宫颈上皮内瘤变与人类乳头瘤病毒不同亚型感染的关系

目的:探讨宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)与人类乳头瘤病毒(human papillomavirus,HPV)不同亚型感染之间的关系。方法:采用PCR-反向斑点杂交(PCR-reverse dot blot,PCR-RDB)基因芯片技术分别检测100例宫颈组织活检标本以及其中70例配对细胞刷检标本的HPV感染情况。结果:100例宫颈组织活检标本的HPV总检出率为82%,检出HPV亚型15种。高危型HPV检出HPV-16(37%)、HPV-58(11%)、HPV-33(11%)和HPV-52(7%);高危型HPV检出率自鳞化增生(16.67%)、CINⅠ(57.14%)、CINⅡ(68.18%)、CINⅢ(75.68%)至ICC(85.71%)呈明显增加趋势(P<0.05)。HPV-16在CINⅠ与CINⅡ和CINⅢ组中的检出率均有明显差异(P<0.05)。70例宫颈细胞刷检标本的HPV检出率为64.28%,组织活检标本HPV检出率为80.00%;HPV亚型检测完全一致率不够理想(kappa<0.40)。结论:高危型HPV特别是HPV-16感染与宫颈病变程度明显相关,低危型HPV感染的宫颈病变中常伴有高危型HPV感染,宫颈组织活检标本的HPV检出率高于细胞刷检标本。     

Persistence of HPV infection and risk of high-grade cervical intraepithelial neoplasia in a cohort of Colombian women

Little is known about the dynamics of human papillomavirus (HPV) infection and subsequent development of high-grade cervical intraepithelial neoplasia (CIN2/3), particularly in women >30 years of age. This information is needed to assess the impact of HPV vaccines and consider new screening strategies. A cohort of 1728 women 15–85 years old with normal cytology at baseline was followed every 6 months for an average of 9 years. Women with squamous intraepithelial lesions were referred for biopsy and treatment. The Kaplan–Meier method was used to estimate the median duration of infection and Cox regression analysis was undertaken to assess determinants of clearance and risk of CIN2/3 associated with HPV persistence. No difference in the likelihood of clearance was observed by HPV type or woman''s age, with the exception of lower clearance for HPV16 infection in women under 30 years of age. Viral load was inversely associated with clearance. In conclusion, viral load is the main determinant of persistence, and persistence of HPV16 infections carry a higher risk of CIN2/3.     

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+.     

Cross-sectional analysis of oncogenic HPV viral load and cervical intraepithelial neoplasia

In human papillomavirus (HPV)-associated carcinogenesis, HPV infection characteristics such as viral load may play an important role in lesion development. The purpose of this study was to determine the association between quantitative assessment of oncogenic HPV viral load, and abnormal cytology among women residing along the United States-Mexico border. A cross-sectional study of 2,319 women was conducted between 1997 and 1998. Viral load of oncogenic HPV types (16, 18, 31, 39, 45, 51, 52, and 58) was measured among 173 HPV (+) women using quantitative real-time PCR. Overall, HPV 16, 31, 52 and 58 showed the highest viral load. Single type infection had higher viral loads compared to multiple type infections. HPV viral load declined significantly (p = 0.04) with age. No significant association was observed with other known HPV risk factors such as oral contraceptive use, parity, sexual and STD history. Viral load was independently associated with degree of cervical lesions. An adjusted odds ratio (AOR) of 4.7 for the association between increasing total viral load and Atypical Squamous Cells of Undetermined Significance (ASCUS)/Atypical Glandular Cells of Undetermined Significance (AGUS) was observed (p for trend <0.01). Increased risk of low-grade SIL was observed with higher viral load compared with HPV negative women (AOR = 47.7 for total viral load; AOR = 37.1 for HPV viral load not including HPV16, and AOR = 25.9 for HPV16 viral load). Likewise, increased risk of high-grade SIL with higher viral loads was observed (AOR = 58.4 for high total viral load compared with HPV negative women, AOR = 58.1 for HPV viral load not including HPV16, and AOR = 69.8 for HPV16 high viral load). Results from this study suggest a dose-response relationship between increasing oncogenic HPV viral load and risk of LSIL and HSIL.     

