Association between the HLA DQB1*0301 gene and human papillomavirus infection in high-grade cervical intraepithelial neoplasia.

This study describes the distribution of DQB1genes in Norwegian women treated for high-grade cervical intraepithelial neoplasia (CIN). Formalin-fixed, paraffin-embedded tissue sections from 170 biopsy specimens with diagnoses of CIN II (n = 54) or CIN III (n = 116) were DQB1-typed using allele-specific polymerase chain reaction. The follow-up period for cases was 13 to 15 years. The control material comprised blood samples and endocervical brushes from 213 women without CIN. Both cases and controls had previously been human papillomavirus (HPV)-typed. The DQB1*0301 allele was overrepresented among cases compared with controls (odds ratio [OR] = 1.8). Presence of CIN was related to HPV infection, and HPV 16 positivity was significantly associated with the presence of DQB1*0301 (OR 1.8). The DQBI*0301 allele was significantly more prevalent in CIN III than in CIN II cases. The lesions in two women recurred in the follow-up period, one of whom was carrying the DQB1*0301 allele. Women carrying the HLA-DQB1*0301 allele have an increased risk of developing CIN when infected by HPV 16, although there was not an increased frequency of recurrent disease among women carrying this allele.     

Association between high-risk human papillomavirus DNA load and precursor lesions of cervical cancer in Mexican women

OBJECTIVE: Our objective was to determine the association between viral load of high risk human papilloma virus (HPV) using the Hybrid Capture II (HC II) system and cervical intraepithelial neoplasia (CIN) lesion stage. METHODS: A total of 182 consecutive women with confirmed diagnoses of CIN 1-3 and 182 healthy women with negative Pap were included. All subjects underwent structured interviews focused on socioeconomic and reproductive factors. HC II testing was used to detect human papilloma virus (HPV) DNA. Viral load was measured by light measurements expressed as relative lights unit (RLU) ratio (specimens/control). Log(10)RLU ratios were categorized for analysis into four groups: negative (相似文献   

高危型人乳头瘤病毒载量与宫颈上皮内瘤变病变程度相关性

目的:探讨高危型人乳头瘤病毒(HR-HPV)载量与宫颈上皮内瘤变(cervi-cal intraepithelial neoplasia,CIN)病变程度相关性。方法:对2008年1月~2010年6月于上海市第一人民医院行阴道镜检查的1035例患者,用HCⅡ方法检测其HR-HPV病毒载量,分为阴性组(0.00~1.00)、低度载量组(1.0~10.00)、中度载量组(10.00~100.00)、高度载量组(100.00~1000.00)和极高度载量组(≥1000.00);将病理结果按照宫颈病变程度分为阴性组(慢性黏膜炎和挖空细胞)、低级别病变组(CINⅠ)和高级别病变组(CINⅡ、CINⅢ)。多分类Logistic回归分析HPV病毒载量和CIN病变程度相关性。结果:病理诊断为慢性黏膜炎、挖空细胞、CINⅠ、Ⅱ、Ⅲ的HR-HPV病毒载量的中位数(感染率)分别是2.70(58.22%)、56.00(79.07%)、88.05(79.66%)、323.90(93.27%)和364.07(92.47%),基本呈递增趋势。CIN的各级别病毒载量的分布差异显著(P均<0.05),低级别病变组和高级别病变组的各级别病毒载量组(低度载量组、中度载量组、高度载量组和极高度载量组)对于病理阴性组的危险度(OR值)依次递增:低级别病变组0.677、2.406、2.893和2.943;高级别病变组2.177、4.262、6.354和20.177。结论:CIN的发生与高危型人乳头瘤病毒载量有关,病毒载量越高,CIN发生危险度越高。     

Quantification of human papillomavirus DNA in the plasma of patients with cervical cancer

