Gastric cancer is the fourth most common type of cancer and the second most common among cancer deaths worldwide.¹ While tumors of the cardia, the upper part of the stomach adjoining the esophagus, may be related to gastroesophageal reflux, the majority of noncardia gastric cancers are attributable to chronic mucosal infection by the bacterium Helicobacter pylori.² The presumed mechanism of carcinogenesis is the induction of inflammation and consequent gastritis, the initial lesions in a multistage process.³ In both high- and low-prevalence populations, H pylori infection is commonly acquired in childhood and generally not later. In the United States, prevalence of infection increases with age, reflecting improvements in hygienic conditions and decreased crowding during childhood for younger generations.⁴ Prevalence also varies by race, socioeconomic status, and geographic region,⁵ contributing to population differences in gastric cancer risk.⁶

Independent of CD4 cell count, a low CD4/CD8 ratio in people with HIV (PWH) is associated with deleterious immune senescence, activation, and inflammation, which may contribute to carcinogenesis and excess cancer risk. We examined whether low CD4/CD8 ratios predicted cancer among PWH in the United States and Canada. We examined all cancer-free PWH with 1 or more CD4/CD8 values from North American AIDS Cohort Collaboration on Research and Design observational cohorts with validated cancer diagnoses between 1998 and 2016. We evaluated the association between time-lagged CD4/CD8 ratio and risk of specific cancers in multivariable, time-updated Cox proportional hazard models using restricted cubic spines. Models were adjusted for age, sex, race and ethnicity, hepatitis C virus, and time-updated CD4 cell count, HIV RNA, and history of AIDS-defining illness. Among 83 893 PWH, there were 5628 incident cancers, including lung cancer (n = 755), Kaposi sarcoma (n = 501), non-Hodgkin lymphoma (n = 497), and anal cancer (n = 439). The median age at cohort entry was 43 years. The overall median 6-month lagged CD4/CD8 ratio was 0.52 (interquartile range = 0.30-0.82). Compared with a 6-month lagged CD4/CD8 of 0.80, a CD4/CD8 of 0.30 was associated with increased risk of any incident cancer (adjusted hazard ratio = 1.24 [95% confidence interval = 1.14 to 1.35]). The CD4/CD8 ratio was also inversely associated with non-Hodgkin lymphoma, Kaposi sarcoma, lung cancer, anal cancer, and colorectal cancer in adjusted analyses (all 2-sided P < .05). Results were similar using 12-, 18-, and 24-month lagged CD4/CD8 values. A low CD4/CD8 ratio up to 24 months before cancer diagnosis was independently associated with increased cancer risk in PWH and may serve as a clinical biomarker.

Several case-control studies have found increased prevalence of hepatitis C virus (HCV) in patients with non-Hodgkin lymphoma (NHL) and other B-cell lymphoproliferative disorders. We examined whether HCV infection preceded the development of these neoplasms in a prospective cohort study of 48 420 individuals in northern California. Stored sera from 95 subjects with NHL (n = 57), multiple myeloma (n = 24), or Hodgkin disease (n = 14) diagnosed a mean of 21 years after phlebotomy were screened for antibodies to HCV as well as viral RNA, based on previous reports of antibody-negative viremia. Sera from 4 cases and one of 95 age-, sex-, and race-matched controls were repeatedly reactive by enzyme immunoassay, but none were confirmed by recombinant immunoblot assay; none of the case sera had HCV RNA by reverse transcription– polymerase chain reaction. Although acquisition in later life cannot be ruled out, these prospective data do not support a substantial role of chronic HCV infection in the etiology of B-cell neoplasia.

Improvements in life expectancy among people living with human immunodeficiency virus (PLWH) receiving antiretroviral treatment in the United States and Canada might differ among key populations. Given the difference in substance use among key populations and the current opioid epidemic, drug- and alcohol-related deaths might be contributing to the disparities in life expectancy. We sought to estimate life expectancy at age 20 years in key populations (and their comparison groups) in 3 time periods (2004–2007, 2008–2011, and 2012–2015) and the potential increase in expected life expectancy with a simulated 20% reduction in drug- and alcohol-related deaths using the novel Lives Saved Simulation model. Among 92,289 PLWH, life expectancy increased in all key populations and comparison groups from 2004–2007 to 2012–2015. Disparities in survival of approximately a decade persisted among black versus white men who have sex with men and people with (vs. without) a history of injection drug use. A 20% reduction in drug- and alcohol-related mortality would have the greatest life-expectancy benefit for black men who have sex with men, white women, and people with a history of injection drug use. Our findings suggest that preventing drug- and alcohol-related deaths among PLWH could narrow disparities in life expectancy among some key populations, but other causes of death must be addressed to further narrow the disparities.

A viral etiology of cancer was first demonstrated in 1911 by Peyton Rous who injected cell-free filtrate from a chicken sarcoma into healthy chickens and found it induced a tumour. Since the discovery over 50 years ago of the Epstein-Barr virus as the cause of Burkitt lymphoma, seven other human viruses or groups of viruses—hepatitis B virus, hepatitis C virus, human immunodeficiency virus type 1, some human papillomaviruses, human T-cell lymphotropic virus type 1, Kaposi sarcoma-associated herpesvirus and Merkel cell polyomavirus—have been linked to human cancer. Collectively, these eight viruses cause over 20 different types of cancer and contribute to 10–12% of all cancer, with a greater burden in low- and middle-income countries. For many viruses, immunosuppression greatly increases the risks of persistent infection, development of chronic sequelae and cancer. Although several viruses share similar routes of transmission (especially sexual activity, injection drug use and mother-to-child transmission), the predominant route of transmission varies across viruses, and for the same virus can vary by geographical location. In general, vulnerable populations at the greatest risk for viral infections and their associated diseases include people, especially children, living in low- to middle-income countries, men who have sex with men, people who use injection drugs and female sex workers. This article is part of the themed issue ‘Human oncogenic viruses’.