Comparison of SurePath® and ThinPrep® liquid‐based cervical cytology using positive predictive value,atypical predictive value and total predictive value as performance indicators

P. K. Wright, J. Marshall and M. Desai Comparison of SurePath ^® and ThinPrep ^® liquid‐based cervical cytology using positive predictive value, atypical predictive value and total predictive value as performance indicators Objective: Two liquid‐based cytology (LBC) systems are in widespread use in the UK: ThinPrep^® and SurePath^®. A number of studies have now compared LBC with conventional cytology in cervical screening. However, to date, we are aware of no studies that have compared ThinPrep^® with SurePath^® LBC. As the selection and use of specific diagnostic systems in a laboratory has significant clinical and economic implications, there is a clear need to compare directly existing LBC technology. The objective of this study was to compare ThinPrep^® with SurePath^® LBC in a single cytology laboratory using performance indicators. Methods: Data were collected for all cervical cytology samples processed at Manchester Cytology Centre over a 1‐year period. ThinPrep^® LBC was compared with SurePath^® LBC using positive predictive value (PPV), atypical predictive value (APV) and total predictive value (TPV), reflecting outcome of cervical intraepithelial neoplasia (CIN) grade 2 or worse for high‐grade dyskaryosis (PPV), low‐grade dyskaryosis or borderline (atypical) cytology (APV) and all (total) abnormal cytology (TPV). Results: 2287 (out of 56 467) (ThinPrep^®) and 586 (out of 22 824) (SurePath^®) samples showed borderline or worse cytology after exclusion criteria. PPV, APV and TPV were within acceptable ranges for both ThinPrep^® and SurePath^®. Conclusions: ThinPrep^® and SurePath^® were equivalent based on three performance indicators. We suggest that APV and TPV should be used as an adjunct to PPV and other methods of quality assurance for cervical screening.     

An audit of the positive predictive value of high-grade dyskaryosis in cervical smears: 2001–2002

The positive predictive value (PPV) of high-grade dyskaryosis for cervical intraepithelial neoplasia grade 2 (CIN2) or worse on histology is published annually for the laboratories in the UK National Health Service Cervical Screening Programme (NHSCSP). The PPV fell in 2001 compared with 2000 for four of the five consultants reporting cervical smears in our laboratory, the greatest fall being from 91.6% to 77.9%. Investigation of the possible reasons for the fall suggested the main cause lay outside the laboratory in the type of biopsy taken at colposcopy. We conclude that biopsy type affects accuracy of PPV calculations. There is variation in collection and submission of KC61 data including PPV across laboratories. This factor needs to be taken into account when publishing and comparing laboratory data for the NHSCSP.     

ABC3 Part II: a review of the new criteria for evaluating cervical cytology in England

R.G. Blanks
ABC3 Part II: a review of the new criteria for evaluating cervical cytology in England The new Achievable Standards, Benchmarks for Reporting, and Criteria for Evaluating Cervical Cytopathology, 3rd edn (ABC3) includes radical changes in the criteria for evaluating cervical cytology. First, they include a new mission statement ‘the objective of cervical screening is to reduce cervical cancer incidence and mortality by screening with a high sensitivity for the detection of CIN2 or worse, whilst maintaining a high specificity’. Second, the original four performance measurement criteria where laboratories were examined further if they were below the 10th or above the 90th percentile has been changed to three and laboratories are only mandatorily examined if they fall below the 5th or above the 95th percentile. The old criteria related to the percentage of samples that were inadequate, the percentage of all adequate samples reported as moderate dyskaryosis or worse (equivalent to high‐grade squamous intraepithelial lesion or cancer), the percentage of adequate samples reported as mild dyskaryosis or borderline (equivalent to low‐grade squamous intraepithelial lesion or atypical squamous/glandular cells) and the positive predictive value. The new criteria are percentage of inadequate samples, positive predictive value and a new measure termed referral value. These changes mean that far fewer laboratories will require mandatory examination. Third, a raft of optional performance measures have been introduced to help laboratories examine their annual statistical return to the Department of Health in comparison with other laboratories. These measures have been designed to produce a more uniform national programme, and to help laboratories decide whether they are maximizing the benefit of screening while minimizing the harm, which is the goal of all screening programmes. This review examines in detail the new criteria and explains in more detail some of the thinking behind them.     

