Accuracy of thin-layer cytology in patients undergoing cervical cone biopsy

OBJECTIVE: To compare the accuracy of thin-layer cytology with Autocyte PREP (TriPath Imaging Inc., Burlington, North Carolina, U.S.A.) with conventional smears in 500 women undergoing cervical cone biopsy. STUDY DESIGN: The study was performed among 500 consecutive women presenting for cone biopsy for high grade cervical intraepithelial neoplasia (CIN) on biopsy in 350 (70%) and discrepant cytology/colpohistology in 150 (30%). Before performing a cone biopsy, two cervical samples were collected for conventional smears and thin-layer cytologic slides, with randomization of the order. Conventional smears were stained and diagnosed at Pasteur Cerba, while thin-layer cytologic slides were processed at a local TriPath office (Meylan, France) and sent in a masked fashion for screening at Pasteur Cerba. Any slides initially read as normal were reviewed again and reported without knowledge of the other cytologic or cone biopsy data. The final cytologic diagnoses for the two methods were compared with histopathology of the cone biopsy. RESULTS: The conventional smear was unsatisfactory in 58 (11.6%) of cases, while there were 4 (0.8%) unsatisfactory thin-layer cytologic slides (P < .001). Endocervical cells were missing from 31 (6.2%) of conventional smears and 34 (6.8%) of thin-layer cytologic slides. For the pooled data, sensitivities of conventional smear and thin layer for detecting high grade CIN (0.82% and 0.86%, respectively) were similar as were specificities (0.40% and 0.43%, respectively). When first samples were compared, the sensitivities of the conventional smear and thin layer for high grade CIN were 0.79% and 0.89%, respectively (P = .02), with corresponding specificities of 0.41% and 0.36% (P < .01). CONCLUSION: When controlled for sample order, the sensitivity of thin-layer cytology for detecting high grade CIN was significantly higher than that of conventional smears in patients with previous abnormal cytology, but at the expense of specificity.     

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.     

Utility of imprint cytology for early presumptive diagnosis in clinically suspicious cervical cancer

OBJECTIVE: To determine the utility of imprint cytology (IC) in providing an early presumptive diagnosis of clinically suspected cervical carcinoma. STUDY DESIGN: A total of 219 clinically suspicious cervical cancer cases underwent Pap test, punch biopsy and IC at the same sitting. Correlations were performed between these diagnostic modalities to determine the sensitivity and specificity of IC in diagnosis of cervical cancer. RESULTS: The overall accuracy of IC in detecting cervical cancers was 96.2%. About 78% of squamous cell carcinomas (SCC), 60% of adenocarcinomas and 100% of small cell carcinoma could be accurately typed on imprints. Twelve malignant lesions were diagnosed on IC among 26 unsatisfactory biopsies. Although there was no false positive result, 3.5% false negative diagnoses were given on IC. The sensitivity and specificity of imprint smear cytology to detect malignancy was 96.2% and 100%. Agreement between imprint cytology and Pap smear diagnosis of malignancy was 95.3%. kappa Statistics revealed excellent agreement between imprints and biopsies and between imprints and Pap smears in diagnosis of malignant lesions. CONCLUSION: IC can be used as an adjunctive technique for an early and reliable preliminary presumptive diagnosis of cancer of the uterine cervix.     

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.     

Conservative management of intraepithelial cervical neoplasia.

In a prospective trial cryotherapy was performed in 164 patients with preinvasive cervical neoplasia, most of whom desired future childbearing. Their disease had been evaluated by repeat cytology, colposcopy and colposcopically directed punch biopsies, with endocervical curettage when necessary. This conservative treatment eradicated the disease in 147 (89.6%) of the patients. The remaining 17 underwent complete reinvestigation. The focal residual disease in 12 was successfully treated by conservative means--repeat cryotherapy, focal electrocautery or punch biopsy. The other five required either cone biopsy or hysterectomy because of more extensive lesions.     

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.     

Relative accuracy of cervical and anal cytology for detection of high grade lesions by colposcope guided biopsy: a cut-point meta-analytic comparison

Background

We recently reported, using a receiver operating characteristic area metric, the first meta-analytic comparison of the relative accuracy of cervical and anal cytology in detecting moderate or severe histopathologic lesions by magnification directed punch biopsy. The aim of the present research was to meta-analytically examine cut-point specific operating characteristics (sensitivity, specificity) of cervical and anal cytology in detecting high grade squamous intraepithelial lesion (HSIL) histopathology by colposcope directed punch biopsy.

