高危型人乳头瘤病毒检测对宫颈癌前病变筛查的临床价值

发布时间：2019-07-04 18:01

【摘要】：目的：宫颈癌是最常见的妇科恶性肿瘤，其发病率居女性恶性肿瘤的第2位。据世界范围统计，每年约有46.6万宫颈癌新发病例，其中80%发生在发展中国家。而每年我国宫颈癌新发病例有13万人，高居世界第二位。且患者趋向年轻化，年龄在35岁以下的宫颈癌患者占三分之一，上海疾控中心对上海子宫颈癌的流行趋势分析研究显示，35岁以下发病的女性比例从1970年不足2％增加到2006年超过10％。目前认为宫颈癌的发生、发展是由量变到质变，由渐变到突变的长期过程，且有报道显示，宫颈癌前病变的治愈率高达98%。故有效的筛查及恰当的干预，能阻断其向宫颈癌的进展，从而降低宫颈癌的发病率和死亡率。近40年来由于宫颈细胞学筛查宫颈癌在临床上的普遍应用，使宫颈癌前病变及宫颈癌得以早期发现和治疗，宫颈癌的发病率和死亡率已有明显下降。大量的流行病学研究和病原学研究已经明确了高危型人乳头瘤病毒(high risk human papillomavirus，HR-HPV)持续感染为宫颈癌前病变和宫颈癌发生的根本原因，故HPV检测可作为筛查宫颈癌前病变及宫颈癌的重要手段之一。但目前我国HPV检测在临床工作中尚未得到广泛应用，现阶段临床广泛应用的筛查宫颈病变的主要方法仍是宫颈液基细胞学（Liquid based cytolog，TCT），TCT受很多主观因素影响。本实验通过对比研究HPV、TCT及HPV联合TCT筛查宫颈癌前病变及宫颈癌的检出率，为临床筛查宫颈癌提供更为有价值的筛查方法，从而做到对宫颈癌的早期发现、早期干预，降低其发生率和死亡率。研究HPV分型与宫颈癌前病变的相关性，为临床随访及疗效监测提供参考。方法：选择2013年6月到2013年12月就诊于河北医科大学第二医院妇产科门诊有性生活的女性7622例，随机分组，，其中6387例采用HPV检测（Cobas4800）进行宫颈癌前病变筛查，HPV16或18阳性者部分行TCT，TCT阳性者（按照TBS分类法报告，不能明确意义的非典型鳞状上皮细胞即ASC-US及以上者判断为阳性）行阴道镜，阴性者严密随访。部分直接行阴道镜检查。HPV其他12种高危型阳性者行TCT，TCT结果回报阳性者行阴道镜检查，阴性者亦严密随访。1235例使用TCT进行宫颈癌前病变的筛查，报告阳性者，部分行阴道镜检查的同时行HPV检测。部分直接行阴道镜检查。阴道镜检查必要时取宫颈活组织检查，以组织病理学诊断作为金标准(镜下未取活检者视为慢性宫颈炎)。结果： 1HPV感染者年龄平均为37.33±10.37岁，大部分集中于29-44.25岁，而文献报道HPV感染高峰年龄为17-33岁。CIN患者平均年龄为37.95±10.54岁，其中大部分集中于29-44岁之间，TCT阳性者平均年龄为39.98±17.508岁，高峰年龄为29-47岁，HPV阳性、CIN阳性及TCT阳性者年龄分布无统计学意义（X2=4.68，P=0.0960.05），故认为三者年龄分布无明显区别。 26387例HPV检测的患者中，HPV阳性者701例，阳性率为10.97%。其中HPV16阳性者179例，占25.53%，HPV18阳性者38例，占5.42%，其他12种高危型HPV阳性者402例，占57.34%，混合感染者82例，占11.69%。其中HPV16和HPV18阳性者中16例未行TCT而直接行阴道镜检查，镜下取活检11例，慢性宫颈炎者（包括镜下未取活检者）10例，CINI1例，CINII1例，CINIII4例，即HPV检测对宫颈癌前病变检出率为37.5%（6/16）。其余685例HPV阳性者均行TCT，TCT阳性者277例，阴性者408例，阴道镜下取宫颈活组织送病理者有208例，其中慢性宫颈炎61例，CINI53例，CINII55例，CINIII36例，宫颈癌3例，HPV联合TCT对宫颈癌前病变的检出率为53.06%（147/277）。1235例采用TCT筛查宫颈癌前病变的患者中，TCT阳性169例，阴道镜宫颈活组织检查136例，其中慢性宫颈炎者92例，CINI25例，CINII13例，CINIII6例，TCT对宫颈病变的检出率为26.03%（44/169）。经统计学分析HPV与HPV联合TCT检测宫颈高度病变的检出率无统计学意义（P=0.10.05），即HPV筛查宫颈病变与HPV联合TCT筛查宫颈病变的检出率无明显差异。HPV联合TCT与TCT单独筛查宫颈癌前病变的检出率有统计学差异（P=0.000.05），即HPV联合TCT筛查宫颈病变检出率较TCT单独筛查宫颈癌前病变检出率高。 3阴道镜宫颈活检病理为CINI患者59例，其中HPV16阳性10例，占16.94%，HPV18阳性4例，占6.78%，其余12种阳性36例，占61.01%，混合感染9例，占15.25%。CINII患者者57例，其中HPV16阳性19例，占33.33%，HPV18阳性6例，占10.52%，其余12种阳性19例，占33.33%，混合感染13例，占22.80%。CINIII患者40例，其中HPV16阳性20例，占50%，HPV18阳性5例，占12.5%，其余12种阳性3例，占7.5%，混合感染12例，占30%。三组中HPV感染亚型分布有统计学差异（P0.05）。其中CINI组较CINII和CINIII组HPV16、18阳性率低，差异有统计学意义（P0.05）。CINII和CINIII组中HPV16、18阳性率无统计学差异（P0.05）。结论： 1HPV联合TCT对宫颈癌前病变筛查，可明显提高其检出率，降低漏诊率。故临床应用HPV联合TCT对宫颈癌前病变及宫颈癌进行筛查，可更好的对宫颈癌进行早期发现、早期干预，从而进一步降低宫颈癌的发病率和死亡率。有效预防宫颈癌的发生。 2CINI主要与HPV其余12种感染有关，CINII和CINIII主要与HPV16、18有关。宫颈病变及宫颈癌主要与HPV16、18有关。
[Abstract]:Objective: Cervical cancer is the most common gynecological malignant tumor, and the incidence of cervical cancer is the second place of female malignant tumor. According to the world-wide statistics, approximately 46.6 million new cases of cervical cancer are reported annually, of which 80 per cent are in developing countries. In each year, there are 1.3 million new cases of cervical cancer in China and the second in the world. The prevalence of cervical cancer in Shanghai showed that the proportion of women under 35 years of age increased from less than 2% in 1970 to more than 10% in 2006. At present, the development of cervical cancer is considered to be changed from quantitative