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.     

Comparison of cytology and histology results in English cervical screening laboratories before and after liquid‐based cytology conversion: do the data provide evidence for a single category of high‐grade dyskaryosis?

R. G. Blanks and R. S. Kelly
Comparison of cytology and histology results in English cervical screening laboratories before and after liquid‐based cytology conversion: do the data provide evidence for a single category of high‐grade dyskaryosis? Objective: To determine whether the difference between the positive predictive value (PPV) for cervical intraepithelial neoplasia (CIN) grade 2 or worse (CIN2+) of referral from moderate dyskaryosis and from severe dyskaryosis was reduced after laboratories converted from conventional to liquid‐based cytology (LBC). Furthermore, to explore the cytology/histology agreement after LBC conversion, and to determine post‐LBC whether there was increased support for the use of one single category of high‐grade dyskaryosis (equivalent to high‐grade squamous intraepithelial lesion). Methods: The association between cytology and histology has been examined using annual Korner return data (KC61 returns) collected by laboratories from the English National Health Service cervical screening programme. The study compares return data before and after LBC conversion. Results: The study examined data from 102 laboratories that converted from conventional cytology to LBC. Before conversion the PPV for CIN2+ of severe dyskaryosis was 88% and after increased to 90% (P = 0.003). For moderate dyskaryosis the PPV for CIN2+ increased from 70% to 72% (P = 0.06). The absolute difference of 18% between severe and moderate dyskaryosis was therefore the same pre‐ and post‐LBC conversion. The PPV of mild dyskaryosis for CIN2+ before and after conversion reduced from 23% to 19% (P < 0.001). The agreement between cytology and histology measured using a weighted Kappa statistic increased from 0.52 to 0.60 after conversion to LBC because of small increases in the proportions of severe dyskaryosis or worse with CIN3+ outcomes and mild dyskaryosis with CIN1 or less outcomes. Conclusions: Following LBC conversion there was evidence of a modest increase in the agreement between cytology and histology but no evidence of a change in the absolute difference in PPV for CIN2+ between moderate and severe dyskaryosis. The data support the conclusion that women referred with moderate dyskaryosis will on average have a lower risk of progression to invasive cancer than women referred with severe dyskaryosis. If the data were considered to support the categories of high‐grade dyskaryosis (moderate) and high‐grade dyskaryosis (severe) before LBC conversion then it can be strongly argued that they also support these categories after conversion.     

Outcomes of cervical liquid-based cytology suggesting a glandular abnormality

Objective: To ascertain the positive predictive value of both ?glandular neoplasia (national standard code 6) and borderline change (national standard code 8) in glandular cells in liquid‐based cervical cytology specimens in Cardiff and Vale NHS Trust and to outline the histological outcomes of these cases. Method: Eighty‐nine liquid‐based (Surepath?) cervical cytology cases were retrospectively identified from a 2‐year period (January 2005 to December 2006) and correlated with histopathological diagnoses. Results: Initial punch biopsy histology revealed 18 cases (21%) of cervical glandular intraepithelial neoplasia (CGIN). A further nine cases (10%) of CGIN were identified following local excision or hysterectomy. Ten cases of invasive malignancy were identified: four endocervical adenocarcinomas (all node negative, TNM stage T1b1), five endometrial adenocarcinomas and one squamous cell carcinoma. There were 10 with high‐grade cervical intraepithelial neoplasia (CIN) alone. Women diagnosed with endometrial malignancy presented later with an average age of 64.6 years compared with 34.9 years for endocervical lesions. Taking high‐grade CIN or worse as a positive outcome, the overall positive predictive value (PPV) of glandular abnormalities on cytology (both code 6 and 8) was 58.1% [95% confidence interval (CI) 47.8, 68.4]. PPV for borderline change in glandular cells alone was 24.1% (95% CI 8.5, 39.6) and for ?glandular neoplasia alone 75.4% (95% CI 64.3, 86.5). Conclusion: With our interpretation of the classification, women with cytological diagnoses of glandular neoplasia of the cervix should initially be investigated by local resection rather than punch biopsy, and those with borderline change in glandular cells with repeat cytology.     

