Study Of Human Papillomavirus (HPV) Genotypes Distribution In Cervical Carcinoma And The Relationship With Clinicopathology

BackgroundCervical cancer is the second largest threat to the lives of women.There are 45 -50 million new cases per year and in which 200,000 died,about 80%of these take place in developing countries.Cervical cancer is not only a serious threat to women's health, but also to society and families,it has become a major social problem.In recent years, disease rate of cervical cancer has upgraded obviously,and goes to more youthful.Through substantial epidemiological and laboratory studies,domestic and foreign scholars has confirmed infection with human papillomavims(HPV) is considered as a prerequisite for genesis and progress of the disease.The mechanism of HPV-induced oncogenesis has preliminarily been elucidated through considerable details.Partial integration of viral genome segments into the host DNA,which may be consistent in HPV-infected cells,results in the overexpression of E6 and E7 gene, eventually leading to uncontrolled proliferation and immortalization.More than 200 different genotypes of HPV have been identified thus far,and there are approximately 50 known genital HPVs with geographic differences in the distribution of HPV genotypes.Population studies helped to establish that at least 20 of these viruses have been associated with cervical cancer,led to the development of HPV vaccine which focus on prevention of the cancer-causing infection.HPV vaccine is also expected to complete the primary prevention,screening and treatment strategies of cervical cancer,helping to lowering the disease burden related to society and families. There are two vaccines,the approvaled by FDA quadrivalent Gardasil^TM vaccine(Merck & Co.,Inc.(Merck)),targets the types of HPV 6,11,16 and 18,and unapproved bivalent Cervarix^TMvaccine(GlaxoSmithKline(GSK)) targets the types of HPV 16 and 18.However,the overall preventive effect of the vaccine depends on the basic HPV types people infected.An in-depth study of the prevalence of HPV genotype in various regions can help to determine the high-risk factors and groups of cervical carcinoma,offer the foundations to the government for formulation of the prevention policy,and provide a theoretical basis to the promotion,research and development of HPV vaccine in our region.Clinicopathologic factors for cervical cancer,including International Federation of Gynecology and Obstetrics(FIGO) stage,lymph node metastasis,parametrial or vaginal extension,nonsquamous histology,grade of differentiation,lymphovascular space invasion,and deep stromal invasion,have been noted to be associated with prognosis. Studies have found HPV genotypes is related with the prognosis of patients with cervical cancer,but relational researches are still less,and reports in this area cannot be found in our country.The aim of this study is to investigate the prevalence of main HPV genotypes in cervical cancer in Zhejiang province;Analyze the relationship between the detection rates of HPV genotypes and the clinicopathologic characteristics of patients with cervical cancer by flow-through hybridization and gene chip(HybriMax). Materials and MethodsThe investigated group comprised 1169 patients suffering from cervical cancer, which all visited the Zhejiang Cancer Hospital,since Jan.2007 to Dec.2008.All patients were of the Chinese Han nationality.Their cervical exfoliated cells were check for 21 HPV DNA types by flow-through hybridization and gene chip.Thereafter,the correlation between HPV type and the clinicopathological features of cervical cancer was evaluated.Results1.In 1169 cases the total infection positive rate of HPV was 91.70%(1072/ 1169)and the HR-HPV positive rate was 91.53%,the LR-HPV positive rate was 4.88%.Single infection rate of various HPV genotypes was 77.16%(902 / 1169)in our study;Co-infection by 2,3,4,5 genotypes accounted for 12.23%(143/1169). 1.28%(15 / 1169),0.77%(9 / 1169),and 0.26%(3 / 1169)respectively.Viral genotype 16 ranked first with 62.10%,then followed by 18 with 10.95%,58 with 10.52%,52 with 7.96%,33 with 3.93%,31 with 3.93%,68 with 1.88%,53 with 1.88%,45 with 1.20%,CP8304 with 1.20%,66 with 0.77%,59 with 0.68%,6 with 0.60%,39 with 0.43%,11 with 0.43%,56 with 0.26%,42 with 0.26%,43 with 0.17%,44 with 0.17%,and genotypes of 35,51 were not detected.2.The positive rate of HPV18 in cervical non-squamous cell cancer was 12.99%, which in cervical squamous cell cancer was 6.87%,HPV 18 infection were more common in patients of non- squamous cell cancer(χ²= 3.994,p = 0.046 ).The positive rate of HPV18 was correlated to deep stromal invasion,lymphovascular space involvement,pelvic lymph node metastases confirmed by histopathological examination (χ² = 4.847,15.883,9.592,p = 0.028,0.000,0.002 ).The rate of multiple HPV infection was correlated to deep stromal invasion(χ² = 7.915,p = 0.005 ). Conclusions1.HPV16 is the most important genotype in cervical cancer,which followed by HPV18,58,52,33.2.The relationship between HPV genotypes and the clinic pathologic characteristics maybe indicated HPV genotypes is related with the prognosis in cervical cancer patients.HPV18 is significant related with nonsquamous histology,deep stromal invasion,lymphovascular space involvement and lymph node metastasis and the multiple HPV infection is related to deep stromal invasion.