Hpv Infection And Genotypes Of Non-cervical Squamous Cell Carcinoma In Qingdao Region

Research Background and Objective:Lots of studies have shown that human papillomavirus (HPV) infection is closely related to Squamous cell carcinoma (SCC). Many researches have determined HPV as a important factor induced cervical SCC. Scientists have done preliminary research on the existing or not of HPV in other sites’SCC. Currently HPV infection has been global reported involving of tumor including genital mutilation cancer, penis cancer, lung cancer, head and neck tumor, gastric cancer, breast cancer, colon cancer, skin cancer, esophageal cancer, and so on. Owning to the published studies being various in geographic location, sample volume, means of detection, virus types and etc, subtypes distribution of HPV are often detected in different sites of SCC. Few studies have characterized the distribution of the specific subtypes of the virus in the varying grades of other sites SCC. Before the research carried out, by PubMed and full-text database retrieval system CNKI journals to "HPV, Squamous cell carcinoma," as key words, we search from January2005to June2010in literature, English literature were retrieved1134. The inclusion criteria, in line with the analysis of the literature49. HPV infection and head and neck,skin,lung Squamous cell carcinoma are closely related。HPV infection has a certain correlation with the formation of upper digestive tract Squamous cell carcinoma, but further study should be done to the relationship between it and the lower digestive tract Squamous cell carcinoma. HPV infection is closely related to the formation of the Squamous cell carcinoma in the non-cervical part But subtypes of HPV infected are not associated with all parts of Squamous cell carcinoma in different areas, which still need further large sample test results. Few studies have characterized the distribution of the specific subtypes of the virus in the varying grades of other sites SCCAfter observated five hundred cases of cervical epithelial Squamous cell carcinoma in Qingdao area, we explored the correlation between the different subtypes of HPV and the different site of non-cervical SCC in patients among Qingdao area using PCR detection method, and analysised the influencing factors of HPV and the possible carcinogenic effects of it in different part SCC, in order to provide basis for prevention of tumor vaccines applicated of HPV, which opening a new and effective way for the treatment of non-cervical Squamous cell carcinoma.Method:This study collected pathological tissues of cervical Squamous cell carcinoma in511cases from Qingdao city resident population (including27carcinoma of tongue,79vulva cancer,196lung cancer,24rectal cancer and185esophageal cancer). Using PCR and in situ hybridization for detection of HPV gene, we explored the distribution of5low-risk subtypes and18high-risk subtypes of HPV gene on each epithelial Squamous cell carcinoma, and analysised the relationship of HPVtype and the Broders’ classification in lung Squamous cell cancer. Because many studies had shown the expression intensity of squamous carcinoma antigen (SCCA) and the inhibiting protein survivin apoptosis the prognosis of patients with squamous cell carcinomas, which negatively related to surgery and radiation and chemotherapy sensitivity. So this study also examined correlation of the subtypes of HPV infection in196cases lung SCC and expression intensity of the SCCA and survivin protein, in order to further understand the important value of the distribution of HPV subtype in diagnosis and treatment of lung squamous cell carcinomas.Results:1. Overall HPV was detected in285of511(55.77%) tissues with SCC as compared with55of the511(10.76%)nomal tissues(p<0.01). HPV positive of the tissue in each site of SCC is higher than the normal tissue at the same site. Five HPV genotypes were identified in all SCC tissue including HPV6,16,18,53and58, of which high-risk HPV were composed by HPV16,18,53and58, low-risk HPV was HPV6. HPV6and HPV16comprised a large proportion of the positive HPV infected. One hundred and forty-seven of285(51.58%) cases were positive for high-risk HPV, of which137(48.07%) were associated with HPV16,6(2.11%) with HPV18,2(0.70%) with HPV53, and2(0.70%) with HPV58. Low-risk HPV positivity(138/285,48.42%), was higher than other HPV type, in which the cases with esophageal cancer are the most (P<0.01). In511specimens, there were different positive rate of HPV infection in different parts of Squamous cell carcinoma. The infected HPV subtype is not consistent of each part of Squamous cell carcinoma. Therer was no significant correlation between HPV subtypes distribution and part in normal tissue (P=0.311).2. The correlation of HPV infection and tumor differentiation The infection rate of HPV in stage Ⅳ SCC (15.79%)is significantly lower than the stage Ⅰ (58.10%) and stage