宫颈上皮内瘤变与人类白细胞抗原及人乳头瘤病毒感染相关性的研究

目的:探讨宫颈上皮内瘤变(CIN)与人乳头瘤病毒(HPV)感染及人类白细胞抗原(HLA)的相关性。方法:选取宫颈活检组织病理学诊断为CINⅠ42例、CINⅡ40例、CINⅢ29例、宫颈湿疣40例、慢性宫颈炎90例,从液基薄片检测剩余的保存液中提取宫颈脱落细胞学的基因组DNA,采用PCR方法及HLA试剂盒进行HPV16/18及HLA分型检测。结果:HPV16/18检出率CINⅠ组为21.4%,CINⅡ组为47.5%,CINⅢ组为55.2%,湿疣组为32.5%,宫颈炎组为1.1%。HLA分型表明,DR15(2)、DQ6(1)、DQ4在CIN组中阳性率分别为37.0%、44.0%、12.0%,明显高于宫颈炎组的17.5%、18.8%、3.8%(P<0.05),并且DR4阳性率随着CIN级别增高而增高(CINⅠ5.6%,CINⅡ13.9%、CINⅢ28.6%)。结论:HPV16/18感染和HLA分型与CIN及其分级密切相关,提示HLA在宫颈癌的发生、发展中可能起一定的作用。     

Risk factors for human papillomavirus persistence among women undergoing cold-knife conization for treatment of high-grade cervical intraepithelial neoplasia

Objective

To investigate the risk factors potentially associated with high-risk human papillomavirus (HPV) persistence in women undergoing cold-knife conization (CKC) for treatment of high-grade cervical intraepithelial neoplasia (CIN).

Methods

Medical records of women who underwent CKC for treatment of CIN 2/3 between 2007 and 2012 at a tertiary hospital in Ankara, Turkey, were retrospectively analyzed. Cases involving persistent HPV infection after 1 year of follow-up were identified. Using univariate and multivariate analyses, the impact of various factors such as patient age, menopausal status, parity, high-risk HPV type, excised cone dimensions (width, height, and depth), and surgical margin status on high-risk HPV persistence was assessed.

Results

A total of 292 women underwent CKC for treatment of CIN 2/3 within the study period. After women with a subsequent diagnosis of cervical cancer, subsequent total hysterectomy, and inadequate follow-up data were eliminated, 113 women were eligible for final analysis. High-risk HPV persistence was detected in 24 (21.2%) women, and multivariate analysis revealed that patient age and cone depth were significant independent predictors (P < 0.05).

Conclusion

High-risk HPV persistence may be encountered after CKC procedures. It is important to evaluate persistent HPV infections after treatment because affected women are at increased risk for disease persistence, recurrence, and progression.     

人乳头瘤病毒亚型与宫颈上皮内瘤变的相关性

目的探讨人乳头瘤病毒(HPV)各亚型感染或多亚型感染与宫颈上皮内瘤变(CIN)的相关性。方法 2007年11月至2008年4月在天津医科大学总医院采用PCR扩增、基因芯片探针杂交分型检测法检测98例CIN患者的HPV亚型。以35岁为界将98例CIN患者分为两组,年龄≤35岁者为A组(43例);年龄>35岁者为B组(55例)。结果 98例CIN中HPV阳性率,CINⅠ为72.41%(21/29),CINⅡ为75%(27/36),CINⅢ为96.97%(32/33)。HPV单重感染率在CINⅠ、CINⅡ和CINⅢ中分别为41.38%(12/29),44.44%(16/36)和57.58%(19/33);HPV双重感染率在CINⅠ、CINⅡ和CINⅢ中分别为27.59%(8/29),19.44%(7/36)和27.27%(9/33);HPV多重感染率在CINⅠ、CINⅡ和CINⅢ中分别为3.45%(1/29),11.11%(4/36)和12.12%(4/33)。CINⅠ中主要为低危型HPV感染,CINⅢ中以HPV16为主导感染亚型。AB两组HPV16感染率分别为20.93%(9/43),40%(22/55),差异具...     

