本文選題：官頸癌 + 官頸脫落細胞�。� 參考：《浙江大學》2014年碩士論文

【摘要】：背景： 宮頸癌是目前世界上女性最為常見的腫瘤之一,其發(fā)病率及相關(guān)死亡率均居女性惡性腫瘤的第二,但大多數(shù)宮頸癌及前驅(qū)病變中均可檢出HPV,且由HPV感染到發(fā)展到宮頸癌的時間為3～15年時間不等。因此,常規(guī)進行宮頸癌篩查,采取合理治療,能有效降低宮頸癌的發(fā)生率和死亡率。 當前,比較流行的宮頸癌篩查方式包括宮頸液基細胞學檢測,與HPV-DNA檢測。兩者皆各有長處,而兩者的結(jié)合,在一定程度上更能提高診斷的準確性,但是仍存在著特異性低、陽性預測值不理想等問題,尋找一些具有高靈敏度和高特異度的標志物來輔助診斷受到了廣泛的關(guān)注,提高診斷的準確性,降低假陽性率和假陰性率,避免診斷失誤,或過度治療。 P16基因是近年來發(fā)現(xiàn)的與細胞周期調(diào)控密切相關(guān)的抑癌基因,可作為宮頸癌惡性程度的指標,為正確估計宮頸癌的預后、指導臨床治療提供依據(jù)。 Ki67蛋白是一種多克隆抗體,與細胞的有絲分裂密切相關(guān),被認為是檢測腫瘤細胞增殖活性最可靠指標之一。 PHH3(核分裂特異性抗體)可作為核分裂的特殊標記,快速、有效、客觀地進行細胞增殖的定量分析。 HPV-L1蛋白是HPV的主要衣殼蛋白,是HPV感染復制早期的結(jié)構(gòu)蛋白。通過檢測HPV LI蛋白表達可以分析HPV感染的階段。預測HPV感染后CIN的發(fā)展及預后,防止對某些宮頸癌前病變患者的過度治療。 本文基于實驗研究上述四個標志物在宮頸脫落細胞中的表達水平,探討宮頸脫落細胞中,PHH3、P16、Ki67、HPV-L1的表達對宮頸病變篩查的意義。 目的： 檢測P16、Ki67、PHH3以及HPV-L1在宮頸脫落細胞中的表達情況,評價其在細胞學診斷中的的價值,并與高危HPV DNA檢測方法進行比較,以期提高宮頸癌及其癌前病變篩查的準確性。 方法： 選擇浙江大學醫(yī)學院附屬婦產(chǎn)科醫(yī)院2012年6月～2013年6月門診同時行液基薄層細胞學(ThinPrepTM,Cytyccorp,Boxborough, Massachusetts,USA)檢測和HPVHC-Ⅱ檢測的患者120例,行陰道鏡檢查及組織病理學活檢作為金標準,制成細胞蠟塊,作P16、Ki67、PHH3、HPV-L1檢測。 結(jié)果： 在120例患者中,P16的靈敏度為91.61%,特異度為85.42%,陽性預測值為90.41%,陰性預測值為87.23%；Ki67的靈敏度86.11%,特異度為91.67%,陽性預測值為93.94%,陰性預測值為81.48%；PHH3靈敏度為70.83%,特異度為100%,陽性預測值為100%,陰性預測值為69.57%。 110例宮頸脫落學檢查異常的患者,經(jīng)過HPV-DNA檢測,均為陽性；以HPV-L1殼蛋白檢測,顯示在ASCUS/LSIL組病例中,HPV-L1的表達率為70%,在ASC-H/HSIL組病例中,HPV-L1的表達率為20%,在SCC組病例中,HPV-L1的表達率為O.ASCUS/LSIL中的HPV-L1殼蛋白陽性表達率遠高于ASC-H/HSIL組以及SCC組,經(jīng)統(tǒng)計學檢測,P=0.007,具有統(tǒng)計學意義。 結(jié)論： 結(jié)合P16、Ki67、PHH3三個指標作免疫檢查,可作為宮頸脫落細胞的一種輔助檢查,提高ASC-H的檢測準確性。HPV-L1可對ASCUS/LSIL患者進行有效分流。
[Abstract]:Background: cervical cancer is one of the most common tumors in women in the world. However, HPVs can be detected in most cervical cancer and precancerous lesions, and the time from HPV infection to cervical cancer development varies from 3 to 15 years. Therefore, conventional cervical cancer screening and rational treatment can effectively reduce the incidence and mortality of cervical cancer. At present, the more popular screening methods of cervical cancer include cervical liquid-based cytology, and HPV-DNA detection. Both have their own advantages, and the combination of the two can improve the accuracy of diagnosis to a certain extent, but there are still some problems such as low specificity, poor positive predictive value, etc. Finding some markers with high sensitivity and high heterogeneity to assist diagnosis has attracted wide attention, improving the accuracy of diagnosis, reducing false positive rate and false negative rate, and avoiding diagnostic errors. P16 gene is a tumor suppressor gene found in recent years, which is closely related to cell cycle regulation. P16 gene can be used as an indicator of the malignancy of cervical cancer and to correctly estimate the prognosis of cervical cancer. Ki67 protein is a polyclonal antibody that is closely related to cell mitosis. PHH3 (mitotic specific antibody) can be used as a special marker for mitosis, which can be used as a rapid, effective and objective quantitative analysis of cell proliferation. HPV-L1 protein is the main capsid protein of HPV. HPV infection is the early replication of structural proteins. The stage of HPV infection can be analyzed by detecting the expression of HPV Li protein. In order to predict the development and prognosis of cin after HPV infection and prevent over-treatment of some cervical precancerous lesions, the expression level of the above four markers in cervical exfoliated cells was studied experimentally. Objective: to investigate the significance of the expression of HPV-L1 in cervical exfoliated cells. Objective: to detect the expression of P16H3 and HPV-L1 in exfoliated cervical cells, and to evaluate their value in cytological diagnosis and compare with the methods of high risk HPV DNA detection. Methods: from June 2012 to June 2013, 120 patients with cervical cancer and their precancerous lesions were examined by ThinPrepTMTM CytyccorpBoxborough (Massachusetts USA) and HPVHC- 鈪，

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