Studies On Dependablity Between The Phenotype Of Human Papillomavirus(HPV) Infection In Vulvae And P53/p73Polymorphism

Condyloma accuminatum(CA) is a most common sexual transmitted disease in the clinic of dermatology and venereal diseases, and the possibility of cancerizition should be pay attention to the cases with the infection of high risk HPV. Bowenoid papulosis of vulva(BP) is a viral infection disease with low potential malignancy by the cellular and structural atypia. Different clinical phenotypes will be provoked by HPV, of which most CA are infected by the low risk types and large amount of BP cases suffer high risk HPV types infection. It is a valuable topic whether is there a diversity of the sensibility of HPV, whether the gene polymorphism plays a role in the diversity of manifestation of HR or LR HPV infection.There are quite a mount of papers recently discuss the relation of sensitivity of HPV-related-tumour and the gene polymorphism of the anti-ohcogene p53and p73. Some of the studies observed that the polymorph of p53codon72and the p73exon2have something to do with certain types of HPV-related-tumors. However, the conclusion appears inconsistency among different population and regions.We collected the lesion tissue and blood samples of CA and BP patients as experimental group, the control group came from the risk population who commit the health examination in the venereal clinic and confirmed CA or BP free by specialists, to study the correlation of the polymorph of p53/p73and HPV infection manifestation. To make a preliminary research and reference for the future study.Part1Study of the dependability between the HPV types in CA/BP and the manifestationObjective To investigate the molecular epidemoological characteristics of human papillomavirus(HPV) infections among patients with ondyloma accuminatum(CA) or Bowenoid papulosis of vulva(BP), analyze the distribution of the HPV genotye.Methods DNA isolated from CA/BP specimens were amplified by PCR and sequencing to identify HPV genotype. Type-special primer PCR(TSPHPCR) of HPV2,6,7,11,16,18were also performed to confirm and complete the PCR and sequencing results. And analyze the dependability of HPV types and clinical phenotype of CA and BP.Results124CA cases and14BP cases were enrolled in the study groups. The incidence of the CA in patients with HR-HPV is6.03(7/116), BP is50%(7/14), the difference was statistically significant(χ2=20.76, P<0.01). Of seven patients of CA with HR-HPV infection, there were5cases male,2females;3cases in perianal,1cases next to the frenulum,1case on foreskin,2cases on the labia minora; cauliflower-like5cases papules, papillary1cases. There is no statistical association between gender, location, lesion morphology, and susceptibility to the HR-HPV sensitivity.Conclusion We identified the HPV types of the collected genital condyloma patients, no statistical association was found between the morphous and site of the lesion and HPV types.Part Ⅱ Study of the Gene polymorphism of p53in patients of condyloma accuminatum and Bowen papulosisObjective Blood samples of genital warts and Bowen papulosis patients were Collected, detected p53polymorphism. To analyze the relationshipn of the genetic alterations of the p53codon72and HPV infection of HPV types, clinical presentation.Method To select genital warts patients and pathological diagnosis Bowen papulosis patients from June2010to September2011as Experimental group, gathering their lesion and blood samples. The negative control group from the healthy people suffering from other sexually transmitted diseases with through VD physical examination to exclude genital warts.Blood samples of experimental group and control group were collected to do the p53polymorphism detection. statistical analyze was made with the types of HPV infection in the skin lesions and p53polymorphism of experimental and control group.Result116blood samples of CA patients were collected, within112cases sequencing positive.14BP patients were collected and sequencing positive in all14cases. The results showed there are three types of p53codon72, CGC homozygotes, CCC homozygotes. and CGC/CCC heterozygous of CA/BP patients somatic cells. With statistical analyze, the chance of Arg/Pro genotype suffering from CA is lower than the other two homozygotes. The prevalence of BP has no significant correlation with the three genotypes (P>0.05).No significant correlation was found between p53gene polymorphism and HPV susceptibility.Conlusion We found that the Arg/Pro genotypehave was a protective effect on the risk of CA, but no significant correlation was found in BP. Correlation Analysis between the distribution of two allele Arg and Pro, and the type of HPV infection found no significant correlation. The reason may be related to the limited number of BP cases that we have collected. The follow-up studies need to further expand the sample size and improve the clinical data.Part Ⅲ Study of the Gene polymorphism of p73in patients of condyloma accuminatum and Bowen papulosisObjective Blood samples of genital warts and Bowen papulosis patients were Collected, detected p73polymorphism. To analyze the relationshipn of the genetic alterations of the p73exon2and HPV infection of HPV types, clinical presentation.Method To select genital warts patients and pathological diagnosis Bowen papulosis patients from June2010to September2011as Experimental group, gathering their lesion and blood samples. The negative control group from the healthy people suffering from other sexually transmitted diseases with through VD physical examination to exclude genital warts. Blood samples of experimental group and control group were collected to do the p73polymorphism detection. statistical analyze was made with the types of HPV infection in the skin lesions and p73polymorphism of experimental and control group.Result83out of90blood samples of CA patients were collected and sequencing positive.14BP patients were collected and sequencing positive in all14cases. The results showed there are three types of p73exon2, A4T14/G4C14heterozygous, A4T14homozygotes, and G4C14homozygotes of CA/BP patients somatic cells. With statistical analyze, compared to the control group, the distribution of GC and AT gene has no significant correlation with CA susceptibility, but GC gene lower the risk to suffer BP. Compared with AT/AT genotype, GC/AT and GC/GC genotypes had a protective effect to the risk of CA. However the risk of suffering BP was higher in the AT than GC. Correlation analysis showed that the risk of suffering BP AT/AT>GC/AT>GC/GC. The chance of AT or GC genotype suffering from CA is lower than the other two homozygotes. The prevalence of BP has no significant correlation with the three genotypes (P>0.05).no significant correlation was found between p53gene polymorphism and HPV susceptibility. No significant correlation was found between p73gene polymorphism and HPV susceptibility.Conlusion Carrying the AT gene increases the risk of BP and CA. A4T14/A4T14and G4C14/A4T14genotypes suffering higher BP risk than the G4C4/G4C4genotype. The ones carrying GC/AT and GC/GC gene took the lower risk of CA than the ones carrying the AT/AT gene, o significant correlation was found between allele and genotypes distribution of p73exon2and HR/LR HPV susceptibility of CA and BP in this study...