宫颈癌及上皮内瘤变人乳头瘤病毒基因型的检测

目的:了解宫颈癌及上皮内瘤变人乳头瘤病毒(HPV)的感染率及其基因型的分布。方法:用PCR-RFLP法检测239例宫颈癌及上皮内瘤变患者HPV感染并进行分型。先用PGMY09/11共同引物扩增生殖道粘膜型HPV L1区的高度保守区,然后联合使用RsaⅠ、MseⅠ、PstⅠ和HaeⅢ4个限制性内切酶对阳性PCR产物进行酶切,利用不同的酶切片段鉴定HPV的基因型。结果:在239例宫颈癌及上皮内瘤变患者中共检出205例(85·8%)HPV感染,其中宫颈上皮内瘤变Ⅰ级(CINⅠ)、宫颈上皮内瘤变Ⅱ~Ⅲ级(CINⅡ~Ⅲ)和宫颈癌中HPV感染率分别是66·7%,89·9%和98·3%,差异有统计学意义(P<0·001)。在宫颈癌及上皮内瘤变中共检出22型HPV,其中主要基因型及其感染率分别是HPV16(45·6%)、58(12·1%)和52(6·3%)。结论:宫颈癌及上皮内瘤变中HPV感染的基因型至少可达22型,其中以HPV16、58和52为最常见。     

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。     

Human papillomavirus testing improves the accuracy of colposcopy in detection of cervical intraepithelial neoplasia

To assess the performance of human papillomavirus (HPV) testing and colposcopy in detection of cervical pathology. A series of 389 women referred for colposcopy due to an abnormal Pap smear had cervical swabs analyzed for oncogenic (high-risk [HR]) HPV types using Hybrid Capture II (HC2) assay. Loop electrical excision procedure cone biopsy (88%) or colposcopic biopsy (11%) was used as the gold standard. Of the atypical squamous cells of undetermined significance (ASCUS) smears, 48% were positive for HR HPV, as compared to 76.3% of low-grade squamous intraepithelial lesions (LSIL) smears. HR HPV was detected in 66.7% and 90% of patients with cervical intraepithelial neoplasia (CIN) 1 and CIN2 (or higher), respectively. The sensitivity of the Pap smear using an ASCUS threshold in detecting high-grade CIN was 94.5% (95% confidence intervals (CI): 91-97%) and that of colposcopy 98.5% (95% CI: 95-99%). The respective specificities were 30% (95% CI: 17-28%) and 35.6% (CI: 29-42%). HC2 test had comparable sensitivity, 90% (95% CI: 85-93%), but higher specificity, 54.3% (95% CI: 47-61%). Combining HC2 test with Pap increased specificity, 66.7% and 41.3% for ASCUS and LSIL cutoff, respectively. The minor-abnormality threshold together with HC2 increased specificity of colposcopy with no changes in sensitivity. High viral load (>100 relative light unit/positive control) was associated with significant disease. HPV DNA testing improves the accuracy of colposcopy in the detection of high-grade CIN in women with ASCUS or LSIL smears.     

The relationship between human papillomavirus infection and cervical intraepithelial neoplasia in Turkish women

To compare the prevalence of cervical human papillomavirus (HPV) infection in Turkish women with normal Papanicolaou (Pap) smear and cervical intraepithelial neoplasia (CIN). In between March 2002 and November 2005, the study was designed as case-control study. Cytologic abnormalities in Pap smears were classified according to the Bethesda System (2001). Identification of the presence of HPV was carried out by the Hybrid Capture II test for all patients. To compare the groups, Chi-square test was used. A total of 1353 reproductive aged women were screened. Of them, 1344 (99.3%) had normal or class I Pap smear. Remaining nine cases (0.7%) had CIN at several degrees (five CIN I, three CIN II, and one carcinoma in situ). While all these nine cases with cervical pathologies had HPV, only 20 cases from the other group (1.5%) had HPV (chi(2) 466.1; P = 0.0001). This is the first study of the evaluation of the association between HPV and preinvasive cervical lesions in Turkish population. In spite of low general frequency (2.1%) of cervical HPV colonization in this population, a strong correlation was found between HPV and CIN.     

