Global burden of cancers attributable to liver flukes – Authors' reply
Authors: Martyn Plummer, Catherine de Martel, Silvia Franceschi
Journal: The Lancet Global Health (2017)

We thank Men-Bao Qian and Xiao-Nong Zhou for highlighting their concerns. Although our analysis1Plummer M de Martel C Vignat J Ferlay J Bray F Franceschi S Global burden of cancers attributable to infections in 2012: a synthetic analysis.Lancet Glob Health. 2016; 4: e609-e616Summary Full Text Full Text PDF PubMed Scopus (912) Google Scholar focused on the four main infectious agents (human papillomavirus, hepatitis B virus, hepatitis C virus, and Helicobacter pylori) responsible for 92% of the global burden of infection-attributable cancer worldwide, we welcome any improvements for the rarer infections such as Opisthorchis viverrini and Clonorchis sinensis, which are important causes of mortality and morbidity in endemic populations. According to Fürst and colleagues,2Fürst T Keiser J Utzinger J Global burden of human food-borne trematodiasis: a systematic review and meta-analysis.Lancet Infect Dis. 2012; 12: 210-221Summary Full Text Full Text PDF PubMed Scopus (371) Google Scholar 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,3Qian MB Chen YD Liang S Yang GJ Zhou XN The global epidemiology of clonorchiasis and its relation with cholangiocarcinoma.Infect Dis Poverty. 2012; 1: 4Crossref PubMed Scopus (113) Google Scholar extrapolated from data for South Korea,4Shin HR Oh JK Lim MK et al.Descriptive epidemiology of cholangiocarcinoma and clonorchiasis in Korea.J Korean Med Sci. 2010; 25: 1011-1016Crossref PubMed Scopus (81) Google Scholar 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.5Shin HR Oh JK Masuyer E et al.Comparison of incidence of intrahepatic and extrahepatic cholangiocarcinoma—focus on East and South-Eastern Asia.Asian Pac J Cancer Prev. 2010; 11: 1159-1166PubMed Google Scholar 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.6Randi G Franceschi S La Vecchia C Gallbladder cancer worldwide: geographical distribution and risk factors.Int J Cancer. 2006; 118: 1591-1602Crossref PubMed Scopus (589) Google Scholar A second methodological issue concerns the accuracy of the exposure measurement. Without accurate measurement, different methods for calculating attributable risk that are equivalent in theory are not guaranteed to give compatible results in practice. Previous experience with carcinogenic infections has shown that biomarkers that are both sensitive and able to distinguish high-risk from low-risk infections are essential to elucidate the true strength of cancer risk. For liver flukes, diagnosis is based on detection of eggs in faeces, sputum, or other biofluids, whereas immunodiagnostic techniques and molecular methods are comparatively rare.2Fürst T Keiser J Utzinger J Global burden of human food-borne trematodiasis: a systematic review and meta-analysis.Lancet Infect Dis. 2012; 12: 210-221Summary Full Text Full Text PDF PubMed Scopus (371) Google Scholar The RR of cholangiocarcinoma might be substantially underestimated by current methods of exposure assessment. Some evidence for this underestimate comes from the contrast between analytical and descriptive epidemiology. The RR of 4·47 for C sinensis from pooled case control studies3Qian MB Chen YD Liang S Yang GJ Zhou XN The global epidemiology of clonorchiasis and its relation with cholangiocarcinoma.Infect Dis Poverty. 2012; 1: 4Crossref PubMed Scopus (113) Google Scholar is unable to account for the 60-fold variation in cholangiocarcinoma incidences between geographical regions.5Shin HR Oh JK Masuyer E et al.Comparison of incidence of intrahepatic and extrahepatic cholangiocarcinoma—focus on East and South-Eastern Asia.Asian Pac J Cancer Prev. 2010; 11: 1159-1166PubMed Google Scholar It is therefore plausible that all statistical methods are underestimating the burden with currently available data. We declare no competing interests. Global burden of cancers attributable to liver flukesMartyn Plummer and colleagues (September, 2016)1 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 Opisthorchis viverrini and Clonorchis sinensis, were estimated to have caused 1300 new cases of cholangiocarcinoma in 2012. However, this number might underestimate the real situation. Full-Text PDF Open AccessGlobal burden of cancers attributable to infections in 2012: a synthetic analysisA large potential exists for reducing the burden of cancer caused by infections. Socioeconomic development is associated with a decrease in infection-associated cancers; however, to reduce the incidence of these cancers without delay, population-based vaccination and screen-and-treat programmes should be made accessible and available. Full-Text PDF Open Access