尖锐湿疣亚临床感染的临床治疗及实验研究
发布时间：2018-09-12 08:15
【摘要】：背景:尖锐湿疣(condyloma acuminatum,CA)是由人类乳头瘤病毒(human papilloma virus,HPV)感染引起的一种常见性传播疾病,发病率高,约为70/10万,仅次于非淋菌性尿道炎而居第二位。目前采用分子生物学技术将HPV分为100多种亚型,引起尖锐湿疣的病毒主要是HPV-6、11、16、18等亚型。HPV主要感染上皮组织,近来大量文献及基础临床研究已充分肯定HPV在肛门生殖器癌发生的致病作用,如HPV-16、18、45、56型是最常见导致宫颈癌的亚型。 绝大多数肛门生殖道HPV感染是潜伏感染或亚临床感染,有研究发现90%以上的CA患者有亚临床感染,它们是CA复发的主要原因之一。传统疗法一般仅祛除肉眼所见的疣体,但副作用较大。近来国内外研究表明5-氨基酮戊酸光动力疗法(ALA-PDT)已成功用于CA的治疗,它对增生旺盛的细胞(包括亚临床感染的细胞)有选择性杀伤作用,而对周围正常细胞无明显影响。 MUC4是一种高分子量的跨膜糖蛋白,最近成为多种恶性肿瘤诊断、预后和治疗的新指标。近两年Subhankar Chakraborty等在一项研究中发现从正常宫颈到宫颈上皮内瘤形成再到宫颈癌,宫颈上皮细胞MUC4的表达逐渐增强,且既往研究发现90%以上的宫颈癌组织中可查到HPV,去年Subhankar Chakraborty等在一项研究中发现大约50%的外阴CA皮损中MUC4表达强烈,他们认为HPV和MUC4之间有种新联系。 目的:研究CA亚临床感染的治疗,包括治疗方法的选择及不同治疗方法对CA复发的影响,从而为CA亚临床感染的诊断和治疗提供更科学的方法,最终减少CA的复发;研究外阴CA临床及亚临床组织中MUC4 mRNA及MUC4蛋白的表达情况,探讨MUC4在外阴CA增殖及癌变中的作用。 方法:(1)临床研究对深圳市慢性病防治中心皮肤性病科门诊接收的初诊CA患者,行醋酸白试验和电子阴道镜检查,或部分行组织病理检查,确诊亚临床感染(SPI)患者,亚临床感染阳性率约为90.87%;92例有亚临床感染的CA患者首先用CO_2激光去除临床皮损,再分别采用ALA-PDT与CO_2激光治疗CA亚临床感染组织,经卡方检验及logistic回归分析方法对两种治疗方法的疗效和复发情况进行比较。(2)实验研究分别采用逆转录-聚合酶链反应(RT-PCR)及免疫组化染色方法检测外阴CA临床、亚临床组织与正常包皮组织中MUC4 mRNA及其蛋白的表达情况,用导流杂交技术检测HPV亚型。 结果:(1)CO_2激光治疗组的痊愈率为84.3%,半年后复发率为15.7%;ALA-PDT组的痊愈率为90.2%,半年后复发率为9.8%;经统计学分析,两种治疗方法的痊愈率、复发率差异无统计学意义。(2)外阴CA临床及亚临床组织各32例中MUC4 mRNA阳性表达分别为19例、18例,两者的MUC4 mRNA阳性表达差异无统计学意义(χ~2=0.064, P0.05)。外阴CA临床及亚临床组织各32例中MUC4蛋白阳性表达分别为17例、13例,两者的MUC4蛋白阳性表达差异无统计学意义(χ~2=1.004, P0.05)。32例外阴CA临床组织中MUC4 mRNA与MUC4蛋白共同阳性表达的8例,而32例亚临床组织中MUC4mRNA与MUC4蛋白共同阳性表达的9例,两者间表达差异无统计学意义(χ~2=0.08, P0.05)。CA主要以HPV-6、11型感染为主,MUC4蛋白及mRNA的阳性表达与亚型无关。 结论:(1) CO_2激光治疗组与ALA-PDT组的痊愈率、最终复发率差异无统计学意义;但ALA-PDT组在安全性方面明显优于CO_2激光组;(2)CA患者临床及亚临床组织中MUC4 mRNA及蛋白水平均表达增强,可能与CA过度增殖及癌变有关。
[Abstract]:BACKGROUND: Condyloma acuminatum (CA) is a common sexually transmitted disease caused by human papilloma virus (HPV) infection, with a high incidence of about 70/100 000, second only to non-gonococcal urethritis. At present, HPV is divided into more than 100 subtypes by molecular biology technology, causing condyloma acuminatum acuminatum. HPV-6,11,16,18 are the main subtypes of HPV. HPV mainly infects epithelial tissues. Recently, a large number of literatures and basic clinical studies have fully confirmed the role of HPV in the pathogenesis of anogenital cancer, such as HPV-16,18,45,56 is the most common subtype of cervical cancer.
