亚洲妇女宫颈癌中人乳头状瘤病毒型别分布的Meta分析

通过对84篇文献11429例宫颈癌中人乳头状瘤病毒（HPV）感染情况的Meta分析,了解亚洲女性中HPV的感染型别分布特点,为制定有效的地区性HPV的感染控制以及宫颈癌的预防策略提供科学依据。     

梅州市客家人食管癌与人乳头状瘤病毒感染的关系

目的 探讨梅州市客家人地区食管癌的发病与人乳头状瘤病毒(HPV)感染的关系.方法 采用PCR/导流杂交法检测56例新鲜客家人食管癌组织、癌旁组织及正常食管黏膜组织HPV的表达.结果 食管癌组织HPV阳性率为19.6%,癌旁组织HPV阳性率为23.2%,正常食管黏膜组织HPV阳性率为3.6%.结论 梅州市客家人食管癌组织中存在HPV感染,HPV感染可能与食管癌的发生、发展有关.     

宫颈癌与人乳头状瘤病毒感染的伴同性

本文报告用斑点杂交法测定70例香港华人妇女宫颈癌组织中HPV感染的伴同性,结果显示HPV6、11、16和18型DNA的阳性率分别为8.6％、8.6％、34.2％和15.7％。对48例有完整临床和病理资料的结果作进一步分析显示,临床分期和肿瘤分化程度与HPV感染的型别有一定的关系。病理分化差的宫颈癌中,HPV18DNA阳性率显著高于分化好的宫颈癌,结果提示HPV18感染可能伴同一组侵润性强的宫颈癌。     

人乳头状瘤病毒感染与宫颈病变的相关性分析？

目的：分析宫颈上皮内瘤变（ CIN）及宫颈癌（ CC）中人乳头状瘤病毒（ HPV）亚型,探讨HPV感染与宫颈病变的相关性。方法：慢性宫颈炎或液基细胞学异常的妇女检测21种HPV基因亚型和阴道镜下宫颈定位活检,分析2481例CC和CIN患者的HPV感染情况。结果：在2481例CIN和CC患者中,HPV感染率85．0%,HPV感染与宫颈组织学结果有较强的相关性（P〈0．001,Pearson列联系数=0．648）。 CC及CINⅢ、CINⅡ患者以HPV16、18感染最多见,其次见HPV58、33、31、52、45、59、68等亚型。304例患者宫颈感染HPV16、18、58、52、33等亚型后,发生高度鳞状上皮内病变（HSIL）、不明意义的非典型鳞状细胞（ASCUS）及低度鳞状上皮内病变（LSIL）的频率增加,TCT分型与HPV分型有较弱的相关关系（P=0．002,Pearson列联系数=0．322）。细胞学结果提示HSIL、AS-CUS,宫颈组织学诊断以CC、CINIII和CINII为多,TCT分型与组织学分型也有较弱的相关性（ P=0．026,Pearson列联系数=0．172）。结论：HPV16、18、58、33、52、31、45等高危型HPV感染是宫颈癌（ CC）及癌前病变（ CIN）最常见的风险因素。高危型HPV单独或混合感染宫颈后,细胞学检测HSIL、ASCUS及LSIL的发生率增加,细胞学结果与组织学分型的相关性促进了CC和CIN的及时诊治。     

山东省女性高危型人乳头状瘤病毒感染的检测分析

目的 对山东省各地区医院门诊和常规体检女性高危型人乳头状瘤病毒（high risk human papillomavirus,hrHPV）的感染进行检测分析,以了解山东省各地区、各年龄段女性hrHPV的感染状况。方法 对济南金域医学检验中心2012年1月至2015年8月收集的88 365例标本,采用第二代杂交捕获法（Hybrid Capture Ⅱ,HC Ⅱ）检测hrHPV16型、18型、31型、33型、35型、39型、45型、51型、52型、56型、58型、59型和68型的感染情况。结果 共检出hrHPV感染阳性者19 812例,阳性率为22．4％。hrHPV阳性率最高的地区为莱芜（36.5%）、淄博（36.5%）和泰安（36.4%）,其次为枣庄（33.4%）、济宁（29.3%）和菏泽（28.8%）,继而为临沂（25.6%）、滨州（24.8%）、威海（24.5 %）、聊城（23.3 %）、东营（22.9 %）、烟台（22.6 %）、青岛（20.5%）、日照（20.2%）、德州（19.5%）、潍坊（19.3%）,济南最低（17.6%）。山东省女性hrHPV感染以<20岁组的阳性率最高（34.6%）, 20~24岁组（32.3%）、25~29岁组（23.5%）和30~34岁组（21.4%）的阳性率逐渐下降,50~54岁组的阳性率最低（20.5%）,尔后逐渐升高至55~59岁组的22.9%以及>59岁组的22.0%。威海、青岛、潍坊、泰安、济南、淄博、德州、滨州、东营等具有与山东省总体阳性率相似的年龄分布规律。结论 本结果基本反映了山东省女性hrHPV感染的分布状况,对掌握山东省各地区女性hrHPV感染的流行病学特征,为本地区的子宫颈癌筛查和防治提供了一定的科学依据。     

