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The Research On Relationship Between Human Papillomavirus Related Cervical Carcinogenesis And Vaginal Microbiota At Post-infection

Posted on:2020-07-26Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y Y LiFull Text:PDF
GTID:1364330623957757Subject:Environmental Biology
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Cervical cancer is one of the malignant carcinomas with the highest incidence in female reproductive system.Yunnan is a region with a high incidence of cervical cancer where is located in the southwest border of China.The geographical feature of this region is a complex landform of the plateau,snowy mountains and river valleys,where climate is changeable,area is vast,economic development is unbalanced,the distribution of medical and educational resources and levels is uneven,26 ethnic groups live in a mixed community,and the living habits of different ethnic groups are different.Our previous research found that the prevalence of HPV is ethnically and regionally different in Yunnan province.For example,the HPV infection rate is highest in Dulong ethnic women(27.8%)living in Dulong river region located in southwest of Yunnan,followed by Tibetan women(27.4%)living in cold shangri-la region with a high altitude located in northwest of Yunnan,Hani ethnic women(21.5%)living in hot and humid Honghe region located in southeast of Yunnan,Naxi ethnic women(11.9%)living in Lijiang region where is cold and located in northwest of Yunnan.The lowest infection rate was detected in Dai ethnic women(9.9%)who lived in the Xishuangbanna region at lower altitude that was humid and hot located in south of Yunnan.In addition,there were differences in types among different ethnic groups,including single infection,double infection,triple infection and quadruple infection.Previous study have proved that the diversity of the environment in Yunnan leads to the multifarious prevalence of HPV,the pathogenic agent of cervical cancer,in this region,and the cognition of HPV and related knowledge of different ethnic groups is different.Though,the environment in Yunnan is diverse,how about the differences of cognition of HPV and relevant knowledge between different people’s? How about the prevalence of HPV infection in patients diagnosed with cervical intraepithelial carcinoma and cervical cancer? After infection,what changes have taken place in the vaginal microbiota of the body,especially the numerous HPV subtypes that are prevalent in this region? How will different HPV subtypes affect the vaginal microbiota? At present,there is a lack of research on the above aspects.In this study,we intended to understand the awareness of the pathogenic agent-HPV of cervical cancer among the population,as well as to systematically probe the distribution of HPV subtypes in precancerous lesions and cervical cancer patients and to use the high-throughput sequencing technology based on the 16 S rDNA to probe the vaginal microbiota composition and diversity among the control group,the HPV group,the CINI group,the CINII group,the CINIII group and the CC group,to find out special strains which play a significant role in the progression of the disease,together with the relationship between HPV subtypes and the vaginal microbiota.Through cognitive survey,we found that women in Yunnan Province have low awareness of HPV and related knowledge.People who heard of HPV vaccine were less than 20%,suggesting that we need to strengthen the propagation of knowledge related to HPV and cervical cancer as well as HPV vaccine.To investigate the prevalence and subtype distribution of HPV among patients related with HPV infection in Yunnan,511 women diagnosed with cervical intraepithelial neoplasia and cervical cancer who visited the First People’s Hospital of Yunnan Province from November 2012 to December 2015 were analyzed.Overall,the positive rate of HPV DNA was as high as 73.3%,23 HPV subtypes including 14 high-risk subtypes and 9 low-risk subtypes were detected.For patients with CINI and CINII,23 and 16 subtypes were detected respectively,and the most common subtype was HPV-52.While for patients with CINIII and CC,18 and 19 subtypes were detected and the most common subtype was HPV-16.In women of minority ethnic,the dominant type is HPV-16 independent of disease severity,which was different with women of Han ethnic.Based on the results of the Illumina sequencing platform,we concluded that the structure of the vaginal microflora was associated with the severity of cervical lesion.With the occurrence and development of cervical lesions,the vaginal flora presented a gradual decrease in the number of Lactobacillus and a gradual increase in diversity.In the early stage of infection with HPV,the relative abundance of bacillus velezensis and Yersinia pestis increased significantly,and the Lactobacillus drastically decreased.However,positive expression of HPV E6/E7 mRNA had no obvious effect on the structure and function of vaginal microbiota.Our study of HPV subtypes and vaginal microbiota relationship found the diversity of the vaginal microbiota correlated with the HPV subtype.The proportion of Lactobacillus species was not only associated with HPV infection but also with the combination of HPV subtypes,which accounted for the lowest proportion of multiple infections.In addition,for the single infection group,Lactobacillus accounted for the lower risk HPV infection group in high risk HPV infected individuals.In summary,this study aimed to understand local women’s awareness of HPV-related knowledge,lay the foundation for cervical cancer screening,HPV infection prevention and vaccine promotion,elucidate the prevalence and distribution of HPV subtypes in people diagnosed with different levels of precancerous lesions and cervical cancer,and use high-throughput sequencing of the 16 S rDNA to reveal the vaginal microecology of healthy subgroup and HPV positive subgroups of different grades of cervical lesions after HPV infection.The relationship between HPV subtype and vaginal microbiota was referenced for subsequent adjustment of vaginal microbiotical treatment for HPV infection and cervical lesions.Our research was helpful for the prevention and treatment of cervical precancerous lesions and cervical cancer caused by HPV infection.It was significant for follow-up studies and clinical practice.
Keywords/Search Tags:human papillomavirus, cervical intraepithelial neoplasia, cervical cancer, vaginal microbiota, amplicon sequencing
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