Rapid (partial) prescreening of cervical smears: the quality control method of choice?

Rapid rescreening of all negative and inadequate smears is the quality control method of choice in the UK. The sensitivity of primary screening of laboratory and individual screeners are major indicators of screening quality and are dependent on the number of false negative smears found by rapid screening for their calculation. High sensitivity may indicate good quality primary screening or poor quality rapid review. Quantifiably high quality rapid rescreening is essential if these sensitivity figures are to be meaningful. A 12-month study was undertaken in routine practice using the prescreening mode to ascertain the sensitivity of rapid (partial) screening in our department. The final results of smears were compared with those of rapid prescreening. The calculated sensitivity ranged from 92-54% for high-grade abnormalities and 75-33% for all grades, revealing a wide range of performance between individual prescreeners. Rapid prescreening can identify individuals best suited to rapid screening in routine practice. By using these prescreeners only, the sensitivity of cervical screening could be raised. Rapid (partial) prescreening should be considered as the quality control method of choice.     

Rapid review in cervical cytology: a retrospective review of cases detected on rapid review within a DGH cytology department and subsequent outcome

We retrospectively reviewed smears detected by rapid review within a district general hospital (DGH) laboratory over a period of 33 months and the subsequent histological or cytological outcome. Sixty-three cases had adequate follow-up data: 32 subsequently had two negative smears and 31 had a histological abnormality on subsequent biopsy. Twenty were high-grade lesions (CIN2, CIN3 or a glandular lesion) and eight of these were preceded by a low-grade smear abnormality. We reviewed and compared the pattern and distribution of smear abnormalities in these 63 cases. Abnormalities were often present within few cells (76%, n = 48 with 50 abnormal cells or less) or in micro-biopsies (27%, n = 17). There was no statistical difference in the pattern and distribution of smear abnormality between the rapid review-detected smears with a biopsy-proven abnormality and those with negative follow-up smears. Overall, the positive predictive value for high-grade CIN detected by rapid review (75%) was within NHSCSP achievable standards targets. This review of rapid review-detected abnormalities and the biopsy and cytological follow-up reiterates the importance of the method in cervical screening.     

Rapid pre-screening is more sensitive in liquid-based cytology than in conventional smears

Rapid pre-screening (RPS) is a useful tool to measure and improve performance in the cytology laboratory. Whether RPS is more or less effective in liquid-based cytology than in conventional smears is unknown. We compared the estimated sensitivity in a laboratory of 11 cytotechnologists which converted from conventional smears to SurePath? (Becton Dickinson, Franklin Lakes, N.J., USA) liquid based cytology. In the 9 months prior to conversion, 23,286 smears were screened compared with 30,610 smears in the 12 months immediately after conversion. The estimated sensitivity of rapid pre-screening for 90 s improved significantly with liquid based cytology for all abnormalities (58.7 vs. 68.7%, p<0.001), atypical squamous cells of undetermined significance+low-grade squamous intra-epithelial lesion (52.6 vs. 63.1%, p<0.001), and high-grade squamous intra-epithelial alone (76.2 vs. 85%, p<0.001). Histologic follow up for 156 cases identified by rapid pre-screening of SurePath slides showed 32 (21%) cases of CIN1 or greater and 18 cases (12%) with CIN3 or worse. We conclude that rapid pre-screening is significantly more sensitive in liquid-based cytology compared with conventional smears, and detects significant lesions that are missed by routine screening.     

Use of the ThinPrep Imaging System for internal quality control of cervical cytology

