The Influence And Mechanism Of Human Papillomavirus,P16 And Rb In Occurrence Of Cervical Neoplasia

【Objective】①To investigate the clinic significance of Thin-prep Cytology Test(TCT)combined with human papillomavirus DNA hybrid captureⅡ(HC-Ⅱ) in diagnosis of cervical diseases.To explore the relationship between viral load of HPV and grade of cervical intraepithelial neoplasia(CIN)lesion.②Detecting the expression of tumor suppressor gene p16 and RB, mensurating the sub-types of human papillomavirus(HPV)in normal uterine cervix and cervical intraepithelial neoplisia and in cervical carcinoma.Studying the relationship among HPV,p16 and Rb,so we can realize how cervical cancer occurs and develops more deeply.【Methods】①Cervical exfoliate cells from 2350 women were collected to detect HC-Ⅱand TCT.Women with abnormal results of TCT were examined by colposcope and biopsy.②14 cases of CINⅠ,28 cases of CINⅡ-Ⅲand 58 cases of cervical carcinoma were collected to detect HPV sub-types through gene chips technology.③20 cases of normal cervical tissues,35 cases of CINⅠ,40 cases of CINⅡ-Ⅲand 85 cases of cervical carcinoma were collected to detect expression of p16 and Rb protein through immunohistochemistry with SP method.【Results】①895 cases are detected positive of HPV,the positive rate is 38.09%.Among the TCT results,the HPV positive rate is:normal 27.60%,ASCUS 52.30%,ASC-H 61.31%,LSIL 86.11%,HSIL 91.25%.According to the classification of HPV viral load from low quantity to high,the rate of abnormal TCT is 12.92%,25.93%,40.56%,50.85%,61.96%and 75.47%in turn, while the rate of abnormal pathologic results is 10.11%,31.75%,41.38%,53.02%,54.23%in turn. ②Positive rate of HPV in CINⅠ,CINⅡ-Ⅲand cervical cancer is 50.00%,64.29%,87.93%.The top three subtypes of HPV is that CINⅠwith HPV16, HPV33,HPV11,CINⅡ-Ⅲwith HPV16,HPV58,HPV33,cervical cancer with HPV16,HPV18,HPV52.We get no differences among single infection,double infection and multiple infection of HPV.The total positive rate of HPV is connected with the patients' age,lymph node metastasis and tumor size.The main subtype of HPV is HPV16 in squama cervical carcinoma(68.49%)while HPV 18 in adenocarcinoma.(36.36%).③The positive expression rate of p16 is 50.00%,69.70%,75.00%and 89.47%in turn in normal cervical tissues,CINⅠ,CINⅡ-Ⅲand cervical carcinoma.Rb is 100.00%,90.63%,80.95%,68.67%in turn.The expression of p16 and Rb is contrary to each other(P=0.0246).The expression of p16 is connected with the patients' age and tumor size while Rb relates to the patients' age only.The total positive rate of HPV is 42.86%,77.78%,92.86%,100.00% with the expression of p16 from negative to positive(P=0.0020)while 94.44%,89.47%,75.00%,60.00%with Rb(P=0.1894).【Conclusions】①In the women with abnormal TCT result,the more severe of cervical diseases,the more incidence of high risk HPV infection can be detected. HPV viral load is associated with the incidence and the severity of cervical diseases.②HPV16 is still the most important subtype and more oncogenic in cervical cancer.Multiple infection of HPV is not oncogenic.Women who have been infected with HPV are younger than before.The total positive rate of HPV is connected with lymph node metastasis and tumor size.The main subtype of HPV is HPV16 in squama cervical carcinoma while HPV 18 in adenocarcinoma..③The positive expression rate of p16 protein increases gradually with more severe of cervical diseases.And that of Rb decreases.They are contrary to each other.The positive expression rate of p16 protein decreases with the increase of patients'age(＞40),tumor size(＞4cm)and lymph node metastasis. After infected with HPV,E7 has the priority to combine with Rb,so it makes the expression rate of p16 protein increase.The main point of HPV leading to cervical cancer is the combination of E7 and Rb.