乌鲁木齐市维吾尔族和汉族高度子宫颈上皮内瘤变中人乳头瘤病毒亚型临床分析

目的探讨高度子宫颈上皮内瘤变（CIN）中人乳头瘤病毒（HPV）亚型的感染状况。方法选择2010年1月至2013年1月新疆医科大学第一附属医院经病理证实的乌鲁木齐市高度CIN患者387例,采用基因芯片技术检测其宫颈组织中的HPV亚型。结果387例高度CIN患者HPV感染率为84．50％（327／387）,其中维吾尔族（简称维族）为89．19％（132／148）,汉族为81．59％（195／239）,两者比较,差异无统计学意义（P〉0．05）。CIN2组与CIN3组HPV感染率分别为79．21％（160／202）和90．27％（167／185）,两组比较,差异有统计学意义（P〈0．05）。其中,CIN2组患者维族与汉族HPV感染率分别为82．05％（64／78）和77．42％（96／124）,CIN3组患者分别为97．14％（68／70）和86．09％（99／115）,两组比较,差异均无统计学意义（P〉0．05）。在387例高度CIN患者中,汉族前四位HPV感染亚型为HPV16,52,18,58型;维族前四位HPV感染亚型为HPV16,18,56,58型;其中HPV16型（53．75％,208／387）是维族和汉族共同的高危HPV亚型,其次为HPV18型（7．75％,30／387）和HPV58型（6．20％,24／387）。CIN2组和CIN3组患者HPV多重感染率分别为22．28％（45／202）和23．78％（44／185）,两组比较,差异无统计学意义（P〉0．05）。结论乌鲁木齐市维族女性HPV感染率与汉族相似,均随CIN的加重,HPV感染率升高;乌鲁木齐市维族和汉族妇女感染HPV亚型大同小异,HPV16型为感染率最高的共同高危型。     

Oral contraceptives and clinical recurrence of human papillomavirus lesions and cervical intraepithelial neoplasia following treatment.

OBJECTIVE: To evaluate the effect of oral contraceptive use on the recurrence rate of human papillomavirus (HPV) lesions and cervical intraepithelial neoplasia (CIN) following ablative or excisional procedures in a long-term follow-up. METHOD: The study was conducted with 650 oral contraceptive users presenting with HPV lesions and/or CIN, and 670 women who had these lesions but did not use oral contraceptives acted as controls. The participants underwent cytologic evaluations, colposcopy, and direct biopsy, followed by either ablative treatment by laser carbon dioxide vaporization or excision by a loop electrosurgical excision procedure or cold knife conization. They were then followed up for a minimum of 5 years. RESULTS: The recurrence rates did not differ statistically between the case and control groups. CONCLUSION: Oral contraceptive use was not found to increase the recurrence rate of HPV lesions and/or CIN after ablative or surgical treatment.     

Value of human papillomavirus testing after conization by loop electrosurgical excision for high-grade squamous intraepithelial lesions

OBJECTIVE: The aim of the study was to evaluate human papillomavirus (HPV) testing during the follow-up of patients after conization by loop electrosurgical excision for high-grade squamous intraepithelial lesion. METHODS: A prospective study was conducted on 205 patients who underwent conization for high-grade squamous intraepithelial lesion (CIN 2 or 3). Loop electrosurgical excision procedure (LEEP) was used in all cases. High-risk HPV testing was realized by the Hybrid Capture II system before and 3 months after conization. RESULTS: Of the 205 patients, 193 (94.1%) were positive for the HPV test before conization. Seventy-one were HPV positive after conization (34.6%). The margins were positive in 36.1%. Residual disease was observed in 27 cases (13.2%). Four patients (2%) developed a recurrence after a mean follow-up of 18.1 months (+/-12). There was no correlation between pretreatment HPV testing and the residual disease or recurrence. Patients with positive margins were significantly more likely to have residual disease than those with negative margins (P < 0.0001). Residual disease was more likely to occur when the posttreatment HPV test was positive (P < 10(-7)). All recurrences were observed in patients with a positive posttreatment HPV test (P < 0.05). Residual disease and recurrence were correctly predicted with a sensitivity of 81 and 100%, respectively, and a negative predictive value of 96 and 100%. CONCLUSION: Posttreatment HPV testing could be useful in the follow-up of patients after conization. In case of negative posttreatment HPV testing, the frequency of follow-up could be reduced, particularly in those patients with free margins.     