The majority of HPV infection in the anal and reproductive tract is latent infection or subclinical infection. Studies have found that more than 90% of CA patients have subclinical infection, which is one of the main causes of CA recurrence. It has been successfully used in the treatment of CA. It has selective killing effect on proliferative cells, including subclinical infected cells, but has no obvious effect on peripheral normal cells.
MUC4, a high molecular weight transmembrane glycoprotein, has recently become a new marker for the diagnosis, prognosis and treatment of many malignant tumors. Subhankar Chakraborty et al. found in a recent two years that the expression of MUC4 in cervical epithelial cells increased gradually from normal cervix to cervical intraepithelial neoplasia to cervical cancer, and more than 90% of previous studies have found that the expression of MUC4 in cervical epithelial cells HPV is found in about 50% of vulvar CA lesions in a study last year by Subhankar Chakraborty et al. They believe there is a new link between HPV and MUC4.
Objective: To study the treatment of subclinical infection of CA, including the choice of treatment methods and the influence of different treatment methods on the recurrence of CA, so as to provide a more scientific method for the diagnosis and treatment of subclinical infection of CA, and ultimately reduce the recurrence of CA. The role of Yin CA in proliferation and carcinogenesis.
Methods: (1) The positive rate of subclinical infection (SPI) was about 90.87% in the newly diagnosed CA patients received by the dermatology and Venereology clinic of Shenzhen Chronic Disease Prevention and Treatment Center. 92 CA patients with subclinical infection were first diagnosed by CO_2 laser. After removing the clinical lesions, the subclinical infected tissues of CA were treated with ALA-PDT and CO_2 laser respectively. The curative effect and recurrence of the two methods were compared by Chi-square test and logistic regression analysis. (2) The clinical features of vulva CA were detected by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical staining. The expression of MUC4 mRNA and its protein in subclinical and normal prepuce tissues was detected by flow-through hybridization.
Results: (1) The cure rate of CO_2 laser treatment group was 84.3%, and the recurrence rate was 15.7% after half a year; the cure rate of ALA-PDT group was 90.2%, and the recurrence rate was 9.8% after half a year; statistical analysis showed that there was no significant difference in the recovery rate and recurrence rate between the two treatment methods. (2) The positive expression of MUC4 mRNA in vulvar CA clinical and subclinical tissues was 19 cases respectively. There was no significant difference in MUC4 mRNA expression between the two groups (_~2=0.064, P 0.05). The positive expression of MUC4 protein in vulvar CA clinical and subclinical tissues was 17 cases and 13 cases respectively. There was no significant difference in MUC4 protein expression between the two groups (_~2=1.004, P 0.05). There was no significant difference between the positive expression of MUC4 mRNA and MUC4 protein in 9 of 32 subclinical tissues (_~2=0.08,P 0.05). HPV-6,11 infection was predominant in CA, but the positive expression of MUC4 protein and mRNA was not related to the subtype.
Conclusion: (1) There was no significant difference in the cure rate and the final recurrence rate between the CO_2 laser treatment group and the ALA-PDT group, but the safety of the ALA-PDT group was significantly better than that of the CO_2 laser group; (2) The expression of MUC4 mRNA and protein in the clinical and subclinical tissues of CA patients was enhanced, which may be related to CA hyperplasia and carcinogenesis.
