Patients with a subtype of non-Hodgkin lymphoma (NHL) associated with an infectious etiology may be at increased risk of developing particular second solid tumor malignancies also linked to specific types of underlying infection, according to findings from a study reported in Blood Advances.

Certain infectious agents have been associated with different subtypes of NHL, such as HIV in diffuse large B cell lymphoma (DLBCL) and Burkitt lymphoma, Helicobacter pylori in gastric marginal zone lymphoma (MZL) and gastric DLCBL, and hepatitis C virus (HCV) infection in DLBCL and MZL. In contrast, other forms of NHL, such as chronic lymphocytic leukemia (CLL)/small cell lymphoma (SLL) and follicular lymphoma (FL) have not shown a strong association with specific types of infection.

The aim of this retrospective study was to evaluate the risks of developing certain solid tumor second malignancies associated with an infectious etiology (eg, oropharynx/tonsil, anal, and cervical cancers [human papillomavirus (HPV)], stomach cancer [H pylori], liver cancer [HCV]) for those with DLBCL, MZL, CLL/SLL, and FL compared with the general population.

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“Whereas current guidelines from the National Comprehensive Cancer Network include recommendations for treating particular infections before starting immunosuppressive therapy/chemotherapy after NHL diagnosis, no clear recommendations exist for long-term second cancer surveillance among NHL survivors with these infections,” the study authors noted.

This study included US population-based data for 127,044 adult patients with a diagnosis of first primary NHL between 2000 and 2014 who were included in 17 Surveillance Epidemiology and End Results (SEER) program registries. Patient follow-up occurred from 1 year of primary NHL diagnosis until diagnosis of second primary malignancy, death, age 85 years, end of follow-up, or end of study, whichever occurred first. Mean follow-up time was 4.5 to 5.2 years following diagnosis of primary NHL.

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A key finding of this study was that survivors of DLBCL were at increased risk of developing cancers of the liver (shared incidence ratio [SIR], 1.85; 95% CI, 1.46-2.31), stomach (SIR, 1.51; 95% CI, 1.16-1.94), and anus (3.71; 95% CI, 2.52-5.27) compared with the general population. A similar result was observed for MZL survivors with respective SIRs for liver cancer (SIR, 1.98, 95% CI, 1.34-2.83), stomach cancer (SIR, 2.78; 95% CI, 2.02-3.74), and anal cancer (SIR, 2.36; 95% CI, 1.02-4.64) compared with the general population. In contrast, these elevated risks were not observed for survivors of CLL/SLL or FL. In addition, compared with the general population, the risk of cervical and oropharyngeal/tonsil cancers was not increased in any of the NHL subgroups.

An important limitation of this study, as noted by the study authors, was the absence of patient-specific data related to HCV and H pylori infection status.  Furthermore, details related to treatment, along with its potentially immunosuppressive effects, were not available.

Although the study authors urged caution when interpretating these findings until they are evaluated in studies that include both treatment and infection status, they remarked that their “results suggest shared infectious etiology has implications for subsequent cancer risks among DLBCL and MZL survivors, which may help inform surveillance for these survivors.”


Herr MM, Schonfeld SJ, Dores GM, et al. Risk for malignancies of infectious etiology among adult survivors of specific non-Hodgkin lymphoma subtypes. Blood Adv. 2019;3(13):1961-1969.