Study On The Interactive Effects Of Female Hormone And HPV In Cervical Cancan

Human papillomavirus (HPV) type 16 infects the genital tract and is generally acknowledged to be a causative agent of cervical cancer. The gene transfer studies have identified the E6 and E2 genes to be the major viral oncogenes. The HPV-16 E2 protein is required for virus replication and modulates viral gene expression whereas the HPV- 16 E6 protein is required for cell transformation. The transcription of the oncogenic E6 genes are regulated by the viral E2 protein. However, HPV infection alone is not sufficient to induce cervical cancer and other factors such as steroid hormones are thought to play a role in the establishment and/or progression of this disease. The previous research indicated that use of oral contraceptives (OCs) increases the risk of cervical cancer. However, as ectogenesis female hormones, the effects of OCs may depend on the susceptibilities of bodies, type and dose of drugs and some other factors. The level of endogenous estrogens alters in live with menstrual cycle, and maintains a relative constant level in a centain period of individuals. Thus, it is more objectively to examine the relations between endogenous estrogens and cervical cancer. Meanwhile, synthetic analysis in combination with the infection status of HPV and the express of oncogenes can investigate the interaction between female hormones and cervical nosogenesis. Howerve, present studies have only concentrated on relations between hormones or HPV oncogenes and cervical cancer. Few datas about the interaction between HPV and female hormones in population have reported, although a few studies have been carried out in anamals or in vitro but produced conflicting results. In the thesis, a case-control study was carried out based on both field and experimental date. Its aim was to investigate the effects of endogenous estrogens , HPV oncogenes, and the interactions on cervical cancer.Part I The expression of HPV and its oncogenes in cervical cancer ObjectivesTo determine the roles of HPV, HPV 16 and oncogenes on cervical cancer, and to explore the ralations between HPV 16 E2, E6 load and cervical cancer. Materials and MethodsThe study population comprised 141 cases of cervical cancer newly diagnosed by pathological methods in Shanxi Tumor Hospital during Nov.2001 to Mar. 2003, 137 patients with hysteromyoma diagnosed by pathology at the same hospital and same time (the first group of control) and 129 heath women who were taking physical health examination from Shanxi People Hospital (the second group of control). The gravidas, patients with ovary diseases, other cancers, psychosis and user of steroid hormone were excluded. All participants provided their informed consent. The cervix exfoliated cells were collected from all objects and cervix tissues collected from cases and the first control group before specific therapy. Phenol-Chloroform Extraction and Fluorescein Isothiocyanate Guanidine Phenol-Chloroform Extraction method were used to extract DNA from cervix tissues and cervix exfoliated cells respectively. HPV L Zona DNA conservative sequence primer was applied to detect HPVs DNA, and specific sequence primers were used to test HPV 16 E2/E6 oncogens with multi-PCR. ResultsThe expressions of HPVs HPV16E6 and HPV16E2 in cancer cases were significantly higher than in two control groups , regardlees of their menopausal status (premenopausal or postmenopausal). But only in premenopause women, a statistically significant difference was obviously. The expressions of HPVs in cases at yanger than 40 year-old was significantly higher than that in controls. It was a serious that disruption or absence of HPV 16 E2 in cervical cancer. The average levels of HPV 16 E2 and E6in cases are significantly higher than that in both controls. Meanwhile, HPVs DNA, HPV 16 E6and HPV 16 E2 were tested for 46 cervix tissues and exfoliated cells simultaneously, the consistency rates of which were 89.13%, 89.13% and 93.48% respectively. ConclusionsThe infection of HPV, especially high-risk HPV 16 was related to the development of cervical ca...