5-氨基酮戊酸光动力疗法治疗高危型HPV感染尖锐湿疣的疗效及局部细胞免疫活性分析
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摘要
目的:观察5-氨基酮戊酸光动力疗法(ALA-PDT)治疗高危型HPV感染尖锐湿疣患者临床疗效及其局部细胞免疫活性变化情况。方法:选取2015年1月至2017年1月47例高危型HPV感染的尖锐湿疣患者,21例为对照组,单纯行手术切除疣体; 26例为观察组,采用ALA-PDT治疗1～5次,观察疣体数目变化及术后6个月两组患者疣体复发情况。并分别切除对照组(T)所有疣体、观察组治疗前(T0)所有> 5 mm的疣体及经1次(T1)、3次(T2)、5次(T3)治疗48 h后较大疣体(> 2 mm),通过免疫组化检测局部尖锐湿疣组织中CD4+、CD8+T细胞、CD4+/CD8+比值、CD68+巨噬细胞变化情况。结果:对照组患者疣体术后完全清除100%(21/21),术后6个月复发率42. 9%(9/21)。观察组经过5次的光动力疗法治疗后,26例患者疣体完全清除率为61. 5%(16/26),部分清除率为26. 9%(7/26),疣体清除效果欠佳11. 5%(3/26),疣体总有效清除率为88. 5%(23/26),无明显溃烂、瘢痕、色素沉着等严重并发症,术后6个月复发率为11. 5%(3/26),明显低于对照组(P <0. 05)。疣体组织免疫组化结果显示:与对照组(T组)和ALA-PDT治疗前(T0组)相比较,ALA-PDT治疗后患者疣体局部组织内CD4+T细胞数量(56. 88±4. 72vs31. 21±6. 23)、CD8+T细胞数量(48. 87±2. 47 vs 25. 31±3. 51)及CD4+/CD8+比值(1. 68±0. 52 vs 1. 21±0. 52)均显著上升(P <0. 05,或<0. 01),而CD68+巨噬细胞数量(22. 31±2. 73 vs 23. 31±1. 54)无明显变化。结论:ALA-PDT治疗高风险型HPV感染尖锐湿疣具有效率高、创伤小、安全性高等特点,并能提高局部组织细胞免疫功能,降低复发率。
Objective:To observe the clinical effects of the 5-aminolevulinic acid photodynamic therapy(ALA-PDT) on condyloma acuminata with high-risk human papillomavirus(HPV) infection and cellular immunoactivity in the local tissue of the patient.Methods:From January 2015 to January 2017,we treated 47 cases of condyloma acuminata with high-risk HPV infection in our hospital by simple excision of the wart(the control group,n = 21) or 1-5 times of ALA-PDT plus wart excision(the observation group,n = 26) and observed the changes in the number of warts and recurrence at 6 months after surgery.We excised all the warts in the control group and those > 5 mm before ALA-PDT and > 2 mm at 48 hours after 1-5 times of ALA-PDT in the observation group,followed by examination of the counts of CD4+and CD8+T cells,CD4+/CD8+ratio,and number of CD68+macrophages in the local tissue by immunohistochemistry.Results:In the control group,the warts were completely removed in all the 21 cases but recurred in9(42.9%) at 6 months after surgery.In the observation group,5 times of ALA-PDT achieved complete removal of the warts in 16(61.5%) of the 26 patients,partial removal in 7(26.9%),and inefficient removal in 3(11.5%),with a total effective removal rate of 88.5%(23/26),a significantly lower 6-month recurrence rate(11.5% [3/26]) than in the control(P < 0.05),but no such severe complications as festering,scarring and pigmentation.Compared with the control group and the baseline,the observation group showed remarkable increases after 1,3 and 5 times of ALA-PDT in the counts of CD4+T lymphocytes(31.21 ± 6.23 and30.27 ± 5.63 vs 56.88 ± 4.72,54.67 ± 2.84 and 42.62 ± 2.31,P < 0.05) and CD8+T cells(25.31 ± 3.51 and 27.35 ±3.78 vs 48.87 ± 2.47,45.41 ± 3.17 and 37.58 ± 3.32,P < 0.01) and the CD4+/CD8+ratio(1.21 ± 0.52 and 1.09 ±0.37 vs 1.68 ± 0.52,1.63 ± 0.45 and 1.42 ± 0.13,P < 0.05 or P < 0.01),but exhibited no significant change in the count of CD68+macrophages in the local tissue(23.31 ± 1.54 and 20.25 ± 1.28 vs 22.31 ± 2.73,23.17 ± 2.41 and 21.35 ± 3.72,P > 0.05).Conclusion:ALA-PDT,with its advantages of high efficiency,little invasion and high safety,is effective for the treatment of condyloma acuminata with high-risk HPV infection and it can also improve cellular immunoactivity in the local tissue and reduce recurrence.
