Clinical Study On The Relationship Between Hepatitis B Virus Infection And Extrahepatic Malignancies

PurposeBoth cancer and hepatitis B virus(HBV)infection are major public health problems.The positive rate of hepatitis B surface antigen(HBsAg)is the highest in children and decline by age in most parts of the world.Liver cirrhosis and liver cancer caused by HBV infection mostly occur after the age of 40,which may be related to the decline after the age of 40,while it is hard to explain the decline in young population.The current research about the association between HBV infection and extrahepatic malignancies is limited.The aim of the study is to explore whether hepatitis B virus(HBV)infection promotes extrahepatic malignancies which mayexplain the decline of HBsAg-age curve in young population.MethodThis study was a multicenter retrospective analysis.Collected the HBsAg status and related clinical parameters of patiens with esophageal,gastric,rectal.nasopharyngeal,cervical malignancies and lymphoma from Nanfang Hospital,Guangdong Provincial People’s Hospital and the Third Affiliated Hospital of Sun vat-sen University from January 2007 to October 2016.Base on the general population HBsAg positive rate,calculated the standardized incidence ratio(SIR)of HBV infection and 95%Confidence Interval(CI).R software 3.3.3 was used to calculate the SIR ’and 95%CI,the CI does not contain "1" is statistically significant.Base on univariate and multivariate Logistic regression modelss,Wilcoxon rank sum test was used to analyze the difference of mean age between HBsAg positive and negative groups,Chi-square test or Fisher’s exact test were used to analyze the differences of sex,region and clinical parameterss between HBsAg positive and negative groups.P value less than 0.05 indicates a statistically significant difference.Result1.A total of 24301 patients were enrolled,including 5620 patients with rectal malignancies,6962 patients with gastric malignancies,4325 patients with esophageal malignancies,4260 patients with lymphoma,1317 patients with nasopharyngeal malignancies,and 1817 patients with cervical malignancies.2.The incidence of HBV infection in patients with lymphoma,nasopharyngeal malignancies,gastric malignancies,cervical malignancies,rectal malignancies,and esophageal malignancies were 2.4,1.8,1.6,1.4,1.3,1.3 times that of the general population,as follows:lymphoma(SIR 2.4,95%CI 2.2-2.5),nasopharyngeal malignancies(SIR 1.8.95%CI 1.5-2.0),gastric malignancies(SIR 1.6,95%CI 1.5-1.7).cervical malignancies(SIR 1.4,95%CI 1.3-1.6),rectal malignancies(SIR 1.3,95%CI 1.2-1.4),esophageal malignancies(SIR 1.3,95%CI 1.2-1.5).3.HBsAg+malignant patients were 1-6 years younger than those with HBsAgregardless of gender and region.HBV infection increased in patients with digestive tract malignancies by 0.7.1.1,0.6,and 0.2 times for those aged 15-29,30-44,45-59,and 60+years,and increased by 1.2,2.5,1.7,and 0.8 times for in patients with lymphoma aged 15-29,30-44,45-59,and 60+years,respectively,the P value was 0.00 among the five groups.4.The HBsAg positive rates of patients with gastric and cervical malignancies among the well,moderate and poor differentiations groups were 14.5%.10.0%.6.6%and 14.6%,9.5%,9.7%respectively,with significantly statistical difference,while HBV infection showed no difference in gender,geogyraph,tumor location,pathological type,clinical stage and other cancer pathogens(Helicobacter pylori,H.pylori,Epstein-Barr virus EBV,Human Papilloma Virus HPV)infection in patients with gastric,esophageal,nasopharyngeal and cervical malignancies from Guangdong Provincial People’s Hospital.5.HBV infection rate of lymphoma patients was higher than other extrahepatic malignancies,The average HBsAg positive rate was about 20.84%with SIR>2,the peak located in the 30-44 year group is 30.25%with SIR 3.5;HBsAg+lymphoma patients were younger than HBsAg-group;according to the data of Guangdong Provincial People’s Hospital,the positive rate of HBsAg in non-Hodgkin’s lymphoma was 19.66%,higher than that of Hodgkin’s lymphoma 10.53%with P=0.01;the positive rates of HBsAg among B-cell,T-cell and NK/T cell lymphoma were 22.21%,14.24%,9.09%with P=0.00.No significant differences were found in HBV infection among subtypes of B-cell,T-cell and Hodgkin’s lymphoma.The HBsAg positive rates were 15.47%,13.45%,29.52%,21.62%among the Ann-Arbor clinical stageⅠ/Ⅱ/Ⅲ/Ⅳ groups,and 34.88%,33.47%,18.42%,15.44%in low,low-moderate,high-moderate and high risk groups respectively,with significant differences(P=0.00).Conclusion1.The incidences of HBV infection in patients with rectal,gastric,esophageal.nasopharyngeal,cervical malignancies and lymphomas were higher than that of the general population,suggesting that HBV may have promoting effects on those malignancies,and the effects on different tumors were different.HBV infection had higher incidence in young patients of extrahepatic malignancies,when compared with older population.2.HBV-infected patients with malignant tumors were younger than those without infection,suggesting that HBV infection may advance the onset age of tumors.3.HBV infection may affect the degree of differentiation of malignant cells.Lymphoma patients w ith HBV-infected have poor clinical outcomes and prognosis.