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    • br Martyn Plummer and colleagues September analyse the globa

    2019-05-24


    Martyn Plummer and colleagues (September, 2016) analyse the global burden of cancers attributable to infections in 2012. Despite the relatively low attributable proportion compared with other infectious agents, liver flukes, including and , were estimated to have caused 1300 new cases of cholangiocarcinoma in 2012. However, this number might underestimate the real situation. As described in Plummer and colleagues\' appendix, parameters applied in estimation included the baseline incidence of cholangiocarcinoma from cancer registry data in Japan, the relative risk (RR) of cholangiocarcinoma in those infected with liver flukes, and the peptide receptors with liver fluke infections. However, Fürst and colleagues used a different approach and reached an annual figure for new cholangiocarcinoma cases attributable to liver flukes of nearly 7000 (). In that study, odds ratios (ORs) of 4·39 for and 6·12 for were combined with the cholangiocarcinoma incidence of a population highly affected by in northeast Thailand. In our earlier study, we also attempted to analyse the cholangiocarcinoma cases attributable to , using data from South Korea. After extrapolation to the global infected population, we estimate that more than 4700 cholangiocarcinoma cases were attributable to this organism, which approaches the figure of 5591 estimated by Fürst and colleagues (). The figure for the infected population in Plummer and colleagues\' analysis is similar to those of the two other studies, and the OR is higher. Thus, their substantially lower estimation of the number of cholangiocarcinoma cases attributable to liver flukes arises from the introduction of baseline cholangiocarcinoma data from Japan. The raw data from case-control studies used to calculate combined ORs were done in liver-fluke-endemic areas. Therefore, the lower cholangiocarcinoma incidence in Japan could not represent that in the control populations in these studies. Because of inadequate studies and insufficient data, and the complex and chronic characteristics of cancers, it is challenging to capture an accurate estimate of the number of cholangiocarcinoma cases attributable to liver flukes. Thus, more research is needed, which will have the added benefit of raising awareness of the importance of liver flukes in east Asia and promote control and elimination.
    We thank Men-Bao Qian and Xiao-Nong Zhou for highlighting their concerns. Although our analysis focused on the four main infectious agents (human papillomavirus, hepatitis B virus, hepatitis C virus, and ) responsible for 92% of the global burden of infection-attributable cancer worldwide, we welcome any improvements for the rarer infections such as and , which are important causes of mortality and morbidity in endemic populations. According to Fürst and colleagues, parasitic diseases are “characterised by highly focal spatial occurrence and scarce, scattered, and patchy information”. The extent of this disease burden is therefore extremely difficult to estimate. As noted by Qian and Zhou, our estimates of infection prevalence and corresponding relative risk (RR) for cholangiocarcinoma are largely similar to other estimates because they are mainly based on the same sources. Differences in the estimates of the burden of cancer must therefore be due to other methodological issues. We would like to highlight two of these. First, for our baseline estimates of cholangiocarcinoma incidence in Japan, we used only data for intrahepatic bile duct carcinoma, whereas the estimates of Qian and colleagues, extrapolated from data for South Korea, also included extrahepatic bile duct carcinoma. Japan and South Korea both have a relatively high proportion of extrahepatic bile duct carcinoma compared with other east and southeast Asian countries. We cannot exclude that some extrahepatic biliary tract cancers are caused by liver flukes, but including all of them would overinflate our incidence estimate as it would also include bile duct cancers due to anomalous pancreaticobiliary duct junction, a congenital malformation that also causes high incidence of gallbladder cancer in Japan and South Korea.