Plasma human papillomavirus (HPV)-DNA level was measured to evaluate the clinical usefulness of circulating DNA for cervical cancer management. DNA extracted from pretreatment plasma of 50 cervical cancer patients and from serial longitudinal plasma of 21 patients was quantified for HPV16/HPV18 by means of quantitative polymerase chain reaction. Another 15 patients with low-grade lesion (LG), 18 patients with high-grade lesion (HG), and 96 normal individuals were studied as controls. Plasma HPV16-DNA was detectable in 50% of cancer patients. The incidence and median level were statistically higher than those in LG patients and normal, but similar to HG patients. Plasma HPV18-DNA was only detected in 6% of cancer patients and 1% of normal. Same type of HPV present in plasma was also detected in its primary tumor; and the level of plasma HPV16-DNA was dependent on the viral load in primary tumor. Plasma HPV-DNA was not detected in 16 of 21 patients after treatment, and those patients had complete response to therapy. HPV-DNA persisted or reappeared in five patients after treatment (one had persistent disease and another had recurrence). Plasma HPV-DNA might be a valuable marker for monitoring therapeutic response and disease progression in cervical cancer.     

宫颈癌发病的年轻化趋势与人乳头状瘤病毒感染的关系

目的探讨人乳头状瘤病毒感染与宫颈鳞状细胞癌发病年龄的关系.方法分析1992年1月至1999年10月在我院住院治疗的75例宫颈鳞癌患者的发病年龄,并对其肿瘤组织进行了HPV16E7检测.结果1992年1月至1999年10月宫颈鳞状细胞癌患者平均发病年龄逐渐减小;HPV16的感染率由25.00%上升到48.71%.年轻宫颈鳞癌患者HPV16的感染率(85.71%)明显高于年龄较大者(28.00%)(P＜0.01).结论随着HPV16感染率的升高,官颈鳞癌患者年轻化趋势愈明显,HPV16感染与官颈鳞状细胞癌年轻化有关.因此,对HPV感染的高危人群应加强监测、随访,作到早诊断、早治疗.     

Advances in cervical cancer screening and human papillomavirus vaccines

Cervical cancer is causally linked to human papillomavirus (HPV) and constitutes a major health problem for women. Nearly 80% of the 510,000 cases reported worldwide each year occur in developing countries which lack organized screening programmes. Cervical screening has effectively reduced the incidence of and mortality from invasive cervical cancer in industrialized countries, but is not completely protective. Cervical screening is now undergoing modernization and has seen several changes in recent years. These aim to enhance the overall efficiency and effectiveness of screening, reduce rates of inadequate sampling, increase sensitivity rates and facilitate ancillary technologies, such as HPV testing. This review discusses these advances and the development of HPV vaccines.     

Association between genital mycoplasmas infection and human papillomavirus infection,abnormal cervical cytopathology,and cervical cancer: a systematic review and meta-analysis

Background

Some studies demonstrated that female genital mycoplasmas play important roles in human papillomavirus (HPV) infection, abnormal cervical cytopathology, and cervical cancer. However, those results remained inconclusive. We aimed to perform a systematic review and meta-analysis to investigate the association between female genital mycoplasmas and those disorders.

Methods

Computerized databases were comprehensively searched before 26 January 2017. Pooled odd radios (ORs) and correlative 95% confidence intervals (CIs) were adopted to evaluate the strength of association.

Results

Our meta-analysis included 22 studies with 16,181 participants. Ureaplasma urealyticum and Ureaplasma parvum were associated with a significantly increased risk of overall HPV infection (OR 1.57, 95% CI 1.05–2.34; OR 3.02, 95% CI 2.10–4.33, respectively), and U. urealyticum and Mycoplasma genitalium were associated with a significantly increased risk of high-risk HPV infection (OR 1.37, 95% CI 1.05–1.80; OR 1.50, 95% CI 1.11–2.02, respectively). In addition, U. urealyticum, U. parvum, and Mycoplasma hominis were associated with a significantly increased risk of abnormal cervical cytopathology (OR 1.51, 95% CI 1.23–1.85; OR 1.41, 95% CI 1.10–1.80; OR 1.48, 95% CI 1.10–1.99, respectively).

Conclusion

We found that U. urealyticum and M. genitalium may increase the risk of high-risk HPV infection, while U. urealyticum, U. parvum, and M. hominis may increase the risk of abnormal cervical cytopathology.