An audit of liquid‐based cervical cytology screening samples (ThinPrep and SurePath) reported as glandular neoplasia

S. A. Thiryayi, J. Marshall and D. N. Rana
An audit of liquid‐based cervical cytology screening samples (ThinPrep and SurePath) reported as glandular neoplasia Objectives: The aims of this study were to assess the number of cases diagnosed as glandular neoplasia (national report code 6) of cervical (6A) and non‐cervical (6B) types on ThinPrep (TP) and SurePath (SP) liquid‐based cytology (LBC) samples and to calculate the positive predictive value (PPV) of these diagnoses for significant glandular and/or squamous pathology for local audit and as a contribution to national data on glandular neoplasia. Methods: A computerized search identified all screening LBC samples reported as glandular neoplasia during the 24‐month period from January 2006 to December 2007. Corresponding histology samples were identified, with a minimum follow‐up period of 6 months for each case. Results: A total of 70 samples, representing 70 patients, were reported as glandular neoplasia, 39 TP (55.7%) and 31 SP (44.3%), with 46 samples (31 TP, 15 SP) reported as 6A and 24 samples (eight TP, 16 SP) as 6B. PPV of glandular neoplasia was calculated for a biopsy diagnosis of cervical glandular intraepithelial neoplasia/adenocarcinoma and/or cervical intraepithelial neoplasia (CIN) 2 or worse. The PPV of 6A was 100% for both TP and SP. The PPV of 6B for adenocarcinoma was 62.5% for TP and 66.7% for SP. The combined PPV for 6A + 6B was 92.3% for TP, 83.3% for SP and 88.4% combined. The overall pick‐up rates for the two methods were significantly different (TP 0.031%, SP 0.052%; P = 0.014). Histology showed only CIN3 with endocervical crypt involvement in nine TP cases and one SP case.     

P16(INK4a) immunocytochemistry in liquid-based cytology samples in equivocal Pap smears: added value in management of women with equivocal Pap smear

OBJECTIVE: To test whether p1l6(INK4a) immunocytochemistry (ICC) in liquid-based cytology (LBC) is useful with colposcopy in abnormal Pap smears. STUDY DESIGN: A series of 248 women with abnormal Pap smear were analyzed for oncogenic (HR) human papillomavirus (HPV) types using the Hybrid Capture II assay and for p16(INK4a) expression using ICC on cervical samples in PreservCyt liquid media. Colposcopic and loop electrosurgical excision procedure (LEEP) cone biopsy were the gold standard. RESULTS: p16(INK4a) ICC did best as predictor of high-grade squamous intraepithelial lesion, with OR 12.18 (2.72-54.57) (p = 0.0001), showing 88.2% sensitivity (SE), 61.9% specificity (SP), 14.6% positive predictive value (PPV) and 98.6% negative predictive value (NPV). In sorting discrepant cases, p16(INK4a) ICC results in 100% SE and 100% NPV in detecting cervical intraepithelial neoplasia (CIN) 2 lesions among Pap+/biopsy- women. In atypical squamous cells undetermined significance (ASCUS) cytology, adding p16(INK4a) ICC improves specificity of colposcopy from 27.3% to 81.8% and PPV from 42.8% to 71.4%. Best performance is obtained with p16(INK4a) ICC and colposcopy: 83.3% SE, 81.8% SP, 71.4% PPV and 90.0% NPV. CONCLUSION p16(INK4a) is useful in sorting clinically relevant discrepant cases, and p16(INK4a) ICC significantly improves SP and PPV of colposcopy in management of ASCUS cytology.     

How predictive is a cervical smear suggesting glandular neoplasia?