to qualitative change, from gradual change to the long-term process of mutation, and it is reported that the cure rate of precancerous lesion of cervical cancer is as high as 98. %. Therefore, effective screening and appropriate intervention can block the progression of cervical cancer, thereby reducing the incidence and death of cervical cancer. The rate of cervical cancer and the early detection and treatment of cervical cancer and the incidence and mortality of cervical cancer have been known in the past 40 years due to the widespread use of cervical cytology in the screening of cervical cancer. A significant number of epidemiological studies and etiological studies have identified the underlying causes of high risk human papillomavirus (HR-HPV) infection for pre-cervical and cervical cancer, and the detection of HPV can be an important hand in the screening of precancerous lesions and cervical cancer. However, at present, the detection of HPV in our country has not been widely used in the clinical work, and the main method for screening cervical lesions in the present stage is still the liquid-based cytology (TCT), and the TCT is subject to many subjective factors. In this experiment, the positive rate of HPV, TCT and HPV combined with TCT in the screening of pre-cervical cancer and cervical cancer was compared, and a more valuable screening method was provided for the clinical screening of cervical cancer, so that the early detection, early intervention and the reduction of the incidence of cervical cancer were achieved. Mortality. The correlation between HPV types and pre-cervical lesions was studied and the clinical follow-up and efficacy monitoring were provided. for reference Methods: From June,2013 to December,2013, there were 7622 women who had sex life in the second hospital of Hebei Medical University, and the random group, of which,6387 cases were screened by HPV detection (Cobas4800), and HPV16 or 18 was positive. the partial row of TCT and TCT positive (according to the TBS classification report, the atypical squamous epithelial cells that cannot be clearly defined, that is, the ASC-US and the above are judged to be positive) are the colposcope, Strict follow-up of the negative. The colposcopy was examined by colposcopy colposcopy. The results of TCT and TCT in the other 12 high-risk positive cases of HPV were examined by colposcopy and the negative was closely followed up.1235 cases of pre-cervical cancer were screened with TCT, the positive and partial colposcopy were the same. Time line HPV detection. Partial straight The colposcopy was examined by the colposcopy. The colposcopy was examined for the biopsy of the cervix when necessary to organize the pathological diagnosis as a gold standard (the biopsy was not taken under the microscope). Chronic Results: The average age of HPV-infected persons was 37.33-10.37 years, most of which were in the age of 29-44.25 years. The peak age was 17-33 years. The average age of CIN was 37.95 to 10.54 years, and most of them were between 29 and 44 years. The average age of the patients with TCT was 39.98 and 17.508 years. The peak age was 29-47 years. The positive rate of HPV, the positive of