Nuclear DNA analysis of koilocytic and premalignant lesions of the uterine cervix.

Cervical biopsy samples were taken from 79 patients who had various grades of cervical intraepithelial neoplasia or who showed evidence, in the form of koilocytosis, of human papillomavirus infection of the uterine cervix and from 10 women with normal cervices. The DNA content of the cells in the samples was analysed by flow cytometry. Analysis of the data obtained showed that the biopsy samples from women with cervical intraepithelial neoplasia and human papillomavirus lesions contained significantly more dividing cells (31.2% of cells from human papillomavirus lesions with no cervical intraepithelial neoplasia and 33.06%, 29.89%, and 31.76% of cells from cervical intraepithelial neoplasia grades I, II, and III, respectively) than those from women with normal cervices (21.6%). The proportion of aneuploid samples from the group who showed evidence of human papillomavirus infection only (18.2%) did not differ significantly from the group with cervical intraepithelial neoplasia grade III (21.2%). Aneuploidy and an increased rate of cellular proliferation are recognised characteristics of malignancy. These results therefore support the view that human papillomavirus plays an important part in the aetiology of cervical carcinoma and are relevant to the clinical management of patients.     

Mild and moderate dyskaryosis: can women be selected for colposcopy on the basis of social criteria?

OBJECTIVE--To describe the distribution of cervical intraepithelial neoplasia grades among women with mild and moderate dyskaryosis after a single cervical smear and to determine whether social criteria could help identify women who are at increased risk of grade II or III disease. DESIGN--Cross sectional analysis within a randomised prospective study. Subjects had a repeat smear, a colposcopic examination, and an excision biopsy of the transformation zone. In addition, women were asked to complete a social questionnaire. SETTING--Colposcopy clinic, Aberdeen. SUBJECTS--228 women with a single smear test showing mild or moderate dyskaryosis. MAIN OUTCOME MEASURES--Histology, age, sexual and contraceptive history, cigarette smoking. RESULTS--159 (70%) women had cervical intraepithelial neoplasia grades II or III. Among current smokers the prevalence of grade II and III disease was higher in women who smoked greater than or equal to 20 cigarettes a day (84%) than among those who smoked less (66%; p less than 0.04). Women with more than one sexual partner also had a higher prevalence (75%) than women with only one partner (50%; p = 0.0028). Use of oral contraceptives and younger age were not significantly associated. The prevalence of grade II or III disease was up to 66% in the lower risk groups. CONCLUSIONS--Because of the high prevalence of cervical intraepithelial neoplasia grades II and III in both the high and the low risk groups social factors are not useful for selecting women with mild or moderate dyskaryosis for either early referral to colposcopy or cytological surveillance.     

Screening for cervical intraepithelial neoplasia in north east Scotland shows fall in incidence and mortality from invasive cancer with concomitant rise in preinvasive disease.

OBJECTIVE--To assess the effect of screening for cervical intraepithelial neoplasia on the incidence of and mortality from invasive squamous cell carcinoma of cervix in north east Scotland and to discover why cases of invasive cancer still occur. DESIGN--(a) Analysis of data on cases of cervical intraepithelial neoplasia obtained from the cytology data bank; (b) analysis of data on 612 women presenting with invasive squamous cancer during 1968-91, obtained from cancer registry and hospital records; (c) analysis of death rates obtained from the registrar general''s (Scotland) annual reports, the Information Services Division of the Home and Health Department (Scotland), and local records for 1974-91; (d) case-control studies on 282 cases of invasive cancer and 108 deaths which occurred in 1982-91. Cases were matched with two controls both for age and for having a negative smear test result at the time of presentation of the case. SETTING--North east Scotland (Grampian region, Orkney, and Shetland). SUBJECTS--Women (n = 306,608) who had had cervical smear tests between 1960 and 1991. RESULTS--There had been a substantial increase in cases of cervical intraepithelial neoplasia grade III since 1982. The incidence of invasive cancer has fallen since the start of screening in 1960, the fall occurring mainly in the well screened age group 40-69 years. There was a rise in women aged under 40 and over 70. Women with invasive disease seen between 1982 and 1991 mostly presented at stage I. Of these, half were unscreened, one third were poorly screened, 11% were found in retrospect to have had abnormal cells, 3% had recurrence of disease after treatment for cervical intraepithelial neoplasia grade III, and 3% were lost to follow up. Death rates had fallen, most noticeably in women aged 45-64, who had had the opportunity to be screened and rescreened. There was a disturbing rise in deaths among women under 45. Most deaths (65%) occurred in unscreened women. Case-control studies showed that the longer the time and absence of a smear test before presentation the higher was the risk of invasive cancer and of death. CONCLUSIONS--Screening has been effective in reducing the incidence of and mortality from cervical cancer in north east Scotland. Most cases and deaths occurred in unscreened women or in those who had had few smears at long intervals. An increase in cases of cervical intraepithelial neoplasia grade III in women screened for the first time occurred during 1982-91.     