广元及周边地区宫颈疾病妇女人乳头状瘤病毒感染现状分析

目的分析广元地区宫颈疾病妇女人乳头状瘤病毒（HPV）感染的现状。方法选取2012年10月11日至2013年6月17日间门诊及住院就诊的1260名患宫颈疾病患者。采集患者的宫颈脱落细胞标本,应用导流杂交基因分型技术（HybriMax）对其进行HPV检测和基因分型。分析广元地区宫颈疾病感染HPV的概率、高危型HPV（HR-HPV）的感染率,以及比邻地区HPV亚型的分布现状。结果宫颈疾病HPV感染率为36.6%,重叠感染率为13.4%,高危型（HR-HPV）感染率为47.5%,低危型（LR-HPV）感染率为27.9%,HR-HPV感染率高于LR-HPV感染率。排在前5位的感染型为HPV-58、52、16、53、33;人群HPV年龄段总感染率在≤24岁组出现高峰,而后又在35～39岁组出现高峰,45～49岁组出现低谷,≥60岁出现升高,≥60岁组HPV感染率最高。宫颈炎症患者感染HPV类型谱以高危型HPV-16、58及低危型HPV 11为主,宫颈不典型增生患者感染HPV类型谱以高危型HPV-16、52、58为主,宫颈癌患者HPV类型谱以高危型HPV-16为主。结论广元地地宫颈疾病妇女人乳头状瘤病毒（HPV）感染现状为高感染率和高重叠感染率,HPV的亚型不同,且不同地区HPV亚型的分布也不同。     

人乳头状瘤病毒感染与恶性肿瘤的关系

人乳头状瘤病毒(Humanpapillomavirus,HPV)是一类特异性地感染人皮肤、粘膜的肿瘤病毒,HPV感染后可以导致被感染细胞的过度增殖和恶性转化。近年来的研究表明,宫颈癌等许多人类恶性肿瘤的发生、发展与HPV感染有密切关系,并认为HPV的致癌机制是由于HPV的E6、E7蛋白分别作用于P53和Rb,继而影响其它调节因子,使细胞周期发生紊乱,引起细胞恶变。掌握和了解HPV感染的途径以及明确HPV感染与恶性肿瘤病因学之间的关系,对于人类恶性肿瘤的早期诊断、预防和临床免疫、基因治疗、预后评价有重要的意义。     

60例喉乳头状瘤人类乳头状瘤病毒感染分析

[目的]研究人类乳头状瘤病毒感染与喉乳头状瘤发生的关系。[方法]利用免疫组织化学、原位分子杂交及PCR检测60例喉乳头状瘤、15例喉鳞状非典型增生上皮和10例正常喉黏膜上皮中人类乳头状瘤病毒(HPV)16/18E6蛋白的表达。[结果]免疫组化显示在正常喉黏膜、非典型增生上皮及喉乳头状瘤组织中HPV16/18E6蛋白的阳性率分别为10.0%(1/10)、33.3%(5/15)和80.0%(48/60);瘤组织中HPV16/18E6蛋白的阳性率明显高于非典型增生上皮和正常喉黏膜(P<0.05),非典型增生上皮中HPV16/18E6蛋白的阳性率亦明显高于正常喉黏膜(P<0.05)。原位杂交显示在正常喉黏膜、非典型增生上皮及喉乳头状瘤组织中HPV16/18E6DNA的阳性率分别为10.0%(1/10)、40.0%(6/15)和83.3%(50/60);瘤组织中HPV16/18E6DNA的阳性率明显高于非典型增生上皮和正常喉黏膜(P<0.05),非典型增生上皮中HPV16/18E6DNA的阳性率亦明显高于正常喉黏膜(P<0.05)。PCR显示在正常喉黏膜、非典型增生上皮及喉乳头状瘤组织中HPV16的阳性率分别为10.0%(1/10)、46.7%(7/15)和86.7%(52/60);瘤组织中HPV16的阳性率明显高于非典型增生上皮和正常喉黏膜(P<0.05),非典型增生上皮中HPV16的阳性率亦明显高于正常喉黏膜(P<0.05)。[结论]高危型HPV16/18型感染可能在喉乳头状瘤的发生中起重要作用。     

