Trimodal spectroscopy for the detection and characterization of cervical precancers in vivo

OBJECTIVE: The objective of this study was to assess the potential of 3 spectroscopic techniques (intrinsic fluorescence, diffuse reflectance, and light scattering) individually and in combination (trimodal spectroscopy) for the detection of cervical squamous intraepithelial lesions. STUDY DESIGN: The study was conducted with 44 patients who underwent colposcopy for the evaluation of an abnormal Papanicolaou smear. Fluorescence and reflectance spectra were collected from colposcopically normal and abnormal sites and analyzed to extract quantitative information about tissue biochemistry and morphologic condition. This information was compared with histopathologic classification, and diagnostic algorithms were developed and validated with the use of logistic regression and cross-validation. RESULTS: Diagnostically significant differences exist in the composition of fluorescing biochemicals, the scattering properties, and the epithelial cell nuclear morphology of cervical squamous intraepithelial lesions and non-squamous intraepithelial lesions. Trimodal spectroscopy is a superior tool for the detection of cervical squamous intraepithelial lesions than any 1 of the techniques alone. CONCLUSION: Trimodal spectroscopy has the potential to improve the in vivo detection of precancerous cervical changes.     

子宫颈红区靶向活检在子宫颈病变诊断中的价值

目的:探讨阴道镜下在子宫颈血液循环丰富的红区靶向连续活检识别子宫颈癌前病变及子宫颈癌的价值.方法:收集2019年10月至2020年1月在北京大学第一医院妇产科行阴道镜检查并依据R-way阴道镜诊断术语进行阴道镜拟诊和定位活检的202例病例,统计分析在红区获取的536块活检组织的定位、病理组织分布情况及阴道镜未见异常时细...     

Laparoscopic photodynamic diagnosis of ovarian cancer using 5-aminolevulinic acid in a rat model

OBJECTIVE: The objective of this study was to determine the efficacy and sensitivity of laparoscopic photodynamic diagnosis to detect 5-aminolevulinic acid (ALA)-induced fluorescent tumors in an animal model. METHODS: Cancer cells were injected into the peritoneum of rats to induce peritoneal carcinomatosis. After 3-4 weeks, ALA was administered to establish fluorescence in tumor nodules. All intraperitoneal surfaces were inspected using fluorescence and white light laparoscopy. Suspicious lesions were then biopsied in vivo under either fluorescence or white light laparoscopic guidance. Fluorescence intensities of the cancerous lesions compared to normal tissues were determined. A pathologist blinded to our clinical impression analyzed all biopsied specimens. We compared the sensitivity of fluorescence and white light laparoscopic-guided detection of cancerous lesions and determined the clinical utility of fluorescent photodynamic diagnosis in detecting metastatic ovarian cancer. RESULTS: Forty-three biopsies were performed in vivo under laparoscopic fluorescent guidance and 42 biopsies were taken using white light in various regions of the peritoneal surface from nine rats. Ten biopsies were also removed from nonfluorescent regions as nontumor controls. Cancerous lesions showed significantly higher fluorescent intensity compared to noncancerous lesions. Cancerous lesions that were difficult to differentiate from normal surrounding tissue under white light conditions were clearly detected by ALA-induced fluorescence. The average size of these metastatic lesions biopsied under fluorescent light was 1.0 mm (range: 0.3-2.5) compared to 1.5 mm (range: 0.5-2.9) with white light illumination (P < 0.05). CONCLUSIONS: Fluorescent laparoscopic detection of micrometastatic ovarian cancer using ALA is significantly more sensitive than white-light laparoscopy in detecting smaller cancerous lesions in an ovarian cancer rat model. Human trials are indicated.     

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。     

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.     

