Association of the plasma riboflavin levels and riboflavin transporter (C20orf54) gene statuses in Kazak esophageal squamous cell carcinoma patients

To evaluate the association of the plasma riboflavin level in Kazak esophageal cancer patients and their riboflavin transporter (C20orf54) gene statuses. Plasma riboflavin levels were detected by high performance liquid chromatography in Kazak patients with esophageal squamous cell carcinoma (ESCC) and healthy controls. C20orf54 mRNA and protein expression were analyzed by real-time fluorogenic quantitative polymerase chain reaction and immunohistochemistry in samples from 61 ESCC patients consisting of both tumor and normal tissue, respectively. C20orf54 mRNA expression was decreased in ESCC (0.279 ± 0.102) than in normal counterpart tissue (0.479 ± 0.287; P = 0.049) significantly. Tumors exhibited low C20orf54 protein expression (42.6, 26.2, 18.0 and 13.1 % for no C20orf54 staining, weak staining, medium staining and strong staining, respectively), which was significantly lower than that in the normal mucous membrane (13.1, 26.2, 41.0 and 19.7 % for no C20orf54 staining, weak staining, medium staining and strong staining, respectively). Defective expression of C20orf54 in tumor cells was significantly associated with poor differentiation. However, other parameters such as depth of invasion and lymph node metastasis had no significant relationship with C20orf54 expression. The average blood concentration of riboflavin was 2.6468 ± 1.3474 ng/ml in ESCC patients lower than control group (4.2960 ± 3.2293 ng/ml, P = 0.015). A positive correlation of plasma riboflavin levels with defective expression of C20orf54 protein was found in ESCC patients (F = 8.626; P = 0.038). Defective expression of C20orf54 is associated with the development of Kazak esophageal squamous cell carcinoma and this may represent a mechanism underlying the decreased plasma riboflavin levels in ESCC.     

宫颈鳞癌演进过程P16INK4a及Hh-Gli信号通路相关蛋白表达及其相关性研究

探讨P16^INK4a及Sonic hedgehog(Hh-Gli)信号通路蛋白在宫颈癌及癌前病变(CIN)中的表达相关性及其意义．采用Western-blot方法检测HPV16阳性及HPV18阳性宫颈癌细胞系P16^INK4a及Hh-Gli信号通路蛋白Smo、Ptch及Gli表达．免疫组化检测组织芯片P16^INK4a、Shh、Smo、Ptch及Gli表达,包括20例正常宫颈、18例癌旁组织、54例CIN及28例宫颈鳞癌组织．分析P16^INK4a与Hh-Gli信号通路蛋白间表达相关性及与临床病理因素的关系．结果显示P16^INK4a、Smo、Ptch及Gli蛋白在HPV16及HPV18阳性宫颈癌细胞系中表达无显著差异(P>0.05)．P16^INK4a、Shh、Smo、Ptch及Gli蛋白在宫颈癌中表达强度显著高于癌旁及正常组织(P<0.05),在CINⅠ与正常组织间差异不显著(P>0.05)．P16^INK4a、Shh、Smo及Gli蛋白,在CINⅠ、CINⅡ与CINⅢ之间均有显著性差异(P<0.05)．相关分析显示,CINⅡ-CINⅢ中P16^INK4a与Shh和Smo蛋白表达正相关,浸润癌中P16^INK4a与Shh、Smo和Gli蛋白正相关．结论认为,P16^INK4a及Hh-Gli信号通路异常激活与宫颈癌发生及演进密切相关,且二者间具有相关性．Hh-Gli信号通路的激活可能是Shh配体增高调控Smo高表达而上调Gli蛋白所致．     

Screening For High- and Low-Risk Human Papillomavirus Types In Single Routine Cervical Smears By Non-Isotopic In Situ Hybridization

