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.     

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.     

P-9A COMPARISON OF THE REPORTING MORPHOLOGICAL FEATURES OF GLANDULAR NEOPLASIA FOR CONVENTIONAL AND LIQUID BASED CYTOLOGY FOR CERVICAL SAMPLES

Cervical cancer accounts for approximately 15% of cancer diagnosed in women worldwide with up to 190 000 deaths per annum. One of the major causes of cervical cancer is the infection of human papillomavirus (HPV), a DNA virus. This virus is epidermotropic; there are over 75 subtypes and subtypes 16, 18, 31 and 33 are associated with cervical intraepithelial neoplasia (CIN) and carcinomas. Since the start of the cervical screening in mid 1960s, the cervical cancer rate has decreased. There are two techniques used for slide preparation and staining: conventional cytology and liquid based cytology (LBC). Due to the differences in sample collection and preparation, certain aspects of cell morphology, architecture and patterns will present differently from each other on the slide. The study was conducted in a County Hospital. Twenty conventional slides and eight LBC slides already reported as ? Glandular neoplasia were reviewed and assessed with regards to their morphological features. Moreover, conventional slides were compared with LBC slides to determine the differences in their cell morphology, sensitivity and specificity. Furthermore, a semi-quantitative method was used and also true-positive and false-positive rates were evaluated using positive predictive value (PPV). The findings indicated that despite the differences in cell morphology there are many similarities between the two techniques. The study also showed that it was difficult to distinguish between abnormal glandular cells and abnormal squamous cells, which may end in a false positive result and over reporting of glandular neoplasia. Finally, it showed that LBC slides were easier to screen and also had a higher positive predictive value (PPV) resulting in higher sensitivity and specificity. In conclusion, the LBC technique is more accurate and conversion to this technique is the positive step in the screening program.     

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.     

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.     

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.     

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.     

Decrease in numbers of glandular cell groups in post-LLETZ liquid-based cytology preparations

Objective:  Large loop excision of the transformation zone (LLETZ) has become standard of care in the management of cervical squamous neoplasia and with cone biopsy glandular intraepithelial neoplasia. Controversy remains about the long-term effects of this traumatic procedure. The aim of this study was to count and compare the number of endocervical glandular cell groups in pre- and post-LLETZ cervical preparations using liquid-based cytology to establish a cyto-morphological correlate of destruction of the transformation zone.
Methods:  The cytology/histology correlation audit records of the Cytopathology Department of St Luke's Hospital in 2003 and early 2004 were used to select patients with a cytological diagnosis of high grade dyskaryosis followed by LLETZ. Only those cases with post-LLETZ cytological follow-up were selected. Cases using conventional smears were excluded. One hundred and twenty slides (60 pairs of slides) in total were retrieved. The cases underwent review and all groups of >3 glandular cells in each slide were counted by AM while blinded as to whether smears were pre- or post-LLETZ. Medians were compared using a Mann–Whitney U -test.
Results:  The median number of groups of endocervical glandular cells of the pre-treatment group was 5.5 and of the post-treatment group was 2.0. There were significantly fewer endocervical glandular cell groups in the post-LLETZ population ( P  = 0.03).
Conclusions:  The number of endocervical glandular groups in cervical cytological preparations decreases significantly following LLETZ procedure. This suggests that cytological follow-up may not be as useful in glandular neoplasia cases. Few or absent glandular cell groups in post-LLETZ preparations may have implications for adequacy assessment.     