Methodology/Principal Findings

The primary eligibility requirement was availability of tabulated cytology (normal, atypical cells of unclear significance [ASCUS], low grade squamous intraepithelial lesion, HSIL or atypical squamous cells cannot rule out high grade [ASC-H]) and biopsy (Conclusions/SignificanceUsing a cytology cut-point of HSIL or ASC-H, anal cytology is less sensitive but comparably specific to cervical cytology. However, using a cut-point of ASCUS, differences in accuracy were of borderline significance.     

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.     

Comparative study of cytology and punch biopsy in cervical intraepithelial neoplasia during pregnancy. A preliminary report

To elucidate the accuracy of cytology in diagnosing cervical intraepithelial neoplasia (CIN) during pregnancy, cytologic screenings for uterine cervical cancer in pregnant women were reviewed for a five-year period. Of the 967 pregnant women screened, abnormal cytologic findings were recorded for 15 (1.6%). Only nine of these were subsequently examined by colposcopy and punch biopsy, which demonstrated CIN in all cases, for an incidence of documented CIN during pregnancy of 0.93%. Including two referral cases also examined by colposcopy and biopsy, cytology and histology agreed on the degree of CIN in four cases and disagreed by one degree in four cases, by two degrees in two cases and by three degrees (mild dysplasia versus carcinoma in situ) in one case. Review of the specimens from these cases did not readily explain the poor concordance between cytology and punch biopsy; some findings suggest that overestimation of the punch biopsy sample may be the explanation.     

Atypical glandular cells of undetermined significance in cervical smears after conization. Cytologic features differentiating them from adenocarcinoma in situ

OBJECTIVE: To evaluate the cytologic features of atypical glandular cells of undetermined significance (AGUS) smears following conization through a comparison with adenocarcinoma in situ (AIS) smears. STUDY DESIGN: Fifty cervical smears, diagnosed as AGUS based on groups of crowded glandular cells that raised the possibility of AIS, from 38 patients who had conization and 24 AIS smears, histologically confirmed, from 17 patients were reviewed. Subsequent follow-up biopsies or hysterectomies in 38 patients were evaluated. RESULTS: Nuclear atypia was a more reliable feature than architectural structure in differentiating postcone effect from AIS on cytology. The predominant cytologic features of the postcone smears were crowded glandular cells with a high nuclear/cytoplasmic ratio and relatively small, hyperchromatic nuclei with rather finely granular and uniformly dispersed chromatin, less distinct nuclear membranes, less frequent mitosis and presence of endometrial-type stromal cells in the background. The architecture of the crowded cells in the postcone smears was sometimes similar to that of AIS. No AIS or high grade squamous intraepithelial lesion histology was encountered in follow-up biopsies or hysterectomy specimens. CONCLUSION: The cytologic features distinguishing AGUS from AIS may be helpful in identifying the postcone effect. Since it is important to avoid miscalling the postcone effect as AIS, it is recommended that one check for a previous history of a cone biopsy.     

Review of negative and low‐grade cervical smears in women with invasive cervical cancer after the first 3 years of the national cervical screening programme in Slovenia

A. Repše‐Fokter, A. Pogačnik, V. Snoj, M. Primic‐Žakelj and M. S. Fležar
Review of negative and low‐grade cervical smears in women with invasive cervical cancer after the first 3 years of the national cervical screening programme in Slovenia Objective: The purpose of the study was to perform a national review of negative, low‐grade and inadequate smears reported during the latest screening period before cervical cancer diagnosis in 2006, after the first 3 years of the screening programme. Methods: Among 162 new cervical cancer cases there were 47 (29%) without previous cytology, 47 (29%) with one high‐grade smear prior to diagnosis and 68 (42.0%) with at least one previous negative, low‐grade, atypical or inadequate smear 1–40 months before diagnosis. Of the latter 68 cases, 37 patients with 59 smears (together with 118 control slides) were included in the review as 31 had smears reported at laboratories no longer operating. Findings were related to the last cytology report before diagnosis as well as to histological type and stage of the cancer. Results: In our study group, 19 (51%) of 37 patients had squamous cell carcinoma, 15 (41%) adenocarcinoma and 3 (8%) adenosquamous carcinoma, compared with 121 (75%), 26 (16%), 12 (7%), respectively, and 3 (2%) other types, for all carcinomas. Twenty‐one of 37 women also had high‐grade cytology prior to diagnosis of cancer. Women with previous cytology (with or without recent high‐grade smears) were more likely to have stage I cancers than those without cytology (P < 0.0001). The expert group upgraded 17/33 smears in the patients with squamous carcinomas, which was more than in those with adeno‐ and adenosquamous carcinomas (5/24, P < 0.05). Conclusion: As expected, a higher proportion of smears preceding adenocarcinomas were true negative. Under‐diagnosed smears were not related to cancer stage or last cytology report before diagnosis.     