Routine cervical smears (n = 262) from a Sexually Transmitted Diseases clinic were screened by non-isotopic in situ hybridization (NISH) stratifying human papillomavirus (HPV) infections into HPV6/11 (low risk) and HPV16/18/33 (high risk) categories. Of 188 patients with cytologically normal smears, HPV sequences were demonstrated in 41%. Of the 128 cases analysed by dual NISH, 16% contained low risk, 20% high risk and 5% both groups. In patients with cytological evidence of wart virus infection (WVI) only, 54% (n = 50) contained high-risk and 22% low-risk HPV types. The comparable incidences in CIN1/2 plus WVI (n = 24) were not significantly different: 54% and 17%, respectively. Cytological criteria underestimate the prevalence of HPV infection in patients with cytologically normal smears. This represents either 'occult' or 'latent' infection. The identical prevalence of HPVB16/18/33 in WVI only, and CIN1/2 plus WVI, suggests that the cytopathic effect induced by these HPVs may represent one end of a spectrum of morphological change which progresses to cervical intraepithelial neoplasia (CIN).     

宫颈癌患者HPV16/18型病毒感染及阴道菌群观察

目的 探讨宫颈癌与人乳头瘤病毒(HPV)感染高危型HPV(HPV16/18)表达及阴道菌群的关系。 方法 回顾性分析我院2018年1月-2020年1月收治的37例宫颈癌患者的临床资料,将其设为宫颈癌组。纳入同期于我院治疗的43例宫颈上皮内瘤变(CIN)患者的临床资料设为CIN组。比较两组基础资料(年龄、绝经情况、孕次、产次、HPV16/18阳性表达、阴道菌群、饮食卫生习惯和家族遗传史)差异,并对有差异信息进行赋值,以多因素Logistic回归模型分析宫颈癌发生的危险因素。 结果 经单因素分析,两组患者年龄、绝经情况、孕次和产次比较,差异无统计学意义(P>0.05);宫颈癌组HPV16/18阳性、阴道菌群失调、饮食卫生习惯较差以及存在家族遗传史患者数显著多于CIN组(P结论 宫颈癌发生危险因素较多,临床应针对存在危险因素的患者加强监测并给予相应干预从而降低宫颈癌发生风险。     

宫颈癌患者人乳头瘤病毒感染情况及STING、ZEB1蛋白水平分析

分析宫颈癌患者人乳头瘤病毒（HPV）感染情况及癌灶组织内干扰素基因刺激因子（STING）、E盒锌指结合蛋白1（ZEB1）表达情况,为该类患者的治疗提供参考。

收集我院病理检验科2019年1月至2022年1月63例宫颈癌标本（宫颈癌组）、55例宫颈上皮内瘤变（CIN）标本（CIN组）及50例正常宫颈标本（正常组）,采用免疫组化法检测各标本内STING及ZEB1表达情况,采用原位杂交法检测各标本内高危HPV感染情况,分析STING及ZEB1蛋白表达情况与宫颈癌病理特征及高危HPV感染之间的关系。

宫颈癌组标本STING及ZEB1表达量均高于CIN组及正常组,CIN组标本ZEB1表达量高于正常组,差异均有统计学意义（均P＜0.05）;CIN组标本STING表达量与正常组比较差异无统计学意义（P＞0.05）。宫颈癌组标本HPV16、18检出率高于CIN组及正常组,CIN组标本HPV16、18检出率高于正常组,差异均有统计学意义（均P＜0.05）。宫颈癌患者FIGO分期及浸润深度与其组织内STING及ZEB1蛋白阳性情况均存在相关性;此外,宫颈癌淋巴结转移及肿瘤分化程度与组织内STING蛋白阳性情况存在相关性,差异均有统计学意义（均P＜0.05）。宫颈癌患者STING及ZEB1蛋白表达与其HPV16、18检出率间均呈正相关（均P＜0.05）。

宫颈癌组标本STING及ZEB1蛋白表达量均高于正常组及CIN组,且其表达量还与宫颈癌浸润、FIGO分期相关。STING和ZEB1可能与HPV16、18感染共同参与宫颈癌的发生及进展。

     