人乳头状瘤病毒感染的宫颈上皮内肿瘤和宫颈鳞状细胞癌中的间期细胞遗传学分析

目的探讨人乳头状瘤病毒（HPV）感染的宫颈上皮内肿瘤（CIN）和宫颈鳞状细胞癌中的间期细胞遗传学改变。方法对HPV感染的9例CIN（其中CINⅠ2例、CINⅡ3例、CINⅢ4例）和4例宫颈鳞状细胞癌的石蜡包埋组织，应用组织切片间期细胞核原位杂交技术检测染色体11、16、17和X的数目异常，3例正常宫颈鳞状上皮作为对照。结果除2例CINⅠ的患者中被检染色体无异常外，其余11例（包括3例CINⅡ，4例CINⅢ以及4例宫颈浸润性鳞状细胞癌）均出现1条或多条被检测染色体的异常，其中4例分别发现了染色体11、17和X单体型。结论HPV16感染与11、16、17及X号染色体数目异常有关，而HPV DNA与宿主细胞染色体整合可能导致染色体的单体型出现。     

Is human papillomavirus testing an effective triage method for detection of high-grade (grade 2 or 3) cervical intraepithelial neoplasia?

OBJECTIVE: Our purpose was to assess the usefulness of the polymerase chain reaction assay for detection of human papillomavirus infection for prognostic value in the triage strategies for high-grade (grade 2 or 3) cervical intraepithelial neoplasia in women referred for colposcopy after abnormal Papanicolaou smears. STUDY DESIGN: A total of 1007 women referred to a colposcopic clinic providing care for an indigent population were studied. Four hundred fifty-four women were referred after two Papanicolaou smears reported as atypical squamous cells of undetermined significance or low grade-squamous cervical intraepithelial lesion, and 553 were referred after a single smear reported as high-grade squamous intraepithelial lesion. All women had a cervical smear, colposcopy-directed biopsy, and endocervical curettage performed. A sample for human papillomavirus deoxyribonucleic acid detection by polymerase chain reaction was obtained. RESULTS: High-risk human papillomavirus types were detected in 463 (46%) of 1007 women studied. There was a significant increase of the frequency of high-risk human papillomavirus by the increasing severity of biopsy findings ranging from 32.7% in women without cervical intraepithelial neoplasia on biopsy to 60% in women having grade 2 or 3 on the biopsy specimen. Women having a negative Papanicolaou smear found to have high-risk human papillomavirus deoxyribonucleic acid at the time of colposcopy had a significantly higher rate of grade 2 or 3 cervical intraepithelial neoplasia on the biopsy specimen than did women without high-risk human papillomavirus. There was no such difference observed in women with a cytologic finding of low- or high-grade squamous intraepithelial lesions at the time of colposcopy. The polymerase chain reaction assay appears to be more sensitive than the commercial human papillomavirus profile test. The positive predictive value for grade 2 or 3 cervical intraepithelial neoplasia of both tests was similar (21.7% and 22.8%, respectively). CONCLUSION: The human papillomavirus is associated with high-grade cervical intraepithelial neoplasia, but the screening for human papillomavirus deoxyribonucleic acid does not have prognostic value in women reported as having atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesions on two precolposcopy Papanicolaou smears. (Am J Obstet Gynecol 1998;178:1235-44.)     

Human papillomavirus DNA and genotypes: prognostic factors for progression of cervical intraepithelial neoplasia

A retrospective study of 227 patients presenting with abnormal cervical cytology was conducted to investigate the relationship between human papillomavirus (HPV) and progression of untreated cervical intraepithelial neoplasia (CIN) lesions. All patients had colposcopically directed biopsies for histologic diagnosis. The patients were followed cytologically and colposcopically for a mean of 19 months (range 6–42 months). Progression of a cervical lesion was defined as progression to a higher CIN grade confirmed histologically by directed biopsy. HPV DNA detection was done on material remaining from the cervical swabs by the general primer polymerase chain reaction (PCR) and type-specific PCR method, which made the detection of HPV types 6, 11, 16, 18, 31, 33 and not yet sequenced DNA types (X) possible. The presence of HPV DNA increased with the severity of the lesion ( P < 0.001). In CIN III, a 100% HPV DNA prevalence was found, with HPV type 16 being the most prevalent type in 75%. Progression was significantly related to the presence of HPV DNA, in particular HPV type 16. The percentage of progressive disease was 21% in the case of HPV DNA positive lesions ( n = 130) and 29% in the presence of HPV type 16, whereas HPV DNA negative lesions ( n = 97) showed no progression. The detection of HPV DNA and HPV genotype can be used to identify patients with high-risk cervical lesions, since the presence of HPV DNA and genotype 16 in particular are closely related to CIN progression.     