The prevalence of endocervical adenocarcinoma and its precursors has increased, in part due to increased diagnostic awareness of these lesions. To date, limited information has been published regarding the predictive value of glandular abnormalities in cervical smears. This study details the histological follow up of 418 cervical smears showing glandular abnormality, reported in our department over a six year period from 1993 to 1998. Histological follow up was available for 395 of the 418 smears (94.50%). The overall positive predictive value (PPV) for this group of smears was 72.66% for either significant glandular or squamous pathology (at least low grade cervical glandular intraepithelial neoplasia or CIN2 on follow up biopsy), and 55.70% for significant glandular pathology alone. Examination of subcategories of abnormal glandular smear showed that the PPV increased with the degree of abnormality reported within the smears.     

Conventional Pap smear and liquid-based cytology as screening tools in low-resource settings in Latin America: experience of the Latin American screening study

OBJECTIVE: To evaluate the performance of the conventional Pap test and liquid-based cytology (LBC) in an ongoing multicenter trial testing optional screening tools (cytology, screening colposcopy, visual inspection with acetic acid, visual inspection with Lugol's Iodine, cervicography and Hybrid Capture II [HCII] (Digene Brazil, S?o Paulo, Brazil) conventional and self-sampling), for cervical cancer in Brazil and Argentina. STUDY DESIGN: A cohort of 12,107 women attending four clinics (Campinas, S?o Paulo, Porto Alegre, Buenos Aires) were randomized into the 8 diagnostic arms. Women testing positive with any of the tests were referred for colposcopy, and cervical biopsies were used as the gold standard to assess performance characteristics of the diagnostic tests. Conventional Pap smears were sampled by all clinics (n = 10,240), and LBC (Autocyte PREP, [TriPath Imaging, Burlington, North Carolina, U.S.A.], n=320, and DNA-Citoliq [Digene Brazil], n =1,346) was performed by 1 of the clinics. RESULTS: Conventional Pap smears showed no squamous intraepithelial lesions (normal) in 8,946 (87.4%) and LBC in 1,373 (82.4%). Using high grade squamous intraepithelial lesions (HSIL) as the cutoff, Pap smears predicted high grade (cervical intraepithelial neoplasia [CIN] 3) with OR 63.0 (95% CI, 36.90-107.70), standard error (SE) 59%, SP 97.8%, positive predictive value (PPV) 68.1% and negative predictive value (NPV) 96.7%. The same figures for Autocyte PREP were: OR 9.0 (95% CI, 2.43-33.24), sensitivity (SE) 33.3%, specificity (SP) 100%, PPV 100% and negative PV (NPV) 88.8%. DNA-Citoliq detected CIN 3 as follows: OR 11.8 (95% CI 2.60-53.26), SE 40.0%, SP 94.6%, PPV 40.0% and NPV 94.6%. Lowering the cutoff to low grade squamous intraepithelial lesions increased SE and NPV but compromised SP and PPV. The detection rates for high grade lesions after an atypical squamous cells of undetermined significance diagnosis were similar with the 3 techniques. In our settings, the 3 methods of cervical cytology were slightly different in performance. The conventional Pap smear had the highest SE, while Autocyte PREP had 100% SP and PPV in detecting CIN3 with the HSIL cutoff. All 3 tests had lower SE but higher SP as compared to HCII.     

Atypical glandular cells of undetermined significance. Cytologic predictive value for glandular involvement in high grade squamous intraepithelial lesions

OBJECTIVE: To verify the cytologic predictive value of a diagnosis of atypical glandular cells of undetermined significance (AGUS) in high grade squamous intraepithelial lesions (HSIL) cases. STUDY DESIGN: In a retrospective study, 98 cases of HSIL were reviewed. All patients were referred for colposcopy and directed biopsy to confirm the cytologic diagnoses. Loop excision of the transformation zone was performed to treat clinical lesions. Sensitivity, specificity, positive and negative predictive value were evaluated. Kappa statistics and logistic regression analysis were used to evaluate the findings statistically. RESULTS: By logistic regression analysis, we found that the chance of finding squamous intraepithelial lesions involving glands in AGUS smears was 5.32 times higher than in those with no AGUS. It was 5.74 times higher in cervical intraepithelial neoplasia (CIN) 3 lesions than in CIN 2. CONCLUSION: The cytologic predictive value for HSIL involving glands is statistically significant when specific and objective criteria are used for the AGUS diagnosis.     