Endometrial carcinoma detected with SurePath liquid-based cervical cytology: comparison with conventional cytology

Introduction: Conventional Pap smears (CPS) have little impact on the detection of endometrial carcinoma. Although liquid‐based cytology (LBC) is replacing CPS in the UK, experience with identification of endometrial cancers with this technique is limited. Aim: To compare the accuracy of the SurePath LBC with that of CPS for detection of endometrial cancers. Methods: Our study group comprised SurePath LBC samples reported as atypical endometrial cells and endometrial adenocarcinoma (classified respectively as borderline, code 8 and ?glandular neoplasia, code 6 for the NHS Cervical Screening Programme statistics) in 2004–2005. CPS reported as atypical endometrial cells or adenocarcinoma in 1993–1998 comprised the control group. Histological follow‐up was obtained. Results: Endometrial abnormalities were reported in 95 (0.073%) of 130 352 LBC samples, comprising 75 (0.058%) atypical endometrial cells and 20 (0.015%) endometrial adenocarcinoma reports. Of 409 495 CPS, 117 (0.029%) were diagnosed as endometrial abnormalities, comprising 59 (0.014%) atypical endometrial cells and 58 (0.014%) endometrial adenocarcinoma reports. Thus, the endometrial adenocarcinoma reporting rate was similar in both groups, but that for atypical endometrial cells was higher with LBC (P < 0.001). The positive predictive value for endometrial cancer of endometrial adenocarcinoma and atypical endometrial cell reports in the LBC group was 73.3 and 18.8%, respectively, compared with 42.3 and 6.7% in the CPS group. The endometrial adenocarcinoma patients in CPS group were older (mean age 62.5 years versus 56.5 years) and most (22/25) were symptomatic, whereas most (13/17) patients in the LBC group were asymptomatic at the time of sampling (P < 0.001). Conclusion: SurePath LBC is at least as accurate a method for detecting endometrial cancer as CPS. SurePath LBC demonstrates enhanced identification of endometrial pathology in asymptomatic women in the cervical screening programme.     

A study to determine the underlying reason for abnormal glandular cytology and the formulation of a management protocol

A retrospective review is presented of 89 patients with glandular dyskaryosis in order to formulate a management protocol. Fifteen patients had cervical intraepithelial neoplasia (CIN) without glandular abnormality (17%). One patient had adenocarcinoma in situ of the cervix and one patient had vaginal intraepithelial neoplasia (VAIN) grade III. Twenty‐two patients had endometrial carcinoma (24.5%) and 11 patients had cervical carcinoma (12.5%). Of the patients presenting with post‐menopausal bleeding as well as having glandular dyskaryosis, 69% had a gynaecological malignancy. In conclusion, colposcopy and out‐patient endometrial sampling are recommended in all cases. Patients with abnormal endometrial sampling require hysteroscopy. Cone biopsy is necessary to exclude occult glandular disease if cytology remains abnormal despite negative colposcopy and sampling.     

Follow-up study of atypical glandular cells in gynecologic cytology using conventional Pap smears and liquid-based preparations: impact of the Bethesda System 2001

OBJECTIVE: This study evaluated the impact of the Bethesda System (TBS) 2001 in reporting of atypical glandular cells (AGC) when using conventional Pap smears (CS) and liquid-based cytology preparations (LBC). STUDY DESIGN: Follow-up information for all atypical glandular cells of undetermined significance (AGUS)/ AGC cases encountered in Queen Mary Hospital from July 2000 to June 2004 was analyzed. The difference in percentages associated with certain end points when using different reporting systems and preparation methods were compared. The age trends and time interval between cytologic diagnosis and detection of positive end points were studied. RESULTS: More than half of these cases turned out to be "negative." The majority with "negative" end points belonged to the "not otherwise specified" (NOS) groups (including atypical endometrial cells) in TBS 2001. The connotation of "favor neoplastic" carried a high positive predictive value for significant lesions. Most of the significant outcomes were discovered within the subsequent 6 months. A decreased reporting of "AGC, NOS" and an increased reporting of "atypical endocervical cells, NOS" were noted when using LBC. CONCLUSION: Subcategorization of AGC in TBS 2001 according to cellular origin and risk of malignancy, which is further enhanced by application of LBC, is useful.     

