子宫颈液基细胞学检查异常的涂片中人乳头状瘤病毒L1蛋白的表达及其意义

目的 探讨人乳头状瘤病毒(HPV)L1蛋白在官颈液基细胞学检查异常涂片中的表达及其意义.方法 选择2006年9月-2008年9月间,在中日友好医院就诊的官颈液基细胞学检查诊断为≥未明确诊断意义的不典型鳞状上皮细胞(ASCUS),且其第2代杂交捕获试验(HC-Ⅱ)榆测HPV DNA结果均为阳性,同时有组织病理学诊断的患者共274例.其中,宫颈液基细胞学检查诊断为ASCUS 105例、低度鳞状上皮内病变(LSIL)119例、不除外高度病变的不典型鳞状上皮细胞(ASC-H)9例、高度鳞状上皮内病变(HSIL)36例、官颈鳞癌5例;组织病理学检查(作为金标准)诊断为炎症96例、宫颈上皮内瘤变(CIN)Ⅰ 85例、CIN Ⅱ 55例、CIN Ⅲ 32例、官颈鳞癌6例.对此274例患者的官颈涂片,采用伞反应抗体的免疫细胞化学染色进行HPV L1蛋白的榆测,分析其对官颈病变进展的预测价值.结果 274例患者中,组织病理学检杏诊断为炎症的组织中HPV L1蛋白阳性表达率为69.8%(67/96),CIN Ⅰ为83.5%(71/85),CIN Ⅱ为41.8%(23/55),CIN Ⅲ为3.1%(1/32),宫颈鳞癌为0(0/6),除CIN Ⅲ与官颈鳞癌比较,差异无统计学意义(P>0.05)外,其他不同病变问比较,差异均有统计学意义(P<0.01);细胞学检查诊断为LSIL的细胞中HPV L1蛋白阳件表达率(75.6%,90/119)最高,其次为ASCUS细胞(63.8%,67/105)和HSIL+宫颈鳞癌细胞(9.8%,4/41),3者问比较,差异有统计学意义(P<0.01).71例未经治疗的ASCUS、LSIL患者中,55例HPV L1蛋白阳性表达者中无一例疾病进展,16例HPV L1蛋白阴性表达者疾病进展的发生率为19%(3/16),两者比较,差异有统计学意义(P<0.01).结论 HPV L1蛋白在宫颈液基细胞学检查异常涂片中的表达情况可以帮助了解宫颈的病变程度,预测宫颈病变的发展趋势,尤其对细胞学检查诊断为ASCUS和LSIL的患者可协助指导临床处理.     

宫颈CIN3的诊断与治疗——附301例病例分析

目的对子宫颈鳞状上皮高度病变（CIN3）患者进行回顾性分析,评估液基细胞学检查、高危型人乳头瘤病毒（HPV）检测、阴道镜下活检和冷刀锥切（CKC）诊断癌前病变的价值。方法回顾性分析2000年1月至2008年10月301例CIN3患者在北京大学人民医院妇科住院行CKC的的临床资料。210例患者在北京大学人民医院门诊行液基细胞学检查,91例在外院行液基细胞学检查。301例患者均经阴道镜下活检、病理学检查确诊为CIN3;229例行高危型HPV-DNA（HC2）检测。结果 301例患者液基细胞学检查结果：高度病变（HSIL）113例（37.54%）,低度病变（LSIL）76例（25.25%）,不典型增生（ASCUS）92例（30.56%）,正常20例（6.64%）。229例患者高危型HPV-DNA检测结果：阳性213例（93.01%）,RLU/CO平均值为548.2pg/ml;阴性16例（6.69%）。301例CKC病理检查结果：188例（62.46%）仍有CIN3病灶存在;9例（2.99%）锥切组织切缘阳性,进一步予以治疗;20例为早期浸润癌（6.64%）,再行子宫颈癌规范手术。结论对TCT、HPV检测阳性者行阴道镜检查及宫颈活检可提高宫颈病变的检出率;宫颈CKC能避免漏诊早期宫颈浸润癌,也是治疗CIN3的有效方法。     

