Incidence And Mortality Of Liver Cancer In The World And In China And The Role Of Biomarkers In The Early Diagnosis Of Liver Cancer

ObjectiveTo describe the international trends in primary liver cancer (PLC) incidence and the disease burden of PLC in China, and to explore the role of the serum tumor biomarker in the early diagnosis of hepatocellular carcinoma (HCC).Contents1. Describing international trends in primary liver cancer (PLC) incidence by from Cancer Incidence in Five Continents Volumes IV-X (CI5 Ⅳ-Ⅹ).2. Describing the PLC incidence and mortality in China from six available data sources.3. Comparison of several potential biomarkers in the diagnosis of early HCC.Methods1. Age-standardized incidence rates by World population (ASRs) of PLC from CI5 over the 35-year period 1973-2007 from 24 populations in Americas, Asia, Europe and Oceania were selected. Joinpoint regression analysis was used to analyze the incidence trends and calculate Annual percent change (APC) and Average annual percent change (AAPC). We examined ASRs of PLC by histologic subtypes for both males and females in 24 populations during the period 2003-2007.2. Six data sources including Chinese Cancer Registration Data, the Three National Death Cause Surveys, China Health Statistics Yearbook, GLOBOCAN 2012, CI5 Ⅳ-Ⅹ and WHO Mortality Database were chosen to describe PLC incidence and mortality rates and trend in China.3. One hundred and eleven cases of HCC,133 cases of liver cirrhosis,110 cases of chronic hepatitis B and 124 healthy controls were recruited from Cancer Institute & Hospital, Chinese Academy of Medical Sciences and Beijing YouAn Hospital, Capital Medical University between Novermber,2013 and December,2014 and then serum levels of a-fetoprotein (AFP), lens culinaris agglutinin-reactive fraction of α-fetoprotein (AFP-L3), des-γ-carboxyprothrombin (DCP) and squamous cell carcinoma antigen (SCCA) were dectcted using electrochemiluminescence immunoassay (ECLIA) and enzyme-linked immunosorbent assay (ELISA), micro centrifugal column, chemiluminescence enzyme immunoassays and enzyme-linked immunosorbent assay (ELISA). The diagnosis accuracy of each of the candidate biomarkers was evaluated using receiver operating characteristic (ROC) curve analysis, reporting the area under the curve (AUC) and its 95% confidence interval (CI).Results1. During the period 2003-2007, the highest ASRs for PLC were observed in some Asian populations, ranging from 19.0 to 26.7 per 100,000 in males and 4.8 to 8.7 per 100,000 in females. The international trends between 1973 and 2007 showed that ASRs World for PLC were declining in several Asian populations (AAPC=-1.4%～-1.8% in males, AAPC=-1.0%～-1.5% in females, respectively). In contrast, ASRs World for PLC were increasing in some American, European and Oceanian populations (AAPC=0.8%～7.5% in males, AAPC=1.0%～5.6% in females, respectively).2. The features of PLC incidence and mortality in China are the following. (1) The proportion of new cases:the proportion of new cases of PLC among all cancer case in China for males was higher than for females, and it was higher in rural areas than in urban areas from 2004 to 2009 based on the China Cancer Registration Data.(2) Trends of incidence rates:ASRs World of PLC for both males and females were decreasing in urban areas from 1988-1992 to 2003-2007, especially in Shanghai. In rural areas, the decreasing trends for both males and females in Jiashan, Changle and Qidong were observed. (3) The proportion of deaths:several data sources showed that the proportion of PLC deaths in males was higher than in females and it was higher in rural areas than in urban areas. (4) Trend of liver cancer mortality rates: The data from The Three National Death Cause Surveys showed that the trends in proportion of deaths of liver cancer was declining in urban areas from 1990-1992 to 2004-2005 whereas increasing in rural areas. China Cancer registration data showed that ASRs World of PLC for both males and females were decreasing in shanghai from 1988-1992 to 2003-2007. The decreasing trends for males in Fusui, Qidong, Changle and Jiashan were observed from 1988-1992 to 2003-2007. Whereas the trends for females kept stable or slightly increasing in rural areas except for Jiashan and Changle.3. Levels of AFP, AFP-L3and DCP were significantly higher in patients with HCC than in patients without HCC (P<0.05) neither for SCCA. ROC indicated that the cut-off value for each biomarker was 7ng/mL for AFP,10% for AFP-L3,37mAU/mL for DCP and 120AU/mL for SCCA. The AUC (95%CI), sensitivity and specificity for AFP was 0.851(0.825-0.874),76.6% and 80.9%,0.693(0.649-0.734),29.7% and 96.2%, for AFP-L3,0.862(0.828-0.891),78.4% and 88.0% for DCP, 0.517(0.453-0.581),52.5% and 55.5% for SCCA, respectively. The better diagnosis accuracy of the combination of DCP and AFP in early HCC (AUC: 0.836[0.796-0.871], sensitivity:77.8%, specificity:80.9%) was observed.Conclusion1. ASRs World of PLC were declining in several Asian countries where the highest incidence rates were still seen between 1973 to 1977 and 2003 to 2007. HBV vaccination programs and screening tests might play an important role in deceasing trends in Asia. On the contrary, ASRs of PLC were increasing in some American, European and Oceanian countries. HCV transmission were likely to have contributed to the pattern. Meanwhile, other possible risk factors such as the consumption of alcohol, obesity, and nonalcoholic fatty liver disease should also be concerned for the burden of PLC.2. The trends in crude incidence rates and mortality rates of PLC were increasing in China whereas the ASRs were decreasing. The burden of PLC is relatively more serious in rural areas than in urban areas which remains to be key areas of prevention and control.3. The diagnosis accuracy of DCP was similar with AFP in HCC. The combination of DCP and AFP might be the best panel for the early diagnosis of HCC.