本文選題：子宮頸癌 + 篩查�。� 參考：《北京協(xié)和醫(yī)學(xué)院》2014年博士論文

【摘要】：研究目的 評價(jià)低成本高危型HPV DNA檢測技術(shù)(careHPV)與E6蛋白檢測技術(shù)(OncoE6)在我國農(nóng)村女性子宮頸癌篩查中的效果,分析其影響因素及改進(jìn)方法,為其在我國農(nóng)村女性子宮頸癌篩查項(xiàng)目中的推廣應(yīng)用提供參考依據(jù)。 材料與方法 2010年10月～2012年8月,在我國3個(gè)農(nóng)村地區(qū)開展了一項(xiàng)采用6種方法(包括OncoE6、careHPV-S、careHPV-C、HC2-S、HC2-C及VIA)聯(lián)合篩查子宮頸癌的前瞻性研究,將所有篩查陽性者及約10%篩查陰性者均轉(zhuǎn)診進(jìn)行第2次VIA及陰道鏡檢查,并按方案要求進(jìn)行活檢和ECC。1年后,對所有基線篩查陽性者及約20%基線篩查陰性者進(jìn)行隨訪。我們分析了人群中HPV感染和E6蛋白表達(dá)情況的年齡趨勢,并解釋了出現(xiàn)HR-HPV感染第二高峰的主要原因；評價(jià)了careHPV和OncoE6在人群初篩中的效果及影響因素,并通過匯總另一項(xiàng)名為快速子宮頸癌篩查技術(shù)研究(START)的數(shù)據(jù)找到careHPV-C和careHPV-S的最佳臨界值。最后,我們探討了不同檢測結(jié)果人群的發(fā)病風(fēng)險(xiǎn)及相應(yīng)的管理辦法。 研究結(jié)果 1.HPV感染與E6蛋白的年齡趨勢分析：HR-HPV、HPV16/18/45和E6蛋白陽性率分別為13.1%、2.9%和1.0%,其中HR-HPV感染率在55～59歲女性中達(dá)到峰值19.3%,而HPV16/18/45與E6蛋白的陽性率均隨年齡增加而上升,在55～65歲女性中HPV與E6蛋白的陽性率均較高。HR-HPV的清除感染率隨年齡增加而下降,但新發(fā)感染率的變化與年齡無關(guān),不同年齡組HR-HPV感染的危險(xiǎn)因素不同。 2.兩種方法在子宮頸癌初篩中的效果：careHPV在醫(yī)生取樣標(biāo)本中的檢出效果優(yōu)于自我取樣標(biāo)本。careHPV-C、HC2-C、careHPV-S和HC2-S篩查CIN3+的靈敏度分別為97.0%、97.0%、83.8%和90.9%；特異度分別為86.8%、86.6%、86.5%和83.1%。OncoE6與VIA的靈敏度相似(53.5%與50.5%),但特異度更高(98.9%與93.4%), OncoE6的陽性預(yù)測值最高(40.8%)。4種HPV DNA檢測的靈敏度基本不隨年齡變化而發(fā)生改變,OncoE6的靈敏度隨年齡增加而上升,VIA的靈敏度則隨年齡增加而下降,在45～65歲女性中OncoE6的靈敏度高于VIA。 3. careHPV的最佳臨界值分析：匯總數(shù)據(jù)顯示,careHPV-C與HC2-C篩查CIN3+的ROC曲線下面積相似(0.948和0.954),均優(yōu)于careHPV-S (0.878)。HC2-C、 careHPV-C和careHPV-S的最佳臨界值(單位：RLU/CO)分別為1.40、1.74和0.85=careHPV-C的臨界值從1.0提高到2.0時(shí),靈敏度變化不大而特異度明顯升高。3種篩查方法在大、小年齡組之間的篩查效果相似,但是醫(yī)生取樣HPVDNA檢測在小年齡組女性中的最佳臨界值較高。 4.篩查陽性人群的管理方法：較高病毒載量(即≥10RLU/CO)的careHPV-C. careHPV16/18/45-C和OncoE6均能有效預(yù)測1年內(nèi)CIN3的發(fā)病風(fēng)險(xiǎn)(RR值≥50);careHPV-C陰性者1年內(nèi)發(fā)生CIN3的風(fēng)險(xiǎn)極低(0.1%,95%CI:0.0-0.3)。在careHPV-C陽性人群中,采用≥10RLU/CO、careHPV16/18/45、OncoE6、陰道鏡和VIA分流后篩查CIN3+的靈敏度分別為88.5%、77.1%、54.2%、63.5%和52.6%；特異度分別為44.7%、76.5%、93.8%、84.4%和86.5%。OncoE6的陽性預(yù)測值(46.4%)和診斷OR值(17.9)均為最高。除≥10RLU/CO以外,其余分流方法在自我取樣標(biāo)本中的分流效果均與醫(yī)生取樣相似。 研究結(jié)論 1.我國農(nóng)村55～65歲女性中HR-HPV、HPV16/18/45及E6蛋白均處于較高水平,值得重視。