Preclinical feasibility study of NMP179, a nuclear matrix protein marker for cervical dysplasia

OBJECTIVE: To evaluate, in a preclinical feasibility study, the efficacy of NMP179, a monoclonal antibody recognizing a cervical tumor-associated nuclear matrix antigen, for the early detection of high and low grade cervical intraepithelial neoplasia. STUDY DESIGN: In a blind study involving two clinical sites, NMP179 immunocytochemical staining data from 261 cervicovaginal Thin-Prep specimens were evaluated. Assay sensitivity and specificity were calculated based upon a positive threshold of > 10 immunostained cells per case, using cytologic diagnosis as an end point. RESULTS: Based upon the examination of squamous epithelial cells, NMP179 detected 96.7% of cases with cytologically diagnosed high grade squamous intraepithelial lesions (HSIL) and 70.5% of low grade squamous intraepithelial lesions. The antibody also reacted with 29.6% of normal (within normal limits or benign cellular changes) smears. CONCLUSION: The NMP179 assay detected HSIL with very high accuracy (96.7%). The assay was 79.3% sensitive for the detection of low and high grade cervical intraepithelial neoplasia (grades 1-3), with a specificity of 70.4%. NMP179 may be an effective marker for the early detection of preneoplastic squamous intraepithelial lesions of the cervix and may be useful as an adjunctive tool for better management of cervical intraepithelial neoplasia.     

Classification of cervical smears with discordance between the cytologic and/or histologic ratings

The problems of diagnostic variability between certified cytotechnologists was studied. Three cytology laboratories submitted a total of 28 cervical smears that had a discordance between the cytologic and/or histologic ratings. Eight independent cytotechnologists provided blind readings on each slide, expressed as "absence of cervical intraepithelial neoplasia (CIN)" to "CIN III." The median rating was absence of CIN or CIN I for 8 slides, CIN II for 5 and CIN III for 15. With a kappa value greater than 0 reflecting agreement beyond chance expectation and a value of 0.40 indicating fair agreement, the kappa value for 8 X 28 ratings was 0.36 (P = .0001), with a 90% confidence interval (CI) between 0.34 and 0.37. The kappa value was 0.14 (P = .10), with a 90% CI between 0.10 and 0.18, on a subsample of nine smears with two or more positive cytology diagnoses but a negative histology. Sixteen of the 28 slides represented cases of histologically proven cancer. Treating cytologic diagnoses of CIN II and CIN III as positive, the sensitivity of the cytologist with reference to histology varied between 71% and 86% while the specificity ranged from 18% to 62%. The positive predictive value was 1/2.5 to 1/1 and the negative predictive value was 1/6 to 1/1. The predictive power (true positives/false positives) ranged from 1.0 to 2.2. The cytodiagnosis of these cervical smears from cases of discordance thus exhibited limited reliability. Standardization of the relevant cytologic knowledge and its routine application is needed to improve the level of performance.     