三阶梯技术在436例宫颈病变中的应用价值探讨

目的:探讨三阶梯技术在宫颈病变诊治中的临床应用价值。方法:对2007年1月至2008年12月在中山大学附属肿瘤医院妇科宫颈病变门诊就诊的436例患者的临床病理资料进行回顾性分析。结果:细胞学诊断为未明确诊断意义的不典型鳞状上皮细胞(ASCUS)、不典型鳞状上皮细胞不除外高度上皮内病变(ASC-H)、低度鳞状上皮内病变(LSIL)、高度鳞状上皮内病变(HSIL)、鳞癌细胞(SCC)及不典型腺细胞(AGC),经活检病理确诊宫颈上皮内瘤变Ⅱ(CINⅡ)及以上病变的比例分别为30.7%、67.5%、43.3%、89.0%、100.0%、33.3%。ASCUS的病例中50.9%经活检病理诊断为慢性宫颈炎。阴道镜检查为正常、LSIL、HSIL、浸润癌与病理诊断的符合率分别为67.3%、31.4%、79.0%、75.9%。初次阴道镜检查可能低估了32.8%(62/189)的HSIL及42.0%(34/81)的浸润癌。阴道镜下多点活检与锥切术后病理结果符合者150例(76.5%),锥切术后确诊宫颈浸润癌39例。结论:对筛查结果有异常者进行阴道镜检查,可以有效地检出宫颈病变;宫颈锥切术是治疗宫颈上皮内瘤变及进一步排除浸润癌的重要手段。     

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.     

Autofluorescence spectroscopy for the diagnosis of cervical intraepithelial neoplasia

Objective To assess the feasibility of autofluorescence spectroscopy in the diagnosis of cervical intraepithelial neoplasia (CIN) using broadband light excitation.
Design Feasibility study.
Setting Colposcopy clinic of an university hospital.
Population Sixty-eight patients at risk for CIN.
Methods After excitation with a broadband light between 375 and 440 nm, spectral distribution of native tissue fluorescence (autofluorescence) was acquired from 685 cervical sites for the localisation and differentiation of CIN, and compared with colposcopically directed biopsy and human papillomavirus (HPV) DNA testing.
Main outcome measure Detection of CIN.
Results The evaluation of spectral measurements revealed significantly lower autofluorescence values for CIN 3 lesions compared with normal tissue (   P < 0.001  ), and compared with CIN 1 or CIN 2 (   P < 0.002  ). High grade CIN lesions (CIN 2/3) presented with a significant reduced autofluorescence compared with CIN 1 (   P < 0.002  ). Patients with a positive HPV DNA testing showed a significantly lower autofluorescence than patients tested negative for HPV DNA (   P < 0.05  ). Severe inflammation such as chronic cervicitis may lead to false positive results.
Conclusions Autofluorescence spectroscopy represents an interesting approach for the detection of cervical neoplasia. Using an excitation wavelength band between 375 and 440 nm, significant differences between normal and precancerous lesions of the cervix can be seen.     

Passive cigarette smoking is a risk factor in cervical neoplasia

OBJECTIVES: To determine the role of spouse's cigarette smoking in the detection of high-grade squamous intraepithelial lesions of the cervix. DESIGN: Prospective cohort study with multivariate analysis. SETTING: Colposcopy clinic in a tertiary hospital. PARTICIPANTS: Women referred to a colposcopy clinic for evaluation of abnormal Papanicolaou smears showing either repeated inflammatory changes, low-grade squamous intraepithelial lesion (LSIL), or high-grade squamous intraepithelial lesion (HSIL). Data collection. The women were interviewed with a structured questionnaire for sexual history, use of oral contraceptive pills, personal and spouse cigarette-smoking history, and obstetric history. RESULTS: There were 623 women in the cohort. They were grouped into normal, LSIL, and HSIL categories based on colposcopy and histologic assessment. There were very few women who had had more than one sexual partner or a history of sexually transmitted diseases (STDs). The prevalence of oral contraceptive pill usage was 2.9% among the women in the normal group, 4.3% in women with LSIL, and 5.1% in women with HSIL. The incidence of cigarette smoking by the women was 2.5%, 3.2%, and 6.8% for the three groups of women, respectively. The incidence of spouse cigarette smoking was 25%, 35%, and 43% respectively. Compared to women in the normal group, women with HSIL were younger at first sexual intercourse, more likely to smoke cigarettes, and have spouses who smoked cigarettes. After controlling for age, age at first sexual intercourse, usage of combined contraceptive pills, and the woman's own cigarette-smoking habit, the odds ratio for HSIL was 1.046 for every stick of cigarette smoked by the spouse. In other words, the risk of detection of HSIL increased by 4.6% for every stick of cigarette her spouse smoked. CONCLUSIONS: Among women attending a colposcopy clinic, the risk of detection of HSIL increases with the spouse's cigarette-smoking habit. Further studies are warranted in quantifying the risk in a general population.     