     

Association of human immunodeficiency virus-induced immunosuppression with human papillomavirus infection and cervical intraepithelial neoplasia

Human papillomavirus infection plays an important causal role in cervical intraepithelial neoplasia and carcinoma. The rate of infection with human papillomavirus as well as the incidence of cervical intraepithelial neoplasia and carcinoma are increased in immunosuppressed patients. We report a possible association between infection with human immunodeficiency virus and cervical intraepithelial neoplasia with human papillomavirus infection.     

人乳头瘤病毒基因亚型与宫颈病变的关系

目的 研究不同程度的子宫颈癌前病变者感染HPV的基因亚型，以探讨不同基因型HPV感染的致癌性。方法 研究对象系3．56例宫颈HPV感染的患者。以第二代杂交捕获（HC1I）试验检测13种HPVH，同时采用核酸分子快速杂交基因分型技术进行21种HPV-DNA亚型分析；所有研究对象均行宫颈薄层液基细胞学检测（LCT）及阴道镜下宫颈多点活检。根据细胞与病理学诊断有无宫颈病变及其病变程度分组。①宫颈癌与高度鳞状上皮内瘤变（HSIL）组：包括宫颈浸润癌9例、CINⅢ57例、CINⅡ53例；②低度鳞状上皮内瘤变（LSIL）组：包括CINⅠ112例、HPV感染52例；③正常或炎症组：宫颈细胞与组织学正常或炎症者73例。通过HPV-DNA亚型分布，分析HPV感染基因型与宫颈病变程度的关系。结果 HPV-H与宫颈癌变密切相关，本组高度病变以上患者中HPV-H阳性率达98．4％；随着宫颈病变程度加重，HPV-H双重与多重感染有增加趋势，在正常与炎症组、LSIL组与HSIL组中两种以上HPV-H基因型感染者分别占13．7％、17．7％和36．6％，HSIL组明显高于其他两组，差异有显著性（P〈0．01）；本组HPV亚型感染频度由高到低依次为HPV-16（32．9％）、58（18．8％）、52（16．9％）、18（9．0％）、33（8．2％）、68（7．3％）、11（低危型，6．5％）、31（6．2％）、53（5．6％）、39（5．3％）、CP8304（5．1％）、66（3．9％）、6（2．5％）和51、56、45、35、59、43、44、82等少见型；HPV-16、58、33、52与18型在高度鳞状上皮内瘤样病变（HSIL）中感染率分别为56．4％、19．3％、16．0％、12．6％和8．4％，说明这些亚型致癌性更强；两种HPV-DNA检测技术所获结果，具有很高的一致性。结论本组宫颈病变患者感染HPV型别以16、58、52、18、33较为多见，HPV-16、58、33、52与18型致癌性较强；HPV-DNA分型检测在临床诊断与判断预后上具有重要意义。     

复发性流产与人类白细胞抗原DQB1基因多态性关系的研究

目的探讨复发性流产与人类白细胞抗原DQB1（HLA-DQB1）基因多态性的关系。方法应用PCR限制性片段长度多态性方法（PCR-RFLP）,分析36例无不良妊娠史的正常妇女（对照组）和61例复发性流产患者[观察组,其中抗心磷脂抗体阳性31例,抗心磷脂抗体阴性30例;早期流产28例,晚期流产22例,早晚期流产（2次以上的流产分别发生在早期或晚期）11例]的DQB1基因型。结果（1）观察组0201等位基因频率为16．4％（20／122）,明显高于对照组的8．3％（6／72）,但两组比较,差异无统计学意义（P〉0．05）;观察组DQB1第57位非天门冬氨酸频率明显高于对照组,两组比较,差异有统计学意义（P〈0．05）;观察组中早期流产者0201等位基因频率为23．2％（13／56）,明显高于晚期流产者的4．5％（2／44）,两者比较,差异有统计学意义（P〈0．05）;晚期流产者0303等位基因频率为27．3％（12／44）,明显高于早期流产者的7．1％（4／56）,两者比较,差异也有统计学意义（P〈0．05）。（2）观察组中抗心磷脂抗体阳性者0303等位基因频率为26％（16／62）,明显高于抗心磷脂抗体阴性者的7％（4／60）,两者比较,差异有统计学意义（P〈0．05）。结论DQBl第57位非天门冬氨酸可能与复发性流产的发生有关,DQB1＊0201等位基因可能与早期流产有关,DQB1＊0303等位基因可能与晚期流产及抗心磷脂抗体阳性者的流产发生有关。     

Prevalence of human papillomavirus in elderly women with cervical cancer.