高危型人乳头状瘤病毒的病毒负荷量与宫颈癌及宫颈上皮内瘤变的关系

目的探讨高危型人乳头状瘤病毒(HPV)的病毒负荷量与宫颈癌及宫颈上皮内瘤变(CIN)的相关性。方法选取2013年6月至2016年6月间北京市健宫医院收治的1056例行宫颈癌筛查的患者,对高危型HPV的脱氧核糖核酸(DNA)行第2代杂交捕获试验(HC-Ⅱ)半定量检测,予以受试者工作特征曲线(ROC曲线)分析,对CINⅡ及以上宫颈病变理想RLU/CO界值进行判定。结果慢性宫颈炎592例(56.1%);CIN395例(37.4%),CINI级110例(10.4%),CINⅡ~Ⅲ级285例(27.0%);宫颈癌69例(6.5%)。高危型HPV病毒负荷量随着宫颈病变程度的加深而增高,差异有统计学意义(P<0.05)。慢性宫颈炎、CINI级、CINⅡ~Ⅲ级及宫颈癌患者高危HPV-DNA病毒负荷量中位数分别为33.24、58.37、103.48和172.56。ROC曲线分析,预测CINⅡ级及以上宫颈病变的最佳RLU/CO值为3.173,其灵敏度和特异度分别为89.0%和58.0%,Youden指数为0.587。结论高危型HPV病毒负荷量与宫颈癌及前期病变有着显著的相关性,会随着病情严重程度的加深而增加,预测CINⅡ及以上宫颈病变高危HPV最佳负荷量值为3.173。     

女性下生殖道HPV感染与宫颈上皮内瘤变及宫颈癌关系的病理研究

目的：探讨女性下生殖道高危型人乳头状瘤病毒（high risk human papillomavirus,HR－HPV）感染与宫颈上皮内瘤变（cervical intraepithelial neoplasia,CIN）及宫颈癌的关系。方法：选择2013年2月－2015年4月我院收治的236例CIN及宫颈癌患者为观察组,进行下生殖道HPV（人乳头状瘤病毒）检测,分析CIN及宫颈癌与HPV感染的关系,并与对照组有宫颈炎但无CIN及宫颈癌的126例患者进行对比研究。结果：HR－HPV感染率随着患者CIN 的严重程度而升高,宫颈癌的HR－HPV感染率最高为91．89％,明显高于对照组差异具有统计学意义（P＜0．05）。HR－HPV双重感染率以及HR－HPV多重感染率与单一HR－HPV患者的病毒感染率相比较高,差异具有统计学意义（P＜0．05）。且患者随着病情的加重,单型、双重、多重HR－HPV感染率从CINⅠ期、CINⅡ期、CINⅢ期呈递增趋势。结论：HR－HPV感染及HR－HPV多重感染是导致宫颈上皮内瘤变及宫颈癌发生的重要诱因,对高危型 HPV 病毒的持续感染,及时的诊断并予以有效的治疗,能够阻滞癌前病变的发展,对于预防宫颈上皮内瘤变及宫颈癌,降低宫颈癌的死亡率具有重要临床意义。     

Association between carotenoids and outcome of cervical intraepithelial neoplasia: a prospective cohort study

Background

It has been suggested that micronutrients such as alpha-tocopherol, retinol, lutein, cryptoxanthin, lycopene, and alpha- and beta-carotene may help in the prevention of cervical cancer. Our aim was to investigate whether serum concentrations and/or dietary intake of micronutrients influence the regression or progression of low-grade cervical abnormalities.

Methods

In a prospective cohort study of 391 patients with cervical intraepithelial neoplasia (CIN) grade 1–2 lesions, we measured serum micronutrient concentrations in addition to a self-administered questionnaire about dietary intake. We evaluated the hazard ratio (HR) adjusted for CIN grade, human papillomavirus genotype, total energy intake and smoking status.

