The Preliminary Study On Changes Of Dendritic Cell And Its Mechanisms In Cervical Lesions Caused By Hpv Infection

Background and purposeHuman papilloma viruses (HPV) are small DNA virus, which characteristicallyinfect squamous epithelial cells of the skin and mucosa. HPV infection could causeepithelium hyperproliferation even malignant tumor. As a sexual transmitted disease,HPV infection is characterized by a very high rate of acquisition. It is generallyaccepted that HPV infection is the most important factor in the development ofcervical cancer. The individual could not establish the effective immune response.Immune escape or immune deficiency often exists in patients of persistant HPVinfection. Local immune disturbance can often be seen in repeated or prolonged HPVinfected patients. The changes in the number and function of Dendritic cell(DC) inthe infection site might play an important role in the presence of persisting HPVinfection in cervical lesions and the malignant transformation of infected cells.DC is the most powerful professional antigen-presenting cell, and it canefficiently uptake, processing and presenting antigen. Immature DC has a strongability to migrate. Mature DC can effectively activate naive T cells and it is at thecentral link of starting, controlling and maintaining of the immune response. CD1aand CD83 molecules represent, respectively, as a sign of the differentiation, maturation of DC (including Langerhans cells(LC)) and improvement of immunefunction.DCs change their number and function from time to time in the process ofthe development and prognosis of the cervical lesions caused by HPV infection, andmaybe associated with the extent of the lesions.The aim of this research is to detect the expressions and mutual relationship ofCDla and CD83 molecules and their mRNA in different cervical lesions caused byHPV.In addition, the study is also to detect the infected subtypes of HPV genes inthe specimens from in normal cervix, condyloma accuminatum (CA), and squamouscarcinoma of the cervix and analyze the infected relationship between normal cervix,CA and squamous carcinoma of the cervix and different genotypes of HPV infected.Methods1 The expressions of CD1a and CD83 were detected by streptavidin peroxidasemethod in the specimens with cervical CA(30 cases) and cervical cancer(30 cases)and normal of paraffin block, which were all confirmed histopathologically.2 CD1a and CD83 mRNA were measured by reverse transcriptase PCR in 10 freshcervical CA lesions,10 fresh cervical cancer lesions and 10 normal controls.3 The genotype of HPV-DNA were detected by the PCR genetyping method in thespecimens with cervical CA(30 cases) and cervical cancer(30 cases) and normal ofparaffin block which were all confirmed histopathologically.Results1 In the development of cervical neoplasm, there was a decline in the number ofimmature CD1a+ dendritic cells(DCs) in CA and a further decline in population incarcinoma as compared to the normal ectocervix(normal ectocervix: 3.45 cells/HPF,CA:2.89 cells /HPF,cancer:2.41 cells /HPF). However there was a significant increase in the mature CD83+ DCs population in CA as compared to the normalectocervix(CA:0.056cells /HPF, normal ectocervix:0.019 cells/HPF). there was alsoan increase in the mature CD83+ DCs population in the neoplastic lesion(cancer:0.039cells /HPF).2 The expressions of CD1a and CD83 mRNA: Compared with normal tissues(0.901±0.043), the expression of CD1a mRNA was down-regulated in CA lesions(0.566±0.033) (p<0.05),and significantly down-regulated in cervical cancer lesions(0.352±0.030)(p<0.05). Compared with normal tissues(0.071±0.007), the expression ofCD83 mRNA was significantlyup-regulated in CA lesions(0.599±0.036)(p<0.05),and up-regulated in cervical cancer lesions(0.316±0.013)(p<0.05).3 The condition of HPV6/11 infection: HPV6/11-DNA could not be found in normalcervical tissues.The expression rate of HPV6/11-DNA was 73.3% (22/30) in CA and3.3% (1/30) in cancer. There was a significant difference in HPV6/11 infection in CAgroup comparing with normal group (P<0.05), while there was a statisticalsignificance in CA comparing with cervical cancer (P<0.05).4 The condition of HPV16/18 infection: HPV16/18-DNA could not be found innormal cervical tissues. The expression rate of HPV16/18-DNA was 6.67% (2/30) inCA and 56.67% (17/30) in cancer. There was a significant difference in HPV16/18infection in cancer group comparing with normal group(P<0.05), while there was astatistical significance in cancer comparing with CA(P<0.05).ConclusionsOur result shows that there is a certain immune response both in the CA andcancer lesions, which may prevent the infected cervical tissues from progressing toinvasive carcinoma. While comparing with CA, the expression of mature DCs incancer is lower, and this shows that the presence of antigen presenting cells within the carcinoma population is insufficient to mount adequate immune response to preventinvasion into the stroma. Low risk HPV(LRHPV) infection is an important factor toCA and CA has obvious relation with HPV6/11 infection.High risk HPV(HRHPV)infection is an important factor to cervical cancer and cervical cancer has obviousrelation with HPV16/18 infection.