Objective:To observe the clinical effects of the 5-aminolevulinic acid photodynamic therapy(ALA-PDT) on condyloma acuminata with high-risk human papillomavirus(HPV) infection and cellular immunoactivity in the local tissue of the patient.Methods:From January 2015 to January 2017,we treated 47 cases of condyloma acuminata with high-risk HPV infection in our hospital by simple excision of the wart(the control group,n = 21) or 1-5 times of ALA-PDT plus wart excision(the observation group,n = 26) and observed the changes in the number of warts and recurrence at 6 months after surgery.We excised all the warts in the control group and those > 5 mm before ALA-PDT and > 2 mm at 48 hours after 1-5 times of ALA-PDT in the observation group,followed by examination of the counts of CD4+and CD8+T cells,CD4+/CD8+ratio,and number of CD68+macrophages in the local tissue by immunohistochemistry.Results:In the control group,the warts were completely removed in all the 21 cases but recurred in9(42.9%) at 6 months after surgery.In the observation group,5 times of ALA-PDT achieved complete removal of the warts in 16(61.5%) of the 26 patients,partial removal in 7(26.9%),and inefficient removal in 3(11.5%),with a total effective removal rate of 88.5%(23/26),a significantly lower 6-month recurrence rate(11.5% [3/26]) than in the control(P < 0.05),but no such severe complications as festering,scarring and pigmentation.Compared with the control group and the baseline,the observation group showed remarkable increases after 1,3 and 5 times of ALA-PDT in the counts of CD4+T lymphocytes(31.21 ± 6.23 and30.27 ± 5.63 vs 56.88 ± 4.72,54.67 ± 2.84 and 42.62 ± 2.31,P < 0.05) and CD8+T cells(25.31 ± 3.51 and 27.35 ±3.78 vs 48.87 ± 2.47,45.41 ± 3.17 and 37.58 ± 3.32,P < 0.01) and the CD4+/CD8+ratio(1.21 ± 0.52 and 1.09 ±0.37 vs 1.68 ± 0.52,1.63 ± 0.45 and 1.42 ± 0.13,P < 0.05 or P < 0.01),but exhibited no significant change in the count of CD68+macrophages in the local tissue(23.31 ± 1.54 and 20.25 ± 1.28 vs 22.31 ± 2.73,23.17 ± 2.41 and 21.35 ± 3.72,P > 0.05).Conclusion:ALA-PDT,with its advantages of high efficiency,little invasion and high safety,is effective for the treatment of condyloma acuminata with high-risk HPV infection and it can also improve cellular immunoactivity in the local tissue and reduce recurrence.
引文
[1]Cong X,Sun R,Zhang X,et al.Correlation of human papillomavirus types with clinical features of patients with condyloma acuminatum in China.Int J Dermatol,2016,55(7):775-780.
[2]鲁严,王修来,吴迪,等.72例男性肛周尖锐湿疣的临床特征及流行病学调查.中华男科学杂志,2006,12(10):923-926.
[3]林秋兰,林竞,赵丽华,等.基因芯片检测尖锐湿疣患者HPV感染及分型研究.现代中西医结合杂志,2013,22(30):3325-3328.
[4]Giomi B,Pagnini F,Cappuccini A,et al.Immunological activity of photodynamic therapy for genital warts.Br J Dermatol,2011,164(2):448-451.
[5]Bailey M,Cunitz B,Dunmire B,et al.Ultrasonic propulsion of kidney stones:Preliminary results of human feasibility study.IEEE Int Ultrason Symp,2014,2014:511-514.
[6]张云凤,缪飞,王宏伟,等.氨基酮戊酸光动力治疗尖锐湿疣局部免疫反应的研究.中华皮肤科杂志,2013,46(5):309-312.
[7]曹嘉力,何焱玲,张秀英.尖锐湿疣患者HPV感染与细胞免疫功能的相关性.中国皮肤性病学杂志,2012,26(5):383-385.
[8]Konishi I,Fujii S,Nonogaki H,et al.Immunohistochemical analysis of estrogen receptors,progesterone receptors,Ki-67 antigen,and human papillomavirus DNA in normal and neoplastic epithelium of the uterine cervix.Cancer,1991,68(6):1340-1350.
[9]王雄,王珏,孔霞,等.HPV亚型与尖锐湿疣复发率复发时间关系的分析.中国皮肤性病学杂志,2008,22(11):675-676.
[10]沈跃莉,王大海,刘群花.ALA-PDT对尖锐湿疣患者临床疗效及炎性因子水平影响分析.中国性科学,2017,26(2):68-70.
[11]杨梅,高坤,曹泸丹,等.5-氨基酮戊酸-光动力疗法治疗复发性尖锐湿疣76例观察.现代临床医学,2014,40(3):200-201.
[12]王秀丽,王宏伟,王海山,等.5-氨基酮戊酸光动力治疗尿道尖锐湿疣临床与实验研究.应用激光,2005,25(2):139-141.
[13]Belicha-Villanueva A,Riddell J,Bangia N,et al.The effect of photodynamic therapy on tumor cell expression of major histocompatibility complex(MHC)class I and MHC class I-related molecules.Lasers Surg Med,2012,44(1):60-68.