高危型人乳头状瘤病毒DNA检测与细胞学联合检查对子宫颈癌前病变筛查的研究

目的评价高危型人乳头状瘤病毒(HPV)DNA检测联合宫颈细胞学检查对宫颈癌前病变筛查的效果。方法2003年1月至2004年6月,对广东省人民医院妇科门诊5210名妇女进行宫颈癌前病变筛查,采用第二代杂交捕获试验(HC-Ⅱ)检测高危型HPV DNA联合细胞学检查,同时进行阴道镜检查,并以宫颈活检的组织病理学结果为确诊标准。结果受检者平均年龄(34±9)岁,筛查并最后经病理诊断为HPV感染890例,宫颈上皮内瘤变(CIN)Ⅰ级83例,CINⅡ73例,CINⅢ80例,宫颈浸润癌54例,子宫内膜癌5例,阴道上皮内瘤样病变1例,宫颈结核1例。以组织病理学为确诊标准,高危型HPV DNA检测CINⅡ、Ⅲ的敏感度是92·22%,特异度是74·71%,阳性预测值5·19%,阴性预测值99·84%。宫颈细胞学筛查CINⅡ、Ⅲ,以未明确诊断意义的不典型鳞状上皮细胞(ASCUS)为分界点的敏感度、特异度、阳性预测值和阴性预测值分别是90·00%、80·34%、11·94%和99·63%;以低度鳞状上皮内病变(LSIL)为分界点的敏感度、特异度、阳性预测值和阴性预测值分别是70·13%、91·58%、11·11%和99·51%;以高度鳞状上皮内病变(HSIL)为分界点的敏感度、特异度、阳性预测值和阴性预测值分别是48·05%、98·46%、31·90%和99·21%。高危型HPV DNA检测联合细胞学检查筛查CINⅡ、Ⅲ的敏感度、特异度、阳性预测值和阴性预测值分别是98·70%、73·08%、5·21%和100·00%。高危型HPV DNA在不同宫颈病变中的阳性率分别是:宫颈癌85·2%(46/54),CINⅢ92·5%(74/80),CINⅡ86·3%(63/73)和CINⅠ45·8%(38/83)。结论高危型HPV DNA检测在宫颈癌前病变的筛查中有很高的敏感度和阴性预测值,高危型HPV DNA检测联合细胞学检查可使敏感度和阴性预测值有提高,但特异度未能提高。     

子宫颈上皮内瘤变筛查方法的综合评价

目的　对宫颈上皮内瘤变 (CIN)筛查方法即宫颈涂片自动检测系统 (papnetcytologycomputertechnology ,CCT)和新柏氏程控超薄细胞检测系统 (thinpreppaptest,TPT)两种细胞学检查方法进行综合评价。方法　对因细胞学检查异常而行阴道镜下多点活组织检查 (活检 )及病理检查的 374例患者的临床资料进行回顾性分析。结果　细胞学检查诊断为炎症者 9 1% ,低度鳞状上皮内瘤变(LSIL) 4 3 3% ,高度鳞状上皮内瘤变 (HSIL) 2 0 3% ,可疑癌 1 9% ;经阴道镜下多点活检及病理检查 ,诊断为炎症者增加到 5 3 5 % ,CINⅠ减少到 17 9% ,CINⅡ、CINⅢ、原位癌占 2 5 4 % ,可疑早期浸润癌和浸润癌增加到 3 2 %。 2 5 4 %的细胞学不能明确诊断意义的不典型鳞状上皮病变中 ,5 2 6 % (5 0 /95 )为炎症或未见异常 ,4 7 4 % (45 /95 )为CINⅠ以上的病变。 374例患者中 ,行CCT检查者 188例 ,TPT检查者 186例 ,两种细胞学检查结果分别与阴道镜检查结果相比 ,TPT的符合率显著高于CCT(P<0 0 1)。细胞学检查诊断为LSIL及以下病变的符合率 (79 7% )显著高于诊断为HSIL以及癌变者的符合率 (2 0 3% ) ,两者比较 ,差异有显著性 (P <0 0 1) ,而两种细胞学检查方法间无差别。人乳头状瘤病毒 (HPV)感染的发生率为 34 0 % ,阴道镜检查的     

Cervical intraepithelial neoplasia in adolescent women: incidence and treatment outcomes