Accuracy of colposcopy in the diagnostic setting compared with the screening setting

OBJECTIVE: To estimate the accuracy of colposcopy to identify cervical precancer in screening and diagnostic settings. METHODS: As part of a larger clinical trial to evaluate the diagnostic accuracy of optical spectroscopy, we recruited 1,850 patients into a diagnostic or a screening group depending on their history of abnormal findings on Papanicolaou tests. Colposcopic examinations were performed and biopsies specimens obtained from abnormal and normal colposcopic sites for all patients. The criterion standard of test accuracy was the histologic report of biopsies. We calculated sensitivities, specificities, likelihood ratios, receiver operating characteristic curves, and areas under the receiver operating characteristic curves. RESULTS: The prevalence of high-grade squamous intraepithelial lesions (HSIL) or cancer was 29.0% for the diagnostic group and 2.2% for the screening group. Using a disease threshold of HSIL, colposcopy had a sensitivity of 0.983 and a specificity of 0.451 in the diagnostic group when the test threshold was low-grade squamous intraepithelial lesions (LSIL), and a sensitivity of 0.714 and a specificity of 0.813 when the test threshold was HSIL. Using the same HSIL disease threshold, in the screening group, colposcopy had a sensitivity of 0.286 and a specificity of 0.877 when the test threshold was LSIL, and a sensitivity of 0.191 and a specificity of 0.961 when the threshold was HSIL. The colposcopy area under the receiver operating characteristic curve was 0.821 (95% confidence interval 0.79-0.85) in the diagnostic setting compared with 0.587 (95% confidence interval 0.56-0.62) in the screening setting. Changing the disease threshold to LSIL demonstrated similar patterns in the tradeoff of sensitivity and specificity and measure of accuracy. CONCLUSION: Colposcopy performs well in the diagnostic setting and poorly in the screening setting. Colposcopy should not be used to screen for cervical intraepithelial neoplasia. LEVEL OF EVIDENCE: II.     

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.     

Post-radiation Pap smear for Chinese patients with cervical cancer: a ten-year follow-up

BACKGROUND: To study the performance of routine follow-up Pap smears after curative radiotherapy (RT) for Chinese cervical cancer (CC) patients. METHODS: In 1996, 50 patients with non-metastatic CC received curative RT. Forty-six patients had routine follow-up Pap smears and constituted the study group. Details regarding clinical characteristics were retrospectively abstracted. Pap smear results were obtained via national Pap smear database linkage and chart review. The Pap smear results during recurrence-free survival (RFS) were analyzed and compared with clinical outcomes to study the performance characteristics. RESULTS: After 34 (2 approximately 105) months' median follow-up, the clinical outcomes were isolated central recurrence (ICR), other recurrence (OR), and no evidence of disease (NED) for six, 20, and 20 patients, respectively. During 22 months' median RFS (range 2-105), 422 Pap smears (including missing data, n = 33) were performed. Most of the Pap smear results were within normal limits (65.8%) or benign (reactive changes or atrophy with inflammation) (25.2%). Atypical cells, low-grade squamous intraepithelial lesion (LSIL), high-grade intraepithelial lesion (HSIL), and carcinoma were found in ten (2.6%), 11 (2.8%), 11 (2.8%), and three (0.8%) specimens, respectively. Follow-up of the 21 atypical cells/LSIL smears among seven patients revealed five NED with normal/benign smears, one NED with HSIL and one OR with HSIL. Follow-up of the 11 HSIL smears among four patients revealed two ICR, one OR and one NED with HSIL. Follow-up of the three carcinoma smears revealed three ICR (one followed by HSIL in a repeat Pap smear before ICR). The sensitivity for the detection of ICR by carcinoma smears was 50%, with a specificity and positive predictive value (PPV) of 100%. CONCLUSION: Few (approximately 3%) of the routine follow-up Pap smears after CC patients receiving curative RT were HSIL/carcinoma, but most (4/6) of these patients turned out to be ICR.     

