.58%), with high heterogeneity (I² = 99.99%). The pooled TB prevalence in Europe was 7.04 (95% CI = 1.09% to 12.99%). The prevalence of TB in a single study in North America was 8.78% (95% CI = 8.45% to 9.10%). A higher TB prevalence was observed in patients with solid tumors (6.84%, 95% CI = 4.30% to 9.38%), followed by hematologic malignancies and solid tumors (3.63%, 95% CI = 1.46% to 5.80%). Pulmonary and extrapulmonary TB were 3.05% and 0.77%, respectively. The rate of TB-related death was 0.04%. In meta-regression, publication year and sample size did not affect heterogeneity.

Conclusion

There is a considerable burden of TB (3.69%) in patients with cancer, which calls for routine TB screening and early treatment of cases to reduce complications.

Introduction

Tuberculosis (TB) remains a substantial public health problem worldwide.¹ An estimated one-fourth of the world’s population is infected with Mycobacterium tuberculosis, and 5%-10% of individuals infected will develop TB in their lifetime.² TB is associated with a risk of progression from latent to active TB.³ Approximately 18 million new cases of cancer were diagnosed in 2018; the most common types were lung (2.09 million cases), breast (2.09 million cases), and prostate (1.28 million cases). Cancer has the greatest clinical, social, and economic impact,⁴ and treating cancers effectively with chemotherapy requires repeated use of drug combinations to eliminate enough tumor cells while avoiding severe side effects and tumor cell resistance.⁵

Patients with cancer may exhibit deficits in cell-mediated immunity as either a direct effect or an indirect effect related to chemotherapy or the underlying disease and are especially susceptible to developing the disease.⁶ Immunocompromised individuals are at increased risk of latent TB reactivation, which includes patients with hematologic malignancies and patients undergoing immunosuppressant cancer therapies, such as chemotherapy.⁷ Several systematic reviews and meta-analyses have focused on the association between lung cancer and TB infection,^8-11 but recent studies have reported a variety of TB prevalence in patients with cancer. To the best of our knowledge, no systematic review and meta-analysis has reported the prevalence of both pulmonary and extrapulmonary TB infection among patients with malignancy. To improve the prognosis of patients with cancer, implement preventative measures, and assess the efficacy of therapy, it is critical to provide global summary data on the burden of TB. Thus, this systematic review and meta-analysis determined the global pooled prevalence of TB and its impact on the mortality of patients with cancer.

Methods

Reporting and protocol registration

The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used to conduct this systematic review and meta-analysis (Table S1). The study protocol has been registered in the International Prospective Register of Systematic Reviews with the assigned number CRD42024582357 (https://www.crd.york.ac.uk/prospero/#recordDetails).

Search strategy

This study focused on the burden of TB infection in patients with cancer. A COCOPOP (Condition [TB], Context [global], and Population [cancer]) paradigm was used to determine the suitability of the included studies for this meta-analysis. The search included all available studies published; the most recent search was performed between February 1 and February 15, 2025. We used the PubMed/Medline, Scopus, EMBASE, Google Scholar, Hinari, Web of Science, Science Direct, Cochrane Library, and African Journals Online databases to identify articles reporting the prevalence of TB in patients with cancer. We used search terms alone or in combination with boolean operators such as “OR” or “AND.” An example of a PubMed search strategy used was as follows: (((((((Mycobacterium) OR (Mycobacterium tuberculosis)) OR (M. tuberculosis)) OR (Mtb)) OR (tuberculosis)) OR (active tuberculosis)) AND ((((malignancy*) OR (cancer)) OR (oncology)) OR (solid tumor*))) AND ((global) OR (worldwide)). A manual search of the references of the included studies and other reviews was conducted. The retrieved articles were imported into EndNote X9 bibliographic software manager (Clarivate Analytics).

Outcome of interest

The study aimed to determine the worldwide pooled prevalence of TB infection among patients with cancer. In addition, this study provided data on the prevalence of pulmonary and extrapulmonary TB. The study further assessed the TB-related death rate among patients with cancer.

Study selection and eligibility criteria

The titles and abstracts of the studies were screened by 5 authors (M.A., M.T., G.G., A.S., and A.A.) independently. The full-text articles were then assessed for eligibility, and any disagreements between the authors were resolved through discussion. This study included articles published in English without limit on the study period. Studies with unclear results, case reports, communications, letters to editors, opinions, reviews, meta-analyses, and studies on populations other than cancer were excluded.

Quality assessment of the studies

The full-text articles were retrieved for review, and relevant information was extracted. The Joanna Briggs Institute critical appraisal checklist for simple prevalence was used to assess the quality of included studies.¹² Articles of high and medium quality were included in this systematic review and meta-analysis (Tables S2 and S3).