T. Heard, A. Chandra, G. Culora, S.S. Gupta, A. Herbert and M. Morgan
Use of the ThinPrep Imaging System for internal quality control of cervical cytology Objective: To audit the use of the ThinPrep Imaging System (TIS) for internal quality control (IQC) in the place of rapid review (RR), and to compare its performance with routine primary screening. Method: During 9 months, 16 462 ThinPrep slides were processed by TIS. Slides were initially reviewed using the TIS review scope, as recommended by the manufacturer: 22 fields of view were observed and, if considered abnormal, a full microscopic review was conducted using the review scope. Different biomedical scientists (BMSs), working on each procedure in rotation, performed batches of TIS‐assisted quality control and routine primary screening independently on unmarked slides. Any slides with abnormalities detected by either method were referred to a consultant pathologist or advanced BMS practitioner for a final report. TIS results were compared with both previous records of RR and routine primary screening carried out on the same slides. We used the UK terminology in which ‘dyskaryosis’ is equivalent to squamous intraepithelial lesion (SIL) and borderline to atypical (including squamous and glandular cells). Results: TIS preview detected significantly more high‐grade dyskaryosis compared with RR during the previous 4 years: 2.0–4.2 compared with 0.1–1.8 detected per 1000 slides (P = 0.0001). TIS and routine screening were equivalent in sensitivity and specificity for the final cytology result, but BMSs were significantly more likely to classify slides as dyskaryotic rather than borderline when using TIS compared with routine screening. Referrals for potentially high‐grade abnormalities detected by TIS‐assisted IQC alone found 28 biopsies of at least cervical intraepithelial neoplasia grade 2 (CIN2+), whereas 15 CIN2+ biopsies were found on routine screening but missed using TIS. There was no significant change in the rates of inadequate tests, high‐ or low‐grade cytological abnormalities, or positive predictive value for CIN2+ when TIS was in use. Conclusions: Screening with TIS was more sensitive than RR for IQC, providing a rescreening method equivalent to routine primary screening in overall accuracy.     

Estimating the sensitivity of cervical cytology: errors of interpretation and test limitations

The objective of this study was to estimate: (i) the sensitivity of cytologists in recognizing abnormal smears; (ii) the sensitivity of cervical cytology as a method of detecting abnormal smears among those obtained in the presence of cervical intraepithelial neoplasia (CIN). Study subjects were 61 women with a histologically confirmed CIN identified through colpohistological and cytologic screening. For objective (i) new smears were taken from study subjects just before treatment, mixed with routine preparations, interpreted by unaware cytologists and then blindly reviewed by a group of three expert supervisors, who reached a consensus diagnosis. Cytologists classified as positive for squamous intraepithelial lesion (SIL) 30 of the 34 smears judged as positive by supervisors (100% of smears classified as high-grade and 67% of smears classified as low-grade SIL by the supervisors). Our approach, based on creating a set of smears with a high a priori probability of being positive, proved to be an efficient way of estimating errors of interpretation. For objective (ii), smears taken at the moment of diagnosis, just before biopsy, were also reviewed by the same supervisors. These CIN cases were identified among asymptomatic women independently of cytological findings and results are therefore not subject to verification bias. Among the 33 histological CINII/III, four (12%) smears had no atypical cells (three negatives and one unsatisfactory) at review. The same proportion was 26% (four negatives and one unsatisfactory) among the 19 histological CINI. No significant differences in smear content were found between the seven ‘false negatives’ and a sample of ‘true positives’ and ‘true negatives’ for a number of formal adequacy criteria (including presence of endocervical cells). Strong differences were found between positive smears taken just before biopsy and those taken just before treatment (in 11 women the first smear only was positive, while the opposite was never observed), suggesting an effect of punch biopsy in removing lesions.     

Rapid screening: a comparative study

Although rapid screening of negative and inadequate cervical smears is a quality assurance requirement for all UK laboratories, there has been little attempt to standardize the method and laboratories make use of a number of different techniques and times. The aim of this study was to assess the sensitivity of these various techniques by measuring their ability to pick out known false-negative smears. Completed questionnaires from 123 laboratories across England revealed that 52% of laboratories use a "step" technique, 19% use "turret", 15% use random paths and 34% attempt to rescreen the whole slide quickly. Twenty-two percent of laboratories use a mixture of techniques. Timings are also variable, with the majority of laboratories allowing screeners to review slides at a pace decided by themselves but usually between 1 and 2 min. The study involved 120 participants who performed a total of 24 000 rapid screens. The results showed that, of the 90 abnormal slides used in the study, 62 cases (69%) were identified as abnormal or needing review by more than 50% of participants. Overall rapid screening picked out 58% of high-grade squamous abnormalities, 59% of low-grade abnormalities and 72% of glandular lesions. Step screening performed best, followed by whole slide/random and then turret. One minute was the optimum time and there was a significant fall in performance once individuals attempted to rescreen large numbers (>50). The most significant finding was the marked variation in the performance of individuals using the same slide sets.     