CIN and the age distribution of the patients with TCT were not of statistical significance (X2 = 4.68, P = 0.0960.05), it is considered that There was no significant difference among the three age distributions. Among the 26387 patients with HPV, HPV-positive 70 In 1 case, the positive rate was 10.97%. Of these,179 cases (25.53%) of HPV16 were positive (5.42%), and 402 (57.34%) of the other 12 high-risk HPV-positive cases (57.34%). Among the patients with HPV16 and HPV18,16 of HPV16 and HPV18 were examined by colposcopy,11 cases of biopsy,11 cases of chronic cervicitis (including non-biopsy under the microscope),11 cases of CINI,1 case of CINI, and 4 cases of CINIII4. The rate was 37.5% (6/16). The remaining 685 cases of HPV positive were TCT,277 cases of TCT,408 cases of negative, and 208 cases of cervical biopsy under colposcopy, including 61 cases of chronic cervicitis,53 cases of CINI,55 cases of CINI, CI The positive rate of cervical cancer was 53.06% (147/277) in NIII36 and 3 cases of cervical cancer. In 1235 cases of pre-cervical cancer with cervical cancer were screened by TCT,169 cases of TCT were positive,136 cases were examined by colposcopy and cervical biopsy. Among them,92 cases of chronic cervicitis,25 cases of CINI,13 cases of CINI,6 cases of CINI and 2 cases of cervical lesions were detected by TCT. 6.03% (44/169). The detection rate of HPV and HPV combined with TCT in the detection of cervical height was not significant (P = 0.05). There was no significant difference in the detection rate of cervical lesions. The detection rate of HPV combined with TCT and TCT alone was different (P = 0.0005), that is, the detection rate of HPV combined with TCT was higher than that of TCT. The positive rate of HPV16 in cervical carcinoma was higher than that of the patients with CINII. The positive rate of HPV16 was 16.94%, HPV18 was positive in 4 cases (6.78%), the remaining 12 were positive (61.01%), mixed infection (9 cases) (15.25%) and CINII (33.33%). The positive of V18 in 6 cases (10.52%), the remaining 12 (33.33%), mixed infection (13 cases) (22.80%), CINIII (40 cases), HPV16 positive 20 cases (50%), HPV18 positive 5 cases (12.5%) and the remaining 12 positive cases (7%). 5%, mixed infection in 12 cases, accounting for 30%. HPV infection in three groups There was a significant difference in the distribution of HPV16 and 18 in CINII and CINIII groups (P0.05). sex-rate-free Statistical difference (P0.05). Conclusion:1 HPV combined with TCT in the treatment of cervical cancer The detection rate of the cervical cancer can be obviously improved and the missed diagnosis rate can be obviously improved, so that the clinical application of the HPV combined with the TCT can screen the precancerous lesion and the cervical cancer of the cervical cancer, and the early detection and the early intervention of the cervical cancer can be better performed. Thereby further reducing the cervical cancer. The incidence and mortality of cervical cancer can be effectively prevented. CINI is mainly related to the remaining 12 types of HPV infection. I and CINIII are mainly related to HPV16 and 18.
【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R737.33

【引证文献】