OBJECTIVE: We sought to estimate the incidence of cervical intraepithelial neoplasia (CIN) and treatment outcomes in adolescents with abnormal cytology. METHODS: Adolescent women (ages 14-21 years) referred to colposcopy clinic for abnormal cytology from 1992 to 2004 were identified by computerized database. Only adolescents with biopsy-proven CIN were evaluated. Demographic and risk factor data were obtained from medical records. Referral cytology, histology on biopsy and loop electrosurgical excisional procedure (LEEP), and follow-up cytology were analyzed and compared. Statistical analysis was performed by chi(2) or Fisher exact test, Student t tests, and logistic regression. RESULTS: Of 1,678 adolescents, 517 had biopsy-proven CIN and follow-up. Seventy-seven patients were referred with atypical squamous cells of undetermined significance (ASCUS) cytology; 174 patients were referred with low-grade squamous intraepithelial lesions (LSIL), 258 with high-grade squamous intraepithelial lesions (HSIL) and eight with atypical glandular cells (AGC). The rate of CIN 2/3 in patients with ASCUS, LSIL, and HSIL was 35% (95% confidence interval 24-46%), 36% (29-43%), and 50% (44-56%), respectively. A total of 192 patients with biopsy-proven CIN 2/3 underwent a LEEP. No patients were diagnosed with cervical carcinoma. Fifty-five percent (95% confidence interval 48-62%) of patients had abnormal cytology on follow-up, suggesting recurrence or reinfection. CONCLUSION: Adolescents with abnormal cytology have a high incidence of CIN2/3 and high rates of abnormal cytology after LEEP. Cervical intraepithelial neoplasia 2/3 is common in adolescents with abnormal cytology, yet no cases of cancer were identified. Importantly, LEEP fails to meet its therapeutic goals given a high incidence of abnormal follow-up cytology and may represent overly aggressive therapy because the majority of human papillomavirus infections are transient with high regression rates. LEVEL OF EVIDENCE: III.     

Reporting of "LSIL with ASC-H" on cervicovaginal smears: is it a valid category to predict cases with HSIL follow-up?

Recently it has been shown that there is a 15-30% risk of associated cervical intraepithelial neoplasia (CIN 2-3 or greater) for a low-grade squamous intraepithelial lesion (LSIL) diagnosis. We tried to define a subgroup of "LSIL with atypical squamous cells of undetermined significance. High-grade squamous intraepithelial lesion (LASC-H)" in cervicovaginal screening which may aid in predicting the cases associated with high risk cannot be ruled out. In the years between 2001 and 2003 a total of 21,342 cervicovaginal smears were evaluated. The smears with pure LSIL and LASC-H diagnosis which had histologic follow-up were selected. The cases with diagnosis of LASC-H contained numerous typical cells of LSIL and only a few cells with features suggesting high-grade squamous intraepithelial lesion (HSIL). Eight (61%) of 13 cases with a diagnosis of LASC-H but three (11%) of 27 cases with a diagnosis of pure LSIL resulted in CIN 2-3 histology (p < 0.05). Diagnosis of LASC-H may be a valid diagnostic category in distinguishing patients with LSIL that would have HSIL in follow-up.     

Frequency of cervical intraepithelial neoplasia grade II or worse in women with a persistent low-grade squamous intraepithelial lesion seen by Papanicolaou smears

Purpose

We investigated the frequency of cervical intraepithelial neoplasia (CIN) grade II or worse in low-income Brazilian women with persistent low-grade squamous intraepithelial lesions (LSIL).

Methods

A retrospective review of medical records was performed for all patients who underwent a loop electrosurgical excision procedure (LEEP) with "see and treat" strategy for persistent LSIL seen on Papanicolaou (Pap) smears (persisting >12 months in at least two consecutive tests, over a 50-month period. We assessed the colposcopy and histopathology results at the time of the procedure and at follow-up, using Pap and histopathology.

Results

Of 106 women, 48 (45.3 %) had no dysplasia by histopathology, 18 (17.0 %) had CIN I, 29 (27.4 %) had CIN II and 10 (9.4 %) had CIN III. Among the patients with CIN, 38 (66.7 %) performed the follow-up. Of these, only 4 (10.5 %) were classified as follow-up (+), all had CIN I. Women with initial CIN I had 16.7 % (n = 2) recurrences; those with initial CIN II had 5.9 % (n = 1); and those with initial CIN III had 11.1 % (n = 1) (p > 0.05).