TLR4在宫颈癌与不同HPV亚型宫颈癌细胞株中表达及意义

目的 探讨TLR4在正常宫颈组织、宫颈上皮不典型增生、宫颈癌组织以及不同HPV亚型宫颈癌细胞株中表达与意义.方法 采用SP免疫组织化（IHC）检测TLR4在12例正常宫颈组织、30例宫颈轻度不典型增生（cervical intraepithelial neoplasia Ⅰ,CINⅠ）、30例宫颈中-重度不典型增生（cervical intraepithelial neoplasiaⅡ-Ⅲ,CIN Ⅱ-Ⅲ）以及49例宫颈癌（invasive cervical carcinoma,ICC）组织中的表达;应用细胞免疫荧光法、逆转录聚合酶链反应（RT-PCR）检测TLR4在不同HPV亚型宫颈癌细胞株HPV18（＋）HeLa、HPV16（＋）Siha以及HPV（-）C33a宫颈癌细胞株上的表达.结果 TLR4的表达随着宫颈病变程度的增高逐渐增强,在正常宫颈组织、CINⅠ、CIN Ⅱ～Ⅲ、ICC中阳性表达率分别为8.33 %（1/12）、20.00 %（6/30）、26.67 %（8/30）和55.10 %（27/49）,ICC与正常宫颈组织、CINⅠ、CINⅡ～Ⅲ之间均有显著性差异（P＜0.01）.TLR4表达与HPV感染有关,在HPV阳性宫颈癌细胞株上表达强于HPV阴性细胞株.结论 TLR4可能参与宫颈癌起始、发展,TLR4的表达与功能与HPV感染有关.     

宫颈不同疾病患者合并HPV感染的病原菌感染状况及免疫功能

目的 调查分析宫颈不同疾病患者合并人乳头瘤病毒（HPV）感染的病原菌感染状况及免疫功能。方法 选择2015年3月至2018年1月在我院就诊的96例宫颈不同疾病患者为研究组,其中宫颈炎组18例,宫颈上皮内瘤变组54例（CINⅠ组15例,CINⅡ组17例,CINⅢ组22例）,宫颈癌组24例;并以同期在我院进行体检的80例健康女性为对照组,检测所有研究对象的HPV感染、阴道菌群情况和宫颈分泌物CD4+、CD8+细胞数。结果 研究组HPV感染率明显高于对照组（P0.05）。宫颈炎组、CINⅠ组、CINⅡ组、CINⅢ组、宫颈癌组CD4+ T细胞表达阳性率呈下降趋势,宫颈癌组与宫颈炎组、CINⅠ组比较差异有统计学意义（P0.05）;CD4+/CD8+<1患者所占比例呈上升趋势,宫颈癌组、CINⅢ组、CINⅡ组与宫颈炎组比较差异有统计学意义（P<0.05）。结论 HPV感染、病原菌感染及免疫功能下降与宫颈病变发生发展密切相关,临床中应给予足够重视并及时进行有效干预。     

Prevalence of human papillomavirus genotypes in cervical cancer and precursor lesions

There are no data obtained in biopsy material on the prevalence of human papillomavirus (HPV) and HPV genotypes in Croatian women with cervical carcinoma and precursor lesions. Therefore, the prevalence of HPVand HPVgenotypes was investigated in archival material of cervical carcinoma and precursor lesions kept at Department of Pathology, School of Medicine, University of Rijeka. DNA was isolated from formalin fixed, paraffin embedded tissue, histologically classified as cervical intraepithelial neoplasia (CIN) III (n =43), squamous cell carcinoma (SCC) (n =54) and adenocarcinoma (ADC) (n =40). HPV testing was performed bypolimerase chain reaction (PCR) using generic and genotype specific primers. The prevalence of HPV DNA was 93.02%, 92.59%, and 92.5% in CIN III, SCC and ADC, respectively. In CIN III and SCC, HPV-16 was the most common high-risk genotype, identified in 65% and 52%, followed by HPV-18 in 22.5% and 28% of cases, respectively. HPV-18 showed a statistically significant prevalence in ADC (67.6%) as compared with SCC (chi(2)=9.924; p_ 0.01). Study results revealed a high prevalence of HPV-DNA in examined cervical lesions (>90%). HPV-16 predominated in SCC and HPV-18 in ADC. Single infection was more frequently present than multiple infections in all three histological groups.     