Data extraction

Data from individual studies were extracted using the designed extraction tool in Microsoft Excel 2019 by 4 independent authors (M.A., M.T., A.A., and G.G.). The type of information collected from eligible studies were author, year of publication, study area, study design, age group, number of patients with malignancy, type of malignancy, number of patients with TB, type of TB, and number of deaths due to TB infection.

Data analysis

Data were exported to Stata, version 17.0, software (StataCorp LP) for analysis. The pooled prevalence of TB and 95% confidence intervals (CIs) were visually displayed using a forest plot. Subgroup analysis was performed based on continent, study design, age group, and type of malignancy. The heterogeneity between the included studies was evaluated using an index of heterogeneity (I² statistic) value of 0% (no heterogeneity), 25% or less (low), 25%-50% (moderate), 50%-75% (substantial), and 75% or higher (high).¹³ A Galbraith plot was also used to confirm heterogeneity. In all pooled analyses, heterogeneity resulting from differences in effects across studies was determined using a random-effects model. A sensitivity analysis of each study’s effect on overall prevalence was also conducted. Publication bias was statistically investigated using the Egger test¹⁴ and visual inspection of funnel plots. P < .05 in the Egger test was considered as evidence of statistically significant publication bias. A univariate meta-regression analysis was performed to assess the effect of sample size and publication year on TB prevalence. The results are presented in tables, text, and figures.

Results

Search results

In this study, 1682 potentially relevant articles were identified. After reviewing the titles and abstracts, 55 studies were excluded because they were duplicates, and the full text of 41 possibly related articles was screened. Depending on the evaluation of the exclusion and inclusion criteria and the quality of the articles, 13 full-text articles were eligible for the systematic review and meta-analysis (Figure 1).

Figure 1.

Flow diagram describing the selection of studies for the systematic review and meta-analysis on the prevalence of tuberculosis among patients with cancer.

Characteristics of the included studies

A total of 13 full-text articles,^7,15-26 which studied 2 135 402 patients with cancer, were included in this systematic review and meta-analysis. Nine studies were cohort, and 4 were cross-sectional studies. Among the studies, 10 were from Asia, 1 was from North America, 1 was from Africa, and 1 was from Europe. The minimum and maximum numbers of study participants were 71 in Georgia¹⁹ and 1 105 009 in Taiwan,²⁶ respectively (Table 1).

Table 1.

Summary of studies on TB infection among patients with cancer.

Author, year of publication	Country	Continent	Study year	Study design	Age group	Type of malignancy	Sample size, No.	TB case
Roy et al., 20247	India	Asia	2019-2022	Cross-sectional	All ages	Hematologic and solid tumor	906	42
Aldabbagh et al., 202216	Saudi Arabia	Asia	2020-2021	Cross-sectional	All ages	Hematologic and solid tumor	203	25
Chen et al., 202125	China	Asia	2016-2018	Cohort	All ages	Hematologic and solid tumor	32 539	1776
Kumar et al., 202121	Canada	North America	1985-2012	Cohort	Adult	Hematologic and solid tumor	29 448	2585
Nair et al., 202123	India	Asia	2012-2019	Cross-sectional	NR	Hematologic and solid tumor	32 509	56
Nanthanangkul et al., 202018	Thailand	Asia	2001-2015	Cohort	All ages	Hematologic and solid tumor	40 948	472
Cheon et al., 202024	Korea	Asia	2000-2014	Cohort	Adults	Hematologic and solid tumor	34 783	380
Baik et al., 201922	Botswana	Africa	2016-2017	Cohort	Adults	Hematologic and solid tumor	240	2
Shu et al., 201926	Taiwan	Asia	2000-2015	Cohort	All ages	Hematologic and solid tumor	1 105 009	19 906
Seo et al., 201620	Korea	Asia	2008-2012	Cohort	Adults	Hematologic and solid tumor	85 5382	5745
Hashem et al., 201317	Iran	Asia	2009-2011	Cross-sectional	All ages	Solid tumor	380	26
Chen et al., 201115	Taiwan	Asia	1996-2009	Cohort	Adults	Hematologic	2984	53
Malone et al., 200419	Georgia	Europe	2001-2002	Cohort	All ages	Hematologic and solid tumor	71	5

Abbreviations: NR = not reported; TB = tuberculosis.

Pooled prevalence of TB among patients with cancer

Among a total of 2 135 402 patients with cancer, 31 073 had active TB infection. Accordingly, the pooled prevalence of TB was 3.69% (95% CI = 1.79% to 5.58%), with high heterogeneity (I² = 99.99%) and statistical significance (P < .001) (Figure 2). The minimum and maximum TB prevalence reported by the studies was 0.2% in India²³ and 12.3% in Saudi Arabia,¹⁶ respectively, with their respective study population and period (Table 1). The pooled prevalence of pulmonary TB in patients with malignancy was 3.05% (95% CI = 1.46% to 4.63%) (Figure 3). According to 2 study reports,^15,25 the pooled estimate of extrapulmonary TB was 0.77% (95% CI = ‒0.16% to 1.71%) (Figure 4). The prevalence of multidrug-resistant TB has been reported in Taiwan at 1.9%.¹⁵

Figure 2.

