HPV与宫颈病变的相关性及其分型检测与TCT联合筛查宫颈病变的研究

发布时间：2019-01-02 12:20

【摘要】：宫颈癌的早期病变，即宫颈上皮内瘤变（cervical intraepithelial neoplasia，CIN），是一个宫颈癌前细胞病变的循序渐进的过程。近年来的研究表明，CIN的早期发现与治疗可以有效的预防宫颈癌。人乳头瘤病毒（human papilloma virus,HPV）的持续感染可以诱发CIN，进而导致宫颈癌。现在临床应用比较广泛的宫颈病变筛查方法包括：HPV分型检测、液基薄层细胞学检测、阴道镜检查及阴道镜下组织活检等，这些方法在早期筛查中各有优劣。如何组合这些方法使筛查更快速准确有待进一步研究。目的： 1．本文通过对在大连妇产医院门诊妇女HPV感染情况进行流行病学特征分析，初步了解HPV多重感染情况，HPV基因型和不同年龄的分布，为以后HPV疫苗的研制提供本地的流行病学依据； 2．研究HPV及其高危型与各级别宫颈病变的相关性； 3．研究TCT和HPV分型检测以及二者联合检测在宫颈病变筛查中的应用价值。方法：收集大连妇产医院7355例做HPV分型检测和TCT检查的患者，分析感染HPV的型别和年龄分布特征。再以其中做阴道镜检查及活检的患者340例为研究对象，以病理诊断作为金标准，将TCT和HPV结果的单独应用及两种方案联合应用与组织学诊断结果作分析。结果： 1．在7355名患者中，HPV阳性1957人，总感染率为26.6%，21种型别均有检出，感染率最高的型别是HPV16(16.3%)，感染率最低的型别是HPV43(0.2%)，高危型中检出率前四位的依次为16(16.3%)、58(12.9%)、18(12.4%)、53(10.3%)。HPV感染率最高的是15-19岁年龄组。检出高危型例数在各年龄所占比例最高的是35-39岁年龄组。HPV感染以单一感染为主，感染率为21.2%，多重感染率为5.4%。 2．340例不同年龄组患者中，低级病变率最高的是20-24年龄组（87.0%），高级病变率最高的是≥55年龄组（58.3%）。HPV感染率为62.6%(213/340)，其中高危型阳性率40.3%(137/340)，HPV的多重感染率31.9%(68/213)。在高级别病变中高危型以HPV16为主，占42.1%，，之后依次为18、58、52、31、33型，高级别病变组患者中这些高危型HPV的检出率显著高于炎症组和低级别病变组（P0.05）。 3．将340例病理学结果高级别病变为阳性，低级别病变为阴性，其中HPV高危型为阳性，低危型和阴性定为阴性，TCT结果≥LISL为阳性，≤ASC-H为阴性。TCT检测宫颈病变的灵敏度：71.0%，特异度：76.8%，阳性预测值：58.5%，阴性预测值：85.2%，误诊率：23.2%，漏诊率：29.0%。HPV检测宫颈病变的灵敏度：74.8%，特异度：75.5%，阳性预测值：58.4%，阴性预测值：86.7%，误诊率为：24.5%，漏诊率为：25.2%。诊断宫颈病变联合检测方案1以TCT阳性和（或）HPV阳性为阳性，二者都阴性为阴性，灵敏度：97.2%，特异度：13.3%，阳性预测值：34.0%，阴性预测值：91.2%，误诊率：86.7%，漏诊率：2.8%。方案2以TCT阴性和（或）HPV阴性为阴性，二者都阳性为阳性，灵敏度：56.1%，特异度：93.1%，阳性预测值：78.9%，阴性预测值：82.2%误诊率：6.9%，漏诊率：43.9%。结论： 1. HPV总感染率26.6%，21种型别均有检出，其中16型感染率最高其次为58型。感染年龄高峰出现在青年期，以低危型感染为主，中年高危型HPV感染达到高峰。 2.不同年龄组中宫颈病变率不同，随年龄增加高级病变发生率增加。HPV在宫颈病变中感染率较高，并随着病变程度的增加，HPV感染率特别是高危型HPV感染率升高。 3.联合检测方案1可明显提高灵敏度、阴性预测值，降低漏诊率，在筛查和阴性排除方面优于单独应用HPV检测或TCT方法。方案2可明显提高特异度、阳性预测值，降低误诊率，在定位疑似病例方面优于单独检测。
[Abstract]:The early stage of cervical cancer, that is, cervical intraepithelial neoplasia (CIN), is a step-by-step process of pre-cervical cancer. Recent studies have shown that early detection and treatment of CIN can be effective in the prevention of cervical cancer. The persistent infection of human papillomavirus (HPV) can induce CIN and lead to cervical cancer. There are now a wide range of cervical lesions screening methods for clinical applications, including HPV type detection, liquid-based thin-layer cytology, colposcopy and colposcope biopsy, which are excellent in early screening Poor. How to combine these methods allows for more rapid and accurate screening to be further developed To study. Objective: To study the incidence of HPV infection and the distribution of HPV genotypes and different ages in the clinic of women and women in Dalian, and to provide a local flow for the development of the later HPV vaccine. Pathologic basis; 2. Study of HPV and its high-risk and various levels Correlation of cervical lesions; 3. Study on the detection of TCT and HPV typing and the combination of the two in the detection of cervical disease Application value in variable screening. Methods: 7355 patients with HPV type detection and TCT examination were collected in Dalian Maternity Hospital, and the infection of HP was analyzed. The type and age distribution of V were characterized by the study of 340 cases of patients with colposcopy and biopsy, and the application of TCT and HPV as the gold standard and the combination of the two schemes. and the organization The results of this study were as follows: 1. In the 7355 patients, the HPV positive in 1957, the total infection rate of 26. 