Analysis Of Risk Factors For Cervical Cancer And Establishment Of Early-warning System Based On TDI-FP

Objective: Worldwide, cervical cancer is the second most common malignant disease among women, with 500,000 new cases and 200,000 deaths annually. It has been confirmed that infection with human papillomavirus (HPV) is the primary cause in development of cervical cancer, especially the high risk ones like HPV16 and HPV18. More than 90% of cervical cancers contain HPV DNA, with HPV 16 the most common one which accouts for 40%-60% of infection. However, most HPV infections regress spontaneously, and for the cases that do progress to cancer, a long period of latency is normally required.This indicates that some other factors contribute to the carcinogenic process. Aside from environmetal and life style factors, hereditary component of HPV and genetic background of the host are associated with the development of this disease. Among genetic factors that could participate in the susceptibility to this tumor and disease outcome, polymorphic genes of the human leukocyte antigen (HLA), a particular polymorphism in p53 gene as well as polymorphism of HPV gemome have been intensely investigated. We intended to analyse the causal role of these factors in the susceptibility forcervical cancer and lay a foundation for establishing an early-warning system for cervical cancer based on a rapid, high-throughput, automatic and cost-effective platform.Methods: TDI-FP technology is a compounded reaction including PCR, probe hybridization and base incorporation with high speciality and sentivity. Applying HPV genotyping and point mutation detection system based on TDI-FP, we genotyped the HPV infected, detected mutation of HPV16 E6ntl78 and polymorphism of p53 codon72 in the subjects.We also detected HLA-DQB1*03, DR15 alleles by SSP-PCR.Results: This study analysed the infection rate of HPV genotypes, frequency of HPV16 E6 ntl78T-G mutation, p53 codon 72 arginine homozygotes and HLA-DQB1*03, DR15 alleles in patients with benign cervical lesion and invasive cervical cancer . We found that high-risk HPV infection rate and frequency of HLA-DQB1*03 alleles are significantly higher in invasive cancers than in benign lesions and the OR are 10.5 and 2.6 respectively.The frequency of HPV16 E6 ntl78T — G mutation , p53 codon72 arginine homozygotes and HLA-DR15 alleles are higher in invasive cancers than in benign lesions but are not statistically significant.The OR are 1.4, 2.2 and 1.1 respectively.Conclusion: We analysed the candidate risk factors which have been reported intensely by applying the HPV genotyping and point mutation detection system based on TDI-FP and SSP-PCR method. From our analysis of 188 samples in Shaanxi area, we found evidences to indicate that infection with...