Conclusions

A very high proportion of the women with persistent LSIL had CIN II/III on post-LEEP histopathology. Recurrence rates were equal to than those that originally caused the patients to be subjected to LEEP (LSIL). The benefits of the "see and treat" protocol by LEEP for persistent LSIL outweigh the risk of overtreatment, principally in low-resource settings where poor patient compliance is expected, as in Brazil.     

Usefulness of human papilloma virus testing in the screening of cervical cancer precursor lesions: a retrospective study in 314 cases

OBJECTIVE: To assess the usefulness of human papilloma virus (HPV) typing for predicting pre-malignant and malignant cervical lesions. STUDY DESIGN: 314 women, who underwent colposcopy, biopsies and high and low-risk HPV typing after a confirmed abnormal routine Pap test were studied. HPV-DNAs were typed by using PCR technique. RESULTS: We found a significant increasing rate of high-risk-HPV by the increasing severity of histology, ranging from 40% in negative cases to 86.9% in those with CIN3 lesions. The positive predictive value of high-risk-HPV ranged from 13.3% in patients with atypical squamous cells of undetermined significance (ASCUS) to 29.4% in those with HSIL. By contrast, negative predictive value was 96% in patients with ASCUS, 97.2% in low-grade squamous intraepithelial lesions (LSIL), and 71.4% in high-grade squamous intraepithelial lesions (HSIL). Sensitivity and specificity for detecting CIN2 or CIN3 was 86.0% and 41.3%, respectively. CONCLUSIONS: The high negative predictive value of high-risk HPV testing suggests that HPV negativity could be used for predicting the absence of important cervical lesions, and therefore avoiding unnecessary colposcopy in ASCUS and LSIL cases.     

人端粒酶RNA基因检测在子宫颈病变筛查中的意义

目的 探讨人端粒酶RNA(hTERC)基因检测在宫颈病变筛查中的意义.方法 选择经宫颈液基细胞学检查为正常一高度鳞状上皮内瘤变(HSIL)的301例患者为研究对象,采用人乳头状瘤病毒(HPV)杂交捕获2代(HC2)方法检测其高危型HPV感染状况,病理学检查明确其病变性质,荧光原位杂交(visa)技术检测其hTERC基因异常扩增情况.以病理学结果为金标准,将FISH技术检测结果与液基细胞学和HC2方法检测结果进行比较.结果 301例患者中,宫颈液基细胞学检查为正常、不典型鳞状细胞(ASC)、低度鳞状上皮内瘤变(LSIL)与HSIL细胞中,hTERC基因异常扩增率分别为3.0%(6/203)、21.2%(14/66)、44.4%(8/18)和92.9%(13/14),两两比较,差异均有统计学意义(P<0.05～0.01).有病理检查结果的98例患者中,炎症或湿疣、宫颈上皮内瘤变(CIN)Ⅰ、CIN Ⅱ、CIN Ⅲ和浸润癌患者的hTERC基因异常扩增率分别为4.4%(2/45)、20.0%(4/20)、6/8、86.7%(13/15)和100.0%(10/10),炎症或湿疣、CIN Ⅰ细胞中hTERC基因异常扩增率明显低于其他病变(P<0.01).23例高级别CIN(即CINⅡ～Ⅲ)患者中,FISH技术检测为hTERC基因异常扩增阳性19例(82.6%,19/23),液基细胞学检查为HSIL者仅4例(17.4%,4/23),FISH技术检测筛出高级别CIN的敏感度明显高于液基细胞学检查(P<0.01).高危型HPV DNA感染率,CIN Ⅰ患者为75.0%,高级别CIN和浸润癌患者均为100.0%.hTERC基因异常扩增检出高级别CIN和浸润癌的敏感度分别为82.6%和100.0%,分别与高危型HPV DNA检测检出高级别CIN和浸润癌的敏感度(均为100.0%)比较,差异均无统计学意义(P>0.05);而特异度前者明显高于后者(分别为67.8%～73.5%和25.6%～27.7%,P<0.01).FISH技术检测结果显示,CIN Ⅰ细胞中hTERC基因异常扩增信号为2:3型者占84.9%,2:4型占15.1%,4:4型为0;CIN Ⅱ～Ⅲ细胞中异常扩增信号为2:3、2:4和4:4型者分别占44.6%、24.8%和17.8%,与CIN Ⅰ比较,2:3型比例明显下降(P<0.01),2:4型比例呈上升趋势(P>0.05),4:4型比例明显升高(P<0.01).结论 应用FISH技术检测hTERC基因异常扩增情况可辅助液基细胞学检查和HPV HC2方法诊断高级别CIN;且hTERC基因异常扩增信号为2:4和4:4型以上可能是进展为高级别CIN的预测指标.     