人乳头状瘤病毒疫苗新进展

在第12届国际妇科肿瘤学会（IGCS）大会上,多位学者报告了预防性人乳头状瘤病毒（HPV）疫苗研究的新进展。经过6年的研究随访,美国默克公司的宫颈癌疫苗Gardasil^TM与葛兰素史克公司的疫苗Cervarix^TM充分证实宫颈癌疫苗的安全性和有效性,结果令人振奋。     

人乳头状瘤病毒感染与头颈部恶性肿瘤的关系

人乳头状瘤病毒是一种致瘤性ＤＮＡ病毒，在其９０个亚型中以高危型ＨＰＶ－１６，ＨＰＶ－１８，ＨＰＶ－３３等与人类头颈部恶性肿瘤关系密切。其致部机理是通过引起Ｐ５３，ｐＲＢ基因的突变，从而导致细胞转化及过度增殖，在不同部位的头颈部恶性肿瘤中ＨＰＶ的检出率存在差异，口腔、吕咽及喉部鳞状细胞癌中ＨＰＶ检出率高而鼻咽癌中检出率低，在头颈部腺癌和淋巴瘤中ＨＰ的感染鲜见报道，颈总转移淋巴结中ＨＰＶ的检测可以帮助临床提高原发病灶的检出率。     

Prevalence and Genotype Distribution of HPV among Women Attending a Cervical Cancer Screening Mobile Unit in Lampang,Thailand

A growing body of literature is evidence that identifying subtypes of high-risk human papillomavirus (HR-HPV) has impacted on various steps of cervical cancer prevention.Thus, it is mandatory to determine the background prevalence and distribution of HPV subtypes for designing and implementing area-specificmanagement. The present study was conducted to evaluate prevalence and distribution of HPV subtypes among women aged 30-70 years living in Lampang, an area with a high incidence of cervical cancer, through use of a mobile screening unit. Of 2,000 women recruited in this study, 108 (5.40%, 95%CI: 4.45-6.48) were found to have HR-HPV infection. Risk was significantly correlated with age and number of partners. Singly or in combination, the most common genotype was HPV 52 (17.6%), followed by HPV 16 (14.81%), HPV 58 (13.89%), HPV 33 (11.11%), HPV 51 (11.11%), and HPV 56 (9.26%). HPV 18 was found in only 5.6% of cases. Together, HPV 16/18 were noted in approximately 20.4% of cases. Eighteen(16.67%) women were positive with multiple subtypes of HR-HPV. Co-infection most frequently involved HPV 16 or HPV 58. These findings have obvious implications for vaccine policy.     

Extended duration of the detectable stage by adding HPV test in cervical cancer screening

The human papillomavirus test (HPV) test could improve the (cost-) effectiveness of cervical screening by selecting women with a very low risk for cervical cancer during a long period. An analysis of a longitudinal study suggests that women with a negative Pap smear and a negative HPV test have a strongly reduced risk of developing cervical abnormalities in the years following the test, and that HPV testing lengthens the detectable stage by 2-5 years, compared to Pap smear detection alone.     

深圳市原住居民女性生殖道HPV感染

[目的]了解深圳市原住居民女性人群的生殖道高危型人乳头瘤病毒（HPV）感染现状、宫颈上皮内瘤样病变（CIN）和宫颈癌的现患率。[方法]2009年6月至2009年10月在深圳市龙岗区坑梓街道办事处辖区25~59岁、3年内未做过宫颈癌筛查的原住居民女性进行整群抽样,并以同一辖区外来移民女性为对照。所有接受筛查女性均行宫颈液基细胞学检查及第二代杂交捕获技术（hybrid captureⅡ,HC-Ⅱ）高危型HPV检测。HPV阳性和/或细胞学≥ASCUS的女性行阴道镜检查和活检。[结果]共有942名原住居民妇女和1183名外来移民女性参加了本次调查。原住居民与外来移民妇女HPV阳性率分别为16.9%和11.8%（P〈0.05）。原住居民妇女CIN现患率为9.7%,其中CINⅡ及以上病变现患率为6.3%,外来移民CIN现患率5.1%,其中CINⅡ及以上病变现患率为2.6%。原住居民妇女CIN和CINⅡ及以上病变现患率均明显高于外来移民（P〈0.001）,尤以30~39岁年龄组最为明显。[结论]30~39岁年龄组妇女HPV感染和CIN现患率均较高,应作为宫颈癌防治的重点监测对象。     