Clinical value of repeat Pap smear at the time of colposcopy

OBJECTIVE: To determine the clinical value of a repeat (second) Pap smear at the time of colposcopy in the management of patients with recent cytologic abnormalities. STUDY DESIGN: A study of paired Pap smears and their corresponding cervical biopsies during a two-year period, commencing in June 1996, was undertaken. Pap smears and cervical biopsies from 614 patients were evaluated in the Department of Pathology, Royal Darwin Hospital, Northern Territory, Australia. To maintain uniformity, the cytologic and histologic findings were assessed according to the Bethesda System. RESULTS: The original (first) Pap smears included 288 high grade and 326 low grade lesions. The second smears showed 200 high grade, 221 low grade, 167 normal and 26 unsatisfactory cases. Punch biopsies revealed 242 high grade, 300 low grade and 72 inflammatory/reactive lesions. The changes noted in the second Pap smears and in the punch biopsies in the group originally diagnosed as having high grade disease were generally less advanced. The second Pap smears and corresponding cervical punch biopsies showed more advanced changes in the group originally diagnosed as having low grade disease. Removal of part of the abnormal epithelium during the first Pap smear and the desire of the colposcopist not to damage the surface epithelium prior to performing a cervical biopsy may account for some of these findings. Sampling errors and morphological misinterpretation may explain some of the findings. CONCLUSION: In the second smears, new cases of high grade abnormality were discovered mainly in patients with low grade changes on the first smears. Therefore, a second Pap smear at the time of colposcopy is justifiable in the group with low grade changes on the first smear.     

Atypical squamous cells and low‐grade squamous intraepithelial lesion in cervical cytology: cytohistological correlation and implication for management in a low‐resource setting

N. Gupta, R. Srinivasan, R. Nijhawan, A. Rajwanshi, P. Dey, V. Suri and L. Dhaliwal Atypical squamous cells and low‐grade squamous intraepithelial lesion in cervical cytology: cytohistological correlation and implication for management in a low‐resource setting Objectives: To perform an audit of all cervical smears reported as atypical squamous cells (ASC) and low‐grade squamous intraepithelial lesion (LSIL) as in the Bethesda system (TBS) 2001, and determine their histological follow‐up and outcome when available, in order to define the threshold for colposcopic referral. Material and methods: A total of 25 203 cervical smears were screened over a period of 3 years (January 2006 – December 2008) and all ASC and LSIL smears were reviewed with the corresponding histological follow‐up. All cervical intraepithelial neoplasia (CIN) grade 2 lesions and above (CIN2+) were considered as clinically significant lesions for analysis. Results: Out of 25 203 cervical smears, 424 (1.7%) were reported as ASC and 113 (0.4%) as LSIL. Additionally, three were reported as atypical cells, not otherwise specified. The ASC : SIL ratio was 2.18 : 1. Follow‐up histology was available in 153 (36.8%) of the ASC cases and revealed CIN2+ lesions in 22 (14.4%). Follow‐up histology was available in 50 (44.2%) of LSIL cases and revealed clinically significant abnormalities in five (10%), all of which were CIN2. CIN3 and invasive squamous carcinomas were seen in 5.9% and 1.4%, respectively, of cases of ASC, and not seen in LSIL. Reclassification of ASC smears into ASC‐US (ASC‐undetermined significance) and ASC‐H (ASC‐ high grade SIL not excluded) revealed ASC‐H in 2.6% of all ASC smears, with a clinically significant outcome in 45.4%. Conclusion: In a low‐resource setting where human papillomavirus testing is unaffordable, the threshold for colposcopic referral and follow‐up histology should be ASC rather than SIL.     

The Cytological Prediction of Cervical Intraepithelial Neoplasia In Colposcopically Directed Biopsies

The tissue sections and preceding cervical smears of 1262 women who had colposcopic cervical biopsies were reviewed and the reports correlated. Close correlation between the cytological and histological findings, to within one histological grade of cervical intraepithelial neoplasia (CIN), was noted in 86% of cases. However, the biopsy was negative, or contained evidence of wart virus infection only, in 24% of cases where dyskaryotic cells had been observed in the cervical smear. Of particular concern was the fact that negative histological findings were recorded in 13% of cases where the smear contained cells showing a moderate dyskaryosis and in 1.26% of cases where the smear showed severe dyskaryosis. This suggests that colposcopically directed biopsies do not always reflect the underlying pathological changes in the cervix. Management of these cases is discussed. In 45 women with a normal cervical smear prior to biopsy, histology revealed seven cases of CIN 3 and one case of invasive squamous carcinoma. This indicates that referral for colposcopy is advisable whenever there is clinical suspicion of cancer, even if the cervical smear report is normal.     

