宫颈癌患者人乳头瘤病毒感染分布特点

目的：探讨人乳头瘤病毒（HPV）各亚型在广西沿海地区宫颈癌患者中的分布情况,HPV感染与宫颈癌患者的年龄、临床分期、病理类型、分化程度、肿瘤盆腔淋巴结转移及肿瘤的复发的关系。方法：通过凯普导流杂交HPV DNA检测法,对76例宫颈癌患者宫颈脱落细胞进行21种HPV亚型的检测。结果：宫颈癌HPV总阳性率为90.8%。宫颈癌患者HPV阳性各亚型出现的频率排序为：HPV16（56.5%）,HPV18、33、58各（7.2%）,HPV52、53各（5.8%）,HPV31（4.3%）,HPV45（2.9%）,HPV35、51、56、66、68各（1.4%）。HPV6（5.8%）,HPV11、44、43各（1.4%）均合并在高危感染中。HPV感染与临床分期、肿瘤分化程度、肿瘤盆腔淋巴结转移及肿瘤的复发关联无显著性（P〉0.05）,与年龄密切相关,鳞癌HPV阳性率明显高于腺癌及其它癌,差异有统计学意义（P〈0.05）。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。HPV感染与宫颈癌的临床分期、肿瘤分化程度、肿瘤盆腔淋巴结转移及肿瘤的复发无明显相关性,与发病年龄、病理类型有关。     

子宫颈癌患者血清、盆腔淋巴结HPV检测及其相关性探讨

目的:检测宫颈癌患者原发灶、血清及其盆腔淋巴结中HPV DNA及亚型,探讨其相关性及临床意义。方法:选取16例行广泛全子宫切除术和盆腔淋巴结清扫术宫颈癌患者的原发灶组织、术前静脉血与盆腔淋巴结石蜡组织,运用PCR方法对上述标本进行HPV DNA及亚型的检测。结果:宫颈癌原发灶组织、血清标本中HPV DNA阳性率为50%(8/16)。16例盆腔淋巴结石蜡组织中13例为HPV DNA阳性(13/16,81.25%),其中总共切除的133个淋巴结中60个为阳性(60/133,45.1%),8例淋巴结HPV DNA阳性的病例其对应的原发灶组织也为阳性且两者亚型相同。盆腔淋巴结中的HPV DNA阳性率为45.1%(60/133),显著高于病理证实的淋巴结转移率1.5%(2/133)。6例患者(6/16,37.5%)原发灶、血清、盆腔淋巴结同时均为HPV DNA阳性;2例患者(2/16,12.5%)原发灶、盆腔淋巴结中HPV DNA表达阳性,而血清为阴性;1例患者(1/16,6.25%)淋巴结、血清HPV DNA阳性,而原发灶为阴性;未发现原发灶、血清HPV DNA表达阳性而淋巴结为阴性的病例,而且以上HPV DNA阳性的病例同一个患者对应的HPV亚型也相同。结论:宫颈癌患者血清中HPV DNA检出率与临床分期无关。宫颈癌患者盆腔淋巴结的HPV DNA检测可提高病理诊断淋巴结转移的阳性率,并且淋巴结中HPV DNA的检出率与原发灶的分化程度相关。宫颈癌原发灶、血清、盆腔淋巴结中HPV感染可能存在相关性。     

宫颈癌盆腔淋巴结转移相关因素分析

目的:探讨宫颈癌盆腔淋巴结转移相关因素。方法:回顾性分析634例广泛性子宫切除及盆腔淋巴结清扫术后宫颈癌患者的临床分期及病理资料。结果:盆腔淋巴结总转移率为18.76%(119/634),年龄、临床分期、肿瘤浸润深度、肿瘤生长形态、肿瘤细胞分化程度与淋巴结转移显著相关。病理类型、病灶大小、术前放化疗与淋巴结转移无相关性。结论:年龄≤35岁,临床分期晚,肿瘤浸润≥1/2,溃疡型肿瘤,病理分化差均为宫颈癌淋巴转移高危因素。     