Risk of high-grade cervical intra-epithelial neoplasia based on cytology and high-risk HPV testing at baseline and at 6-months

Adding a test for high-risk human papillomavirus (hrHPV) to cytological screening enhances the detection of high-grade cervical intraepithelial neoplasia (>or=CIN2), but data are required that enable long-term evaluation of screening. We investigated the >or=CIN2 risk for women participating in population-based screening as a function of hrHPV and cytology testing results at baseline and at 6 months. We included 2,193 women aged 30-60 years participating in a population-based screening trial who received colposcopy or a repeat testing advice at baseline. The main endpoint was histologically confirmed >or=CIN2 diagnosed within 36 months. hrHPV testing was more sensitive than cytology for >or=CIN2 (relative sensitivity 1.4, 95%CI: 1.3-1.5; absolute sensitivity 94.1 and 68.0%, respectively). The 18-month >or=CIN2 risks in women with a hrHPV-positive smear and in women with abnormal cytology were similar (relative risk 0.9, 95%CI: 0.8-1.1). Women with HPV16 and/or HPV18 had a higher >or=CIN2 risk than other hrHPV-positive women irrespective of the cytological grade. Repeat testing showed that both cytological regression and viral clearance were strongly associated with a decrease in >or=CIN2 risk. Notably, women who had a double negative repeat test at 6 months had a >or=CIN2 risk of only 0.2% (95%CI: 0.0-1.1) and hrHPV-negative women with baseline borderline or mild dyskaryosis and normal cytology at 6 months had a >or=CIN2 risk of 0% (95%CI: 0.0-0.8). Using hrHPV and/or cytology testing, risk of >or=CIN2 can be assessed more accurately by repeat testing than single visit testing. Hence, when hrHPV testing is implemented, patient management with repeat testing is a promising strategy to control the number of referrals for colposcopy.     

Multi-site study of HPV type-specific prevalence in women with cervical cancer, intraepithelial neoplasia and normal cytology, in England

Background:

Knowledge of the prevalence of type-specific human papillomavirus (HPV) infections is necessary to predict the expected, and to monitor the actual, impact of HPV immunisation and to design effective screening strategies for vaccinated populations.

Methods:

Residual specimens of cervical cytology (N=4719), CIN3/CGIN and cervical cancer biopsies (N=1515) were obtained from sites throughout England, anonymised and tested for HPV DNA using the Linear Array typing system (Roche).

Results:

The prevalence of HPV 16 and/or 18 (with or without another high-risk (HR) type) was 76% in squamous cell carcinomas, 82% in adeno/adenosquamous carcinomas and 63% and 91% in CIN3 and CGIN, respectively. Of all HR HPV-infected women undergoing cytology, non-vaccine HPV types only were found in over 60% of those with mild dyskaryosis or below, and in <20% of those with cancer. In women of all ages undergoing screening, HR HPV prevalence was 16% and HPV 16 and/or 18 prevalence was 5%.

Conclusion:

Pre-immunisation, high-grade cervical disease in England was predominantly associated with HPV 16 and/or 18, which promises a high impact from HPV immunisation in due course. Second-generation vaccines and screening strategies need to consider the best ways to detect and prevent disease due to the remaining HR HPV types.     

HPV prevalence and accuracy of HPV testing to detect high-grade cervical intraepithelial neoplasia

Concern was raised on using testing for high-risk (HR) human papillomavirus (HPV) in cervical cancer screening in populations where HPV prevalence is high. The impact of HR HPV prevalence on the efficiency of HPV test-based screening has never been directly evaluated. A meta-regression of the relationship between HR HPV prevalence and the specificity and positive predictive value (PPV) of HPV DNA testing for the presence of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was performed. Only studies that used Hybrid Capture 2 (HC2) were included. Country income (low-medium vs. high) was used as a proxy of previous screening. Twenty-six populations from 20 studies were included. For a 10% increase in HR HPV prevalence, HC2 specificity decreased by 8.41% [95% confidence interval (CI): 8.02-8.81], whereas PPV increased by 4.74% (95% CI: 2.45-7.03). HR HPV prevalence explained 98% of the variability in HC2 specificity and 38% of the variability in PPV. Country income did not affect specificity, but low-medium income was associated with higher PPV (3.81%; 95% CI: 1.53-6.10) after adjustment for HR HPV prevalence. When HR HPV prevalence is high, the specificity of HPV testing for CIN2+ decreases, but PPV does not decrease and it is high in inadequately screened populations. The number of HPV-positive women needing further assessment or treatment per CIN2+ case detected will therefore decrease and screening efficiency will improve. This is explained by the fact that HR HPV causes CIN2+: an increase in HR HPV prevalence is inevitably accompanied by an increase in CIN2+.     