Diagnostic value of cytology and colposcopy for squamous and glandular cervical intraepithelial lesions

The main objective of work was to determine a diagnostic value of cytology and colposcopy as a method of screening and differential diagnosis, as well as to determine the relative value of some colposcopic features of squamous and glandular cervical intraepithelial lesions. Cytological diagnosis and colposcopy findings is compared with histological ones for 187 patients with intraepithelial lesions (142 squamous and 45 glandular ones with or without squamous components) and determined the sensitivity and positive predictive value of cytology and colposcopy, including the types of colposcopic abnormalities associated with squamous/glandular intraepithelial lesions. The sensitivity of cytology as a screening method for SIL (squamous intraepithelial lesions) is 89% and for GIL (glandular intraepithelial lesions) 98%. Positive predictive value of differential cytology for SIL is 59% and for GIL 53%. Sensitivity of colposcopy for both lesions' type is 87%. Acetowhite epithelium occurs for more often with SIL, whereas atypical vessels and unequal, dilated gland openings with GIL (p < 0.05). Cytology and colposcopy as screening methods have a high sensitivity. Nevertheless, cytology is far more accurate in determining differential diagnosis of SIL than GIL and some colposcopy abnormalities suspicious of GIL should be further tested in praxis.     

Diagnostic and prognostic significance of image cytometric DNA ploidy measurement in cytological samples of cervical squamous intraepithelial lesions

D. Demirel, N. Akyürek and I. Ramzy
Diagnostic and prognostic significance of image cytometric DNA ploidy measurement in cytological samples of cervical squamous intraepithelial lesions Objective: To study the DNA ploidy pattern of uterine cervical squamous intraepithelial lesions (SILs) and its diagnostic and prognostic significance. Methods: The study included 31 cases of SIL: 11 low‐grade (LSIL) and 20 high‐grade (HSIL). Feulgen–pararosaniline staining was performed on previously Papanicolaou‐stained smears and a DNA image cytometric study was performed. An internal reference was used to calibrate the samples. Results: All 31 cases of SIL, either LSIL or HSIL, were non‐diploid. Of the 11 cases of LSIL, four were tetraploid and seven were aneuploid, whereas, of the 20 cases of HSIL, four were tetraploid and 16 were aneuploid. Stemline aneuploidy was not a significant discriminator between LSIL and HSIL (P = 0.32). Based on single‐cell analysis, HSIL cases had significantly higher DNA content than LSIL cases (P < 0.01). When a mean of 30% or more was used for the 6c‐exceeding event (6cEE) value, the sensitivity and specificity to indicate HSIL were 83% and 64%, respectively, with a positive predictive value (PPV) of 81% and negative predictive value (NPV) of 65%. All HSIL cases were cervical intraepithelial neoplasia grade 2 or worse (CIN2+) on biopsy. In addition, cases which showed recurrence had more DNA content by single‐cell analysis than those with an indolent clinical behaviour: P = 0.04 and P = 0.03 for LSIL and HSIL, respectively. Conclusions: Image cytometric DNA analysis is a useful technique for diagnostic and prognostic purposes in uterine cervical SIL when appropriate ‘c’ values are used in single‐cell analysis. We propose that a >6c DNA content of 30% is useful as a cut‐off level for predicting cases with CIN2+ in DNA image cytometry of cervical smears.     

Improved rate of high-grade cervical intraepithelial neoplasia detection in human papillomavirus DNA hybrid capture testing

BACKGROUND: Numerous studies have established a link between human papillomavirus (HPV), squamous intraepithelial lesions (SIL) and carcinoma of the cervix. Testing for HPV DNA in addition to cytology in screening programs for cervical cancer has been suggested to increase detection rates. STUDY DESIGN: HPV DNA testing (performed by hybridization antibody capture assay I or II), cytology and biopsy (performed within 1 month of each other) were retrospectively reviewed for a series of 155 women. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of HPV testing vs. cytology were calculated using biopsy as the gold standard. These values were also calculated in a subgroup of 37 individuals older than 35 years. RESULTS: The sensitivity, specificity, PPV and NPV of DNA hybrid capture HPV testing for detecting high-grade cervical intraepithelial neoplasia (CIN) were 86%, 44%, 26% and 93%, respectively. The respective values for cytology detection of high-grade CIN were 17%, 97%, 56% and 82%. CONCLUSION: HPV testing was significantly more sensitive for detecting high-grade CIN than cytology (86% vs. 17%). Our data support immediate colposcopy and biopsy, rather than follow-up Papanicolaou testing, if the test for HPV DNA is positive for an intermediate- to high-risk type.     