Results

In non-smoking regression subjects, regression was significantly associated with serum levels of zeaxanthin/lutein (HR 1.25, 0.78–2.01, p = 0.024). This benefit was abolished in current smokers. Regression was inhibited by high serum levels of alpha-tocopherol in smokers (p = 0.042). In progression subjects, a significant protective effect against progression to CIN3 was observed in individuals with a medium level of serum beta-carotene [HR 0.28, 95 % confidence interval (CI) 0.11–0.71, p = 0.007), although any protective effect from a higher level of serum beta-carotene was weaker or abolished (HR 0.52, 95 % CI 0.24–1.13, p = 0.098). Increasing beta-carotene intake did not show a protective effect (HR 2.30, 95 % CI 0.97–5.42, p = 0.058).

Conclusions

Measurements of serum levels of carotenoids suggest that regression is modulated by smoking status. Maintaining a medium serum level of beta-carotene has a protective effect for progression; however, carotene intake is not correlated with serum levels of carotenoids.

     

妊娠合并子宫颈上皮内瘤变患者高危型人乳头瘤病毒感染的临床观察

目的探讨妊娠合并子宫上皮内瘤变患者高危型人乳头瘤病毒(HR-HPV)感染的临床特点。方法选取2015年9月至2018年6月间上海市复旦大学附属中山医院青浦分院收治的132例妊娠合并宫颈上皮内瘤变(CIN)患者,CINⅠ期36例,CINⅡ期49例,CINⅢ期47例。同期选取62例正常妊娠期女性体检者为对照组。观察并比较两组参与研究者孕期及产后HPV阳性感染率、载量和种类。结果 CINⅠ组、Ⅱ组和Ⅲ组患者单一感染率为75. 0%、83. 7%和97. 9%,均显著高于对照组的11. 3%,差异均有统计学意义(均P <0. 05)。CINⅡ组和Ⅲ组患者单一感染率显著高于CINⅠ组单一感染率,CINⅢ组患者显著高于CINⅡ组患者,差异均有统计学意义(均P <0. 05)。CINⅠ组、Ⅱ组和Ⅲ组患者多重感染率为8. 3%、10. 2%和14. 9%,均显著高于对照组的1. 6%,差异均有统计学意义(均P <0. 05)。CINⅠ组、Ⅱ组和Ⅲ组患者单一感染率为41. 7%、59. 2%和89. 4%,显著高于对照组的1. 6%,差异均有统计学意义(均P <0. 05)。CINⅡ组和Ⅲ组患者的单一感染率显著高于CINⅠ组,CINⅢ组患者的单一感染率显著高于CINⅡ组患者,差异均有统计学意义(均P <0. 05)。CINⅠ组、Ⅱ组和Ⅲ组患者的多重感染率为5. 6%、8. 2%和12. 8%,显著高于对照组的0. 0%,差异均有统计学意义(均P <0. 05)。CINⅡ组患者多重感染率显著高于CINⅠ组,CINⅢ组患者多重感染率显著高于CINⅡ组,差异均有统计学意义(均P <0. 05)。CINⅠ组、Ⅱ组自然转阴率显著高于CINⅢ组和对照组,差异均有统计学意义(均P <0. 05)。CINⅠ组、Ⅱ组和Ⅲ组患者孕期HRHPV DNA载入量显著高于对照组,差异均有统计学意义(均P <0. 05)。且CINⅡ组和Ⅲ组患者孕期HR-HPV DNA载入量显著高于CINⅠ组,CINⅢ组显著高于Ⅱ组患者,差异均有统计学意义(均P <0. 05)。CINⅠ组、Ⅱ组和Ⅲ组患者产后6个月HR-HPV DNA载入量显著高于对照组,CINⅡ组和Ⅲ组患者孕期HR-HPV DNA载入量显著高于CINⅠ组,CINⅢ组显著高于CINⅡ组患者,差异均有统计学意义(均P <0. 05)。CINⅡ组和Ⅲ组患者产后6个月时的HR-HPV DNA载入量显著高于孕期,差异均有统计学意义(均P <0. 05)。结论随着妊娠合并CIN患者的宫颈病变级别的升高,HR-HPV阳性率和荷载量随之升高,呈正相关,而产后HPV自然转阴率随之降低,HPV阳性率和荷载量可作为妊娠合并CIN患者的早期诊断指标。     