CIN in pregnancy: antepartum and postpartum cytology and histology

OBJECTIVE: To determine the rates of antepartum and postpartum cervical intraepithelial neoplasia (CIN) 2 or worse in pregnant women with abnormal cervical cytology. STUDY DESIGN: A prospective, cohort study of 283 pregnant women referred for colposcopy between 1992 and 1999 for the evaluation of abnormal Pap smears. In this analysis, the population was stratified by severity of referral cytology (atypical squamous cells of undetermined significance [ASCUS] or low grade squamous intraepithelial lesion [LSIL] versus high grade squamous intraepithelial lesion [HSIL] and atypical glandular cells of undetermined significance [AGUS]). RESULTS: Sixty-seven women (24%) had ASCUS, 147 (52%) LSIL, 67 (24%) HSIL and 2 (0.7%) AGUS. As compared to women with HSIL or AGUS, women with ASCUS or LSIL were less likely to undergo antepartum biopsy (relative risk [RR] .34, 95% CI .23-.51) and if biopsied, less likely to have CIN 2 or worse (OR .49, 95% CI .24-.99). Women with antepartum ASCUS or LSIL were less likely to have postpartum HSIL (OR .29, 95% CI, .17-.52) and tended to have fewer histologically severe biopsies as compared to women with antepartum HSIL (OR .55, 95% CI .31-1.05). CONCLUSION: Among those biopsied, pregnant women with mildly abnormal cytology (ASCUS or LSIL), as compared to pregnant women with HSIL, were less likely to have either antepartum or postpartum CIN 2 or worse.     

The colposcopic impression. Is it influenced by the colposcopist's knowledge of the findings on the referral Papanicolaou smear?

OBJECTIVE: To determine whether the colposcopic impression is influenced by the colposcopist's knowledge of the referral Papanicolaou smear. STUDY DESIGN: Using a community hospital database, the accuracy of the colposcopic impression (accuracy = proportion of women with histology greater than cervical intraepithelial neoplasia [CIN] 2 that have colposcopic impressions of greater than CIN 2) when referral smears were atypical squamous cells of uncertain significance (ASCUS), atypical glandular cells of uncertain significance (AGUS) or low grade squamous intraepithelial lesion (LSIL) was compared to that when smears showed high grade squamous intraepithelial lesion (HSIL) or cancer. The analysis was repeated with a screening study database in which colposcopic impression was assigned without knowledge of the Papanicolaou smear. Univariate and logistic regression analysis of the second database determined the relative importance of size and grade of lesion and Papanicolaou result to the accuracy of the colposcopic impression. RESULTS: In the community database, colposcopic accuracy was 60/510 (12%) when smears were ASCUS, AGUS or LSIL and 77/132 (58%) when smears were HSIL or cancer (P < .001); in the second database, it was 2/19 (11%) when smears subsequently were reported as negative, ASCUS, AGUS or LSIL and 33/65 (54%) when smears were HSIL or cancer (P < .005). An accurate colposcopic impression was seen in 5/39 (13%) women with one-quadrant lesions, 8/18 (44%) with two-quadrant lesions and 23/27 (85%) with three- or four-quadrant lesions (P < .005). None of 19 women with smears reported as negative, ASCUS, AGUS or LSIL had lesions involving three or four quadrants of the cervix, while 27/65 (42%) women with smears reported as HSIL or cancer had such lesions (P < .005). With logistic regression, the more quadrants of the cervix involved, the more accurate the colposcopic impression. Once controlled for lesion size, there was no improvement when worst histologic grade or Papanicolaou smear result was considered. CONCLUSION: Through lesions greater than CIN 2 were more often overlooked when referral smears were negative, ASCUS, AGUS or LSIL than when they were HSIL or cancer, the real reason that the lesions were not detected by colposcopy was that they were small.     

