女性生殖道HPV感染与宫颈病变的关系及宫颈癌的自然史模型研究

发布时间：2018-06-29 00:02

本文选题：子宫颈癌 + 人乳头瘤病毒　；参考：《北京协和医学院》2014年博士论文

【摘要】：研究目标系统探讨中国女性人群生殖道HPV感染与宫颈病变的关系以及宫颈癌的自然史,为我国宫颈癌预防策略的制定提供数据支持和科学依据。研究内容 1.比较中国女性宫颈鳞癌和宫颈腺癌的HPV感染率和型别分布的差别； 2.比较女性生殖道不同部位HPV型别和病毒载量的分布情况及其与宫颈病变的关系,评价不同部位取样标本对宫颈病变的筛查效果； 3.构建多状态模型研究中国女性人群宫颈癌的自然史。研究方法首先,我们汇总两项以医院为基础的多中心研究,包括在全国7个地理大区收集的宫颈鳞癌和宫颈腺癌患者的资料,全面比较我国女性人群宫颈鳞癌和宫颈腺癌的HPV感染率和型别分布的情况。其次,依托一项多中心宫颈癌筛查研究项目,比较我国女性人群的生殖道不同部位HPV型别和病毒载量的分布情况,探讨生殖道不同部位取样标本对于女性宫颈病变的筛查效果,并解释自体取样标本HC2检测诊断价值较低的原因。最后,利用一项1]年随访研究的数据,建立多状态模型来研究我国女性宫颈癌的自然史,计算不同病理状态之间的转移强度、转移概率、平均停留时间等,探索适合我国实际情况的宫颈癌筛查策略。研究结果 1.2005年至2010年,宫颈腺癌在宫颈癌中所占的比例以及腺癌中的HPV感染率均有所增加。宫颈鳞癌和腺癌的HPV感染率分别为97.6%和74.5%,鳞癌的病毒载量显著高于腺癌。HPV感染率在腺癌中存在地区差异(P0.001),但在鳞癌中未见地区差异存在(P=0.623)。HPV16和(或)HPV18感染的鳞癌和腺癌患者疾病诊断年龄均小于其他高危型别HPV感染的患者(P值均0.05)。 2.低危型HPV阳性率在下阴道标本中最高,宫颈标本中最低。生殖道不同部位标本高危型HPV型别总的kappa值在正常、CIN1和CIN2+人群中均呈现出较好的一致性。在CIN2+人群中,宫颈部位标本高危型HPV病毒载量(557.25RLU/CO)显著高于上阴道(96.43RLU/CO, P0.001)、下阴道(36.51RLU/CO, P0.001)和自体取样标本(206.83RLU/CO,P=0.003)。采用LA检测的自体取样标本预测CIN2+病变的灵敏度为95.7%,与宫颈部位标本采用HC2检测的灵敏度差异无统计学意义(P0.05)。 3.研究对象在CIN1状态上的平均停留时间为1.4693年(95%CI：1.1215,1.9251),在CIN2状态上的平均停留时间为2.9822年(95%CI：1.9790,4.4938)。病理状态为CIN1的女性,逆转为正常病理状态的转移概率随着时间的增加而增加。然而,从CIN1进展为CIN2的转移概率则相对较低,3年、5年和10年的转移概率分别为0.1415、0.1066和0.0437。从CIN2逆转为正常/CIN1的5年转移概率是从CIN2进展为CIN3+的5年转移概率的2.74倍。研究结论 1.宫颈鳞癌标本不仅具有较高的HPV感染率,还具有较高的病毒载量。HPV16和HPV18是宫颈鳞癌和腺癌的最主要型别,但是在鳞癌和腺癌中的作用有区别。宫颈鳞癌和腺癌的疾病诊断年龄与HPV型别存在一定的关系。此外研究结果提示,我国宫颈腺癌的发病率呈现逐年上升趋势。 2.女性生殖道不同部位高危型HPV的分布一致性较好,特别是在CIN2+病变中,但是病毒载量在不同部位差别较大。采用基于PCR技术的HPV DNA检测方法LA进行检测,能显著提高自体取样标本的筛查诊断效果。 3.CIN1人群具有较大的逆转概率。CIN2人群逆转为正常/CIN1的概率高于进展为CIN3+的概率。研究结果对于我国建立和评价科学的宫颈癌筛查策略可能具有较为重要的意义。总之,宫颈鳞癌与宫颈腺癌中HPV型别分布不同,使得采用HPV疫苗以及基于HPV DNA筛查的预防效果会产生差别。而女性生殖道不同部位HPV分布的特点,也使得不同部位的取样标本检测宫颈病变的能力有所差别。针对不同取样标本,采用合理有效的检测方法,并结合宫颈癌的自然史情况,制定适合我国实际情况的宫颈癌筛查策略,可以有效的降低宫颈癌的发病率。
[Abstract]:Research goals
The relationship between HPV infection and cervical lesions and the natural history of cervical cancer in Chinese women were systematically investigated, which provided data support and scientific basis for the formulation of cervical cancer prevention strategies in China.
research contents
1. to compare the difference of HPV infection rate and type distribution between cervical squamous cell carcinoma and cervical adenocarcinoma in Chinese women.
2. to compare the distribution of HPV type and viral load in different parts of female genital tract and the relationship with cervical lesions, and to evaluate the screening effect of samples of different parts on cervical lesions.
3. construct a multi state model to study the natural history of cervical cancer in Chinese women.
research method
First, we summarize two hospital based multicenter studies, including data on cervical squamous and cervical adenocarcinoma collected in 7 geographical areas in the country, and compare the HPV infection rate and type distribution of cervical squamous and cervical cancer in Chinese women. Secondly, relying on a multi center cervical cancer screening and research project, The distribution of HPV types and viral load in different parts of the reproductive tract of the female population in China was compared, and the results of screening samples of different parts of the reproductive tract for female cervical lesions were discussed, and the reasons for the low diagnostic value of autologous sample HC2 were explained. Finally, a multi state model was established by using a 1] year follow-up study. To study the natural history of female cervical cancer in China, to calculate the metastasis intensity, transfer probability and average residence time between different pathological states, and to explore the screening strategy for cervical cancer in China.
Research results