Forest plot shows the pooled prevalence of tuberculosis among patients with cancer. CI = confidence interval.

Figure 3.

Forest plot shows the pooled prevalence of pulmonary tuberculosis among patients with cancer. CI = confidence interval.

Figure 4.

Forest plot shows the pooled prevalence of extrapulmonary tuberculosis among patients with cancer. CI = confidence interval.

Heterogeneity analysis

According to the I² result of 99.99%, as displayed on the forest plot (Figure 2) and the Galbraith plot (Figure 5), there is high heterogeneity among the included studies.

Figure 5.

Galbraith plot shows the heterogeneity between the studies. CI = confidence interval.

Subgroup analysis

Because of the high heterogeneity between the included studies, subgroup analysis was conducted to identify the source of variation. The pooled TB estimate of 10 studies in Europe was 7.04% (95% CI = 1.09% to 12.99%). The prevalence of TB in a single study in Canada, North America, was 8.78% (95% CI = 8.45% to 9.10%) (Figure S1). Based on the study design, a higher prevalence of TB was observed in cross-sectional studies (5.65%, 95% CI = 0.88% to 10.42%) (Figure S2). According to age group, the TB prevalence was high in all age groups (5.09%, 95% CI = 2.52% to 7.66%), followed by adults (2.64%, 95% CI = ‒0.41% to 5.68%) (Figure S3). The combined prevalence of TB among cancer types showed that the highest rate of TB was shown in solid tumors (6.84%, 95% CI = 4.30% to 9.38%), followed by hematologic malignancies and solid tumors (3.63%, 95% CI = 1.46% to 5.80%) (Figure S4). The test of group differences indicated statistically significant differences (P < .01) based on region, age, and malignancy type, whereas the test of group differences in the effect sizes based on study design was not statistically significant (P = .30).

Publication bias

The presence of potential publication bias was determined statistically using the Egger test. The result of the Egger test indicated the absence of publication bias (P = .28) (Table 2). In addition, it was depicted graphically by a funnel plot, which showed an uneven distribution of the studies (Figure S5). Although the nonsignificant Egger test provides some reassurance against strong statistical evidence of publication bias, visual inspection of the funnel plot raised a potential concern for some asymmetry, possibly indicating a lack of studies with lower prevalence. It would be valuable to consider the potential reasons for this asymmetry beyond just publication bias, such as the differences in the characteristics of the studies on the right side compared with the left.

Table 2.

Publication bias using the Egger test.

Standard effect	Coefficient	SE	t	P > t	95% CI
Slope	0.85	0.24	3.60	.004	0.33 to 1.37
Bias	10.91	9.64	1.13	.28	‒10.32 to 32.13

Abbreviation: CI = confidence interval.

Sensitivity analysis

A sensitivity analysis was performed using a random-effects model because of the results’ extreme heterogeneity. Step-by-step removal of each study was applied to determine how each study affected the pooled prevalence of TB. The results showed that the omitted studies do not have a significant effect on the pooled prevalence of TB in patients with cancer (Figure S6).

TB-related death in patients with cancer

From the 13 articles included in our study, 2 studies^15,26 reported the number of patients with malignancy who died because of TB: in total, 169 deaths among 1 107 993 patients with cancer. Thus, the combined prevalence of death due to active TB infection was 0.04% (95% CI = ‒0.04% to 0.11%) (Figure S7).

Meta-regression

In this study, we included population-based and single-center studies in the analysis. For this reason, we conducted a meta-regression to determine the effect of sample size variation on the pooled prevalence of TB. Accordingly, the result showed no statistically significant association between the pooled estimate of TB and sample size (P = .28). Moreover, we determined the effect of publication year on TB prevalence, and the result showed no statistically significant association (P = .96) (Table 3).

Table 3.

Meta-regression, by publication year and sample size.

Variable	Coefficient	SE	t	P > t	95% CI
Publication year	0.01	0.21	0.06	.96	‒0.46 to 0.48
Sample size	‒3.02	2.66	‒1.13	.28	‒8.88 to 2.85

Abbreviation: CI = confidence interval.