宫颈高级别病变“即诊即治”的可行性分析

目的回顾性分析宫颈病变的各项检查结果,探讨宫颈高度病变＂即诊即治＂价值。方法选取经LEEP治疗后病理结果为CIN2及CIN3 194例,对其资料进行回顾性分析,对比研究TCT、阴道镜拟诊、宫颈活组织检查结果。结果 TCT结果HSIL 38例（19.59%）,ASC-H 35例（18.04%）,LSIL 44例（22.68%）,ASC-US 66例（34.02%）,炎症11例（5.67%）。阴道镜拟诊HSIL 124例（63.92%）,宫颈活组织检查高级别病变185例（95.36%）。TCT为HSIL及炎症的患者,阴道镜拟诊和宫颈活组织检查高级别病变的检出率差异无统计学意义（P〉0.05）。TCT为其他结果的患者,高级别病变检出率差异有统计学意义（P〈0.05）。结论宫颈病变筛查以三阶梯法为主,对于TCT为HSIL,阴道镜拟诊仍HSIL的患者可以直接行LEEP术。     

Hypermethylation of two consecutive tumor suppressor genes, BLU and RASSF1A, located at 3p21.3 in cervical neoplasias

OBJECTIVES: Although initiated by human papillomavirus (HPV), cervical carcinogenesis demands other cofactors to shape its natural course. Epigenetic effects such as DNA methylation, are considered to contribute to carcinogenesis process. METHODS: The methylation status of BLU and RASSF1A, as well as the HPV infection status, were assessed in a full spectrum of cervical neoplasia, including 45 low-grade squamous intraepithelial lesions (LSIL), 63 high-grade squamous intraepithelial lesions (HSIL), 107 squamous cell carcinomas (SCC), 23 adenocarcinomas (AC), and 44 normal control tissues. RESULTS: The BLU was methylated in 76.9% of SCC, 57.4% of HSIL, 20.0% of LSIL and 12.5% of normal tissues (P<0.001). The RASSF1A was methylated in 15% of SCC, 17.5% of HSIL, but not in LSIL or normal tissues (P<0.001). In AC, 43.5% of patients showed BLU methylation and 26.1% RASSF1A methylation, significantly higher than the corresponding control frequencies of 12.5% (P=0.005) and 0% (P=0.001), respectively. There was an insignificant trend toward loss of BLU methylation with advancing clinical stages of SCC (84.8%, 67.7%, and 63.6% in stages I, II, and III/IV, respectively; P=0.08). Patients with LSIL infected with high-risk HPV showed a higher rate of BLU methylation than those without HPV (38.8% vs 9.1%, respectively; P=0.057). The methylation of RASSF1A was inversely related to HPV infection in patients with HSIL/SCC (P=0.003). CONCLUSIONS: These results suggest that the methylation of BLU and RASSF1A genes is associated with cervical carcinogenesis, which could be clinically important in the future molecular screening of cervical neoplasia.     

PAX1甲基化检测对细胞学异常(ASCUS、LSIL和ASC-H)患者的分流作用

目的:探讨配对盒基因家族1(PAX1)甲基化检测在细胞学异常女性中的分流作用.方法:选取212例宫颈细胞学(TCT)诊断为意义未明的不典型鳞状细胞(AS-CUS)、不除外高度鳞状上皮内病变(ASC-H)、低度鳞状上皮内病变(LSIL)的病例进行PAX1甲基化检测和高危HPV检测,进行阴道镜检查和宫颈活检.以组织病理结果...     