[14]Stanley MA.Genital human papillomavirus infections:Current and prospective therapies.J Gen Virol,2012,93(Pt 4):681-691.
[15]何丹华,李其林,黄永华,等.尖锐湿疣患者人乳头瘤病毒亚型与细胞免疫功能的相关性.广东医学,2012,33(13):1914-1916.
[16]李敏,易恒安,邱宇芬.艾拉光动力联合CO2激光治疗尖锐湿疣后的免疫功能及病灶组织中病情分子的表达情况.海南医学院学报,2016,22(15):1666-1669.
[17]廖晖,胡柏根,徐胜利.半袖套式包皮环切术治疗阴茎多发性尖锐湿疣80例.中华男科学杂志,2012,18(10):945-946.
[18]张世栋,张明荣,庄桂山,等.派特灵与微波治疗阴茎复发性尖锐湿疣临床疗效对比.中华男科学杂志,2017,23(12):1141-1143.
[19]蔡锦楠,吴华红,陈松波.5-氨基酮戊酸光动力疗法治疗尖锐湿疣临床疗效观察.现代诊断与治疗,2015,26(6):1355-1356.
[20]韩凯,曾抗.尖锐湿疣的细胞免疫研究进展.皮肤性病诊疗学杂志,2011,18(4):279-282.
[2]鲁严,王修来,吴迪,等.72例男性肛周尖锐湿疣的临床特征及流行病学调查.中华男科学杂志,2006,12(10):923-926.
[3]林秋兰,林竞,赵丽华,等.基因芯片检测尖锐湿疣患者HPV感染及分型研究.现代中西医结合杂志,2013,22(30):3325-3328.
[4]Giomi B,Pagnini F,Cappuccini A,et al.Immunological activity of photodynamic therapy for genital warts.Br J Dermatol,2011,164(2):448-451.
[5]Bailey M,Cunitz B,Dunmire B,et al.Ultrasonic propulsion of kidney stones:Preliminary results of human feasibility study.IEEE Int Ultrason Symp,2014,2014:511-514.
[6]张云凤,缪飞,王宏伟,等.氨基酮戊酸光动力治疗尖锐湿疣局部免疫反应的研究.中华皮肤科杂志,2013,46(5):309-312.
[7]曹嘉力,何焱玲,张秀英.尖锐湿疣患者HPV感染与细胞免疫功能的相关性.中国皮肤性病学杂志,2012,26(5):383-385.
[8]Konishi I,Fujii S,Nonogaki H,et al.Immunohistochemical analysis of estrogen receptors,progesterone receptors,Ki-67 antigen,and human papillomavirus DNA in normal and neoplastic epithelium of the uterine cervix.Cancer,1991,68(6):1340-1350.
[9]王雄,王珏,孔霞,等.HPV亚型与尖锐湿疣复发率复发时间关系的分析.中国皮肤性病学杂志,2008,22(11):675-676.
[10]沈跃莉,王大海,刘群花.ALA-PDT对尖锐湿疣患者临床疗效及炎性因子水平影响分析.中国性科学,2017,26(2):68-70.
[11]杨梅,高坤,曹泸丹,等.5-氨基酮戊酸-光动力疗法治疗复发性尖锐湿疣76例观察.现代临床医学,2014,40(3):200-201.
[12]王秀丽,王宏伟,王海山,等.5-氨基酮戊酸光动力治疗尿道尖锐湿疣临床与实验研究.应用激光,2005,25(2):139-141.
[13]Belicha-Villanueva A,Riddell J,Bangia N,et al.The effect of photodynamic therapy on tumor cell expression of major histocompatibility complex(MHC)class I and MHC class I-related molecules.Lasers Surg Med,2012,44(1):60-68.
[14]Stanley MA.Genital human papillomavirus infections:Current and prospective therapies.J Gen Virol,2012,93(Pt 4):681-691.
[15]何丹华,李其林,黄永华,等.尖锐湿疣患者人乳头瘤病毒亚型与细胞免疫功能的相关性.广东医学,2012,33(13):1914-1916.
[16]李敏,易恒安,邱宇芬.艾拉光动力联合CO2激光治疗尖锐湿疣后的免疫功能及病灶组织中病情分子的表达情况.海南医学院学报,2016,22(15):1666-1669.
[17]廖晖,胡柏根,徐胜利.半袖套式包皮环切术治疗阴茎多发性尖锐湿疣80例.中华男科学杂志,2012,18(10):945-946.
[18]张世栋,张明荣,庄桂山,等.派特灵与微波治疗阴茎复发性尖锐湿疣临床疗效对比.中华男科学杂志,2017,23(12):1141-1143.
[19]蔡锦楠,吴华红,陈松波.5-氨基酮戊酸光动力疗法治疗尖锐湿疣临床疗效观察.现代诊断与治疗,2015,26(6):1355-1356.
[20]韩凯,曾抗.尖锐湿疣的细胞免疫研究进展.皮肤性病诊疗学杂志,2011,18(4):279-282.