HPV检测联合人髓细胞增生原癌基因检测对宫颈癌前病变筛查的临床价值

摘要 目的：探讨人乳头状瘤病毒（HPV）检测联合人髓细胞增生原癌基因（C-MYC）检测对宫颈癌前病变-宫颈上皮内瘤变（CIN）筛查的临床价值。方法：选择2018年6月至2020年12月在本院妇科保存的宫颈上皮内瘤变标本140份,采用免疫组化法检测C-MYC表达情况,采用PCR检测HPV16、HPV18表达情况并进行相关性分析。结果：在140份标本中,HPV16与HPV18的阳性率为62.9 %与61.4 %;CIN 1级标本HPV16、HPV18阳性率分别为26.8 %和24.4 %,2级标本分别为62.7 %和58.8 %,3级标本分别为93.8 %和95.8 %,对比有差异（P<0.05）。C-MYC阳性率为83.6 %,不同CIN分级程度的标本组织中C-MYC阳性率对比有差异（P<0.05）。Spearsman相关分析显示HPV16、HPV18、C-MYC阳性率与CIN分级呈相关性（P<0.05）。二分类Logisitc回归分析显示HPV16、HPV18、C-MYC阳性率都为影响CIN分级的重要危险因素（P<0.05）。结论：随着宫颈上皮内瘤变级别的增加,HPV16、HPV18的阳性率也在升高,同时伴随C-MYC的过表达,两者具有相关性,是导致患者病情加重的重要危险因素。     

Expression and Functional Analysis of Toll-like Receptor 4 in Human Cervical Carcinoma

Toll-like receptors are expressed in human immune cells and many tumors, but the role of toll-like receptor 4 (TLR4) in the development of tumors is controversial. We demonstrated the expression, distribution, and functional activity of TLR4 in tissues of normal cervix, cervical intraepithelial neoplasia (CIN), invasion cervical cancers (ICC), and different human papillomavirus (HPV)-infected cervical cancer cells. The results showed that TLR4 expression was in accordance with the histopathological grade: higher in ICC than in CIN, and low in normal cervical tissues and malignant cervical stroma. Expression was higher in SiHa (HPV16+) than in HeLa (HPV18+) cells, but was not observed in C33A (HPV?) cells. After treatment with its agonist, lipopolysaccharide (LPS), the expression levels of TLR4 was increased and apoptosis resistance was induced in SiHa cells, but not in HeLa or C33A cells. Meanwhile, LPS treatment did not alter the cell cycle distribution in SiHa cells. The mechanism of apoptosis resistance may be related to HPV16 infection and not correlated with the cell cycle distribution. Targeting TLR4 in combination with traditional drug treatment may serve as a novel strategy for more effectively killing cancer cells.     

Human papillomavirus and cervical intraepithelial neoplasia in women who subsequently had invasive cancer.

In a retrospective case-control study biopsy specimens of cervical intraepithelial neoplasia (CIN) lesions from 47 women in whom invasive cancer subsequently developed (cases) and from 94 control subjects in whom CIN was diagnosed within 6 months of the diagnosis for the matched case subject but invasive disease did not develop were tested for human papillomavirus (HPV) DNA with tissue in-situ hybridization. There were no significant differences in the frequency of detection of HPV DNA between the two groups. In a cross-sectional survey the prevalence of HPV DNA was found to be 11% in specimens without CIN, 27% in those with CIN I, 49% in those with CIN II and 56% in those with CIN III. The positivity rates for HPV 16/33 DNA increased with the severity of CIN, but this was not observed for HPV 6/11 and 18 DNA. A comparison of the results of the case-control and cross-sectional studies suggested that the younger cohort of women had higher prevalence rates of HPV DNA than the older cohort.     

Balance of IgG subclasses toward human papillomavirus type 16 (HPV16) L1-capsids is a possible predictor for the regression of HPV16-positive cervical intraepithelial neoplasia

Human papillomavirus type 16 (HPV16) is known to be a major causative agent of cervical cancer. To test the hypothesis that an enhanced Th1 response favors the natural course of cervical intraepithelial neoplasia (CIN), we measured IgG subclasses toward HPV16 L1-capsids because IgG1/IgG2 balance reflects Th2 and Th1 responses, respectively. We examined IgG2/IgG1 ratios in sera from 67 anti-HPV16 L1-positive women; 18 were cytologically normal women, 29 were CIN patients, and 20 were cervical cancer patients. The IgG2 dominance (IgG2/IgG1 ratio >1) was observed in 94, 48, and 5%, respectively (p < 0.001). The regression rate of CIN lesions was significantly different between patients with and without IgG2 dominance: 83.3% (5/6) versus 16.7% (1/6), respectively (p < 0.05). These findings raise the possibility that IgG2 dominance toward HPV16 L1-capsids, i.e., Th1 dominance, may be a useful marker to predict viral clearance or the regression of HPV16-positive CIN.     