人群中出現(xiàn)HR-HPV感染第二高峰現(xiàn)象的主要原因包括：(1)隊(duì)列效應(yīng)；(2)大年齡女性中的新發(fā)感染率較高；(3)大年齡女性中的清除感染率較低。 2. careHPV是適用于我國農(nóng)村地區(qū)的子宮頸癌初篩方法。取樣方法和檢測臨界值會影響careHPV在人群中的篩查效果,其中醫(yī)生取樣標(biāo)本的檢測效果優(yōu)于自我取樣標(biāo)本,兩者的最佳臨界值分別為2.0RLU/CO和1.0RLU/CO,年齡是影響最佳臨界值的一個(gè)因素。 3. OncoE6在人群初篩中的效果優(yōu)于VIA,并且年齡越大篩查效果越好。增加對我國子宮頸癌中常見HPV型別的檢測可以提高OncoE6的靈敏度。 4.較高病毒載量的careHPV陽性者、careHPV16/18/45陽性者及OncoE6陽性者發(fā)病風(fēng)險(xiǎn)高,應(yīng)該采取積極的防治態(tài)度；而對careHPV陰性者則可以適當(dāng)延長其篩查間隔。careHPV陽性人群的分流方法各有利弊,應(yīng)綜合考慮各地的衛(wèi)生資源、經(jīng)濟(jì)狀況及篩查重點(diǎn)選擇適當(dāng)?shù)姆椒ā?br/>[Abstract]:research objective
To evaluate the effect of low cost high risk HPV DNA detection technology (careHPV) and E6 protein detection technology (OncoE6) in the screening of cervical cancer in rural women in China, analyze its influencing factors and improve methods, and provide reference for the promotion and application of the cervical cancer screening project in rural women in China.
Materials and methods
From October 2010 to August 2012, a prospective study was carried out in 3 rural areas of China with 6 methods (including OncoE6, careHPV-S, careHPV-C, HC2-S, HC2-C and VIA) for cervical cancer screening. All the screening positive persons and about 10% negative individuals were transferred to second VIA and colposcopy, and the program was required to be performed. After ECC.1 years, all baseline screening positive persons and about 20% baseline screening negative people were followed up. We analyzed the age trends of HPV infection and E6 protein expression in the population, and explained the main reasons for the emergence of the second peak of HR-HPV infection, and evaluated the effect and influence factors of careHPV and OncoE6 in the screening of the population. The best critical value of careHPV-C and careHPV-S was found by a summary of the data of the rapid cervical cancer screening study (START) study. Finally, we explored the risk and management of different results of the population.