Guest Lecture 8.45–9.30 Monday 15 September 2003 Endocervical Adenocarcinoma and its Precursors

The incidence of malignant and pre‐malignant endocervical glandular lesions is increasing. Part of this is an apparent increase due to a reduction in the number of invasive cervical squamous carcinomas but there is evidence that there is a real increase in malignant and pre‐malignant endocervical glandular lesions. Different terminologies are in use in the UK where the term cervical glandular intraepithelial neoplasia (CGIN) is commonly used and the rest of the world where pre‐malignant lesions are classified as glandular dysplasia and adenocarcinoma in situ (AIS) (WHO classification). It is well established that high‐grade CGIN (AIS in WHO terminology) is a precursor lesion of cervical adenocarcinoma but it is controversial whether a recognizable precursor to high grade CGIN (namely low‐grade CGIN) exists and criteria for diagnosing this are poorly established and poorly reproducible. Most cases of CGIN are of usual or endocervical type but other morphological subtypes described include endometrioid, intestinal, tubal and stratified mucinous intraepithelial lesion (SMILE). The presence of skip lesions and lesions high up the endocervical canal has been overemphasised in CGIN with most cases occurring close to the transformation zone. Treatment is on an individualized basis but local excision with negative margins and close cytological follow‐up may be employed. There is evidence in the literature that early invasive adenocarcinomas behave in a similar fashion to early invasive squamous carcinomas and that, on selected occasions, conservative therapy can be safely undertaken. However, further studies are needed to ascertain the behaviour and natural history of early invasive cervical adenocarcinoma. In 10%–15% of cases it may be impossible to ascertain whether a malignant endocervical glandular lesion is invasive or in situ. There are many benign mimics of CGIN and adenocarcinoma, including tuboendometrial metaplasia (TEM), endometriosis and microglandular hyperplasia (MGH). Although careful morphological examination usually allows confident distinction of these lesions, a panel of immunohistochemical stains including MIB1, bcl2 and p16 may assist.     

Fractal Analysis of Cervical Intraepithelial Neoplasia

Introduction

Cervical intraepithelial neoplasias (CIN) represent precursor lesions of cervical cancer. These neoplastic lesions are traditionally subdivided into three categories CIN 1, CIN 2, and CIN 3, using microscopical criteria. The relation between grades of cervical intraepithelial neoplasia (CIN) and its fractal dimension was investigated to establish a basis for an objective diagnosis using the method proposed.

Methods

Classical evaluation of the tissue samples was performed by an experienced gynecologic pathologist. Tissue samples were scanned and saved as digital images using Aperio scanner and software. After image segmentation the box counting method as well as multifractal methods were applied to determine the relation between fractal dimension and grades of CIN. A total of 46 images were used to compare the pathologist''s neoplasia grades with the predicted groups obtained by fractal methods.

Results

Significant or highly significant differences between all grades of CIN could be found. The confusion matrix, comparing between pathologist''s grading and predicted group by fractal methods showed a match of 87.1%. Multifractal spectra were able to differentiate between normal epithelium and low grade as well as high grade neoplasia.

Conclusion

Fractal dimension can be considered to be an objective parameter to grade cervical intraepithelial neoplasia.     

Cervical intraepithelial neoplasia grade III (CIN III) and invasive cervical carcinoma: the yawning gap revisited and the treatment of risk

In a 3-year study of the population of Southampton and south-west Hampshire there were 10 times as many cases of CIN III compared with invasive squamous carcinoma (700 compared with 70). The peak incidence of CIN III per 1000 screened women years was in those aged 25-29 years, which was 20 years earlier than the peak incidence of invasive cervical cancer per 1000 women years at risk. Ninety percent of CIN III was diagnosed in women under 50 years. There were 14 cases of cervical glandular intraepithelial neoplasia grade III (CGIN III), three coexisting with CIN III, all in women aged under 50 years: the gap between intraepithelial and invasive lesions was not seen for glandular neoplasia. Although referral was for at least moderate dyskaryosis in 86.8% of women with CIN III or CGIN III, most had been screened previously, either having had mild abnormalities requiring repeat cytology (39.8%) or negative cytology (34.5%). Only 12 women aged > or = 50 years had previous negative cytology: 21.4% compared with 35.6% of women aged < 50 years (P = 0.034). The results of this study suggest that the best opportunity for preventing invasive squamous cell carcinoma lies in screening women aged 20-39 years when the incidence of CIN III in the screened population is highest and before the peak incidence of invasive disease. The results also indicate the importance of repeated screening and follow up of minor cytological abnormalities in the detection of CIN III. The benefit of screening must be regarded as a treatment of risk, since it is almost certain that a high proportion of CIN III regresses or persists unchanged.     