Inflammatory atypia and the false-negative smear in cervical intraepithelial neoplasia

The effectiveness of cervical cytologic screening is compromised by the increasingly recognized prevalence of false-negative smears. Our previous studies suggested that some false-negative cytologies can be accounted for by smears showing cervical intraepithelial neoplasia (CIN) reported as inflammatory atypia; we found that at least 4% of 5,752 consecutive smears had been underreported in this manner. In the present study, that data was reanalyzed to derive 95% confidence limits for the number of CIN smears reported as inflammatory atypia. Using several differing estimates of cytologic screening sensitivity, it is speculated that, under certain testable assumptions, colposcopy of patients with cytologic diagnoses of inflammatory atypia may be one cost-effective approach to finding CIN cases missed by screening. If confirmed, these findings imply that laboratory quality assurance efforts, traditionally directed to the most serious cytologic diagnoses, should also focus in part on nondysplastic atypia.     

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.     

Rapid cervicovaginal smear screening: method of quality control and assessing individual cytotechnologist performance

AIM: To validate the method of rapid screening (RS) in the detection of cervical lesions and false-negative results as well as in quality control of cytotechnologist performance. MATERIAL AND METHODS: The RS method was validated on Papanicolaou-stained and initially conventionally analysed vaginal, cervical and endocervical (VCE) smears collected in an opportunistic programme for the detection of cervical carcinoma. The study included 3680 VCE smears from the Department of Gynaecologic Cytology, University Department of Gynaecology and Obstetrics, Zagreb University Hospital Center, Zagreb and from the Department of Clinical Cytology, Osijek University Hospital, Osijek. Histologically verified abnormal findings accounted for 10% of the study samples. Thirteen cytotechnologists, with no previous experience in RS, performed the test. Each slide was examined using the 'step' technique for 1.5 minutes, the findings were classified as negative or abnormal, and the abnormal ones were also classified according to differential cytological diagnosis. The results were compared with those obtained on initial screening. Abnormal findings from a group of initially negative findings were reanalysed using conventional methods to make definitive cytological diagnosis. RESULTS: RS yielded a sensitivity of 83.7%, specificity of 93.7%, positive predictive value of 62.4%, negative predictive value of 97.9% and diagnostic accuracy of 92.6%. Relative to the initial abnormal differential cytological diagnosis, the diagnostic value of RS increased with lesion severity [54.8%, 68.0% and 91.3% for cervical intraepithelial neoplasia (CIN) I, CIN II and CIN III respectively]. RS detected 38 additional positive findings; 94.2% of these were atypical squamous cells of undetermined significance (ASCUS)/abnormal glandular cells undetermined significance (AGUS) and CIN I. The rate of additional positive findings was 1.14% (38/3135). The false-negative rate of initial screening was 9.4% (38/406), and individual cytotechnologist sensitivity was 60.0-100.0%. CONCLUSION: RS could be introduced as an efficient method of quality control to improve the sensitivity of cytological screening as well as for quality control of cytotechnologist performance.     

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.     

Rapid rescreening of cervical smears as a quality control method in a high-risk population

OBJECTIVE: Cancer of the cervix is one of the commonest cancers in South Africa. Accurate cytological diagnosis is one of the prerequisites for an effective cervical screening programme and requires the implementation of appropriate quality assurance modalities. This study was undertaken to determine if rapid review of reportedly negative cervical smears is a useful internal quality assurance modality in an unscreened population with very high rates of cervical carcinoma. METHOD: Approximately 26% of all cervical smears received at the study institution between 1 January 1998 and 31 December 2003, and initially reported as negative or inadequate, underwent rapid review. RESULTS: A total of 62,866 (26%) cervical smears out of 241,796 reportedly negative or inadequate cervical smears underwent rapid review. An amended report was sent out in 373 (0.59%) of these 62,866 cervical smears. This included 101 cases of high-grade squamous intraepithelial lesion (HSIL) and high-grade atypical squamous cells (ASC-H), 143 low-grade squamous intraepithelial lesions, 54 atypical squamous cells of undetermined significance (ASC-US) and 33 atypical glandular cells that were not reported initially. The false-negative proportion for HSIL and ASC-H (combined) in this study was 5.76%. No squamous cell carcinomas were diagnosed on rapid review but one patient with HSIL/ASC-H on review had squamous cell carcinoma on biopsy. Three cytotechnologists had a lower sensitivity of primary screening and required retraining. CONCLUSIONS: Rapid review is beneficial as an internal quality assurance modality in an unscreened high-risk population and increases the detection of women with significant cervical lesions requiring treatment. The relatively low cost of rapid review compared with other rescreening modalities makes this an attractive option in low resource settings.     