P-5AN UNUSUAL FORM OF THYROID PAPILLARY CARCINOMA: COLUMNAR CELL VARIANT WITH NEUROENDOCRINE FEATURES

Introduction:  Quality assurance guidelines for the UK cervical screening programme recommend that more than 80% of cervical samples from women aged 20–50 years should contain adequate numbers of Transformation zone (TZ) cells i.e. 10 or more endocervical or squamous metaplastic cells. This study was conducted to assess the frequency of TZ component in Liquid Based Cytology (LBC) both for ThinPrep (TP) and SurePath (SP) LBC. Also to assess the degree to which this is recorded by individual screeners and to determine the percentage of samples with evidence of TZ component for the different smear takers.
Method:  All LBC cervical specimens received at a tertiary cytology centre in the year 2004 from women aged 20–50 years were included in the study. Evidence of TZ sampling was recorded as: TP = TZ present (10 or more TZ cells)TA = TZ absentTS = TZ scanty (less than 10 TZ cells)TN = atrophic smears, TZ cells not recognisable
Results:  The total number of LBC cervical cases was 7445. TP = 4300 (mostly primary care) and SP = 3145 (mostly colposcopy). Overall TZ sampling rate in LBC was 82%. TP = 77.17%; SP = 88.24%. When scanty TZ was included, the standard was met for both systems (TP = 93.7%; SP = 88.24%). Presence/absence of TZ component was recorded in 6370 cases (85.1%); range 0%–97.79%. 56.7% of smear takers achieved the minimum standard for TZ sampling.
Discussion:  The percentage of ThinPrep samples containing adequate TZ cells was 77.17% compared to SurePath, which was 88.24%. This may be due to different patient populations i.e. primary care versus colposcopy. Screeners recorded TZ sampling in approximately 85% of samples. 56.7% of smear takers met the standard for TZ sampling.     

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.     

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.     

Clinical significance of atypical glandular cells by the 2001 Bethesda System in cytohistologic correlation

OBJECTIVE: To evaluate incidence, cytology findings and pathology outcome of atypical glandular cells (AGC) in Pap smears according to the 2001 Bethesda criteria. STUDY DESIGN: From 103,073 consecutive Pap smears, 113 (0.1%) AGC cases were identified. Of these, 91 (80%) had adequate histologic evaluation included in this study. RESULTS: Abnormal histology findings were seen in 38 patients (42%). Final pathology results revealed 14 endometrial adenocarcinomas, 5 endocervical adenocarcinomas, 1 cervical squamous cell carcinoma, 1 endometrial stromal sarcoma, 6 other malignancies, 4 endocervical adenocarcinomas in situ, 4 cases ofendometrial complex byperplasia, 1 case of endocervical glandular dysplasia and 2 cases of cervical intraepithelial neoplasia 3 with glandular involvement. Women with AGC, favor neoplasia, were more likely to have significant pathology than those with AGC, not otherwise specified, 74% vs. 33% (p = 0.002). Some characteristic background cytologic findings were also noticed in most cases of endometrial, fallopian tube and endocervical adenocarcinoma. CONCLUSION: A diagnosis of AGC is more clinically significant by the 2001 Bethesda System, especially the "AGC, favor neoplastic" category. Some background cytologic features are important because they are indicators of malignancy.     

A retrospective clinical audit of cervical smears reported as 'glandular neoplasia'.

The aims of this study were to review the diagnostic pathway of women with smears reported as 'glandular neoplasia' and to outline the management, colposcopy findings, treatment and final histological diagnosis in these women. The design was a retrospective review. A total of 114 women were identified over a 5-year period from the cytology database at the Royal Liverpool University Hospital Cytology Department, whose hospital case notes were available for review. Methods included a review of the case notes for the demographic details, indication for smear, colposcopic findings, investigation and/or treatment procedures, histology, final diagnosis and current disease status. Of 114 smears reported as 'glandular neoplasia', 67 were reported as consistent with cervical glandular intra-epithelial neoplasia (CGIN), six with endocervical adenocarcinoma, 36 with endometrial adenocarcinoma and five with other glandular neoplastic abnormalities. The average age was 46.5 years. 79 (69.3%) smears were routine call/recall and 36 (30.7%) women were symptomatic. The positive predictive value (PPV) for a significant histological abnormality in the CGIN smear group was 80.6% (23.9% invasive carcinomas, 43.3% CGIN and 13.4% CIN) and the PPV of an 'endometrial adenocarcinoma' smear was 86.1%. Smears indicating glandular neoplasia are associated with a high probability of clinically significant lesions, the PPV of a CGIN smear being over 80%. Immediate referral for colposcopy and assessment by an experienced colposcopist is recommended.     