LEEP治疗中度宫颈上皮内瘤变对HPV感染的影响

目的：探讨高危型人乳头瘤病毒（HPV）感染的中度宫颈上皮内瘤变（CINⅡ）患者在宫颈环形电切术（LEEP）治疗后的转归。方法选取206例CINⅡ合并高危型HPV阳性患者,予以LEEP治疗,分别于术后3、6、12及24个月随诊,行宫颈液基细胞学（TCT）、第二代捕获杂交法（HCⅡ）和23种HPV分型检查。结果206例CINⅡ患者LEEP治疗后3、6、12及24个月HR-HPV转阴率分别为39.3%、74.8%、92.7%和96.6%;随访24个月, HPV依然阳性的患者中,96.6%（199/206）患者HPV转阴,未转阴的患者中,HPV的负荷量降低幅度≥50%的患者比率为1.9%（4/206）,高于降幅﹤50%患者的0.1%（2/206）及上升患者的0.4%（1/206）。在治疗后第3个月,54.0%（53/98）感染16型或者包括16型在内的多重感染转阴,与其他高危型感染25.9%（28/108）相比,差异有统计学意义（χ2=4.25,P﹤0.05）;而在治疗后的6、12及24个月,两者比较差异无统计学意义。结论高危型HPV感染的CINⅡ患者在LEEP治疗后多数在2年内转阴,治疗6个月后,16型或者包括16型在内的多重感染与其他高危型感染无差别。     

HPV and cervical neoplasia: review of case-control and cohort studies.

Epidemiological studies on the association between human papillomavirus (HPV) and cervical cancer are reviewed. Studies using HPV DNA hybridization methods to assess the presence of viral markers have yielded compelling evidence that HPV has a causal role in the disease: the association is strong, consistent and specific to a limited number of viral types. A dose-response relationship has been reported between increasing estimated viral load and risk of cervical cancer. Indirect evidence suggests that HPV DNA detected in cancer cells is a good marker of HPV infection occurring before cancer development. An increased risk for progression to more advanced CIN lesions has been reported among HPV 16/18-positive women as compared to women with other HPV types or to women without any viral DNA.     

人乳头瘤病毒变异株与宫颈疾病

人乳头瘤病毒(HPV)感染是发生宫颈癌的必要条件。根据病毒基因组核苷酸序列,在亚型的基础上可以进一步将HPV分为不同的变异株。HPV变异株的分布与地理位置关系密切。某些特定的HPV变异株感染可能增加发生宫颈癌的风险,其可能的机制是免疫逃逸、改变病毒癌基因的表达等。     

Molecular mapping of high-grade cervical intraepithelial neoplasia shows etiological dominance of HPV16

Women with high-grade cervical intraepithelial neoplasia (HGCIN) frequently present with multiple cervical lesions and multiple concomitant Human papillomavirus (HPV) genotype infections. To elucidate HPV genotype attribution in different regions on the cervix, we performed molecular mapping of cervical disease in women with HGCIN. Thirteen subjects referred to colposcopy for abnormal cervical cancer screening results were included. A cervical smear and biopsies from 4 different areas on the cervix were collected. HPV genotyping using Linear Array (for cytology) or SPF(10) LiPA(25) (for histology) were performed in 13 smears, 52 whole sections from biopsies and 138 tissue regions isolated with laser capture microdissection (LCM). Twelve subjects had a diagnosis of CIN3 and one subject had a diagnosis of CIN2 based on the worst histology found in 4 biopsies. Eight of the 13 smears (62%) showed multiple genotype infections. Four of 13 women (31%) had multiple HPV infections in their biopsies. After performing LCM-PCR, only one woman (8%) had two different carcinogenic HPV types in morphologically distinct, but colliding HGCIN lesions. HPV16 was identified as the causal type in all women with HPV16 in cytology. A large proportion of other HPV types found in cervical smears were not detected at the tissue level. Using tissue-based genotyping and LCM-PCR analysis, we were able to attribute an individual HPV type to each area of CIN lesions. We demonstrate that HPV16 is even more etiologically dominant than previously thought, based on various genotype attribution models.     