Assessment of the Accuracy of Cytology In Women Referred For Colposcopy and Biopsy: the Results of a 1 Year Audit

The results of weekly colposcopy review meetings have been audited for 1 year and cases where there was a discrepancy between the referral cervical smear and the initial colposcopy biopsy have been analysed. New referrals (n = 476) for colposcopy were studied. In the final outcome 80% of 326 women referred for moderate or severe dyskaryosis were found to have cervical intraepithelial neoplasia (CIN) grade II or III or invasive carcinoma. Three women found to have invasive carcinoma had been referred for severely dyskaryotic smears. Twenty women were referred for smears with cell changes suggesting glandular neoplasia: five were found to have adenocarcinoma in situ, whereas eight had CIN and seven had negative biopsies. The results justify the referral policy and demonstrate the need for further investigation when initial colposcopic biopsies are negative.     

Inadequate cervical smears: results of an educational slide exchange scheme

Fifty-six slides, predominantly inadequate and of varying difficulty, were circulated to 12 laboratories as an educationally based slide exchange scheme. Three slides failed to achieve an agreed majority consensus opinion. Seventy percent of participants agreed with the consensus opinion in 80% of slides. Of the slides originally reported as inadequate, the consensus diagnosis was inadequate in 78%, negative in 12% and abnormal in 10%. The latter included two cases of high-grade dyskaryosis. There was good agreement for the two most frequent causes of inadequacy in submitted slides (obscured and poor cellularity). There was poor consistency in reporting the presence or absence of endocervical and immature squamous metaplastic cells, to an extent that questions their use in the assessment of smear adequacy. Three inadequate slides on consensus opinion were associated with subsequent cervical intraepithelial neoplasia (grade III) or invasive squamous cell carcinoma. In the latter case, the slide had originally been reported as negative by the submitting laboratory.     

Is it possible to define a better ASCUS class in cervicovaginal screening? A review of 187 cases

OBJECTIVE: To try to better define the cytologic diagnosis of atypical squamous cells of undetermined significance (ASCUS) in a cervical screening protocol. STUDY DESIGN: Smears from 187 patients with cytologic diagnoses of ASCUS and histologic or two years' cytologic/colposcopic follow-up were reviewed. When an ASCUS diagnosis was confirmed, it was done strictly on the basis of the morphologic criteria recommended by the Regione Emilia Romagna Screening Protocol in 1997, trying also to subclassify ASCUS into favor reactive or favor neoplasia. RESULTS: Seventy ASCUS cases were negative (37.4%). Three cases (1.6%) were low grade squamous intraepithelial lesion, and seven (3.8%) were high grade squamous intraepithelial lesion. One hundred seven ASCUS cases (57.2%) were confirmed. Among the 70 negative cases, 36 (51.4%) had reactive changes on biopsy, 30 (42.9%) koilocytosis, 3 cervical intraepithelial neoplasia (CIN 1) and one CIN not otherwise specified (5.7% total). CONCLUSION: Reclassification of ASCUS cases using tighter criteria reduced them to a rate of 57.2% but missed 30 patients with histologic diagnoses of koilocytosis and 4 with histologic diagnoses of CIN.     

Routine colposcopic survey of patients with squamous atypia. A method for identifying cases with false-negative smears

Routine colposcopy was performed on 376 women with cervical squamous atypia (originally reported as "inflammatory atypia"). Colposcopy showed no abnormalities in 240 cases and a lesion in 136 cases; the latter were sampled by colposcopy-guided biopsy. The biopsy samples showed evidence of human papillomavirus (HPV) infection and/or grade I cervical intraepithelial neoplasia (CIN I) in 42 cases (11.1%), CIN II in 4 cases (1.1%) and CIN III in 5 cases (1.3%); the other 85 biopsied cases were histologically negative. Most cases of HPV/CIN I (35 of 42) and all of the cases of CIN II-III occurred in women under the age of 40. The detection rates were 4.4% for CIN II-III in women under the age of 40, 4.0% for HPV/CIN I in women 40 and older and 17.2% for HPV/CIN I in women under the age of 40 (P less than .001). It thus appears that women under the age of 40 who show cytologic evidence of squamous atypia would benefit from colposcopic examination.     