To investigate the relation between the prevalence of human papillomavirus (HPV) and age in cervical cancer patients, material from 93 patients with Ia-IIb cervical carcinoma was analyzed for the presence of HPV by both type-specific and general primer polymerase chain reaction. Patients were divided into 2 groups: 64 years or younger, and 65 years and older. There was no statistically significant difference in either the prevalence of HPV DNA or distribution of genotypes amongst the 2 groups. Therefore, HPV detection can be equally well used in the management and follow-up of elderly cervical cancer patients.     

Lack of association between HLA DQB1 alleles with HPV infection and histology findings in cervical cancer in Australian women

Chen S, Tabrizi SN, O'Sullivan H, Fairley CK, Quinn MA, Garland SM. Lack of association between HLA DQB1 alleles with HPV infection and histology findings in cervical cancer in Australian women. Int J Gynecol Cancer 1999; 9: 220–224.
The association of human leukocyte antigen (HLA) types with cervical cancer and human papillomavirus (HPV) infection is controversial. In this study we examined 186 Australian women who had biopsy-confirmed cervical cancer and detected HLA DQB1 alleles and HPV DNA, using the polymerase chain reaction (PCR) amplification and sequence specific oligonucleotides probe (SSOP) hybridization methods. We analyzed the frequencies of 11 DQB1 alleles according to HPV DNA status (HPV positivity and HPV genotyping) and histology (tumor type, staging, grades, lymphocyte infiltration and nodal status). No significant differences among these 11 HLA DQB1 alleles were found with respect to HPV status and histology.     

Evaluation of antibodies to human papillomavirus as prognostic markers in cervical cancer patients

OBJECTIVES: We wished to evaluate whether the presence of antibodies to HPV or to the HPV oncoproteins E6 and E7 or type of HPV DNA is related to prognosis among cervical cancer patients. METHODS: Blood samples were drawn from 313 patients with incident, untreated cervical cancer on admission to two hospitals in Sweden. Patients were followed from enrollment in 1984-1991 until death or up to June 1999. Clinical information was obtained from a review of medical records. Survival and cause of death were ascertained from both medical records and population-based cancer registries. The correlation of survival with antibodies to HPV16, to oncoproteins E6 and E7, and to type of HPV DNA was evaluated using multivariate Cox regression analysis, including stage, age, histology, and hospital in the model. RESULTS: Stage was the only significant prognostic factor influencing cervical cancer patient survival (OR = 3.62, 95% CI = 2.71-4.83). Age over 50 was associated with increased death rate among stage I-IIa patients (OR = 2.29, 95% CI = 1.12-4.68). Presence of antibodies to the oncoproteins E6 and E7 or to the HPV16 capsid or type of HPV DNA did not associate significantly with disease prognosis. CONCLUSIONS: Antibodies to HPV16 capsids and to oncoproteins E6 and E7 or type of HPV DNA do not appear to be useful as indicators of cervical cancer prognosis.     

Distribution of human papillomavirus genotypes in women with cervical cancer in Slovenia

Objective

The purpose of the present study was to establish the distribution of human papillomavirus (HPV) genotypes in a representative population of women with cervical cancer in Slovenia in order to contribute to the lacking data on HPV in cervical cancer and to assess the potential local benefit of future prophylactic HPV vaccination.

Study design

A total of 284 samples of cervical cancer were analyzed including archival samples, cervical scrapes and fresh tissue samples. Polymerase chain reaction with GP5+/GP6+ primers was performed in all samples for HPV deoxyribonucleic acid (DNA) detection. All GP5+/GP6+ negative samples were additionally tested using CPI/CPIIg primers and INNO-LiPA HPV genotyping assay.