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.     

Is a liquid‐based cytology more sensitive than a conventional Pap smear?

K. Sigurdsson
Is a liquid‐based cytology more sensitive than a conventional Pap smear? Background: The comparative sensitivity of liquid‐based cytology (LBC) test and conventional Papanicolaou (Pap) smears is controversial. Material and methods: This study analyses the distribution of cytology, histology, colposcopy and large loop excision of the transformation zone among women screened in Iceland with LBC at the Cancer Detection Clinic in Reykjavik and with a conventional Pap smear outside the Detection Clinic in 2007–2011. The study material included 42 654 LBC tests from 20 439 women and 103 909 Pap smears from 61 574 women. The period 2000–2004 is used to correct for potential bias as a result of unequal distribution of the studied parameters between the study sites before the introduction of LBC. Results: The observed results indicated that women screened with an LBC sample had significantly decreased detection rates of inadequate smears, increased detection of low‐grade squamous intraepithelial lesion (LSIL)/atypical cytology and referrals to colposcopy, and an increased detection rate of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) irrespective of age. LBC increased significantly the detection rates of high‐grade squamous intraepithelial lesion or worse (HSIL+) cytology and CIN3+ histology only in women under 40 years of age. Taking into consideration the unequal prevalence of the studied parameters between the study sites in 2000–2004 indicated, however, that LBC only affected the rate of inadequate and low‐grade cytology tests under the age of 40 years. Positive predictive values for CIN2+ were not significantly different between the tests. Conclusions: The study results support the view that LBC is no more sensitive than Pap smears for the detection of HSIL+ and CIN2+ irrespective of age. LBC decreased the rate of inadequate smears, but increased the rate of low‐grade cytology under the age of 40 years and decreased the total rate of abnormal smears over the age of 40 years.     

O-9Uncommon subtypes of borderline nuclear changes: cytological features and predictive value

Introduction:  To establish the significance of cytological features which could predict clinically significant endometrial pathology, and therefore guide reporting practice in cervical samples.
Methods:  A retrospective review of SurePath liquid-based cytology (LBC) cervical samples between 2002 and 2006, obtained at screening and colposcopy. These smears contained normal endometrial cells present at inappropriate times of the menstrual cycle, endometrial cells with atypia (borderline change) and with features suspicious / diagnostic of endometrial carcinoma (glandular neoplasia). False negative and false positive cases detected on subsequent histology were also included. The control group comprised negative samples and a few abnormal smears. All smears were randomly assigned and blinded to menopausal status, age, use of oral contraceptive pill and hormone replacement therapy and presence of intrauterine device. Each smear was reviewed for 16 cytologic criteria and a cytological diagnosis was given for each.
Results:  A total of 219 smears were available for review; 137 were negative, out of which 85 contained normal endometrial cells, 41 contained endometrial cells with atypia, 10 contained endometrial cells with features suggestive of adenocarcinoma and 31 contained endometrial cells with features diagnostic of adenocarcinoma. The feature most associated with benign endometrial cells is top hat with central cell condensation. In contrast, the features associated with malignant endometrial cells are smooth nuclear membrane, pale chromatin, small nucleoli and scalloped borders.
Discussion:  The criteria identified in this study do not definitively define a neoplastic process, but appear to be helpful in individual cases. This study emphasises that endometrial changes should be always interpreted with the relevant clinical information, which would otherwise lead to overdiagnosis in premenopausal women.