6% and the 21 types were detected. The highest infection rate was HPV16 (16. 3%), the lowest infection rate was HPV43 (0.2%), the first four in the high-risk type were 16 (16. 3%), 58 (12. 9%), 18 (12.4%), 53 (10.3%). HPV The highest staining rate is the age group of 15-19 years. The number of high-risk patients in all ages The highest proportion is the age group of 35-39. HPV infection is dominated by a single infection, and the infection rate is 2. 1. 2%, the multiple infection rate was 5. 4%. Of the 340 patients with different age groups, the highest rate of low-grade lesions was the 20-24 age group (87.0%). The highest rate of high-grade lesions was in the 55 age group (58.3%). The infection rate of HPV was 62.6% (213/ 340), of which the high-risk positive rate was 40.3% (137/ 340), and the HPV was much higher. The prevalence of high-risk HPV was significantly higher in the high-risk group than in the high-risk group (42.1%), followed by 18, 58, 52, 31, 33 and high-level lesions. In the group of inflammation and low-grade lesions (P0.05). 3. The high-level lesions of 340 cases were positive and the low-grade lesions were negative, with the HPV high-risk being positive, low-risk and negative, and the TCT-junction The sensitivity of TCT in the detection of cervical lesions was 71.0%, specificity: 76.8%, positive predictive value: 52.5%, negative predictive value: 85.2%, misdiagnosis rate: 22.8%, and specificity: 77.5%.%, positive predictive value: 58.4%, negative predictive value: 86.7%, misdiagnosed The positive predictive value was 97.2%, specificity: 13. 3%, positive predictive value: 34. 0%, negative predictive value: 91.2%. The misdiagnosis rate was 86.7%, the rate of missed diagnosis was 2.8%. The negative of the negative and/ or HPV negative of the scheme 2 was positive, the sensitivity was 56.1%, the specificity was 93.1%, the positive predictive value was 78.9%, the negative predictive value was 88.2.% Misdiagnosis Results: 1. The total infection rate of HPV was 26. 6% and 21 species. The type of infection was the highest, followed by 58. The peak in the age of the infection was in the blue period. The high-risk HPV infection of middle-aged and middle-aged patients with low-risk-type infection has reached the peak. In the age group, the rate of cervical lesion was different, and the incidence of high-grade lesions increased with age. The infection rate of HPV in the cervical lesion was high, and with the course of the lesion the increase of the degree, the HPV infection rate, especially the high-risk HPV infection rate, 3. the joint detection scheme 1 can obviously improve the sensitivity, the negative predictive value, and reduce the missed diagnosis rate, in that aspect of screening and negative elimination, the HPV detection or the TCT method is better than that of a single application. the scheme 2 can obviously improve the specificity,
【学位授予单位】：大连医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R737.33

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