Borderline nuclear change,high‐grade dyskaryosis not excluded: current concepts and impact on clinical practice

S. S. Hoo, A. Patel, H. Buist, K. Galaal, J. D. Hemming and R. Naik Borderline nuclear change, high‐grade dyskaryosis not excluded: current concepts and impact on clinical practice Objective: Borderline nuclear change, high‐grade dyskaryosis not excluded (B/HG) is a subcategory of the borderline category recommended by the British Society for Clinical Cytology as warranting direct referral to colposcopy. This subcategory is equivalent to the Bethesda category of atypical squamous cells, cannot exclude high‐grade squamous intraepithelial lesion (ASC‐H). The purpose of this study was to determine the validity and accuracy of using B/HG to identify potential cervical intraepithelial neoplasia (CIN) grade 2 or worse (CIN2+). Methods: Data were collected from the hospital pathology database for borderline, B/HG and high‐grade cytology (moderate dyskaryosis and above), and their respective histological and colposcopic outcomes. SPSS was used for data analysis. Results: Of the 84 799 total cytology samples screened between July 2006 and December 2009, 5225 (6.1%) were reported as borderline, 309 (0.4%) as B/HG and 1222 (1.4%) as high‐grade cytology. Thus, B/HG comprised 5.9% of the overall borderline category, in keeping with national guidelines (<10%). CIN2+ was confirmed in 86.6% of high‐grade, 40.8% of B/HG and 3.0% of borderline cytology. Of 309 women reported with B/HG cytology, 239 had colposcopy. Colposcopic appearances showed a positive predictive value (PPV) of 71.8% for detecting CIN2+ and a negative predictive value of 60.7%. Conclusions: The B/HG category was associated with a significantly higher incidence of CIN2+ compared with borderline cytology as a whole. This refining performance justifies its existence. Colposcopic appearances had a high PPV for detecting CIN2+. Therefore, colposcopy is recommended in patients with B/HG cytology and treatment should be offered if high‐grade colposcopic changes are seen.     

Human papillomavirus testing with a liquid-based system: feasibility and comparison with reference diagnoses

OBJECTIVE: To validate the utilization of cervical specimens collected in the fixative liquid used in the CYTO-screen System (SEROA, Monaco) for oncogenic human papillomavirus (HPV) DNA detection by the Hybrid Capture II technique (HCII) (Digene, Gaithersburg, Maryland, U.S.A) by reference to cytologic and/or histologic results. STUDY DESIGN: A technical feasibility study was conducted on 3 modalities of sample preparation before HCII technique, 1 with a proteinase digestion, I with PBS washing and I using the Digene sample conversion kit recommended for ThinPrep medium preparation (Cytyc Corp., Boxborough, Massachusetts, U.S.A.). The stability of cells after storage at days 28, 60 and 90 was tested on 26 positive samples (13 with high initial indices and 13 with low initial indices). Results of HPV testing were compared to cytologic and histologic results on a sample of 98 smears already identified as high grade squamous intraepithelial lesion (HSIL) (48) or low grade squamous intraepithelial lesion (LSIL) (50). A retrospective analysis was then performed on 995 HPV tests perfornmed routinely in 2003 in terms of comparison with the corresponding cytologic and/or histologic results. RESULTS: The HCII technique after direct treatment by proteinase K appeared to be as effective as the Digene sample conversion kit. By using the first technique, all 26 positive cases remained positive at 60 days, but 4 of 13 (30%) with low indices became negative at 90 days. The sensitivity of HPV testing for detecting biopsy- proven cervical intraepithelial neoplasia (CIN) 2 or worse was 100% in the 50 LSIL and 98% in the 48 HSIL samples. In the retrospective study (n = 995), the cytologic diagnoses of atypical squamous cells of undetermined significance (ASC-US) (n=278), LSIL (n = 137) and HSIL (n = 28) were associated with a positive HPVtest in 44%, 75% and 96% of cases, respectively. On a subsample of 156 patients among 278 with a diagnosis of ASC- US, the sensitivity of HPV testingfor detecting CIN 2 or worse was 88%, specificity 57%, positive predictive value 10% and negative predictive value 99%. Performing HPV testing by the HCII technique for cervical specimens collected in the fixative liquid used in the CYTO-screen System is feasible in the context of an ASC-US cytologic diagnosis.     