HPV多重感染与宫颈癌患者临床病理学特征分析

目的:对宫颈癌患者中HPV感染率及型别分布进行研究,探讨宫颈癌患者HPV多重感染与临床病理特征的关系.方法:选取2008年9月至2009年4月浙江省肿瘤医院因宫颈癌就诊且有临床病理确诊的患者171例,采用导流杂交基因芯片技术对HPV感染进行基因诊断和分型,并进一步比较HPV多重感染、单一感染、无感染者在年龄、临床分期、病理类型和淋巴结转移上的差异.结果:171例宫颈癌患者中HPV感染者为122例(71.35%),其中单一感染者103例(60.2%)、多重感染者19例(11.1%);HPV多重感染中以二重感染最常见(15例)、三重感染及四重感染各2例.单一感染主要是HPV16、18、58,多重感染主要是HPV16+58/52.无论是单一感染还是多重感染,均以含HPV16为主要的感染型别.年龄≥52岁宫颈癌患者中HPV多重感染的比例明显高于<52岁患者,且两者存在显著性差异(P<0.05).在临床分期、病理分型及淋巴结转移上,HPV多重感染与单一感染或无感染者之间均无差异.结论:HPV多重感染与宫颈癌患者年龄有关,但与临床分期、病理类型、淋巴结转移等预后因子均无关系,可能是独立的预后预测因子.导流杂交基因芯片技术适合临床筛查HPV感染及对HPV进行基因分型.     

子宫颈癌与HPV感染关系的临床研究

目的分析子宫颈癌组织HPV检测的结果及相关临床资料,探讨HPV与子宫颈癌的临床生物学行为之间关系。方法收集200例有完整临床病历资料的子宫颈癌患者病灶组织,采用HPV分型基因芯片检测系统,进行HPV阳性率及其亚型的检测并对相关资料加以分析。结果HPV检出率94．0％,其中HPV16阳性率65．6％;HPV18阳性率15．5％。HPV阳性率与子宫颈癌临床分期、病理分级无相关性（P=0．25、P=0．75）;HPV阳性率与肿瘤的盆腔淋巴结转移、肿瘤的治疗后复发亦无相关性（P=0．29、P=0．47）;鳞状细胞癌的HPV检出率明显高于腺癌（P〈0．005）。结论子宫颈癌组织中的HPV阳性率很高,主要为16、18型。HPV感染与鳞状上皮恶变的关系更密切;HPV与宫颈癌的临床期别、病理分级、盆腔淋巴结转移、肿瘤的复发无明显相关性。     

宫颈癌盆腔淋巴结转移相关因素分析

目的：探讨宫颈癌盆腔淋巴结转移相关因素。方法：回顾性分析634例广泛性子宫切除及盆腔淋巴结清扫术后宫颈癌患者的临床分期及病理资料。结果：盆腔淋巴结总转移率为18.76%（119/634）,年龄、临床分期、肿瘤浸润深度、肿瘤生长形态、肿瘤细胞分化程度与淋巴结转移显著相关。病理类型、病灶大小、术前放化疗与淋巴结转移无相关性。结论：年龄≤35岁,临床分期晚,肿瘤浸润≥1/2,溃疡型肿瘤,病理分化差均为宫颈癌淋巴转移高危因素。     