Research results
The age trend analysis of 1.HPV infection and E6 protein: the positive rates of HR-HPV, HPV16/18/45 and E6 were 13.1%, 2.9% and 1%, respectively, of which the peak value of HR-HPV infection reached 19.3% in 55~59 year old women, while the positive rate of HPV16/18/45 and E6 protein increased with age, and the positive rate of HPV and E6 protein in 55~65 year old women were higher.HR-H. The infection rate of PV decreased with age, but the change of new infection rate was not related to age. The risk factors of HR-HPV infection in different age groups were different.
2. the effect of two methods in the initial screening of cervical cancer: careHPV was better than the self sampling specimen.CareHPV-C, HC2-C, careHPV-S, and HC2-S were 97%, 97%, 83.8% and 90.9%, respectively, and the specificity was 86.8%, 86.6%, 86.5% and 83.1%.OncoE6 were similar to VIA, respectively (53.5% and 50. .5%), but the specificity was higher (98.9% and 93.4%), the positive predictive value of OncoE6 (40.8%) the sensitivity of.4 HPV DNA detection did not change with age, the sensitivity of OncoE6 increased with age, and the sensitivity of VIA decreased with age, and the sensitivity of OncoE6 in 45~65 year old women was higher than VIA..
3. careHPV's optimal critical value analysis: the aggregated data show that the area under the ROC curve of the careHPV-C and HC2-C screening CIN3+ is similar (0.948 and 0.954), which are superior to careHPV-S (0.878).HC2-C, and the optimum critical value of careHPV-C and careHPV-S (unit: RLU/CO) is the sensitivity change from 1 to 2 when the critical value of 1.40,1.74 and 0.85=careHPV-C is increased from 1 to 2, respectively. The screening effectiveness of.3 screening methods was similar in large and small age groups, but the best critical value of HPVDNA detection in small age groups was higher than that of small age groups.
4. the management methods of screening positive people: high viral load (or more than 10RLU/CO) careHPV-C. careHPV16/18/45-C and OncoE6 can effectively predict the risk of CIN3 in 1 years (RR value > 50); careHPV-C negative individuals have a very low risk of CIN3 in 1 years (0.1%, 95%CI:0.0-0.3). In careHPV-C positive population, careHPV16/18/ is greater than 10RLU/CO, careHPV16/18/ 45, OncoE6, colposcopy and VIA shunt screening CIN3+ sensitivity were 88.5%, 77.1%, 54.2%, 63.5% and 52.6%, and the specificity was 44.7%, 76.5%, 93.8%, 84.4% and 86.5%.OncoE6 (46.4%) and the diagnostic OR value (17.9) were the highest. Except for more than 10RLU/CO, the distributary effect of the other distributary methods in the sample samples were all The doctors were similar in sampling.
research conclusion
1. of the 55~65 year old women in rural areas of China, HR-HPV, HPV16/18/45 and E6 are all at a high level. The main reasons for the second peak of HR-HPV infection in the population include: (1) the queue effect; (2) the new infection rate in the older women is higher; (3) the rate of scavenging infection among the older women is lower.
2. careHPV is a preliminary screening method for cervical cancer in rural areas of China. Sampling method and detection critical value will affect the screening effect of careHPV in the population. The results of sample samples by doctors are better than those of self sampled specimens. The best critical values are 2.0RLU/CO and 1.0RLU/CO, and the age is the best critical value. A factor.
The effect of 3. OncoE6 in the screening of the population is better than that of VIA, and the older the screening results, the better. Increasing the detection of common HPV types in cervical cancer in China can improve the sensitivity of OncoE6.
4. careHPV positive people with high viral load, careHPV16/18/45 positive and OncoE6 positive people have high risk of disease and should take a positive attitude to prevent and cure, while those with careHPV negative can appropriately extend the methods of distributary of.CareHPV positive people at screening interval. The health resources, economic conditions and screening should be taken into consideration. Choose the right way.

【學(xué)位授予單位】：北京協(xié)和醫(yī)學(xué)院
【學(xué)位級別】：博士
【學(xué)位授予年份】：2014
【分類號】：R737.33

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