应用TERC基因检测子宫颈病变的临床研究

目的 探讨TERC基因作为宫颈病变筛查指标的临床意义.方法 选取在北京大学人民医院和北京大学深圳医院妇科门诊进行官颈病变筛杳的715例患者为研究对象,对其宫颈脱落细胞行液基细胞学榆查,并行第2代杂交捕获试验(HC-II)检测高危型人乳头状瘤病毒(HPV),必要时行阴道镜活榆及病理检查.荧光原位杂交(FISH)技术检测细胞内TERC基因的异常扩增情况.以病理检查结果为"金标准",将TERC基因异常扩增结果与液基细胞学检查和高危型HPV检测结果进行比较.结果 在宫颈液基细胞学检查结果为正常、未明确诊断意义的不典型鳞状上皮细胞(ASCUS)、不除外高度病变的不典型鳞状上皮细胞(ASC-H)、低度鳞状上皮内病变(LSIL)、高度鳞状上皮内病变(HSIL)和不典型腺细胞(AGC)中,TERC基因异常扩增率分别为5.8%、22.2%、30.8%、27.8%、86.4%和1/1,正常、ASCUS、ASC-H和LSIL者均明显低于HSIL者(P<0.01).在病理检查结果为官颈上皮内瘤变(CIN)I、CIN Ⅱ～Ⅲ和浸润癌中,TERC基冈异常扩增率分别为9.3%、77.8%和96.7%,CIN I明显低于后两者(P<0.01).HPV检测结果为阳性患者的TERC基因扩增阳性率明显高于HPV阴性者(分别为33.5%和5.2%,P<0.01).TERC基因异常扩增诊断CIN Ⅱ及以上病变的敏感度为81.88%,明显高于细胞学检查的36.96%(P<0.01);其特异度(93.32%)明显高于HPV 检测的33.93%(P<0.01);阳性预测值(81.29%)与细胞学检查(86.44%)相似(P>0.05);而阴性预测值(93.56%)低于HPV检测(97.06%,P<0.05).结论 随着宫颈病变程度的加重,TERC基因异常扩增率增加,且其扩增与HPV感染有关.应用FISH技术检测TERC基因异常扩增作为分子遗传学指标,可以辅助细胞学榆查和HPV检测,协助筛出CIN Ⅱ及以上的高度病变和宫颈癌.     

Is colposcopy needed following laser ablation for dysplasia?

AIMS: To evaluate the effectiveness of cytology and colposcopy in the follow up of women treated by laser CO(2) ablation for cervical intraepithelial neoplasia (CIN). METHODS: A retrospective analysis of 1784 patients with CIN treated with laser CO(2) ablation from 1998 to 2003 at the Royal Women's Hospital, Melbourne. Data were collected prospectively in a computerised colposcopy database utilised in the Dysplasia Unit. RESULTS: There was equal distribution in the study population treated for low-grade intraepithelial neoplasia (LSIL) and high-grade intraepithelial neoplasia (HSIL), with no significant age difference in both groups (mean 27.6 years). The success rate of treatment of LSIL (94%) was similar to that of HSIL (92%). Fifty-seven per cent of all failures occurred within the first year of treatment. Colposcopy was more sensitive in detecting intraepithelial neoplasia (SIL) than cytology, whereas cytology was more specific. No case of cancer was diagnosed on follow up. CONCLUSIONS: CO(2) laser ablation was equally effective in treating different grades of CIN. There is a continuing incidence of recurrent CIN, even up to five years after initial treatment, which suggests that it is necessary for patients to adhere to long-term follow up. The combination of cytology and colposcopic assessment is essential for surveillance of SIL in the initial two years after treatment.     

液基细胞学联合P16INK4a和cyclin E用于诊断宫颈上皮内瘤变的意义

目的:探讨液基细胞学(liquid-based cytology test,LCT)联合p16INK4A和cyclin E用于诊断宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)的价值。方法:225例宫颈病变患者,其中宫颈鳞状细胞癌(squamous cell carcinomas,SCC)56例,高度鳞状上皮内病变(high grade squamous intraepithelial lesions,HSIL)41例,低度鳞状上皮内病变(low grade squamous intraepithelial lesions,LSIL)76例,不典型鳞状细胞(atypical squamous cell lesions,ASC)32例,正常范围(within normal limits,WNL)20例。采用免疫组化法检测p16INK4A和cyclin E的表达。比较单纯LCT及LCT联合p16INK4A和cyclin E的病理诊断符合率。结果:单纯LCT病理诊断符合率为LSIL 52.08%,HSIL 77.14%,SCC 98.21%;LCT联合p16INK4A和cyclin E的病理诊断符合率为LSIL 87.50%,HSIL97.14%,SCC 100%,差异有统计学意义(P(0.05)。32例ASC的LCT联合p16INK4A和cyclin E的阳性病理诊断符合率为85.71%,与单纯LCT的差异有统计学意义(P(0.05)。结论:LCT联合P16INK4a和cyclin E可用于筛查CIN,尤其对ASC的确诊,较单纯LCT有更高的病理诊断符合率,可以提高CIN的诊断准确性。     

