关键词: 宫颈疾病；宫颈肿瘤；宫颈上皮内瘤变；人乳头瘤病毒；T淋巴细胞, 调节性

Abstract: Background　Persistent infection of high-risk human papillomavirus （HR-HPV） is necessary but not sufficient for the occurrence of cervical cancer.Multiple changes in genome，microenvironment and immune system，and inflammation contribute to carcinogenesis.Therefore，the biomarkers of HR-HPV infection detected simply and noninvasively that can accurately and quantitatively reflect the changes in biological behavior of cervical cancer，become a focus of clinical research.Objective　To examine the changes in HR-HPV load and regulatory T Cells （Treg） in the same microenvironment of cervical lesions，and based on this，to discuss their interactions and expressions in the development of cervical lesions.Methods　We enrolled 342 cervical lesions patients with persistent HR-HPV infection from First Affiliated Hospital of Henan Polytechnic University during January 2012 to July 2015，including 55 with chronic cervicitis，73 with cervical intraepithelial neoplasia（CIN）Ⅰ，71 with CINⅡ，72 with CINⅢ and 71 with squamous carcinoma of the cervix （SCC）．QF-PCR was used to detect the HR-HPV load.According to the level of HR-HPV load （copy number of HPV DNA），we divided the participants into 4 groups：low load （HPV DNA 104-105 copies/ml，n=69），medium load （HPV DNA>105-106 copies/ml，n=90），high load （HPV DNA>106-107 copies/ml，n=106）and very high load （HPV DNA>107 copies/ml，n=77）．Flow cytometry was used to determine the number of Treg from cervical samples collected using a cytology brush.Results　There were significant differences in the number of Treg among different load groups （P<0.05）．The number of Treg increased with the growth of HR-HPV load，namely，low load group had less number of Treg than other 3 groups（P<0.05），so did the medium load group when compared with other 2 high groups （P<0.05），and as did the high load group when compared with very high group （P<0.05）．The number of Treg differed significantly in patients with different cervical lesions （P<0.05）．Chronic cervicitis patients had less number of Treg than other patients，so did CINⅠpatients when compared with CINⅡ，CINⅢ and SCC patients，and so did CINⅡpatients when compared with CINⅢ and SCC patients，and as did the CINⅢ patients when compared with SCC patients（P<0.05）．The number of HR-HPV load differed significantly in patients with different cervical lesions（P<0.05）．Chronic cervicitis and CINⅠpatients had less HR-HPV load than other patients，so did CINⅡ and CIN Ⅲ patients when compared with SCC patients （P<0.05）．Clustered boxplot diagram showed that chronic cervicitis and SCC patients were found with a total of 3 slightly abnormal values，but other patients without；the distribution of HR-HPV load was dispersed in SCC patients，but comparatively concentrated in other cervical lesion patients.The distribution of cervical lesions in different HR-HPV load groups was significantly different （P<0.05）．Correlation analysis showed that HR-HPV load was positively correlated with the severity of cervical lesions and the number of Treg （r=0.631，0.683，P<0.05），and there was a positive correlation between the severity of cervical lesions and the number of Treg （r=0.863，P<0.05）．Conclusion　The level of HR-HPV load is not always positively correlated with the severity of cervical lesions.The roles of Treg in the development of different cervical lesions differ by their expressions in the local cervical microenvironment.There are different pathogenicities，which causes immune imbalance，a key link in the development of cervical cancer.

Key words: Uterine cervical diseases；Uterine cervical neoplasms；Cervical intraepithelial neoplasia；Papillomavirus；T-lymphocytes, regulatory