Large performance variation does not affect outcome in the Finnish cervical cancer screening programme

S. Lönnberg, P. Nieminen, L. Kotaniemi‐Talonen, H. Kujari, J. Melkko, G. Granroth, M. Vornanen, T. Pietiläinen, J. Arola, J. Tarkkanen, T. Luostarinen and A. Anttila Large performance variation does not affect outcome in the Finnish cervical cancer screening programme Objective: Cytology screening for prevention of cervical cancer can reduce incidence and mortality by more than 80% in settings with good organization and rigorous quality control. Audit studies are essential for reaching and maintaining a high quality of screening. The aim of this study was to evaluate variation in performance indicators by screening laboratory and assess the impact on the effectiveness of screening as indicated by cervical intraepithelial neoplasia grade 3 and above (CIN3+) rates after a negative screen. Methods: Seven cytology screening laboratories operating during 1990–1999 with a total of 953 610 screening tests performed were included in the study. By linking screening and cancer register files, all cases of CIN3+ diagnosed in the screened population were identified. For 395 CIN3+ cases with a preceding negative screen and 787 controls, a re‐evaluation of smears was undertaken to uncover false negative screening tests. Performance parameters and rates of CIN3+ after a negative screen were analysed for interlaboratory heterogeneity. Results: The rates of follow‐up recommendations and referrals varied by up to 3.6‐ (2.8–10.2%) and 4.0‐fold (0.03–0.12%), respectively. CIN1, CIN2 and CIN3+ screen detection rates differed by up to 8.5‐ (0.02–0.17%), 5.4‐ (0.05–0.25%) and 3.3‐fold (0.05–0.18%). False negative rates determined by re‐evaluation showed up to 2.1‐fold differences (29–62%). Rates of CIN3+ after a negative screen (0.023–0.048%) and as a proportion of total CIN3+ (15–31%) in the screened population were low and did not vary significantly. Conclusions: There were large variations in the sensitivity–specificity trade‐off between laboratories, reflected in all performance indicators as well as in the test validity estimates of the re‐evaluation phase, but not in screening effectiveness. Even though performance variations do not always have an impact on the effectiveness of screening, they lead to variations in cost, treatment and psychological burden, and should be addressed.     

The role of cervical cytology and colposcopy in detecting cervical glandular neoplasia

Objective:  To determine the role of cervical cytology and colposcopy in the management of endocervical neoplasia.
Setting:  Colposcopy unit and cytology laboratory in a teaching hospital.
Sample:  Group 1 included 184 smears showing endocervical glandular neoplasia from 129 patients and group 2 included 101 patients with histology showing endocervical abnormalities in a 6-year period (1993–1998). Follow-up of 6–11 years to 2004 was available.
Methods:  Group 1 were identified from the cytology computer records. Group 2 were identified from histology records on the cytology database and a record of histology cases kept for audit purposes. The clinical records were examined retrospectively.
Results:  The positive predictive value (PPV) of abnormal endocervical cells in smears was 81.1% for significant glandular/squamous [cervical glandular intraepithelial neoplasia (CGIN)/cervical intraepithelial neoplasia grade2 (CIN2 or worse)] lesions. The PPV of colposcopy was 93.5% for significant glandular/squamous lesions of the cervix. The postcolposcopy probability of a significant lesion when colposcopy was normal was 87.5%. The sensitivity of colposcopy in detecting endocervical lesions was 9.8%. The sensitivity of cervical smears in detecting a significant endocervical abnormality (CGIN or worse) was 66.3%. The false negative rate for cytology of endocervical glandular lesions was 4.0%.
Conclusions:  Endocervical glandular neoplasia detected on cytology is predictive of significant cervical pathology even when colposcopy is normal, which supports excisional biopsy in the primary assessment of these smears. The high concomitant squamous abnormality rate justifies the use of colposcopy to direct biopsies from the ectocervix. Cervical cytology is the only current screening method for cervical glandular abnormalities but sensitivity is poor.     

O-5UNIDIRECTIONAL VERSUS BIDIRECTIONAL SCREENING OF SUREPATH® LIQUID BASED CYTOLOGY SLIDES –PITFALLS & PERILS OF STUDY DESIGN

