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Page 8 of 17 Chen et al. Hepatoma Res 2019;5:12 I http://dx.doi.org/10.20517/2394-5079.2019.03

the lung, colon-rectum, upper digestive tract (esophagus and stomach), and liver. Residents at ages of 40-
69 were enrolled into the screening groups. About one to two medium-sized or more cities in each of 14
Provinces/Municipalities across the country joined the project. During the first 5-year round (2012-2016)
of screening, it aimed to cover areas of some 3,500,000 of the population, and to screen about 700,000
individuals at high risk [100] . So far, 42 cities of 20 provinces were included into CanSPUC. However, there
have not been any reports to show the findings of the detection rate or the effectiveness of screening for liver
cancer, except on medical expenditures for liver cancer in urban China. The CanSPUC program analyzed
the medical expenditure for liver cancer during 2002-2011 in urban areas of China [101] and found that the
medical expenditure per case for liver cancer diagnosis and treatment was ¥31,020 ($4,528) from the year
2002 to 2011 and ¥35,248 ($5,146) from the year 2009 to 2011, indicating that the economic burden of liver
cancer is high in China and the related medical expenditures are increasing.

Recent advances in screening from 2 rural areas
As one of the bases for demonstration of early detection and early treatment of liver cancer, Qidong
[97]
launched its Special Fiscal Transfer Payment Project of the Central Government in 2006 . The screening
scheme followed the recommendations of the Expert Committee of Early Detection and Early Treatment by
China Cancer Foundation [96,98] . The high risk population screened was defined as those with positive HBsAg
at ages of 35-64 for men and of 40-64 for women. Periodically diagnostic screening by using combined
methods of AFP and US monitoring were recommended. Since 2007, a target population of 38,016 has been
screened in the Qidong area: 3,703 (9.74%) individuals with positive HBsAg were found. Excluding for 29
patients with liver cancer at the initial screening, 3,674 persons in the cohort were followed up until the 31st
of March, 2016. The 268 patients with liver cancer were detected from the 33,199 person-times screened, with
an annual detection rate of 1.12%. Of them, 186 patients were found via repeated periodic screening (Group
A), in which 149 patients were the early cases, with an early detection rate of 80.11%. Some participants with
positive HBsAg were not followed by the suggested periodical screening schedule, but they (82 cases) were
diagnosed as outpatients within the intervals of screening points (Group B). Calculated by the life-table
method, the 1-, 3-, 5-, and 8-year survival of all patients with liver cancer in Group A were 77.16%, 49.04%,
38.53%, and 24.25%, and in Group B were 36.25%, 21.21%, 21.21%, and 0%, respectively, with significant
differences between two groups (P < 0.01). This finding shows that the screening of individuals at high-
risk with semiannual AFP and US detection is effective not only in increasing detection rate of early stage
[102]
liver cancer but also in improving patients’ survival. Ji et al. reported another example from Zhongshan,
Guangdong Province that started in 2012. The biannual screening also used serum AFP and US examination
for subjects positive for HBsAg. Of the 68,510 eligible residents, 17,966 were screened for HBsAg. Within
the first 4 years of follow-up, 57 incident cases of liver cancer (43 from 2,848 HBsAg-positive participants,
14 from 15,118 HBsAg-negative participants) were found. Compared with cases (104) identified from non-
participants (50,544), the cases detected among screening participants were more likely to be at early stage
and had better survival than those among non-participants. The 1-, 3-year overall survival rates for liver
cancer cases in the screened group were 48.7% and 29.1%; and in non-screened group were 36.9% and 15.5%,
respectively, showing better prognosis in screened group (HR = 0.64, 95%CI: 0.42-0.98, after adjustment for
gender and age). However, this screening study did not show a reduction in liver cancer mortality within the
first 4 years of follow-up by comparison of the two groups (RR = 1.04, 95%CI: 0.68-1.58).

glObAl DIsPUTes AND CONseNsUs ON lIveR CANCeR sCReeNINg
Notable randomized trials of screening from China
Whether liver cancer is suitable for screening, or whether screening has a significant effect, has caused
much controversy globally. As one of the methods of cancer control, the values of population screening
are often disputed because of differences in understanding of goals, benefits, disadvantage, costs, and
potential adverse effects of screening, and of disagreements in assessing the effectiveness of screening [103] .
Two randomized trials of screening for liver cancer were published in early this century: one from Qidong