Long-Term Follow-Up of HPV16-Positive Women: Persistence of the Same Genetic Variant and Low Prevalence of Variant Co-Infections

HPV16 variants correlate with geographic origin and ethnicity. The association between infection with a specific variant and the cervical disease risk remains unclear. We studied the prevalence, persistence and association with cervical intraepithelial neoplasia (CIN) of different HPV16 variants, using cervical swabs and whole tissue sections (WTS) of biopsies from 548 women in the placebo group of a HPV16/18 vaccine trial. In HPV16-positive samples, HPV16 variants were identified by a reverse hybridization assay (RHA). Laser-capture micro-dissection (LCM) was performed for localized detection of HPV. HPV16 variants were determined in 47 women. Frequency of mixed HPV16 variant infections was lower (8.5%) than for multiple HPV genotypes (39.1%). Among 35 women having consecutive HPV16 variant-positive swabs, 32 (91.4%) had the same variant while in three (8.6%) women a change in variant(s) was observed. HPV16-positive WTS were obtained from 12 women having consecutive HPV16 variant-positive swabs. The same variant was present in WTS of 10 women, while two were negative. WTS of five women were histologically normal. A single HPV16 variant was detected in four women having CIN1-3, while additional HPV genotypes were found in three other women having CIN2 and CIN3. In the WTS of one woman with mixed genotypes, the HPV16 variant was assigned to a CIN2 lesion by LCM. HPV16 variant infections can be effectively studied in cervical swabs and tissue specimens by the HPV16 variant RHA. Multiple HPV16 variants in one woman are rare. The HPV16 genotype consistently detected in follow-up samples usually involves a persistent infection with the same variant.     

TGF-beta signalling pathway factors in HPV-induced cervical lesions

Human papillomaviruses (HPV) are considered the etiological agents of cervical cancer, especially high-risk genotypes. TGF-beta (transforming growth factor-beta) is well known for its anti-proliferative effects but the neoplastic cells often lose their sensitivity to TGF-beta. A characteristic alteration associated with malignant progression is the loss of responsiveness to TGF-beta1-induced cell growth inhibition. The aim of the present study was to establish the possible role of some members of TGF-beta signalling pathway during cervical cancer development and the possible relationship with HPV infection. In order to establish TGF-beta gene expression levels in cervical oncogenesis, TGF-beta1, TGF-beta1 receptors and Smad2 were investigated in precancerous and cervical cancer samples (Quantitative Real-Time PCR). The study revealed that 84.5% of patients were positive for HPV DNA. The most prevalent HPV genotypes were high-risk HPV 16 and 18 in single or co-infections. Expression of TGF-beta1 decreased as tumor cells progressed from cervical intraepithelial neoplasia to cervical carcinoma. Furthermore, we observed that cervical lesions without HPV infection expressed significantly less TGF-beta1. TGF-betaRI and Smad2 gene expression levels were found to be decreased in SCC and AC samples in contrast with CIN1 and CIN2/3 samples. Our results showed that in human cervical cancer the disruption of TGF-beta/Smad signalling pathway might contribute to the malignant progression of cervical dysplasia. These data emphasize the importance of canonical TGF-beta pathway integrity in carcinogenesis.     