子宫颈癌患者血清、盆腔淋巴结HPV检测及其相关性探讨

目的：检测宫颈癌患者原发灶、血清及其盆腔淋巴结中HPVDNA及亚型,探讨其相关性及临床意义。方法：选取16例行广泛全子宫切除术和盆腔淋巴结清扫术宫颈癌患者的原发灶组织、术前静脉血与盆腔淋巴结石蜡组织,运用PCR方法对上述标本进行HPVDNA及亚型的检测。结果：宫颈癌原发灶组织、血清标本中HPVDNA阳性率为50％（8／16）。16例盆腔淋巴结石蜡组织中13例为HPVDNA阳性（13／16,81．25％）,其中总共切除的133个淋巴结中60个为阳性（60／133,45．1％）,8例淋巴结HPVDNA阳性的病例其对应的原发灶组织也为阳性且两者亚型相同。盆腔淋巴结中的HPVDNA阳性率为45．1％（60／133）,显著高于病理证实的淋巴结转移率1．5％（2／133）。6例患者（6／16,37．5％）原发灶、血清、盆腔淋巴结同时均为HPVDNA阳性;2例患者（2／16,12．5％）原发灶、盆腔淋巴结中HPVDNA表达阳性,而血清为阴性;1例患者（1／16,6．25％）淋巴结、血清HPVDNA阳性,而原发灶为阴性;未发现原发灶、血清HPVDNA表达阳性而淋巴结为阴性的病例,而且以上HPVDNA阳性的病例同一个患者对应的HPV亚型也相同。结论：宫颈癌患者血清中HPVDNA检出率与临床分期无关。宫颈癌患者盆腔淋巴结的HPVDNA检测可提高病理诊断淋巴结转移的阳性率,并且淋巴结中HPVDNA的检出率与原发灶的分化程度相关。宫颈癌原发灶、血清、盆腔淋巴结中HPV感染可能存在相关性。     

影响子宫颈癌盆腔淋巴结转移因素

 目的　了解影响宫颈癌盆腔淋巴结转移的影响因素。方法　对 116例宫颈癌临床资料进行回顾性分析。结果　Ⅰ期宫颈癌盆腔淋巴结转移率为 6 .6 7% ,Ⅱ期宫颈癌淋巴结转移率为 34.6 1% ,放疗未控及复发癌盆腔淋巴结转移率为 35 .2 9%。盆腔淋巴结转移率与患者的临床分期、病理类型、肿瘤体积及生长方式有直接关系。结论　宫颈癌病人的临床分期、病理类型、肿瘤体积、生长方式是影响宫颈癌盆腔淋巴结转移的预后因素 ,术前应充分考虑这些高危因素     

老年宫颈癌患者术后复发的高危因素及其病理特征

目的:探讨分析老年宫颈癌患者术后复发高危因素及其病理特征。方法:回顾性分析2011年3月至2015年6月我院收治的老年宫颈癌（I-IIa期）并行宫颈癌根治术的338例患者临床资料,将术后复发患者56例作为复发组,其余未复发患者282例作为对照组,对可能影响患者术后复发的各因素进行单因素及多因素Logistic回归分析。结果:对患者进行术后随访,术后复发56例,术后复发率16.57%,其中鳞癌患者46例（82.14%）、非鳞癌患者10例（17.86%）。单因素分析结果显示,临床分期、肿瘤大小、组织分化程度、盆腔淋巴结转移、宫颈浸润深度、术后放疗、术后化疗以及术前SCC表达对老年宫颈癌患者术后复发有显著影响（P＜0.05）。多因素Logistic回归分析结果显示,盆腔淋巴结转移、临床分期、宫颈浸润深度、术后化疗以及SCC表达情况进入回归模型（P＜0.05）。结论:盆腔淋巴结转移、临床分期高、宫颈浸润深、术前SCC表达异常是老年宫颈癌患者术后复发的独立危险因素,而术后化疗是老年宫颈癌患者术后复发的保护因素。     

宫颈癌淋巴结阴性患者的预后及其危险因素

目的 :探讨Ⅰb～Ⅱb期宫颈癌盆腔淋巴结阴性患者的预后以及影响预后的危险因素。方法 :回顾性分析了 1993年 11月～ 1997年 12月 2 36例Ⅰb～Ⅱb期 (FIGO分期 )宫颈癌根治术后证实盆腔淋巴结阴性患者的预后。生存曲线用Kaplan Meier方法。生存率比较采用Logrank检验。Cox比例风险模型分析预后因素。 结果 :本组盆腔淋巴结阴性患者的五年总体生存率为 82 0 % ,中位生存时间 10 0 0月。本组患者的复发和 (或 )转移率为19 5 % ,五年生存率为 16 9% ,中位生存时间为 15 0月。单因素分析结果显示临床分期Ⅱb ,宫颈肿瘤巨大 ,非鳞癌组织类型 ,低分化 ,深肌层浸润 ,宫旁浸润 ,阴道残端有癌残留 ,脉管有癌栓的患者预后不良 (P <0 0 5 )。Cox比例风险模型对可能影响预后的 12个临床因素进行了多因素分析 ,结果显示 :年龄 ,宫颈肿瘤大小 ,组织学类型 ,分化程度 ,宫旁浸润和阴道残端癌残留是影响无淋巴结转移患者预后最重要的危险因素 (P <0 0 5 )。结论 :Ⅰb～Ⅱb期宫颈癌盆腔淋巴结阴性患者的预后较好 ,但宫颈肿瘤巨大 ,非鳞癌类型 ,低分化 ,宫旁浸润及阴道切缘阳性的患者预后不良 ,也应给予必要的治疗 ,以减少盆腔复发和远处转移。     

