HPV分型及p53表达对宫颈癌放疗敏感性影响

Impact of HPV typing and p53 expression on radiosensitivity in patients with cervical cancer

目的 探讨宫颈癌患者中HPV分型及p53表达与放疗敏感性的相关性.方法 收集2014-2016年间宫颈癌患者80例,其中ⅠB＋ⅡA期40例、ⅡB＋ⅢA期40例.检测患者HPV的DNA的感染类型及p53的表达,采用单纯放疗方法对人选患者进行盆腔外和腔内照射,分析近期疗效与HPV分型及p53表达的相关性ox2检验或Fisher＇s精确概率法检验,Spearman等级相关分析.结果 ⅠB＋ⅡA、ⅡB＋ⅢA期放疗不敏感组（SD＋PD）者p53阳性率分别为100％、100％,高于放疗敏感组（CR＋PR）的80.0％、90.0（P=0.044、0.013）.p53的表达强度与放疗敏感性呈负相关（r=-0.427,P=0.000）.ⅠB＋ⅡA、ⅡB＋ⅢA期放疗不敏感组患者中HPV的DNA多重感染率多于单一亚型感染率,分别为65.0％、95.0％和35.0％、5.0％ （P=0.004、0.003）,放疗敏感性患者中HPV的DNA单一亚型感染率多于多重感染率,分别为85.0％、60.0％和15.0％、40.0％（P=0.004、0.003）.所有患者中HPV16的检出率最高为66.3％,放疗不敏感组患者中HPV18的检出率最高为60.0％.结论 p53高表达与宫颈癌放射抗拒有关,HPV的DNA多重感染的宫颈癌患者对放疗敏感性较差,HPV16是双重感染中最常见亚型,放疗后未缓解患者中以HPV18为主的多重感染检出率最高.

Objective To investigate the association of human papilloma virus （HPV） typing and p53 expression with radiosensitivity in patients with cervical cancer.Methods A total of 80 patients with cervical cancer from 2014 to 2016 were enrolled,and among these patients,40 had stage Ⅰ B＋ Ⅱ A disease and 40 had stage Ⅱ B ＋ⅢA disease.HPV genotype was identified and p53 expression was measured.All the patients underwent external and internal pelvic irradiation alone,and the correlation between short-term therapeutic effect and HPV typing/p53 expression was analyzed.The chi-square test or the Fisher＇s exact test was used for statistical analysis,and Spearman rank correlation analysis was also performed.Results The radiotherapy-insensitive （stable disease＋progressive disease） group had higher p53 positive rates than the radiotherapy-sensitive （complete response＋partial response） group （stage Ⅰ B＋ Ⅱ：100％ vs.80.0％,P=0.044;stage Ⅱ B＋ⅢA：100％ vs.90.0％,P=0.013）.The expression of p53 was negatively correlated with radiosensitivity （r =-0.427,P =0.000）.In the radiotherapy-insensitive group of patients with stage I B ＋ Ⅱ and Ⅱ B ＋Ⅲ A,the rate of HPV multiple infections was higher than that of single subtype infection （65.0％/95.0％ vs.35.0％/5.0％,P=0.004 and 0.003）,while in the radiotherapy-sensitive group,the rate of single subtype infection was higher than that of multiple infections （85.0％/60.0％ vs.15.0％/40.0％,P=0.004 and 0.003）.The highest detection rate of HPV16 was 66.3％ in all patients,and the highest detection rate of HPV18 was 60.0％ in the radiotherapy-insensitive group.Conclusions High expression of p53 is associated with radioresistance in patients with cervical cancer.Patients with HPV muhiple infections have poor radiosensitivity,and HPV16 is the most common subtype in dual infection.Among patients who do not achieve remission after radiotherapy,HPV multiple infections with HPV18 as the main pathogen has the highest detection rate.