Meta-analysis On Association Of HPV Infection With Clinicopathological Features And Prognosis In Chinese Lung Cancer

Objective:Systematic evaluation of human papillomavirus(HPV)infection in lung cancer patients in China with different clinicopathological features and its relationship with p53 protein expression and prognosis.Methods:Searching the English and Chinese literatures on the relationship between HPV infection and lung cancer patients in the international literature database of the Pubmed/MEDLINE and the Chinese literature database of CBM,CNKI,Wanfang Medical Database before April 2017.According to the inclusion and exclusion criteria,the literature was screened,data was extracted,and quality assessment was performed.Meta analysis was performed using RevMan 5.3 software,and OR and 95% CI were calculated as the effect amount.Results:Meta analysis showed that the HPV infection rate in lung cancer tissues,SCC patients,moderately/differentiated cancer were significantly higher than that in the normal control group(OR=4.67;95%CI:2.51-8.71;P<0.001),AC patients(OR=42.92;95%CI:2.11-4.03;P<0.0001),well-differentiated cancer tissue(OR=0.43;95%CI:0.29-0.64;P<0.0001).The positive rate of p53 protein was significantly higher in the HPV positive group than that in the HPV negative group(OR=1.39;95%CI:1.09-1.78;P=0.008).Subgroup analysis: According to the difference of PCR amplification primers,the prevalence of HPV in SCC was significantly higher than that in AC in both the specificprimer sets and universal primer sets(OR=3.43;95%CI : 1.65-3.59;P < 0.0001)(OR=4.39;95%CI:2.42-7.95;P<0.0001).There were no significant correlations between HPV infection and sex,smoking,staging,and lymph node metastasis.The expression of p53 protein in HPV positive group was significantly higher than that in HPV negative group(OR=2.41;95%CI:1.54-3.78;P=0.0001).According to the difference of HPV type,HPV16 infection was significantly correlated with the gender(OR=0.39;95%CI :0.16-0.96;P=0.04),but not correlated with smoking,lymph node metastasis,pathological type and clinical stage;HPV18 infection was significantly correlated with the gender(OR=0.21;95%CI:0.09-0.48;P=0.0003)and pathological type(OR=0.50;95%CI:0.32-0.78;P=0.003),but not correlated with smoking,lymph node metastasis and clinical stage;HPV16/18 or mixed infection was significantly correlated with the pathological type(OR=2.58;95%CI:1.54-5.31;P=0.0003),but not correlated with gender,smoking,lymph node metastasis and clinical stage.The results showed that there was no significant correlation between HPV infection and OS of lung cancer(HR=0.90;95% CI 0.65-1.26;P=0.54).Subgroup analysis showed that the OS of patients with HPV-infected lung adenocarcinoma(HR = 0.85;95% CI:0.73-0.98)was significantly better than that of HPV-negative patients.However,HPV infection was not significantly associated with OS in NSCLC and lung cancer patients.According to the difference of treatment,the OS of HPV-infected patients was significantly better than that of HPV-negative patients in the group other treatment methods(including radiotherapy,chemotherapy,TKI inhibitors and/or combination therapy)(HR = 0.85;95%CI:0.73-0.98).However,HPV infection was not significantly associated with OS in only-surgery patients.HPV typing was not significantly associated with OS in lung cancer patients.Conclusions:HPV infection may be one of the important risk factors for the development of Chinese lung cancer other than smoking.The infections of different types of HPV may be different in lung cancer patients with different clinicopathological features.OS in HPV-infected lung adenocarcinoma patients is superior to HPV-negative patients.HPV-infected lung cancer patients may be more sensitive to other treatments(including radiotherapy,chemotherapy,TKI inhibitors,and comprehensive treatment)than HPV-negative patients.