【学位授予单位】：大连医科大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R752.53
[Abstract]:BACKGROUND: Condyloma acuminatum (CA) is a common sexually transmitted disease caused by human papilloma virus (HPV) infection, with a high incidence of about 70/100 000, second only to non-gonococcal urethritis. At present, HPV is divided into more than 100 subtypes by molecular biology technology, causing condyloma acuminatum acuminatum. HPV-6,11,16,18 are the main subtypes of HPV. HPV mainly infects epithelial tissues. Recently, a large number of literatures and basic clinical studies have fully confirmed the role of HPV in the pathogenesis of anogenital cancer, such as HPV-16,18,45,56 is the most common subtype of cervical cancer.
The majority of HPV infection in the anal and reproductive tract is latent infection or subclinical infection. Studies have found that more than 90% of CA patients have subclinical infection, which is one of the main causes of CA recurrence. It has been successfully used in the treatment of CA. It has selective killing effect on proliferative cells, including subclinical infected cells, but has no obvious effect on peripheral normal cells.
MUC4, a high molecular weight transmembrane glycoprotein, has recently become a new marker for the diagnosis, prognosis and treatment of many malignant tumors. Subhankar Chakraborty et al. found in a recent two years that the expression of MUC4 in cervical epithelial cells increased gradually from normal cervix to cervical intraepithelial neoplasia to cervical cancer, and more than 90% of previous studies have found that the expression of MUC4 in cervical epithelial cells HPV is found in about 50% of vulvar CA lesions in a study last year by Subhankar Chakraborty et al. They believe there is a new link between HPV and MUC4.
Objective: To study the treatment of subclinical infection of CA, including the choice of treatment methods and the influence of different treatment methods on the recurrence of CA, so as to provide a more scientific method for the diagnosis and treatment of subclinical infection of CA, and ultimately reduce the recurrence of CA. The role of Yin CA in proliferation and carcinogenesis.
Methods: (1) The positive rate of subclinical infection (SPI) was about 90.87% in the newly diagnosed CA patients received by the dermatology and Venereology clinic of Shenzhen Chronic Disease Prevention and Treatment Center. 92 CA patients with subclinical infection were first diagnosed by CO_2 laser. After removing the clinical lesions, the subclinical infected tissues of CA were treated with ALA-PDT and CO_2 laser respectively. The curative effect and recurrence of the two methods were compared by Chi-square test and logistic regression analysis. (2) The clinical features of vulva CA were detected by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical staining. The expression of MUC4 mRNA and its protein in subclinical and normal prepuce tissues was detected by flow-through hybridization.
Results: (1) The cure rate of CO_2 laser treatment group was 84.3%, and the recurrence rate was 15.7% after half a year; the cure rate of ALA-PDT group was 90.2%, and the recurrence rate was 9.8% after half a year; statistical analysis showed that there was no significant difference in the recovery rate and recurrence rate between the two treatment methods. (2) The positive expression of MUC4 mRNA in vulvar CA clinical and subclinical tissues was 19 cases respectively. There was no significant difference in MUC4 mRNA expression between the two groups (_~2=0.064, P 0.05). The positive expression of MUC4 protein in vulvar CA clinical and subclinical tissues was 17 cases and 13 cases respectively. There was no significant difference in MUC4 protein expression between the two groups (_~2=1.004, P 0.05). There was no significant difference between the positive expression of MUC4 mRNA and MUC4 protein in 9 of 32 subclinical tissues (_~2=0.08,P 0.05). HPV-6,11 infection was predominant in CA, but the positive expression of MUC4 protein and mRNA was not related to the subtype.
Conclusion: (1) There was no significant difference in the cure rate and the final recurrence rate between the CO_2 laser treatment group and the ALA-PDT group, but the safety of the ALA-PDT group was significantly better than that of the CO_2 laser group; (2) The expression of MUC4 mRNA and protein in the clinical and subclinical tissues of CA patients was enhanced, which may be related to CA hyperplasia and carcinogenesis.
【学位授予单位】：大连医科大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R752.53
【共引文献】
相关期刊论文 前10条
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