From 1.2005 to 2010, the proportion of cervical adenocarcinoma in cervical cancer and the rate of HPV infection in adenocarcinoma were increased. The HPV infection rate of squamous cell carcinoma and adenocarcinoma was 97.6% and 74.5% respectively. The viral load of squamous cell carcinoma was significantly higher than that of adenocarcinoma.HPV infection rate in adenocarcinoma (P0.001), but there was no regional difference in squamous carcinoma (P =0.623).HPV16 and / or HPV18 infected patients with squamous cell carcinoma and adenocarcinoma had less diagnostic age than those of other high-risk types of HPV infection (P values were 0.05).
2. the positive rate of low risk HPV was the highest in the specimens of the lower vagina, the lowest in the cervical specimens. The total kappa value of the high-risk HPV types of the specimens of the different parts of the genital tract was normal, and all of the CIN1 and CIN2+ population showed good consistency. In the CIN2+ population, the high-risk HPV virus load (557.25RLU/CO) of the cervical specimens was significantly higher than that of the upper vagina (96.43RLU/). CO, P0.001), lower vagina (36.51RLU/CO, P0.001) and autologous sample specimens (206.83RLU/CO, P=0.003). The sensitivity of CIN2+ lesions was predicted by LA samples. There was no significant difference between the sensitivity and the sensitivity of HC2 detection in cervical specimens (P0.05).
3. the average residence time of the subjects in the CIN1 state was 1.4693 years (95%CI:1.1215,1.9251) and the average residence time in the CIN2 state was 2.9822 years (95%CI:1.9790,4.4938). The metastatic probability of the pathological state was CIN1, and the transfer probability of the normal pathological state increased with the increase of time. However, the metastasis from CIN1 to CIN2 was transferred from CIN1 to CIN2. The probability is relatively low. The transfer probability of the transfer probability of 3 years, 5 years and 10 years is 0.1415,0.1066 and 0.0437. from CIN2 to normal /CIN1, and the 5 year transfer probability is 2.74 times from the 5 year transfer probability of CIN2 to CIN3+.
research conclusion
1. the specimens of cervical squamous cell carcinoma not only have high HPV infection rate, but also have high viral load.HPV16 and HPV18 are the most important types of cervical squamous and adenocarcinoma, but the role in squamous and adenocarcinoma is different. The relationship between the diagnosis age of cervical squamous cell carcinoma and adenocarcinoma and the type of HPV type has a definite relationship. Furthermore, the results of the study suggest that the Chinese palace The incidence of cervical adenocarcinoma is increasing year by year.
2. the distribution of high risk HPV in different parts of female reproductive tract is consistent, especially in CIN2+ lesions, but the viral load is very different in different parts. Using the HPV DNA detection method based on PCR technique, LA can significantly improve the results of screening and diagnosis of autologous sample.
The probability of reverse.CIN2 population reversal to normal /CIN1 in 3.CIN1 population is higher than that of CIN3+. The results may be of great significance for establishing and evaluating the scientific cervical cancer screening strategy in China.
In conclusion, the distribution of HPV types in cervical squamous cell carcinoma and cervical adenocarcinoma is different, which makes the preventive effect of HPV vaccine and HPV DNA screening. The characteristics of HPV distribution in different parts of female genital tract also make the ability to detect cervical lesions in different parts of the cervix. The effective detection method, combined with the natural history of cervical cancer, makes the cervical cancer screening strategy suitable for the actual situation in China, which can effectively reduce the incidence of cervical cancer.
【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R737.33;R-332

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