Prevalence of Human Papillomavirus Types and Phylogenetic Analysis of HPV-16 L1 Variants from Southern India

Background: The human papillomavirus (HPV) and its variants show wide geographical distribution andhave been reported to cause cervical lesions. With cervical neoplasia as the leading cancer in Indian women,the aim of the present study was to evaluate the multiple infection HPV type distribution and variant genotypesin cervical samples from the coastal Karnataka region, India. Materials and Methods: A total of 212 sampleswere screened by nested polymerase chain reaction using PGMY9/11 and GP5+/6+ primers. HPV positivesamples were sequenced to identify the types and a phylogenetic tree was constructed using the neighbor-joiningmethod. Results: Sequence analysis identified a total of 14 HPV types distributed in 20%, 73.3% and 82.5%of non-malignant, pre-malignant [low grade squamous intraepithelial lesion (LSIL) and high grade squamousintraepithelial lesion (HSIL)] and cervical cancer samples. The distribution of high risk HPV in cancer sampleswas HPV 16, 76.4%, HPV18, 11.7%, HPV81, 2.9%, HPV31, 1.4%, HPV35, 1.4% and HPV 45, 1.4%. Multipleinfections were observed in 11.8% of tumor samples with HPV 16 contributing to 62.5% of cases. In non-malignantsamples, 20% of HPV positive samples were detected with HPV16, 82.3%, HPV33, 5.8% and HPV58, 5.8% andvery low incidence of multiple infections. Comparative phylogenetic analysis of HPV variants identified 9 HPVsequences as new papillomavirus species, predominantly classified as European lineage type. Conclusions: Thefindings for HPV infections associated with progression of cervical cancer in coastal Karnataka region and HPVvariant analysis provide baseline data for prevention and HPV vaccination programs.     

Early stage cervical cancers containing human papillomavirus type 18 DNA have more nodal metastasis and deeper stromal invasion.

PURPOSE: To investigate the clinical and pathological factors which might explain the poor prognosis associated with early stage cervical cancers containing human papillomavirus (HPV) type 18 DNA. EXPERIMENTAL DESIGN: A clinical and pathological review of 144 patients with stage IB cervical cancer treated with radical hysterectomy and bilateral pelvic lymph node dissection was done. HPV genotyping was determined from fresh tumor specimens through PCR. Clinical-pathological information, sites of recurrence, use of adjuvant radiation, and survival data were analyzed. RESULTS: Thirty-three (23%) tumors contained HPV 18 DNA. These tumors did not differ from those which contained non-HPV 18 DNA with respect to tumor grade or size. However, HPV 18-containing cancers were more likely to be adenocarcinomas. A higher incidence of pelvic lymph node metastasis was noted among the HPV 18 group (48%) as compared with the non-HPV 18 group (28%), and deeper stromal invasion was more common in HPV 18-associated tumors. Although a slightly higher proportion of patients with HPV 18-containing tumors received adjuvant radiation (67%) than those with non-HPV 18 cancers (49%), recurrences were more common among HPV 18 patients. Eleven (33%) of HPV 18-containing cancers relapsed compared with 18 (16%) of non-HPV18-containing tumors. CONCLUSIONS: The explanation for the worse prognosis associated with stage IB cervical cancers containing HPV 18 DNA treated with radical hysterectomy and bilateral pelvic lymph node dissection appears to be related to deeper cervical stromal invasion and more nodal metastases. Despite an increased use of adjuvant radiation therapy, these cancers are still more likely to relapse.     