Although the characteristics of false negative conventional smears have been well documented there is limited literature available for Liquid Based Cytology (LBC), especially with regard to SurePath ™ samples. We will present the results of a 16 month audit and describe the typical characteristics of false negative cases in a medium sized screening laboratory processing approximately 42 000 samples per annum. Cases were identified either from routine rapid screening or by review of negative samples from women with a known high grade CIN lesion. 153 cases were identified: 149 by rapid screening, the remainder by review of the negative samples from women with known CIN. Of those identified by rapid screening 123 were reported as borderline nuclear change, 11 as mild, 4 as moderate, 8 as severe and 3 as CGIN. Only those cases that were found to have a histological lesion were used in the study ( n  = 27): Twenty-three were identified by rapid review and a 4 by review of previous negative samples. Six were found to have CIN 1, 7 CIN 2, 13 CIN 3 and 1 CGIN. Examples of the typical characteristics will be demonstrated. Features similar to those observed in conventional smears were identified; scanty abnormal cells (less than 30 per preparation), low contrast samples, pale cells and microbiopsies. In contrast to conventional smears, missed abnormal cells were almost always uniformly scattered throughout the sample.     

Benign cellular changes in Pap smears. Causes and significance

OBJECTIVE: We reviewed consecutive cases classified as benign cellular changes (BCC) over a four-month period. STUDY DESIGN: Cases classified as BCC were retrieved from the cytology files. A search was carried out to identify the previous Pap smears and concomitant cervical biopsies. RESULTS: One thousand one hundred three cases (23% of our gynecologic smears) were classified as BCC. Ninety-two patients (8.3%) underwent concurrent cervical biopsies. Specific infections accounted for 8% of BCC cases; reactive changes accounted for 92%. Of the biopsy specimens, 8.3% had no significant pathologic change. The most common biopsy diagnoses were cervicitis (31.5%), immature squamous metaplasia (16.3%) and reserve cell hyperplasia (10.8%). Miscellaneous benign diagnoses accounted for 21.7%. Cervical intraepithelial neoplasia (CIN) 1/human papillomavirus (HPV) was present in 14% of cases. All patients with biopsy diagnoses of CIN 1 had at least two previous abnormal Pap smears. Previous biopsy reports were available for review in 127 (12%) of the 1,103 patients. Of these 127 cases, 53.5% had a previous diagnosis of CIN/HPV; 9.4% had invasive carcinoma. A benign diagnosis was reported in 36.5%. CONCLUSION: The majority of BCC cases are due to reactive and inflammatory processes. In patients with a previous history of CIN, BCC may be of some significance. In patients with no significant prior cervical abnormalities, a Pap smear classified as BCC represents a reactive process.     

P-6SCREENER SENSITIVITY – ALL CHANGE FOR LBC

Introduction:  This poster aims to provide a discussion point for the calculation of screener performance. LBC has brought about changes in the way slides are interpreted, single dispersed isolated dyskaryotic cells take on a new meaning and the process of quality control, rapid review has changed. These changes challenge the rationale behind screener sensitivity calculations especially as many laboratories are in an early learning phase with regard to LBC.
Method:  Screener sensitivities and the PPV of reporting consultants for a period of six months post LBC conversion are compared with those since the introduction of LBC.
Results:  Screener sensitivities have dropped below the 95% threshold for high-grade dyskaryosis.
Discussion:  The change in rapid review or preview from a partial stepped rescreening of a conventional smear to a full rescreening of LBC slides has meant that all missed abnormalities that may not have been visualised in the conventional slide have a greater possibility of detection in the LBC slide. In analysing screener sensitivity a holistic approach that assesses the reasons for missing or misdiagnosing high-grade abnormalities is advised. Over reporting by consultants as indicated by PPV and slide review should be taken into account when there is a suspected poor performer. The recent move to refer all mild dyskaryotic smears for colposcopic assessment and the EQA requirement for screeners to detect dyskaryosis without the necessity for grading suggests that there may be a need to reassess the basis of current screener sensitivity calculations.     

Rapid pre-screening of cervical smears as a method of internal quality control in a cervical screening programme

Objective:  To evaluate the performance of rapid pre-screening (RPS) as a method of internal quality control in the cytopathological examination of cervical smears for cervical cancer screening.
Methods:  The sample consisted of 6135 cervical smears submitted to RPS and routine screening (RS) methods. The smears classified as negative in RPS and RS were considered final diagnoses, and were not, therefore, submitted to any additional review. The smears identified as suspect or unsatisfactory according to RPS were analysed separately by two different cytologists irrespective of the diagnosis reached in RS. Smears considered abnormal or unsatisfactory at RS were also reviewed. When both cytologists issued concordant diagnoses, this was considered the final diagnosis. Discordant results were analysed by a third cytologist and a consensus meeting was held to define the final diagnosis.
Results:  Taking abnormalities detected by RS as the denominator, RPS had a sensitivity of 63.0% for the detection of all abnormal smears and 96.7% for high grade squamous intraepithelial lesion (HSIL). When compared with the final diagnosis, sensitivity of RPS for all abnormal smears was 74.9% and for HSIL 95.0%. Of the 529 abnormal smears confirmed in the final diagnosis, 2.15% were detected only by the RPS.
Conclusion:  RPS is an effective alternative method of internal quality control with high sensitivity for the detection of more severe lesions. It also permits monitoring of the laboratory rate of false-negative results, and allows constant evaluation of the performance both of the pre-screening and RS cytologists.     

