Cancers Attributable to Infections in the US in 2017: A Meta-Analysis

Abstract

Importance: Infections are largely modifiable causes of cancer. However, there remains untapped potential for preventing and treating carcinogenic infections in the US.

Objective: To estimate the percentage and number of incident cancers attributable to infections in the US among adults and children for the most recent year cancer incidence data were available (2017).

Data sources: A literature search from 1946 onward was performed in MEDLINE on January 6, 2023, to obtain the data required to calculate population attributable fractions for 31 infection-cancer pairs. National Health and Nutrition Examination Survey data were used to estimate the population prevalence of hepatitis B and C viruses and Helicobacter pylori.

Study selection: Studies conducted in the US or other Western countries were selected according to specific infection-cancer criteria.

Data extraction and synthesis: Data from 128 studies were meta-analyzed to obtain the magnitude of an infection-cancer association or prevalence of the infection within cancer cells.

Main outcomes and measures: The proportion of cancer incidence attributable to 8 infections.

Results: Of the 1 666 102 cancers diagnosed in 2017 among individuals aged 20 years or older in the US, 71 485 (4.3%; 95% CI, 3.1%-5.3%) were attributable to infections. Human papillomavirus (n = 38 230) was responsible for the most cancers, followed by H pylori (n = 10 624), hepatitis C virus (n = 9006), Epstein-Barr virus (n = 7581), hepatitis B virus (n = 2310), Merkel cell polyomavirus (n = 2000), Kaposi sarcoma-associated herpesvirus (n = 1075), and human T-cell lymphotropic virus type 1 (n = 659). Cancers with the most infection-attributable cases were cervical (human papillomavirus; n = 12 829), gastric (H pylori and Epstein-Barr virus; n = 12 565), oropharynx (human papillomavirus; n = 12 430), and hepatocellular carcinoma (hepatitis B and C viruses; n = 10 017). The burden of infection-attributable cancers as a proportion of total cancer incidence ranged from 9.6% (95% CI, 9.2%-10.0%) for women aged 20 to 34 years to 3.2% (95% CI, 2.4%-3.8%) for women aged 65 years or older and from 6.1% (95% CI, 5.2%-7.0%) for men aged 20 to 34 years to 3.3% (95% CI, 1.9%-4.4%) for men aged 65 years or older. Among those aged 19 years or younger, 2.2% (95% CI, 1.3%-3.0%) of cancers diagnosed in 2017 were attributable to Epstein-Barr virus.

Conclusions and relevance: Infections were estimated to be responsible for 4.3% of cancers diagnosed among adults in the US in 2017 and, therefore, represent an important target for cancer prevention efforts.

Figure 1.. Infection-Attributable Cancers Among Adults in the US in 2017, by Cancer

This figure shows the number of cases attributable to specific infections by cancer site. Due to Helicobacter pylori’s protective effect in esophageal adenocarcinoma, the 1266 cases attributable to esophageal adenocarcinoma get subtracted from the total cases associated with H pylori. DLBCL indicates diffuse large B-cell lymphoma; EBV, Epstein-Barr virus; ENKTL, extranodal natural killer T-cell lymphoma; HBV, hepatitis B virus; HCV, hepatitis C virus; HPV, human papillomavirus; HTLV-1, human T-cell lymphotropic virus type 1; KSHV, Kaposi sarcoma–associated herpesvirus; MALT, mucosa-associated lymphoid tissue; MCPyV, Merkel cell polyomavirus; and SCC, squamous cell carcinoma.

Figure 2.. Infection-Attributable Cancers in the US in 2017, by Sex and Age Group (in Years)

% AC indicates the proportion of the number of incident cancers diagnosed in 2017 attributable to infections; EBV, Epstein-Barr virus; HBV, hepatitis B virus; HCV, hepatitis C virus; H pylori, Helicobacter pylori; HPV, human papillomavirus; HTLV-1, human T-cell lymphotropic virus type 1; KSHV, Kaposi sarcoma–associated herpesvirus; and MCPyV, Merkel cell polyomavirus.