Detection of nonpigmented endometriotic lesions with 5-aminolevulinic acid-induced fluorescence

STUDY OBJECTIVE: To evaluate the feasibility of fluorescence diagnosis of nonpigmented (red and white) endometriotic lesions with 20 mg/kg of 5-aminolevulinc acid (5-ALA) 5-7 and 10-14 hours before surgery. DESIGN: Prospective analysis (Canadian Task Force classification II-2). SETTING: University hospital. PATIENTS: Twenty-four consecutive patients with suspected endometriosis undergoing laparoscopy. INTERVENTION: Laparoscopic surgery under white light illumination and fluorescence diagnosis. MEASUREMENTS AND MAIN RESULTS: The total number of endometriotic lesions detected under white light illumination was compared with the number of lesions detected with fluorescence diagnosis. Fluorescence diagnosis yielded an overall improvement of 35% in the detection of nonpigmented endometriotic lesions compared with white light illumination. Sensitivity (91%) and specificity (79%) were similar 5-7 and 10-14 hours before surgery. CONCLUSION: The dosage of 20 mg/kg body weight of 5-ALA is feasible for fluorescence diagnosis of nonpigmented endometriosis. Sensitivity of fluorescence diagnosis with 20 mg/kg is similar to that achieved with a 30-mg/kg dose. Sensitivity does not change within the application period 5-7 and 10-14 hours before surgery.     

Endocervical glandular involvement, positive endocervical surgical margin and multicentricity are more often associated with high-grade than low-grade squamous intraepithelial lesion

Aim: The aim of this study was to compare the relative frequencies of endocervical glandular involvement (EGI), multicentricity, positive endocervical surgical margins (ESM) and positive vaginal surgical margins (VSM), and adenocarcinoma in situ of the cervix (AIS) between high-grade and low-grade squamous intraepithelial lesions (HSIL and LSIL, respectively). Material and Methods: We identified 238 patients with squamous intraepithelial lesions/cervical intraepithelial neoplasia (CIN) who were treated by loop electrocautery excision (LEEP) or conventional cold-knife conization (CKC). A total of 223 (72 [32.3%] LSIL/CIN I; 85 [38.1%] HSIL/CIN II; 66 [29.6%] HSIL/CIN III; and 151 [67.7%], HSIL/CIN II?+?III) LEEP/CKC slides were histologically reviewed. Results: The frequencies of EGI, positive ESM, and multicentricity were significantly higher in the HSIL/CIN II?+?III group than in the LSIL/CIN I group (P?=?0.001, 0.001, and 0.025, respectively). Eighteen of the 72 (25%) LSIL/CIN I patients, 44 of the 85 (51.8%) HSIL/CIN II patients, and 60 of the 66 (90.9%) HSIL/CIN III patients (P?=?0.001) showed EGI. In four of the 72 (5.6%) LSIL/CIN I patients, 18 of the 85 (21.2%) HSIL/CIN II patients, and 42 of the 66 (63.6%) HSIL/CIN III patients (P?=?0.001), ESM was positive. Two of the 72 (2.8%) LSIL/CIN I patients, seven of the 85 (8.2%) HSIL/CIN II patients, and 11 of the 66 (16.7%) HSIL/CIN III patients (P?=?0.016) were multicentric. Conclusion: The current study showed that EGI, positive ESM and multicentricity were more often associated with HSIL/CIN II?+?III than with LSIL/CIN I. Moreover, the frequencies of EGI, multicentricity, and positive ESM increased with increasing severity of the cervical lesion. This result may influence the preference for the type of surgical procedure used for patients with cytological diagnosis of HSIL.     