成都市人乳头瘤病毒16型感染与宫颈病变的相关性分析

本研究旨在探讨人乳头瘤病毒(human papillomavirus,HPV)16感染与宫颈病变的关系,为宫颈癌防治提供科学依据。通过核酸杂交法进行HPV感染分型,纳入1 057例HPV阳性且行组织切片病理学检查的患者,对各级别宫颈病变中HPV16构成比、不同年龄组HPV16阳性患者中宫颈上皮内瘤样病变(cervical intraepithelial neoplasia,CIN)Ⅱ及以上病变的患病率,以及HPV16单一与多重感染患者中CINⅡ及以上病变的患病率进行分析。结果显示,在1 057例HPV阳性患者中,352例感染HPV16,CINⅢ中HPV16构成比最高,各级别病变中HPV16构成比差异有统计学意义。随着病变级别增加,HPV16构成比有增高趋势(P0.05)。不同年龄组HPV16阳性患者中CINⅡ及以上病变的患病率差异有统计学意义(P0.05),且随年龄增加而升高(P0.05)。HPV16单一、双重与三重以上感染患者中,CINⅡ及以上病变的患病率差异有统计学意义(P0.05),且随着感染型别种类增加,患病率降低(P0.05)。本研究显示,HPV16与高级别宫颈病变有较明显的相关性,老年HPV16阳性患者检出宫颈癌的概率更高。因此,应高度重视HPV16持续性感染,做到及时诊断与治疗,以减少宫颈高级别病变和宫颈癌的发生。     

GRP94和CD8在宫颈病变组织中的表达及意义

目的：探讨葡萄糖调节蛋白94（glucose—regulated protein94,GRP94）和CD8在宫颈病变组织中的表达及与HPV感染的关系。方法：采用免疫组化S—P法检测32例原发宫颈癌、27例宫颈上皮内瘤变（cervical intraepithelial neoplasia, CIN）及40例慢性宫颈炎组织中GRP94和CD8的表达及定位;采用western blot技术检测6例宫颈癌及6例正常宫颈组织中GRP94和CD8的表达。结果：①在宫颈癌、CIN2／3、CIN1及慢性宫颈炎组织中,GRP94的阳性表达率分别为87．5％、82．4％、40％和22．5％;CD8的阳性表达率分别为28．1％、64．7％、90％和97．5％;GRP94在宫颈癌和CIN2／3中的表达均显著高于慢性宫颈炎和CIN1组织（P均〈0．05）;CD8在宫颈癌组的表达显著低于慢性宫颈炎组、CIN1组及CIN2／3组（P均〈0．05）。②Western blot结果示GRP94在宫颈癌组织中的表达显著高于正常宫颈组织（P〈0．01）;CD8在宫颈癌组织中的表达显著低于正常宫颈组织（P〈0．01）。③GRP94的表达与宫颈癌分化程度、有无脉管侵袭有关（P〈0．05）,而与年龄、病理类型、临床分期及有无淋巴结转移无关（P〉0．05）;CD8的表达与有无脉管侵袭有关（P〈0．05）,而与年龄、病理类型、临床分期、分化程度及有无淋巴结转移无关（P〉0．05）。④宫颈病变组织中,GRP94的表达与HPV感染呈正相关（rs=0．377,P=0．000）;cD8的表达与HPV感染呈负相关（rs=-0．395,P=0．000）;GRP94与CD8的表达呈负相关（rs=-0．608,P=0．000）。结论：GRP94表达可能是宫颈CIN进展及宫颈癌预后判断的重要预测指标。     

HLA-I表达与维吾尔族妇女宫颈癌前病变及HPV16感染的关系研究

目的：观察人白细胞相关抗原I（human leukocyte antigen class I,HLA-I）表达与维吾尔族妇女宫颈癌前病变进程及高危型HPV16的关系。方法：收集维吾尔族妇女宫颈炎、宫颈内上皮瘤样病变（cervical intraepithelial neoplasia,CIN）和宫颈鳞癌患者的石蜡包埋组织标本共148例,提取组织DNA,应用PCR的方法检测HPV阳性及HPV16型别;同时采用免疫组织化学SP法检测HLA-I蛋白表达水平。结果：（1）在维吾尔族妇女中HLA-I抗原在宫颈炎、CINI-II、CINIII、SCC组中阳性表达逐渐减少,差异有统计学意义（P〈0.001）。（2）HLA-I的阳性表达下降趋势与宫颈癌临床分期、组织分化程度和淋巴结转移密切相关。（3）HPV在宫颈炎、CINI-II、CINIII、宫颈癌中的感染率分别为13%、46%、82%、95%,差异有统计学（P〈0.001）。（4）HPV16在宫颈炎、CINI-II、CINIII、宫颈癌中的感染率分别为4%、30%、68%、85%,差异有统计学（P〈0.001）。（5）在HPV16阳性标本中,存在HLA-I表达缺失的占71%（58/82）,HPV16感染与HLA-I表达呈负相关（r=-0.625,P〈0.001）。结论：（1）HLA-I表达缺陷可能是宫颈病变进展的重要标志,对宫颈癌的预测预警提供依据。（2）HPV16感染在宫颈病变的发展过程中起到了极大的促进作用,是一个很强的致癌因素。（3）HPV16感染与HLA-I表达之间的关系对揭示宫颈癌发病机制提供了客观依据。     