Long term risk of invasive cancer after treatment for cervical intraepithelial neoplasia grade 3: population based cohort study

Objective To study the long term risk of invasive cancer of the cervix or vagina after treatment for cervical intraepithelial neoplasia grade 3.Design Prospective cohort study.Setting Swedish cancer registry.Participants All women in Sweden with severe dysplasia or cervical carcinoma in situ (equivalent to cervical intraepithelial neoplasia grade 3) treated during 1958-2002 (n=132 493) contributing 2 315 724 woman years.Main outcome measures Standardised incidence ratios with risk of cancer in the Swedish general female population as reference, and relative risks in multivariable log-linear regression model, with internal references.Results Women with previous cervical intraepithelial neoplasia grade 3 had an increased risk of invasive cervical cancer compared with the general female population (standardised incidence ratio 2.34, 95% confidence interval 2.18 to 2.50). The increased risk showed a decreasing trend with time since diagnosis for women treated later than 1970 but the risk was still increased after 25 years. An effect of age was found, with an accentuated increase in risk for women aged more than 50. The excess risk for cervical cancer associated with previous cervical intraepithelial neoplasia grade 3 has steadily increased since 1958. For vaginal cancer the standardised incidence ratio was 6.82 (5.61 to 8.21) but this decreased to 2.65 after 25 years. Adjustments in the multivariable log-linear regression model did not substantially alter these results.Conclusions Women previously treated for cervical intraepithelial neoplasia grade 3 are at an increased risk of developing invasive cervical cancer and vaginal cancer. This risk has increased since the 1960s and is accentuated in women aged more than 50. The risk is still increased 25 years after treatment.     

钙黏附素和β-连接素与宫颈上皮内瘤变进展的关系

目的：观察钙黏附素（E—cadherin）和β-连接素（β-catenin）在不同级别宫颈上皮内瘤变组织中的表达,探讨其与宫颈上皮内瘤变进展的关系。方法：采用免疫组化法检测51例宫颈组织病理存档石蜡包埋组织钙黏附素（E—cadherin）和β-连接素（β-catenin）的表达,阳性信号采用图像分析仪进行定量分析：结果：E—cadherin在柱状上皮移位组及CINT组、C1NII组、CINIⅡ组中的平均光密度值（AOD）分别为：0．0866±0．0392、0．073±0．0122、0．0467±0．0056、0．0396±0．0097;β-catenin在柱状上皮移位组及CIN I组、CIN II组、CIN III组中的平均光密度值（AOD）分别为：0．1101±0．0116、0．1016±0．0108、0．0711±0．0062、0．0515±0．0091。随着CIN病变的升级,钙黏附素和β-连接素的表达均呈下降趋势,二者的平均光密度值（AOD）正相关（r=2．546．P=0．018〈0．05）。结论：钙黏附素、β-连接素与宫颈上皮内瘤变的进展相关,在估计CIN的预后中有一定意义,     

Do qualifiers of ASCUS distinguish between low- and high-risk patients?

OBJECTIVE: To evaluate the qualification of a Pap smear classified as atypical squamous cells of undetermined significance (ASCUS) favor reactive or neoplasia as recommended by the Bethesda System. STUDY DESIGN: The smears from 105 concurrent patients with a cytologic diagnosis of ASCUS not otherwise qualified were reviewed and subclassified as ASCUS favor reactive, low grade squamous intraepithelial lesion (LSIL) or high grade squamous intraepithelial lesion (HSIL) based on the Bethesda System criteria. The cervical biopsy diagnoses were correlated. RESULTS: Of the 105 cases classified as ASCUS, 37 were subclassified as favor reactive, 51 as favor LSIL and 17 as favor HSIL on cytologic review. In the ASCUS favor reactive group, 19 (51%) had reactive changes on biopsy, 17 (46%) had cervical intraepithelial neoplasia (CIN) 1, and 1 (2%) had CIN 3. A total of 48% patients had CIN. In the favor LSIL group, there was CIN 1 in 28 cases (55%), CIN 2 or 3 in 12 (23%) and benign changes in 11 (22%) on biopsy. Seventy-eight percent had CIN. In the 17 cases classified as ASCUS favor HSIL group, all had CIN. CONCLUSION: Of the total 105 cases of ASCUS, 71% had CIN, 29% had reactive changes on follow-up biopsies, and 48% of patients in the ASCUS favor reactive group had CIN. Qualifiers of ASCUS have questionable utility in patient management.     