Chlamydia trachomatis and Human papillomavirus infections in cervical disease in Argentine women

OBJECTIVES: To examine the prevalence of Human papillomavirus and Chlamydia trachomatis DNA in cervical samples among women with normal and abnormal cervical cytology from La Plata, Argentina. METHODS: Two hundred and seventy-nine women (200 with cervical neoplasia or ICC and 79 women with normal cytology) provided cervical samples for the detection of HPV and C. trachomatis DNA by PCR-based assays. RESULTS: HPV DNA increased with the cervical lesion severity, ranging from 30% among women with normal cytology to 99-100% among women with HSIL or ICC. C. trachomatis DNA prevalence increased from low levels in women with normal cytology (11%) to 47% in those with HSIL, but was uncommon among ICC patients (20%). Among women with normal cytology, C. trachomatis prevalence was higher in HPV DNA positive (12.5%) than HPV DNA negative women (10.9%), but this difference was not significant. CONCLUSIONS: HPV prevalence in the general population is slightly higher than those reported for other developing countries. C. trachomatis DNA positivity was associated with a higher risk of both LSIL and HSIL lesions, but not with ICC.     

Colposcopic evaluation after a repeat atypical squamous cells of undetermined significance (ASCUS) smear.

OBJECTIVES: Management of patients with atypical squamous cells of undetermined significance (ASCUS) remains controversial. We chose to repeat the Pap smear after four months. If ASCUS persisted in this second test, the patient was advised to undergo colposcopy. Our objective is to determine the clinical significance and the prediction of neoplasia among these patients through a colposcopic examination. METHODS: Of 29,827 patients who had a Pap smear, ASCUS were detected in 1387 (5%) and persisted in the repeat smear of 225 (16%). Colposcopy and an additional Pap smear were performed on 186 patients. RESULTS: Out of 186 colposcopic evaluations, 91 (49%) were normal and the patients had a negative Pap smear. Colposcopy was abnormal in 95/186 patients (51%) (Table 1). Histology of the directed biopsies revealed 38 (21%) low-grade squamous intraepithelial lesions (LSIL) and 17 (9%) high-grade squamous intraepithelial lesions (HSIL). Forty patients (21%) with normal biopsies had ASCUS for the third time in the Pap smear. CONCLUSIONS: Colposcopic evaluation after a repeated Pap smear with ASCUS is an appropriate cost-effective management. Finding 30% of LSIL or HSIL justifies this additional investigation.     

高级别宫颈鳞状上皮内病变治疗后病灶残留、复发及妊娠

摘要：高度宫颈鳞状上皮内病变（HSIL）是宫颈癌前病变。未接受治疗的HSIL约17%的概率可进展为浸润癌。因此，准确规范地处理宫颈病变,特别是HSIL是预防宫颈癌的重要手段。ASCCP推荐冷刀锥切术（CKC）和宫颈环形电切（LEEP）为主要诊疗手段。然而部分患者接受治疗后仍存在病灶残留、复发及进展的风险。目前各研究报道HSIL治疗后发生病灶残留、复发及进展的差异较大，且术后病灶残留、复发的危险因素、术后随访方式尚无定论。本文旨在综述HSIL治疗后病灶残留及复发危险因素、处理、随访及妊娠相关问题，从而临指导临床治疗。     

