HPV16特异性免疫应答评估宫颈病变风险及转归的临床研究

Clinical research of using HPV16-specific T cell response to evaluate the risk and prognosis of cervical lesions

为探讨重组重叠肽(recombinant overlapping peptide,ROP)-人乳头瘤病毒(human papillomavirus,HPV)16E7蛋白介导的细胞免疫应答在评估HPV16感染患者病变风险及转归中的临床价值及意义,选取HPV16阳性病例131例,其中慢性炎症42例、低度鳞状上皮内病变(low-grade squamous intraepithelial lesion,LSIL)33例、高度鳞状上皮内病变(high-grade squamous intraepithelial lesion,HSIL)39例、宫颈癌17例。利用ROP技术设计ROP-HPV16E7蛋白,通过酶联免疫斑点法(enzyme-linked immunospot assay,ELISPOT)检测HPV16E7特异性T细胞反应,分析HPV16感染患者不同病变阶段特异性T细胞的免疫力。结果显示,在17例宫颈癌患者中只有1例(5.9%)HPV16E7特异性T细胞反应阳性,显著低于癌前病例组(P<0.05)。经1年随访,大多数持续感染HPV的患者没有表现出HPV16E7特异性T细胞反应(28/33,84.8%)。此外,3例组织病理检查显示病情进展的患者(其中1例进展为HSIL,2例进展为LSIL)HPV16E7特异性T细胞反应均为阴性(P=0.001)。HPV16E7特异性T细胞反应阳性的患者均无进一步恶化。该研究提示,HPV16E7特异性T细胞免疫在病毒清除中具有重要意义,并有助于阻止病情的进展,对判断疾病转归具有指导意义,同时可以辅助临床诊断,避免过度干预和治疗。

This study aims to investigate the clinical value and significance of the recombinant overlapping peptide(ROP)-human papillomavirus(HPV)16E7 protein-mediated cellular immune response in assessing the risk and prognosis of patients with HPV16 infection.The research recruited 131 patients with HPV16 infection among which 42 with chronic cervical inflammation,33 with low-grade squamous intraepithelial lesion(LSIL),39 with high-grade squamous intraepithelial lesion(HSIL),and 17 with cervical cancer.ROP-HPV16E7 protein was designed by ROP technology.HPV16E7-specific T cell responses were detected by enzyme-linked immunospot assay(ELISPOT)and the immunity of specific T cells in patients with HPV16 infection at different pathological stages was analyzed.The results showed that only one of 17(5.9%)cancer patients had positive HPV16E7-specific T cell response,dramatically lower than that of precancer patients(P<0.05).After one year of follow-up,most patients(28/33,84.8%)with persistent HPV infection did not exhibit a HPV16E7-specific T cell response.Furthermore,3 malignantly progressed patients(one progressed to HSIL and two progressed to LSIL)showed no HPV16 E7-specific T cell response(P<0.001).None of the patients with a positive HPV16E7-specific T cell response progressed further.Therefore,the study suggests that HPV16 E7-specific T cell immunity is important for viral clearance and contributes to protection against the progression to malignancy.HPV16E7-specific T cell immune response may also be an indicator for disease risk assessment and prognosis to avoid excessive intervention and treatment.