Ploidy patterns in cervical dysplasia

The ploidy patterns determined for groups of patients with cervical dysplasia (cervical intraepithelial neoplasia [CIN]) were subjected to statistical analysis. The patterns were based on the measurement of at least 100 Feulgen-stained nuclei from 30 patients with normal cervices, 10 cases of CIN I, 18 cases of CIN II and 33 cases of CIN III. The scale of the patterns was a log transformation of the ratio of the total extinction (optical density) of the nuclei to that of the 2N reference; this widens the intervals for higher ploidies, alleviating sampling requirements for intervals in which occurrences are rare and helping to maintain a reasonable sample size-to-dimensionality ratio. Pairwise discriminant analyses showed clear distinctions between the ploidy pattern for normal cases and those for CIN I, CIN II and CIN III. The distinctions between the different grades of CIN, based on these modest sample sizes, were less clearcut, largely due to pronounced patient-to-patient variability. Analysis of variance confirmed that the patient groups constitute statistically distinct entities. An aneuploid pattern did not seem to develop until CIN III lesions were involved. The diagnostic and prognostic significance of these preliminary findings require further study using larger data sets and correlations to patient survival.     

Local expression of interferon-alpha and interferon receptors in cervical intraepithelial neoplasia

Purpose  

The present study evaluated mRNA expression of interferon-alpha (IFN-α), IFN-α receptor subunits (IFNAR-1 and IFNAR-2) and an IFN-stimulated gene encoding the enzyme 2′,5′-oligoadenylate synthetase (2′5′OAS) in biopsies on patients with varying grades of cervical intraepithelial neoplasia (CIN I, II and III).     

Diverse glandular pathologies coexist with high-grade squamous intraepithelial lesion in cyto-histological review of atypical glandular cells on ThinPrep specimens

Objective: To identify in cytology, high‐grade squamous intraepithelial lesions with endocervical glandular extension in cases previously diagnosed as atypical glandular cells (AGC), analyse possible reasons for the diagnostic pitfall and document the frequency of glandular pathology coexisting with high‐grade cervical intraepithelial lesion in histology. Methods: Thirty‐nine ThinPrep® cervical smear (Pap) tests reported as AGC of undetermined significance and showing high‐grade lesions on histology [cervical intraepithelial neoplasia (CIN) 2 or 3, endometrial or extrauterine adenocarcinoma] were reviewed retrospectively to identify the cases of high‐grade squamous intraepithelial lesion with endocervical glandular extension, using the Bethesda 2001 system. Cyto‐histological correlation was performed. Results: A high frequency of diverse glandular pathologies coexisted with high‐grade cervical intraepithelial lesions on histology. This included endocervical glandular extension in 63%, benign glandular pathology in 33% and pre‐neoplastic or malignant glandular pathology (endocervical glandular dysplasia, adenocarcinoma in situ and metastatic breast carcinoma) in 17% cases. On cytology, the sensitivity was 40%, specificity was 80% and positive predictive value was 86% for endocervical gland extension in high‐grade squamous intraepithelial lesions. Conclusions: Special efforts to recognize endocervical glandular extension in high‐grade squamous intraepithelial lesions and glandular neoplasia coexisting with squamous intraepithelial lesions from the heterogeneous category of AGC can contribute to increasing the diagnostic accuracy. The identification of endocervical glandular extension on cervical cytology would alert the gynaecologist to perform a thorough assessment of the endocervix during colposcopy. This could also help to decide on the need to perform deeper conization rather than loop electrosurgical excision procedure to ensure negative margins when colposcopic biopsy shows CIN 2 or 3.     