Correlation between Load of HPV 16 DNA in Cervical Cancer and HPV 16 DNA in Lymph Nodes

OBJECTIVE To determine the association between viral load of human papillomavirus 16 (HPV16) DNA in the primary focus of cervical carcinoma and HPV16 DNA in pelvic lymph nodes. METHODS The HPV16 DNA load was measured by fluorescent quantisation polymerase chain reaction (FQ-PCR) in 17 primary foci. HPV16 DNA was detected by polymerase chain reaction (PCR) using HPV16 type-specific primers in 296 pelvic lymph nodes which were from 17 cases of cervical cancer. RESULTS The viral load of HPV16 DNA showed statistically significant differences between tumors with a diameter of < 4 cm and > 4 cm (P < 0.05). Seven of 17 cervical cancer cases had HPV16 DNA positive lymph nodes, designated as the positive group, while the remaining 10 without positive lymph nodes was designated the negative group. The average load of HPV16 DNA showed no significant difference between the 2 groups (P > 0.05). The load of HPV16 in the primary lesion was not associated with that in the lymph nodes. There were 38 HPV16 DNA positive nodes in the total 296 nodes. The rate of positivity of HPV16 DNA in lymph nodes showed statistically significant differences in consideration of maximum tumor diameter, tumor differentiation, histologic type, depth of myometial infiltration and the metastatic status of the nodes, respectively (P < 0.05).CONCLUSION Viral load of HPV16 in the primary cancer focus correlated with the quantity of tumor cells in the primary focus but not with the existence of HPV DNA positive lymph nodes. Detection of HPV DNA may help to find the early metastases that cannot be evaluated histopathologically but the prognostic value of HPV positive lymph nodes needs further examination.     

HPV分型检测在维吾尔族和汉族宫颈癌机会性筛查中的意义*

目的: 探讨人乳头瘤病毒（HPV）分型检测在维吾尔族和汉族宫颈癌机会性筛查中的意义。 方法: 采用宫颈细胞学检查和HPV分型检测对1 140例患者行宫颈癌机会性筛查,共438例患者在阴道镜下行宫颈活检,评价HPV分型检测的诊断价值。 结果: 1 140例HPV总感染率为30.3%（345/1 140）,检出的高危型HPV主要型别依次为HPV16、58、52、18、45型。汉族HPV52型感染率高于维吾尔族,差异具有统计学意义（χ2=8.737,P=0.003）。1 140例患者中单一感染率为22.4%（255/1 140）,多重感染率为6.1%（69/1 140）,HPV分型检测诊断宫颈病变的灵敏度为86.4%（209/242）、特异度为24.5%（48/196）、阳性预测值为58.5%（209/357）、阴性预测值为59.3%（48/81）。 结论: 维吾尔族和汉族HPV感染型别各有其自身特点,HPV分型检测对宫颈病变的诊断有重要价值。      

MMP-2及CK19在早期宫颈癌淋巴结微转移中的表达及其意义

检测MMP-2和CK19在早期宫颈癌盆腔淋巴结中的表达,探讨淋巴结微转移的表达及意义。方法:采用免疫组化法对64例早期宫颈癌患者常规病理光镜检查证实无转移淋巴结902枚进行MMP-2及CK19的检测。结果:1）复发组477枚淋巴结中11枚CK19阳性（2.3%）,来自32例患者中的8例（25.0%）;8枚MMP-2阳性（1.7%）,来自32例患者中的6例（18.8%）,两种检测指标的结果有较好的一致性。未复发组425枚淋巴结中均无CK19及MMP-2阳性表达（0/425）,该组32例患者中CK19及MMP-2的阳性表达率均为0。二者之间比较差异有统计学意义。2）CK19及MMP-2表达与病理类型及组织的分化程度均有相关性（P<0.05）。3）复发组32例患者中带瘤生存25例,死亡7例,且均死于癌症,其中6例患者盆腔淋巴结中的CK-19及MMP-2检测均表达阳性,微转移与术后复发转移有相关性（P<0.05）。结论:采用免疫组化技术检测淋巴结中CK19及MMP-2表达可检测出早期宫颈癌淋巴结中的微转移,显著提高微转移的检出率。通过本研究证实MMP-2及CK19的高表达与宫颈癌的侵袭转移有关,可作为检测早期宫颈癌淋巴转移的生物学指标之一,指导临床治疗。      