陕西省延安地区女性HPV感染及基因分型年龄分布

目的 宫颈癌的发生发展与人乳头瘤病毒(human papillomavirus,HPV)密切相关,本研究分析陕西省延安地区女性宫颈HPV感染情况及基因亚型年龄分布,为本地区女性宫颈癌防治和HPV感染的分子流行病学研究提供重要依据.方法 选择2011-01-01-2015-07-31延安大学附属医院体检(478例)、"两癌"筛查、机会性筛查(2 250例)及就诊(814例)的3 542例女性患者作为研究对象,采用PCR体外扩增和DNA反向点杂交相结合的DNA芯片技术进行HPV基因分型检测.结果 HPV感染率为40.54%(1 436/3 542),其中高危型HPV感染率38.42%(1 361/3 542);低危型HPV感染率3.78%(134/3 542);感染年龄分布以≥61岁年龄组感染率最高,其次是51~60岁年龄组.各年龄组HPV感染率和高危感染率比较差异均有统计学意义,P<0.05;低危感染率比较差异无统计学意义,P>0.05.按年龄组统计,高危亚型检出频次由高到低排列前3位,≤30岁年龄组为HPV16、HPV58和HPV39,其余各组均为HPV16、HPV58和HPV52.低危感染以HPV6和HPV11为主.单一型别感染占总感染人数的74.72%(1 073/1 436),其中单一高危感染占69.56%(999/1 436),单一低危占5.15%(74/1 436).多重感染占总感染人数的25.27%(363/1 436),最高检出四重感染.单一感染率、单一高危感染率最高的为41~50岁年龄组,多重高危感染率和高低危混合多重感染率最高的是≥61岁年龄组,各年龄组高低危混合多重感染率比较差异有统计学意义(P<0.05),其余感染类型差异均无统计学意义,P>0.05.结论 陕西省延安地区HPV感染年龄分布以≥61岁年龄组较高,主要亚型为HPV16、HPV58和HPV52,感染类型以单一感染为主,提示HPV亚型的分析对疫苗的研发和宫颈癌的筛查及防治有指导意义.     

Evaluation of a validated methylation triage signature for human papillomavirus positive women in the HPV FOCAL cervical cancer screening trial

Human papillomavirus (HPV)-based cervical cancer screening requires triage of HPV positive women to identify those at risk of cervical intraepithelial neoplasia grade 2 (CIN2) or worse. We conducted a blinded case–control study within the HPV FOCAL randomized cervical cancer screening trial of women aged 25–65 to examine whether baseline methylation testing using the S5 classifier provided triage performance similar to an algorithm relying on cytology and HPV genotyping. Groups were randomly selected from women with known HPV/cytology results and pathology outcomes. Group 1: 104 HPV positive (HPV+), abnormal cytology (54 CIN2/3; 50 <CIN2); Group 2: 103 HPV+, normal cytology with HPV persistence at 12 mo. (53 CIN2/3; 50 <CIN2); Group 3: 50 HPV+, normal cytology with HPV clearance at 12 mo. (assumed <CIN2), total n=257. For the combined groups, S5 risk score CIN2/3 relative sensitivity, specificity and positive predictive value (PPV) were compared with other triage approaches. Methylation showed a highly significant increasing trend with disease severity. For CIN3, S5 relative sensitivity and specificity were: 93.2% (95%CI: 81.4–98.0) and 41.8% (35.2–48.8), compared to 86.4% (75.0–95.7) and 49.8% (43.1–56.6) respectively for combined abnormal cytology/HPV16/18 positivity (differences not statistically significant at 5% level); adjusted PPVs were 18.2% (16.2–20.4) and 19.3% (16.6–22.2) respectively. S5 was also positive in baseline specimens from eight cancers detected during or after trial participation. The S5 methylation score had high sensitivity and PPV for CIN3, compatible with US and European thresholds for colposcopy referral. Methylation signatures can identify most HPV positive women at increased risk of cervical cancer from their baseline screening specimens.