Risk of significant gynaecological pathology in women with ?glandular neoplasia on cervical cytology

A. Talaat, D. Brinkmann, J. Dhundee, Y. Hana, J. Bevan, R. Irvine, S. Bailey and R. Woolas
Risk of significant gynaecological pathology in women with ?glandular neoplasia on cervical cytology Objective: To review the risk of pre‐invasive and invasive gynaecological pathology in women referred with cervical cytology reporting ?glandular neoplasia. Methods: Review of the case notes of all women referred with cervical cytology reported as ?glandular neoplasia between January 1999 and December 2008 at two UK hospitals: Portsmouth Hospitals NHS Trust and Queen Mary’s Hospital Sidcup. The category of ‘borderline nuclear change in endocervical cells’, result code 8 according to the national health service cancer screening programme (NHSCSP), was excluded from the study. Results: A total of 200 women were identified using the hospitals’ pathology computer systems. Invasive carcinoma was found in 48 women (24%): 28 endocervical adenocarcinomas, eight squamous cell carcinomas (SCC), ten endometrial and two ovarian adenocarcinomas. Pre‐invasive neoplasia was found in 115 (57.5%), including 14 cervical glandular intraepithelial neoplasia (CGIN), 31 cervical intraepithelial neoplasia (CIN) grade 2/3 and 70 concomitant CGIN and CIN2/3. CIN1/HPV was found in 25, simple endometrial hyperplasia in three and no histological abnormality in three. Thirty‐four (70.8%) of 48 invasive carcinomas (of which 23 were endocervical adenocarcinomas) were in asymptomatic women investigated for abnormal cytology. Fourteen of 34 (41.4%) of those with ?glandular neoplasia thought to be endometrial were CGIN or CIN2/3. Colposcopic appearances were normal in 47.6% of women with pure cervical glandular neoplasia (adenocarcinoma or CGIN) compared with 12.8% with squamous cell lesions (CIN2/3 or SCC): P = 0.0001. Thus, colposcopy was more sensitive for detecting squamous cell abnormalities than their glandular counterparts. Although cervical adenocarcinomas are less amenable to prevention by screening than cervical SCC, in our study cervical cytology predominantly detected these abnormalities at their early asymptomatic stages. Conclusion: At least CIN2 was found in 81.5% in women referred with cervical cytology reporting ?glandular neoplasia. A thorough evaluation of the whole genital tract is needed if colposcopy is negative.     

变异性分化抗原簇44（CD44v17）对宫颈癌的临床诊断意义

目的:探讨CD44v17对宫颈癌的临床诊断意义。方法:将CD44v17si RNA、CD44v17、生理盐水转染至传代后的人宫颈癌细胞。检测细胞转染后存活率;检测细胞凋亡率。在裸鼠左肩背部注入人宫颈癌细胞悬液,随机分为CD44v17组、CD44v17si RNA组、对照组。在CD44v17组、CD44v17si RNA组裸鼠瘤体内分别注入CD44v17病毒颗粒、CD44v17si RNA病毒颗粒。检测瘤体的质量与体积。选取疑有宫颈病变患者阴道镜下活检组织80例,正常宫颈组织15例、宫颈上皮内瘤变(CIN)I级组织l5例、CIN II级15例、CIN III级组织15例和宫颈癌组织20例。检测CD44v17在不同组织中的表达量。结果:CD44v17si RNA转染的宫颈癌细胞凋亡率(19.20±2.14%)高于CD44v17转染的宫颈癌细胞凋亡率(6.13±1.08%)(P0.05)。CD44v17组裸鼠瘤体质量(15.9±3.4)g高于对照组裸鼠瘤体质量(11.8±2.7)g(P0.05)。CD44v17在不同组织中的表达量,按正常宫颈、CINⅠ级、CINⅡ级、CINⅢ级、宫颈癌发展过程呈递增趋势(P0.05)。结论:CD44v17能抑制宫颈癌细胞凋亡,促进宫颈癌细胞的生长、增殖。通过降低CD44v17表达量可能是遏制CIN向宫颈癌发展的一个手段。