The Association Of Cervical Disease Progression And High Risk Hpv Infection With The Hla-i Gene Expression In Uighur Women

Objective:To investigate the association of cervical disease progression and HPV (human papillomavirus) infection with expression of HLA-â… (human leukocyte antigen classâ… ) family genes at the mRNA and protein level in Uighur women as well as common characteristics and differences between Uighur and Han women, and to provide important evidences for studying the mechanisms of cervical cancer development of Uighur women. Method:we collected tissue samples of cervical disease lesions from patients with cervicitis, cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma (CSSC), including 78 cases of fresh tissue samples of surgical excision or biopsies of Uighur women,127 and 105 cases of formalin-fixed and paraffin-embedded specimens of Uighur and Han women, respectively. HPV positivity and genotypes were detected by PCR with HPV specific general primers and HPV screening chips for common HPV genotypes, respectively. mRNA expression of HLA-A,-B and-C genes was determined by RT-PCR, to analyze the association of HLA-â… expression with the cervical disease pathogenesis and high risk HPV infection. The protein expression level of HLA-â… protein was detected by immunohistochemistry, and the common features and differences were comparatively analyzed between Uighur and Han women. Result:(1) The infection rate of HPV was gradually increased with the cervical pathogenesis from cervicitis to CIN and CSCC (8.33%,30%and 78.26%, P<0.01), reached the highest rate in poorly or moderately differenciated tumor tissues (84.38%). HPV16 was the predominant genotype in HPV positive specimens. (2) The results of RT-PCR analysis showed that the total loss rate of HLA-A,-B and-C mRNA expression was gradually increased with the development from cervicitis to CIN and CSCC (8.33%,70% and 84.78%, P<0.01), reached the highest total loss rate in tumor specimens with poorly differentiated state and late clinical stage (90.63% and 92.86%),implying an association of cervical disease pathogenesis with the loss of HLA-â… expression differentiation state and clinical stage of the cancer. Moreover,the increasingly loss rate of HLA-â… was also positively correlated with the HPV16 infection (r=0.803,P<0.01). (3) Based on the analysis by immunohistochemistry, the HLA-â… protein expression in cervicitis was normal, the total loss rate was occurred and markedly increased in CIN (26.92%), reached the highest level in CSCC (52.94%), and the difference was statistically significant (P<0.01). The alteration trend of the total loss of HLA-â… almost identical between Uighur and Han women, but in relative greater extent in Uighur women. Conclusion:(1) The increasing in HPV infection rate was positively correlated with cervical disease pathogenesis, and the HPV16 was the predominant genotype of the infection. This is a proof for HPV16 as an important factor in the development of cervical cancer of Uighur women. (2) The downregulation or loss of transcription of HLA-â… family genes (HLA-A,-B and -C) may be an important marker of cervical disease and tumor development, and closely associated with the differentiation state and clinical stage of tumor as well as HPV16 infection. (3) The decreased expression or loss of HLA-â… protein may also be an important marker of cervical disease pathogenesis, and the common features and differences between Uighur and Han ethnic groups may reflect common mechanisms and unique genetic backgrounds in cervical cancer development.