Prevalence of HPV 16 and HPV 18 Lineages in Galicia,Spain

Genetic variants of human papillomavirus types 16 and 18 (HPV16/18) could differ in their cancer risk. We studied the prevalence and association with high-grade cervical lesions of different HPV16/18 variant lineages in a case-control study including 217 cases (cervical intraepithelial neoplasia grade 2 or grade 3 or worse: CIN2 or CIN3+) and 116 controls (no CIN2 or CIN3+ in two-year follow-up). HPV lineages were determined by sequencing the long control region (LCR) and the E6 gene. Phylogenetic analysis of HPV16 confirmed that isolates clustered into previously described lineages: A (260, 87.5%), B (4, 1.3%), C (8, 2.7%), and D (25, 8.4%). Lineage D/lineage A strains were, respectively, detected in 4/82 control patients, 19/126 CIN3+ cases (OR = 3.1, 95%CI: 1.0–12.9, p = 0.04), 6/1 glandular high-grade lesions (OR = 123, 95%CI: 9.7–5713.6, p<0.0001), and 4/5 invasive lesions (OR = 16.4, 95%CI: 2.2–113.7, p = 0.002). HPV18 clustered in lineages A (32, 88.9%) and B (4, 11.1%). Lineage B/lineage A strains were respectively detected in 1/23 control patients and 2/5 CIN3+ cases (OR = 9.2, 95%CI: 0.4–565.4, p = 0.12). In conclusion, lineages A of HPV16/18 were predominant in Spain. Lineage D of HPV16 was associated with increased risk for CIN3+, glandular high-grade lesions, and invasive lesions compared with lineage A. Lineage B of HPV18 may be associated with increased risk for CIN3+ compared with lineage A, but the association was not significant. Large well-designed studies are needed before the application of HPV lineage detection in clinical settings.     

宫颈癌中端粒酶的表达和高危型人乳头瘤病毒感染

目的：研究不同程度子宫颈病变中高危型人乳头瘤病毒HR-HPV感染和端粒酶活性的表达,以探讨两者在宫颈癌及宫颈上皮内瘤变中的作用及相关性。方法：采用第二代杂交捕获技术检测宫颈脱落细胞HPV．DNA含量,并用免疫组织化学EnVision二步法检测宫颈组织标本中端粒酶的表达。结果：（1）端粒酶阳性表达率在对照组、C1NI、CINII、CINⅢ和宫颈癌组分别为10．00％、16．67％、40．00％、70．00％、95．00％,宫颈癌组高于cINⅢ,CINⅢ高于C1NⅡ,C1NII高于CINI,差异均有统计学意5C（X^2=-4．329,P=0．037;xⅫ．327,P=0．038;X^2=4．022,P=0．045）。（2）随着宫颈病变级别的增加,高危型HPV的阳性率和病毒负荷量均增高。高危型HPV的阳性率在宫颈癌和CINⅢ组明显高于对照组、CINI及CINⅡ（X^2=29．501-7．414,P〈0．01）。高危型HPV的病毒负荷量在对照组与其他4组比较,差异均有统计学意K（P〈0．05）;C1NI组分别与CINⅡ、C1NⅢ及宫颈癌组比较差异均有统计学意义（P〈0．05）。（3）随着宫颈病变级别的增加,高危型HPV的阳性率和端粒酶阳性表达率依次递增,两者有明显的相关性（r=0．943,P〈0．01）。结论：高危型HPV感染和端粒酶活性均与宫颈癌前病变及宫颈癌的发生发展密切相关,有望作为子宫颈癌前病变和宫颈癌筛查的监测指标。