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  • In the past two decades several studies

    2019-06-11

    In the past two decades, several studies have consistently found that up to one-sixth of cancers worldwide are attributable to infectious pathogens. Cancers caused by infectious agents present unique opportunities for prevention and treatment; therefore, a detailed understanding of how infections contribute to cancer incidence, as well as the geographical and demographic ARCA and natural history (ie, response to treatment and mortality) of infection-related cancers, is crucial. In , Martyn Plummer and colleagues update an analysis of the global burden of infection-related cancers using data from GLOBOCAN 2012. As an enhancement to their previous publications, the authors now include country-level analyses of the total burden of infection-related cancers. As Plummer and colleagues acknowledge, the proportion of cancers caused by infectious agents is likely to be under-represented in this analysis. Besides the methodological reasons discussed in the Article, two additional factors might also contribute to a higher burden of infection-attributable cancers than recognised at present. First, the authors only counted cancers associated with viral infections as “HIV-associated”. A wide variety of cancers, including many that are not presently associated with pathogens (eg, lung, skin, and kidney cancers, and leukaemia), are now known to have increased prevalence in HIV-infected individuals. HIV is considered a group 1 carcinogen by the International Agency for Research on Cancer, and a direct role of HIV in the genesis of many cancers is also supported by findings from several prospective cohort studies and translational research. Attribution of more cancers to HIV infection among the more than 36 million HIV-infected individuals worldwide would increase the proportion of infection-attributable cancers, especially in HIV-endemic regions. Second, as supported by the discovery of two new human tumour viruses in the past two decades, human herpesvirus type 8 and Merkel cell polyomavirus, there are likely to be additional cancer types that are attributable to novel infectious agents. Lung and lip cancer, as well as squamous cell carcinoma of the conjunctiva, have all been reported to have increased incidence in individuals with immunosuppression and are likely to be caused by infectious agents. Similarly, new pathogens might be identified in the cancers that are only partly attributable to infections at present, such as the substantial fraction of human-papillomavirus-negative penile, vulvar, and oropharyngeal cancers. Although the more than 2 million cases of infection-associated cancer diagnosed annually is substantial, it is notable that nearly two-thirds of such cases occur in less developed regions. It is reasonable to speculate, as the authors do, that economic disparities account for the imbalanced prevalence of infection-associated cancers worldwide. However, it is important to consider other potential contributors because they might inform the biology of infection-related cancers or point to additional prevention strategies. Immunogenetic factors affect both the acquisition of infection-causing pathogens and the rate of progression from primary infection to cancer. Co-infection with other pathogens that are endemic to low-resource regions—eg, HIV, , malaria parasites, and other parasites—might also increase the risk of developing infection-associated cancers. Finally, complex interactions might exist between behavioural, environmental, and infectious factors that predispose individuals to infection-related cancers to a greater extent in sub-Saharan Africa than in other regions. Therefore, elucidating the reasons for the geographical disparities in infection-related cancers is crucial to reducing the burden of these malignancies in settings with limited resources. Unique opportunities for prevention and treatment of infection-related cancers exist. Vaccination against hepatitis B virus and human papillomavirus, as well as screen-and-treat approaches for human papillomavirus, has already begun to decrease the incidence of cancers attributed to these infectious agents. With novel effective treatment regimens for hepatitis C, similar trends can be expected in the future if access is expanded worldwide. However, the four pathogens associated with the highest number of cancers—hepatitis C virus, , Epstein-Barr virus, and human herpesvirus type 8—have no existing vaccines. Furthermore, a vaccine against HIV has enormous public health ramifications, not least of which is a reduction in cancer incidence. Thus, increased efforts and focus on vaccine development are of paramount importance. Other strategies to reduce the incidence of infection-related cancers are also worthy of consideration—eg, chemoprevention (ie, early initiation of antiretroviral therapy in HIV-infected individuals, eradication of , or prophylactic antiviral therapy in high-risk individuals) and behavioural or public health interventions to reduce incident cancer-associated infections. Finally, targeting the infectious cause of cancer might give rise to effective and inexpensive treatment strategies with minimal toxicity, such as the treatment of mucosal-associated lymphatic tumours with antibiotics.