Impact of multiple HPV infection on response to treatment and survival in patients receiving radical radiotherapy for cervical cancer

To obtain information on the incidence and the clinical significance of infection with various types of the human papillomavirus (HPV) in cancer of the uterine cervix, we retrospectively examined the HPV status of 106 patients who had received radical radiotherapy for cervical cancer stages IB to IIIB. DNA was extracted from formalin-fixed, paraffin-embedded biopsies and PCR was carried out to identify HPV types 16, 18, 31, 35, 33 and 45. To detect additional HPV types, consensus PCR products were cloned and sequenced. A catalyzed signal-amplified colorimetric in situ hybridization was carried out in 84 of 106 specimens as a positive control. Response to therapy, progression-free survival (PFS) and cervical cancer-specific survival (CCSS) were the statistical endpoints. Survival analysis was carried out using univariate and multivariate analysis (Cox regression). Ninety-six patients (90.6%) were HPV-positive and 42/96 (43.7%) were positive for multiple HPV types. Eight patients had persistent disease after radiotherapy. From these 8 patients, 7 were infected with multiple HPV types and only 1 patient had an infection with a single HPV type. After a median follow up period of 50 months, patients with multiple HPV infection had a significantly shorter PFS and CCSS compared to those with single HPV infection (24.8% and 34.9% vs. 64% and 60.8%, Log rank, p < 0.01 and 0.04). In multivariate analysis, the presence of multiple HPV types (RR 1.9), node status (RR 2.3), tumor size (RR 3.2) and histologic type (RR 4.8) were independent prognostic factors of CCSS. Our results demonstrate that the presence of multiple HPV types is associated with poor response and with reduced survival in cervical cancer patients who receive radiotherapy as the primary treatment.     

新疆维吾尔族妇女宫颈癌的HPV谱研究

目的：探讨人乳头状瘤病毒（human papilloma virus，HPV）各亚型在新疆维吾尔族宫颈癌患者及正常人群中的分布及其差异，分析维吾尔族官颈癌的HPV谱。方法：采用导流杂交基因芯片技术，对330例新疆维吾尔族宫颈癌患者及100例正常妇女官颈组织中的HPV21种亚型（包括13种高危亚型，5种低危亚型和3种中国人群常见亚型）进行检测。结果：（1）330例宫颈癌组织中HPV（包括单一感染及多重感染），阳性率为85．15％（281／300）；100例对照组中HPV阳性率为7．0％（7／100）。HPV16（94．31％），HPV18（5．34％），HPV68（3．91％），HPV45（2．49％），HPV58（2．49％），HPV39（2．14％），HPV31（1．07％）HPV56（1．07％），HPV59（0．36％）。比较两组HPV总感染率及HPV16的阳性率，两者差异有显著性（P〈0．0001）。（2）HPV21种亚型中12种被检测到，9种未检测到。HPV单一感染率及总感染率在宫颈鳞癌及其他类型的宫颈癌中的比例明显高于官颈腺癌（P〈0．05），而多重感染在各病理类型的宫颈癌中的比例无显著性（P〉0．05）。HPV的多重感染在Ⅰ期，Ⅱ期及Ⅲ期中的比例虽然有逐渐上升趋势，但统计学上无显著性的差异。结论：新疆维吾尔族宫颈癌患者及正常人群中以HPV16感染为主，其次为HPV18，HPV68等，HPV68可能是新疆维吾尔族较易感染的类型，体现了维吾尔族HPV感染类型的独特性。