Prospective parallel randomized trial of the MultiCyte™ ThinPrep® imaging system: the Scottish experience

T.J. Palmer, S.M. Nicoll, M.E. McKean, A.J. Park, D. Bishop, L. Baker and J.E.A. Imrie
Prospective parallel randomized trial of the MultiCyte? ThinPrep^® imaging system: the Scottish experience Background: Computer‐assisted screening of cervical liquid‐based cytology (LBC) preparations using the ThinPrep® Imaging System (TIS) has shown improved qualitative and quantitative gains. The use of Multicyte? has not been described in a well‐established national screening programme with a low incidence of high‐grade dyskaryosis. Objectives: To assess the impact of computer‐assisted screening within the Scottish Cervical Screening Programme (SCSP). Methods: Two groups of three laboratories, each sharing a ThinPrep® Imager, screened 79 366 slides randomized to test and 90 551 to control arms by laboratory accession. Screeners were not blinded. Standard laboratory reporting profiles of the SCSP, sensitivity, specificity and false‐negative rates of all grades of LBC abnormalities with respect to final cytology reports, predictive value for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) on histology; and screening rates were compared for both arms. Results: Inadequate and negative reporting rates were significantly lower and low‐grade reporting rates significantly higher in the imager arm. Imager‐assisted screening showed significantly better specificity than manual screening with respect to the final cytology result. There was no evidence of a significant difference in the detection of CIN2 + or CIN3 + . Positive, abnormal and total predictive values (high‐grade, low‐grade and all abnormal cytology found to be CIN2 + , respectively) were similar in both arms. Productivity was significantly higher in the imager arm. Conclusion: Computer‐assisted screening in a well established screening programme showed significantly improved productivity without loss of quality. These findings should inform future policy for cervical screening programmes.     

Comparison of the conventional cervical smear and liquid-based cytology: results of a controlled, prospective study in the Abruzzo Region of Italy

OBJECTIVE: To compare conventional cervical testing (CCT) and liquid-based cytology (LBC) within a randomized trial performed during 2001-2002 in the Abruzzo Region of Italy, including a cost-outcome comparative analysis. STUDY DESIGN: Study subjects were recruited in the framework of a controlled, randomized study organized in the Abruzzo Region. Women aged 2 6-64 years were randomized to an active arm (LBC) or control arm (CC1). The particip ating laboratories had no previous ex perience with LBC. RESULTS: The inadequacy rate was 4.3% in CCT and 1.3% in the LBC arm (D < 0.001). Atypical squamous cells of undetermined sign ifi cance and atypical glands of undetermined significance reports were more frequent at CCT vs. LBC. A small, insignificant excess of low grade squamous intraepithelial lesions or high grade squamous epithelial lesions+ reports was observed in the LBC arm. The cervical intraepithelial neoplasia 2+ (CIN2+) detection rate was not statistically different in the 2 arms (CCT=0.54%, LBC= 0.66%, p = 0.28). In the overall series positive predictive value was slightly but not significantly higher in the LBC arm. LBC increased costs by 4.2% per both screened women and CIN2+ detected. CONCLUSION: The study reflects the introductory phase of LBC in laboratories without prior LBC experience. In this setting LBC reduced the inadequacy rate and decreased reading and was at least as sensitive as and more specific than CCT. Utilization of LBC in organized screening programs will be based on local feasibility, considering that the high cost of LBC is only partially compensated for by other benefits, such as residual cellular material, available for molecular testing, including human papillomavirus testing.     

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.