Discussion

The morbidity and mortality due to TB infection continue to be major concerns around the globe, and more emphasis should be given to patients with different malignancies. This systematic review and meta-analysis investigated the global prevalence of TB and related death among patients with solid tumors and hematologic malignancies. Based on the studies, the pooled prevalence of TB (including both pulmonary and extrapulmonary cases) was 3.69%. The American Thoracic Society and the Centers for Disease Control and Prevention have both reported that cancer increases the risk of acquiring active TB, and various studies have shown that the prevalence of TB in patients with cancer is higher than in the general population.²⁷ A systematic review stated a 9-fold increased risk of developing active TB in patients with hematologic, head, neck, and lung cancers compared with individuals without malignancy.²⁸ The main reason for TB infection in patients with malignancy is related to the immunosuppressive effects of treatment-related factors such as chemotherapy, radiation therapy, and immunotherapy or other host factors that increase the susceptibility to TB and decrease local infection barriers, leading to the inability to eliminate the infection.¹⁶

Because of the extremely high heterogeneity between the studies, we considered subgroup analysis, meta-regression, and sensitivity analysis. Although the results of meta-regression (by publication year and sample size) and sensitivity analysis showed no statistically significant effect, the subgroup analysis revealed a significant test of group differences in effect size based on study region, age group, and malignancy type. It indicated that the differences in the studies location, patient age, and type of malignancy—whether multiple or single cancer—within the patient were a potential source of heterogeneity between the studies. Among the continents reported to have TB in patients with solid tumors or hematologic malignancy, most of the studies were from Asia, with 3.19% pooled prevalence of TB. From contents reported in a single study, higher prevalence was observed in North America by Kumar et al.,²¹ followed by Europe and Africa. This variation is due to differences in geography, population, socioeconomic factors, education, and the quality of health-care services. There is a strong relationship between TB and socioeconomic characteristics such as crowded and poorly ventilated conditions, malnutrition, comorbidities, alcohol abuse, and smoking.^29,30 In addition, the prevalence of TB was highest in patients with solid tumors, followed by patients with hematologic and solid tumors. A systematic review and meta-analysis showed that all types of cancer increased the risk of active TB infection. The cumulative incidence rate per 100 000 population varied depending on the type of cancer and the incidence of TB; in low-incidence countries, the cumulative incidence rate for hematologic malignancies was highest at 418 per 100 000 population, whereas the rate for solid cancers was 244 per 100 000 population.²⁸

According to 2 studies,^15,26 the prevalence of death due to TB infection was 0.04%. Although these studies were single centered and did not include all patients with cancer and so would not accurately represent the TB prevalence in the country, they are preliminary data for conducting further research. A previous study reported that the mortality directly due to TB (0.83%) and all-cause mortality were approximately 10.5% at 3 months and 20.56% at 12 months. The 12-month all-cause mortality during TB and the 2-year recurrence rate is as high as 20.56% and 5.03%, respectively.²⁶ Another study reported that patients with lung cancer with distant metastasis and co-morbid TB had a 3.01-fold and 2.99-fold significantly increased risk of death compared with patients without co-morbid TB.³¹ It highlights special attention to TB prevention, particularly for patients with hematologic, head and neck, and respiratory tract cancers. Therefore, patients with different malignancies should undergo TB screening and receive early treatment to minimize their susceptibility to death.

Strengths and limitations of the study

This study is the first global report to focus primarily on the current burden of pulmonary and extrapulmonary TB and its effect on the death of patients with cancer. Due to inconsistent results and lack of information from individual studies, we were unable to provide data regarding the risk factors for TB in patients with cancer.

Conclusion

In this study, the prevalence of TB (including the pulmonary and extrapulmonary forms) among patients with cancer was 3.69%. In subgroup analysis, a relatively higher prevalence of TB was observed in North America, patients with solid tumors, and all age groups. Therefore, routine follow-up and diagnosis of TB are recommended among patients with cancer, and patients with TB should receive a standard antibiotic treatment to reduce mortality. Additional studies should be conducted in other parts of the world to sufficiently generalize the burden of TB from a global perspective.

Author contributions

Muluneh Assefa (Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Software, Writing—original draft, Writing—review & editing), Mitkie Tigabie (Data curation, Formal analysis, Methodology, Software), Azanaw Amare (Formal analysis, Methodology, Software), Mebratu Tamir (Formal analysis, Methodology, Supervision), Abebaw Setegn (Formal analysis, Methodology, Software), Yenesew Mihret Wondmagegn (Formal analysis, Methodology, Software), Sirak Biset (Formal analysis, Methodology, Software, Writing—original draft), Wesam Taher Almagharbeh (Methodology, Writing—original draft, Writing—review & editing), and Getu Girmay (Formal analysis, Methodology, Writing—original draft).

Supplementary material

Supplementary material is available at JNCI Cancer Spectrum online.

Conflicts of interest

The authors have no competing interests to declare.

Data availability

All the necessary data are available in the manuscript and supplementary information files. Additional data will be provided upon a reasonable request to the corresponding author.