Coexistence of Low and High Grade Squamous Intraepithelial Lesions of the Cervix: Morphologic Progression or Multiple Papillomaviruses?

Background.The diagnosis of both low (LSIL) and high (HSIL) grade squamous intraepithelial lesions in the same cervical specimen may reflect classification variation, morphologic progressionin situ,and, conceivably, different HPV infections. We addressed these possibilities in cervical specimens previously diagnosed as containing both LSIL (condyloma/CIN1) and HSIL (CIN2/3).Methods.All cases with a histologic diagnosis of LSIL and HSIL from 1994–1996 were reviewed. On review, lesions were scored as (1) no significant variation in lesion grade (classification discrepancies) and showing a (2) one (CIN1–2) or (3) two (CIN1–3) grade shift in the same case. In cases in which a one or two grade shift was confirmed, low (CIN1) and high (CIN2–3) grade foci were microdissected and extracted DNA analyzed for HPV by PCR and RFLP analysis.Results.Of 98 cases available for review, 58 (59%) did not exhibit significant variation in grade (classification discrepancy), and 40 (41%) showed a one (25) or two (15) grade shift. Of the latter group both LSIL and HSIL foci were HPV(+) in 26 (65.0%). The same HPV was present in both LSIL and HSIL foci in 15/15 lesions with a one grade shift (CIN1–2). In contrast, a significantly higher proportion of lesions with a two grade shift (CIN1–3) contained two different HPV types (4/11 vs 0/15;P= 0.01). Combinations of HPVs in the low/high grade foci, respectively, included HPV 11/16 (1), 11/16 + 18 (1), and HPV39/16 (2).Conclusions.Lesions containing LSIL and HSIL which span two grades (CIN1 and CIN2) most likely represent morphologic progression in a single infection. Lesions containing CIN1 and CIN 3 may be attributed to both lesion progression and two coincident infections; the latter sometimes present in the same histologic section. The latter phenomenon has implications for both the diagnosis of CIN and interpretation of “morphologic progression” from very low to high grade in the same case.     

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.     

Contribution of human papillomavirus testing by hybrid capture in the triage of women with repeated abnormal pap smears before colposcopy referral

OBJECTIVE: The purpose of this work was to evaluate the ability of testing for high-risk human papillomavirus (HPV) types using the hybrid capture technique to predict the presence of cervical intraepithelial neoplasia (CIN) II,III in patients with repeated atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LGSIL) on Pap smears. METHODS: Hybrid capture testing and tissue biopsy were performed on 503 consecutive women with ASCUS or LGSIL on repeated Pap smears who were referred for colposcopy. RESULTS: A highly significant association (P < 0.0001) was found between a positive test for high-risk HPV types and CIN II,III, with an 87.0% positive predictive value and a 95.7% negative predictive value. In 226 women with ASCUS on repeated Pap smears, a positive test for high-risk HPV types had a 85.7% sensitivity and a 97% specificity for CIN II,III. In 277 patients with LGSIL on repeated Pap smears, a positive test for high-risk HPV types had an 88.2% sensitivity and a 94.7% specificity for CIN I,II. Reserving colposcopy examination for women who were positive for high-risk HPV types would have reduced the number of referrals for colposcopy to 24.6% and maintained a sensitivity of 87.0% for CIN II,III. CONCLUSIONS: A positive hybrid capture test for high-risk HPV types was highly sensitive and specific for the presence of CIN II,III in patients with ASCUS and LGSIL on repeated Pap smears. We believe that improved methodology will eventually enable more selective colposcopy referrals without affecting patient safety among these women.