宫颈上皮内瘤样病变临床诊断方法的分析

目的　探讨宫颈细胞学、阴道镜和宫颈活检联合检测对宫颈病变的诊断价值。方法　对宫颈细胞学异常 ,进行阴道镜检查及镜下多点活组织病理检查 195例患者的临床资料进行回顾性分析。结果　电脑辅助细胞学检测系统 (CCT)检查共 195例。未明确诊断意义的不典型磷状上皮细胞 (ASCUS) 90例中 ,宫颈活检病理为炎症 2 6例 (30 % ) ;CIN 6 3例 (70 % ) ,其中 ,CINⅠ 5 2例 (5 7 78% ) ,合并人乳头状瘤病毒 (HPV)感染14例 (15 5 6 % ) ;CINⅡ 6例 (6 6 7% ) ;宫颈上皮内瘤样病变 (CIN)Ⅲ 5例 (5 5 6 % )。细胞学诊断低度磷状上皮内瘤变 (LSIL) 71例 ,其中 17例 (2 3 94 % )为炎症 ,符合低度病变为 4 5例 (6 3 38% ) ,高度病变为 9例(12 6 8% ) ,LSIL合并HPV感染 2 4例 (33 8% ) ,病理检查合并HPV感染 2 4例 (33 8% )。细胞学诊断高度磷状上皮内瘤变 (HSIL) 2 8例 ,其中低度病变为 8例 (2 8 5 7% ) ,符合高度病变为 18例 (5 7 14 % )。微小浸润癌 1例(3 5 7% )。结论　细胞学筛查异常者 ,应结合阴道镜下多点活检进一步诊断 ,有利于提高CIN的检出率。有性生活的妇女应定期进行细胞学筛查或阴道镜检查     

LEEP治疗宫颈上皮内瘤变后高危型HPV的变化及意义

目的:探讨各级别宫颈上皮内瘤变(CIN)经宫颈环切术(LEEP)治疗前后高危型人乳头瘤病毒(HR-HPV)的变化规律及临床意义。方法:各级别CIN且HR-HPV阳性患者155例,行LEEP术后6个月再次行膜式液基细胞学检查(TCT)并测定HR-HPV负荷量。结果:(1)CINⅠ、CINⅡ、CINⅢ病变HR-HPV负荷量(RLU/CO)分别为333.23±911.83,303.88±795.30及220.72±680.92,三者差异无统计学意义(P=0.6868);(2)术后6个月HPV总转阴率为62.58%(97/155)。术前HPV负荷量≤300者术后转阴率为71.60%(58/81),300者转阴率为52.70%(39/74),差异有统计学意义(P=0.0294)。并且术后病灶残留与术前高病毒负荷量相关。HPV清除率与年龄及病变程度无相关性;(3)术后6个月HPV负荷量≥10的患者中43.75%(14/32)的患者仍存在不同程度的CIN,而HPV10的患者中只有0.81%(1/123)的患者存在CIN,以10为阈值判断病灶残留的敏感性达93.33%,特异性达87.14%。结论:(1)HPV负荷量高低与病变程度无关,但与术后病毒清除相关;(2)在切缘阴性的前提下,若术前高病毒负荷量,发生病灶残留的风险增高;(3)术后6月宫颈病变的转归与同期检测的病毒负荷量相关。     

宫颈冷刀锥切治疗宫颈上皮内瘤样病变Ⅲ级的评价

目的 探讨阴道镜下多点活检与宫颈冷刀锥切对于宫颈上皮内瘤样病变Ⅲ级（CINⅢ）病理诊断的符合情况。方法 1995—2005年间对北京大学人民医院92例阴道镜下多点活检病理诊断为CINⅢ的患者进行宫颈冷刀锥切治疗，比较阴道镜下多点活检与宫颈冷刀锥切的病理结果之间的差异。结果 92例中有52例多点活检与冷刀锥切的病理结果一致，符合率为56．5％，40例多点活检与冷刀锥切的结果不同，其中11例多点活检诊断为CINⅡ／Ⅲ，而冷刀锥切诊断为微小浸润癌。结论 宫颈锥切是宫颈上皮内瘤样病变的一种重要诊断与治疗方法。阴道镜下多点活检病理提示宫颈上皮内瘤样病变Ⅲ级并伴随腺体受累可能是存在宫颈浸润癌的一个高危因素。人乳头瘤病毒（HPV）感染与宫颈病变有关，但未发现HPV高危型检测数值高低与患者病理级别之间的联系。