Numerical chromosomal aberrations of chromosome 1 and 7 in dysplastic cervical smears

Cervical smears with Papanicolaou's staining (PAP) reveal only morphological characteristics of epithelial cells of the cervix uteri. Since chromosomal aberrations are known to play a role in malignant transition, we analyzed cervical smears for numerical changes of the chromosomes 1 and 7 with fluorescence in-situ hybridization to probe for a diagnostic value of these chromosomes in the characterization of cervical dysplasia. Cervical smears were collected from 21 patients with suspect histology of curettage or biopsy specimen, 14 of them having been subsequently graded as cervical intraepithelial neoplasia (CIN) III and 5 as CIN II. Nineteen normal cervical smears (PAP I-II) served as controls. Smears were hybridized with chromosomal enumeration probes for chromosome 1 and 7. Disomic cells (2 copies of chromosome 1 and 7) were decreased in the CIN II (63%) and CIN III group (57%) with respect to the control group (77%). Cells with 3 signals for chromosome 7 were significantly more frequent in the CIN III and the CIN II group than in the control group (6.7, 6.4 and 0.7%, respectively). Only the CIN II group (10%), but not CIN II (6%), showed a significant trisomy for chromosome 1 as compared with the controls (3.8%). A close correlation between the incidence of trisomy 1 or 7 and PAP grading was observed. PAP III-IIID smears with high trisomy 1 counts corresponded to CIN III histology, while all CIN II patients were PAP III-IIID with low incidence of trisomy 1. We conclude that trisomy of chromosome 7 is a feature of cervical dysplasia and seems to be an early event in dysplastic transition. In contrast, trisomy of chromosome 1 is observed only in high grade dysplasia and may be a marker for pre-malignant lesions.     

Cytologically detected chlamydial changes and progression of cervical intraepithelial neoplasias. A retrospective case-control study

Fifty-four patients with Chlamydia-associated changes on the cervical smears, in whom adequate follow-up had been obtained over a two-year period, were investigated. The progression to biopsy-proven cervical intraepithelial neoplasia (CIN) III in this group was 42.6%, significantly higher than the 15.8% progression rate noted in a control group of patients with similar cytologic abnormalities but unassociated with Chlamydia. This finding suggests that Chlamydia may be a cocarcinogen or a potentiating agent in the progression of CIN.     

HPV triage of women with atypical squamous cells of undetermined significance: a 3-year experience in an Italian organized programme

OBJECTIVE: The purpose of our study was to determine if Hybrid Capture II assay (HCII) on Liquid Based Cytology (LCB) improves the accuracy (higher sensitivity, similar specificity) than the repeat conventional Pap smear in smears with Atypical Squamous Cell (ASC) of Undetermined Significance diagnosis. METHODS: HPV testing was used to manage women, especially the older ones, with cervical abnormalities detected through our triennial organized screening in order to avoid unnecessary colposcopy and excessive follow-up if the woman is HPV negative. The HPV DNA Triage was offered without any charge to 909 women with ASC. The Bethesda System was used for the classification of these equivocal cytological findings and more precisely the 1991 version (ASCUS) until the summer 2001 (315 cases) and the new one 2001 classification (ASC-US and ASC-H) after this date (594 cases). The presence or absence of a cervical intraepithelial neoplasia of grade I or worse [CIN1+], and of grade II or worse [CIN2+], was confirmed by biopsy. RESULTS: The HPV DNA Triage showed a good accuracy (specificity over 94%, sensitivity of 37% and PPV for CIN2+ lesions around 30%). The higher values of ASC-H lesions (.462) for the sensitivity for CIN 2+ probably signify that this lesion is already a SIL. CONCLUSIONS: Our data were comparable with those recently published on the meta-analysis by Arbyn et al., confirming the promising approach of our guidelines for the treatment of these patients even in terms of Health Technology Assessment (HTA).