Results

After exclusion of 6 samples with unsuccessful amplification of beta-globin gene, 262 of 278 cervical cancer samples (94.2%) were HPV DNA positive. HPV genotypes found in the decreasing order of frequency were: HPV 16 (64.9%), HPV 18 (12.2%), HPV 33 (4.7%), HPV 45 (4.1%), followed by HPV 31, 51, 58, 59, 35, 52, 73 and 82 (3.5–0.2%). HPV positive samples were more frequent among squamous cell carcinomas than among adenocarcinomas/adenosquamous carcinomas (95.8% versus 85.5%; P = 0.003). HPV 16 was more frequently found in squamous cell carcinomas than in adenocarcinomas/adenosquamous carcinomas (69.9% versus 37.5%; P < 0.001), while the opposite was true for HPV 18 (6% versus 41.7%; P < 0.001).

Conclusion

Prophylactic HPV vaccination with currently available vaccines could prevent up to 77.1% of cervical cancer in Slovenia, which is caused by HPV 16 or HPV 18.     

Evidence of an association between human papillomavirus and impaired chemotherapy-induced apoptosis in cervical cancer cells

OBJECTIVES: The aim of this study was to determine cervical cancer cell sensitivity to chemotherapy-induced apoptosis based on human papillomavirus (HPV) status. METHODS: CaSki (HPV-positive) and C33A (HPV-negative) cells were treated with camptothecin or cisplatin. Cellular viability was determined by trypan blue exclusion. Apoptotic indexes were determined by flow cytometric analysis of annexin V labeling and morphological changes. Mitochondrial release of cytochrome c was determined by immunofluorescence using confocal microscopy. Caspase 3 activation and bax expression were assessed by immunoblotting. RESULTS: CaSki cells displayed chemoresistance to both camptothecin and cisplatin. Low response to apoptogenic stimuli was evidenced by a marginal increase in the apoptotic cell fraction after camptothecin treatment (22.9 +/- 2.56%) compared with control (17.8 +/- 1.95%). Cisplatin (14.8 +/- 1.01%) caused a slight decrease in apoptosis. Mitochondrial release of cytochrome c and cleavage of caspase 3 could not be demonstrated in CaSki cells after treatment. Despite p53 mutation, C33A cells were sensitive to the antiproliferative effects of camptothecin and cisplatin. Mean apoptotic events were 17.5 +/- 0.33 for control, 42 +/- 1.76 for cisplatin, and 38.1 +/- 0.75 for camptothecin. An intact cytochrome c pathway was demonstrated in C33A cells leading to cleavage of caspase 3 after camptothecin treatment. The constitutive bax expression demonstrated in both cell lines displayed no change after camptothecin treatment. CONCLUSION: HPV-positive cervical cancer cells have an inherent resistance to chemotherapy-induced apoptosis. HPV-dependant inactivation of apoptotic regulators such as p53 and blockage of downstream events such as cytochrome c release and caspase 3 activation might be elemental to this cellular survival advantage provided by high-risk oncogenic papillomavirus.     

广西沿海地区妇女宫颈癌患者人乳头瘤病毒（HPV）感染各亚型分布特点

目的探讨广西沿海地区妇女宫颈癌患者人乳头瘤状病毒（human papillomavirus,HPV）感染分布情况及主要型别,为广西沿海地区临床防治宫颈癌、研制适合该地区的预防性HPV疫苗提供理论依据。方法采用人乳头瘤病毒核酸扩增分型检测试剂盒方法,对76例广西沿海地区妇女经病理确诊宫颈癌患者的宫颈脱落细胞进行HPV基因分型检测。结果 76例宫颈癌患者中有69例HPV阳性,阳性率为90.8%,其中,HPV16感染率最高为56.5%,其他高危型的感染率从高到低依次为HPV18、33、58、52、53、31、45、35、39、51、56、66、68。低危型中HPV6型感染率最高为5.8%,其他低危型的感染率从高到低依次为HPV11、43、44。多重感染率为20.3%。正常对照组60例中有13例HPV阳性（21.7%）。其中,13例阳性标本中,HPV16感染率最高为30.8%,其他高危型HPV31、52、53感染率为15.4%,低危型HPV11、43、44感染率为7.7%。宫颈癌HPV阳性率明显高于正常对照组,差异有统计学意义（P〈0.005）。结论广西沿海地区妇女宫颈癌患者中以HPV16、18、33、58感染为主要型别,可能是广西沿海地区妇女宫颈癌较易感染的型别。