Prognostic factors associated with the clinical outcome of cervical intraepithelial neoplasia: a cohort study in Japan

One hundred and eighty-five Japanese women with cervical intraepithelial neoplasia (CIN) were enrolled in this follow-up study. On the basis of the prevalence of human papillomavirus (HPV) DNA in Japanese cervical cancer patients, HPV types were categorized into three groups as follows: (1) high risk (types 16, 18, 33, 52, and 58), (2) intermediate risk (types 31, 35, 39, 51, 56, 59, 68, and 70), (3) low risk (type 6, 30, 42, 53, 54, 55, 66 and unclassified types). High-risk HPV infection was a risk factor for progression of the disease. The regression rate in the HPV negative group was higher (83.3%) than those in the HPV positive groups, but the differences in regression were no longer significant after adjustment for age and CIN grade. It is also noted that a lower cytomegalovirus IgG level and a smaller number of past pregnancies might be associated with the regression of CIN lesions.     

HPV prevalence and cervical intraepithelial neoplasia among HIV-infected women in Yunnan Province, China: a pilot study

Objectives: To determine the prevalence of HPV and cervical neoplasia among HIV-infected women insouthwestern China. Methods: Cervical cytology, HPV detection by Hybrid Capture-2™ assay, and diagnosticcolposcopy were followed by cervical biopsy if indicated. Logistic regression analysis was used to analyzeassociations between HPV co-infection and cervical intraepithelial neoplasia (CIN), and HIV-related clinicaland laboratory parameters. Results: Colposcopic-histopathologically proven CIN2+ lesions were present in7/83 (8.4%) HIV-infected women. Nearly half (41/83, 43%) were co-infected with carcinogenic HPV genotypes.HPV co-infection was higher in women with colposcopic-histopathologically proven CIN2+ lesions than womenwith 相似文献   

子宫颈上皮内瘤样病变和子宫颈癌组织中Smad2/3和HPV16 E7的表达及意义

背景与目的:Smads蛋白是转化生长因子-β(transforming growth factor-β,TGF-β)超家族信号转导的下游信号蛋白,与多种肿瘤的发生密切相关;人乳头状瘤病毒(human papillomavirus,HPV)感染是宫颈癌的重要致癌因素,但目前对两者在宫颈癌发病过程中相互关系的研究尚不充分.本研究拟检测不同宫颈病变组织中Smad2/3和HPV16 E7蛋白的表达,探讨HPV感染和Smad2/3蛋白变化在宫颈癌形成和演进进程中的相互关系.方法:采用免疫组织化学SP法检测20例宫颈慢性炎症、30例宫颈上皮内瘤样病变(cervical intraepithelial neoplasia,CIN)和30例宫颈癌组织中Smad2/3和HPV16 E7的表达情况,比较其在各种病变中表达水平的差异.结果:Smad2/3蛋白在慢性宫颈炎、CIN和宫颈癌组织中的阳性率分别为50.0%、73.3%和93.3%,宫颈癌组分别与慢性宫颈炎组和CIN组比较,差异有统计学意义(P＜0.05),慢性宫颈炎组与CIN Ⅲ级组相比,差异有统计学意义(P＜0.05).HPV16 E7蛋白阳性率在慢性宫颈炎、CIN和宫颈癌组织中分别为60.0%、66.7%和83.3%,各组间两两比较差异无统计学意义(P＞0.05).Smad2/3阳性率与宫颈癌临床分期、病理类型、组织学分级和淋巴结转移无关(P＞0.05).Smad2/3与HPV16 E7表达呈正相关(r=0.271,P=0.015).结论:Smad2/3蛋白在宫颈癌组织中表达升高,可能在宫颈癌的发生过程中起重要作用;HPV感染与Smad2/3蛋白在宫颈癌组织中表达升高密切相关.     

宫颈上皮内瘤变与宫颈癌中DNA甲基化状态的研究

DNA甲基化与肿瘤发生发展关系的研究越来越受到重视,目前大量研究发现多种基因的异常甲基化与官颈上皮内瘤变及宫颈癌相关.     

宫颈上皮内瘤变与宫颈癌中DNA甲基化状态的研究

DNA甲基化与肿瘤发生发展关系的研究越来越受到重视,目前大量研究发现多种基因的异常甲基化与官颈上皮内瘤变及宫颈癌相关.