Research On The Correlation Between Human Papillomavirus Infections And NSCLC

Background Human papillomavirus(HPV)is DNA virus,have very strong characteristics of eosinophilic squamous epithelium.HPV subtypes is recognized at least 130 species,according to the effect that cause cancer,classified as low risk and high risk.Low-risk type often cause skin warts,genital warts and other benign lesions.High-risk pattern associated with malignant tumors,such as cervical cancer,rectal cancer,head and neck cancer,esophageal cancer,lung cancer,etc.As we all known,High-risk type HPV is the cause of cervical cancer.Sy Ijanen was put forward for the first time there may be a certain relationship between HPV and bronchial lung cancer in 1979.Nearly 30 years around the world the researchers used different methods to study lung cancer associated with HPV.But so far,researchers reported HPV infection rate in lung cancer,and relationship with histology were differences in different regions and different studies.Now the mechanism causing cancer HPV in lung cancer is not entirely clear,more research needs to be confirmed.Objective 1.To investigate the relationship between non small cell lung cancer(NSCLC)and human papillomavirus(HPV)infection;2.To acquaint the infection of high risk HPV16/18 in NSCLC;3.To analyze the correlation between HPV infection and multiple genes mutation,and to predict the possible carcinogenic mechanism of HPV in the pathogenesis of NSCLC.Methods 1.Paraffin embedded tissue specimens(FFPE)of 264 primary and 65 metastatic lesions of NSCLC were collected.The adjacent epithelium of the primary tumor(adjacent to cancer control)and 12 cases of benign lung tissue were used as control group.En Vision two step method was used to detect the expression of HPV L1 protein in all specimens by immunohistochemistry(IHC);2.109 cases(most of HPV L1 protein positive),including 98 cases of primary tumor and 11 cases of lymph node metastasis,were detected HPV16/18 L1 gene sequences by real-time fluorescence quantitative Real-time polymerase chain reaction(q PCR)method;3.90 cases of lung adenocarcinoma specimens were randomly detected EGFR/ALK/KRAS/BRAF genes mutation status.ALK gene mutation status screening was detected by IHC.All ALK positive and suspicious positive samples were detected by using reverse transcription PCR(RT-PCR)for gene status verification.EGFR/KRAS/BRAF genes mutation status were detected by q PCR.Result 1.The positive rate of HPV protein in NSCLC primary tumor was 26.5%(70/264),which was significantly higher than that in adjacent tissues(6/264)(P<0.001)and benign lung tissue(0/12)(0%)(L1)(P=0.041).2.The positive rate of HPV L1 protein in the primary NSCLC was similar to that of metastatic tumor(35.4%,23/65)(P=0.155).The positive rate of HPV L1 protein in lung adenocarcinoma(33.1%,48/145)was significantly higher than that in lung squamous cell carcinoma(16%,16/100)(P=0.003).3.109 cases of NSCLC specimens detected HPV16/18 gene sequence of L1 positive in 11 cases.4.HPV L1 positive lung adenocarcinoma patients with KRAS gene mutation(66.7%,12/18)was significantly higher than HPV negative patients(33.3%,6/18)(P=0.001),EGFR/ALK/BRAF gene status and HPV L1 protein were not significantly correlated.Conclusion 1.HPV infection may be closely related to the occurrence of NSCLC,and lung adenocarcinoma is more closely related to HPV infection than squamous cell carcinoma.2.HPV16/18 are two subtypes of HPV infection in NSCLC.3.Higher KRAS mutation rate in HPV related lung adenocarcinoma indicated that KRAS mutations may play some role in its carcinogenic mechanism.