Ⅱ (51.81%), which with significant difference (P<0.01). But there was no obvious difference of HPV infection rate between stage Ⅰ and stage Ⅱ squamous cell carcinomas (P>0.05). HPV infection rate of stage Ⅲ SCC (30.30%) is middle between grade IV and grade Ⅰ and Ⅱ. Thus infer that although HPV infection may lead to malignant cells, but it may have an effect on the proliferation of tumor cells result in split or because of different subtypes of infection.3. HPV subtype distribution is different in different Broders’grade of SCC. There are33(24.09%) cases in stage Ⅰ among cases of positive HPV16infected,54(39.42%) in stage Ⅱ,39(28.47%) in stage Ⅲ, and11(8.03%) in stage Ⅳ. But in the cases about positive HPV6-infected, there are94(68.12%) in stage Ⅰ,31(22.46%) in stage Ⅱ,13(9.42%) in stage Ⅲ, and no one in stage IV. Only one(16.67%) in stage I,4(66.67%) in stage II and1(16.67%) in stage Ⅲ composed of the HPV18positive infected. There are only two cases infected by HPV53, which1was in stage Ⅰ, the other is in stage Ⅱ. Only two cases in stage Ⅱ were infected by HPV58. The positive rate of HPV in poorly differentiated squamous cell carcinomas is the lowest among various grade SCC. The positive ratio of HPV6is significantly higher in the high differentiated squamous carcinoma differentiation type than the other type, which with significant difference (P<0.01).4. The correlation of HPV infection and lung squamous carcinoma.4.1One hundred and fourteen cases of196pulmonary SCC specimens were found four type different subtypes of HPV infection, in which were the HPV6(24,49%), HPV16(31.12%), HPV18(2.04%) and HPV58(0.51%). The positive rate of HPV infection in. each grade lung SCC was higher than50%, yet the total positive rate comparison showed no significant difference (p>0.05). HPV6was mainly in low-grade SCC (Ⅰ60.87%;Ⅱ5.13%,Ⅲ0%,Ⅳ0%), while HPV16positive (stage I7.25%; stage II42.73%, stage III57.14%, stage IV66.67%) occurs mainly in the middle and height malignant SCC. Can these two indicators be regarded as a judge index of tumor cell differentiation degree?4.2.196cases of lung cancer were positive with SCCA. Various types of HPV infection expressed different intensity of SCCA. HPV positive were most in SCCA "+"(80.70%,92/114), yet short in SCCA "++"(16.67%,19/114) and "+++"(2.63%%,3/114). The intensity of SCCA staining and squamous cell carcinoma was related (P<0.01), but there was no significant correlation with the type of subtype HPV infection (P>0.05).4.3. In the HPV positive infection of lung SCC cases, the negative expression of survivin accounted for41.23%(47/114), survivin positive rate was58.77%(67/114), in which survivin "+" accounted for95.52%(64/67), survivin "++" accounted for4.48%(3/67), survivin "+++" in0cases. Survivin "+++" cases all showed negative in HPV infection.5.The relationship of HPV infection with gender, age, and smoking. The rate of HPV infection in Smoking patients was88.97%, which significantly higher than other age groups (p<0.01); and in male it was78.03%, which significantly higher than other age groups (p<0.01); yet in young it was24,29%, which significantly lower than other age groups,(P<0.01). Are patients with male, young, smoking more susceptible to infection with HPV? Or are this group more likely to develop squamous carcinoma after infection with HPV? Whatever weather Smoking, gender or old age is the important influence factors of HPV infection among SCC.Conclusion:1. After the research we found that the formation of non-cervical squamous cell carcinoma is closely related to HPV infection among patients in Qingdao area.2. Are patients with smoking, male and old are more susceptible to HPV? Or the group infected with HPV were more likely to develop squamous cell carcinoma?3. HPV infection was negatively related to tumor differentiation degree.4. HPV infection is closely related to the formation of lung SCC. HPV6, which is considered to be a Low-risk subtype has positive correlation with low-grade lung SCC. HPV16, which is considered to be a high-risk subtypes has positive correlation with high malignant lung SCC.5. Expression of Survivin was negatively related to lung SCC with HPV6and HPV16positive infection, which suggesting that HPV6and HPV16infection may be a good prognostic factor for lung SCC. The infection rate of HPV is negatively correlated with expression intensity of SCCA. HPV infection may improve the sensitivity of patients with surgery or radiation and chemotherapy, which should be confirmed by further large sample studies.6. The infection of Low-risk type HPV6only exists in low Broders’ grade among no-cervical squamous cell carcinomas. Whether HPV6had the function to promote the cell differentiation? Further study should be done on its role in the development of no-cervical SCC. To exploring the mechanism of highly expression of HPV6in esophageal SCC should be the focus of the followed research.