Effectiveness of screening for cervical cancer in an inpatient hospital setting

OBJECTIVE: To estimate the effectiveness of an inpatient, hospital-based cervical cancer screening program at a single institution. METHODS: Between January 1999 and December 2002, 1,117 women admitted to the Johns Hopkins Hospital underwent Papanicolaou (Pap) test screening during their hospital stay. In that time period, 111,933 women were screened at all of the combined Hopkins outpatient clinics. We compared rates of abnormal Pap tests in these cohorts (retrospective cohort study). Our main outcome measure was the prevalence of abnormal Pap tests among the screening population by age group, ethnicity, and insurance status compared between our outpatient and inpatient populations. RESULTS: The prevalence of abnormal Pap tests in the inpatient cohort was twice as high as that in the outpatient setting (15.5% versus 7%). The prevalence of high-grade squamous intraepithelial lesions (HSIL), the immediate precursor lesion to cervical cancer, was nearly 5-fold higher in the inpatient cohort compared with the outpatient cohort (3% versus 0.7%). In multivariable models, younger women had greater risk for all types of abnormal Pap tests, and black women had greater risk for HSIL. Previous abnormal Pap and human immunodeficiency virus-positive status were associated with all abnormal tests and with HSIL results. CONCLUSIONS: A hospital-based, inpatient Pap test program is an efficient strategy for targeting limited screening funds toward women at high risk of invasive cervical cancer. LEVEL OF EVIDENCE: II-2     

Fluorescence in situ hybridization in cervical smears: detection of numerical aberrations of chromosomes 7, 3, and X and relationship to HPV infection.

BACKGROUND: Human papillomavirus (HPV) is known to play a pivotal role in cervical carcinogenesis. Chromosomal aberrations are known to be related to different biological behaviors of malignant lesions. We analyzed whether numerical chromosomal aberrations, related to more aggressive tumor types, are found not only in high-grade squamous intraepithelial lesions (HSIL) but also in low-grade SIL (LSIL) of the cervix and evaluated their relationship to HPV infection. METHODS: Eighty women (19 to 74 years of age) were included in this study and grouped according to the Bethesda System: within normal limits (WNL), LSIL, and HSIL. By FISH, chromosomes 7 and X, and in part chromosome 3, were analyzed for numerical aberrations. Using the hybrid capture system HPV detection was performed. RESULTS: All 20 patients with cervical smear WNL had regular diploid chromosomal pattern and were negative for HPV. Thirteen of the 29 (41.2%) patients with LSIL showed trisomy 7, in association with trisomy X in 4 cases (12.9%). Single trisomy X was detected in 4 cases (12.9%). In 3 of 15 (20%) cases analyzed for chromosome 3 trisomy was observed. Trisomy 3 was associated with trisomy 7 and X or with trisomy 7 alone. The hybrid capture test was performed in 16 patients of this group. Two patients were positive for HPV probe A, 9 for probe B, and 2 for A and B, and 3 patients were negative. Twenty-three of the 29 patients (79.3%) with HSIL showed trisomy 7. Twelve of the 29 patients (41.3%) had an additional trisomy X. Single trisomy X was seen in only 2 cases (6. 9%). Twenty-two patients with HSIL were tested also for chromosome 3. Nine of the 22 patients (40.9%) showed trisomy 3, associated with trisomy 7 or with trisomy 7 and X. In 25 of the 29 patients HPV detection by the hybrid capture system was performed. HPV probe B was positive in 15 cases (60%). One patient was positive for both probes, A and B. Nine (36%) of the patients with HSIL were negative for both HPV probes. No positivity was observed for HPV probe A alone. CONCLUSION: Our data confirm the pivotal role of HPV in cervical carcinogenesis as it seems to cause changes in the chromosomal pattern of premalignant lesions. Additionally, trisomy 7 may be considered an early event in cervical carcinogenesis, persisting and increasing with progression of the lesion. The roles of trisomy 3 and X need further evaluation.