Human papillomavirus (HPV) in high-grade cervical intraepithelial neoplasia (CIN) detected by morphology and polymerase chain reaction (PCR)—a cytohistologic correlation of 277 cases treated by laser conization

The aims of this study were to evaluate the cytohistologic correlation in women treated for high-grade lesions of the cervix uteri (HG CIN), to assess the distribution of HPV features and finally to test the validity of the morphological criteria of HPV infection. The smears and biopsy specimens from 277 women treated for HG CIN by laser conization were re-evaluated blindly. Tissue blocks (n = 188) and 52 archival smears were examined for HPV DNA using PCR. HPV changes were detected with equal frequency in the smears and biopsy specimens by light microscopy; 63% and 65%, respectively. The prevalence of HPV DNA in biopsies was 88% and in archival smears 85%; agreement was found in 89% of the cases. Using PCR as the gold standard, we found a sensitivity of 63% for cytology and 70% for histology; the specificity was 41% and 37%, respectively. The positive predictive value was > 80%, but the negative predictive value was < 20%. Our study confirms that HPV features are frequently associated with HG CIN and that morphology is a non-specific method of identifying HPV infection and should be followed by PCR, also allowing detection of oncogenic HPV types and latent infections.     

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.     

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.     

Evaluation of a cervical cancer screening program based on HPV testing and LLETZ excision in a low resource setting

We conducted studies in Vanuatu to evaluate potential screening and treatment strategies to assist with control of cervical cancer. In a pilot study of 496 women, visual inspection and cytology were evaluated as screening tests for detection of CIN 2 or worse (CIN2+), observed in 21 of 206 subjects biopsied on the basis of abnormal visual inspection or cytology. Sensitivity of visual inspection with Lugol's Iodine for detection of CIN2+ on biopsy was 0.63, specificity was 0.32, and the positive predictive value was 0.09. For HSIL cytology, sensitivity was 0.99, specificity was 0.77, and the positive predictive value was 0.88. HSIL cytology was significantly more sensitive and had a significantly higher PPV for CIN 2+ than visual inspection (p<0.01). In a further study of 514 women, we compared testing for HR HPV and cytology as predictors of biopsy proven CIN 2+. Sensitivity of HSIL cytology for CIN2+ as established by loop excision of the cervix was 0.81, specificity was 0.94, and positive predictive value was 0.48. Sensitivity of a positive test for HR HPV for detection of CIN2+ was non-significantly different from cytology at 0.81, specificity was 0.94, and positive predictive value was 0.42. Combining the two tests gave a significantly lower sensitivity of 0.63, a specificity of 0.98, and a positive predictive value of 0.68. For women over 30 in a low resource setting without access to cytology, a single locally conducted test for high risk HPV with effective intervention could reduce cervical cancer risk as effectively as intervention based on cytology conducted in an accredited laboratory.     

The detection of endocervical gland involvement by high grade squamous intraepithelial lesions in smears prepared from endocervical brush specimens

The cytologic features of squamous cell carcinoma in situ with endocervical gland involvement have been described in cervical smears. We evaluated the presence of two types of cellular fragments in 43 cervical smears of high grade squamous intraepithelial lesions (HGSIL) to assess their ability to predict glandular involvement by HGSIL in subsequent cone biopsies. an endocervical brush was used to obtain all endocervical specimens. of 16 cases without glandular involvement, fragments were present in 13 smears. of 27 cases with glandular involvement, fragments were absent in 11 smears. No statistical association was identified between the presence of abnormal cellular fragments on cervical smears of HGSIL and endocervical gland involvement on cone biopsies.     

Accuracy of liquid-based Pap tests: comparison of concurrent liquid-based tests and cervical biopsies on 782 women with previously abnormal Pap smears

OBJECTIVE: To evaluate the diagnostic performance of a liquid-based Pap test, the ThinPrep Pap test (TP) (Cytyc Corp., Boxborough, Massachusetts, U.S.A.), by comparing concurrent TP and cervical biopsy results on 782 patients who were referred for colposcopy because of previously abnormal conventional Pap smears (CPs). STUDY DESIGN: The ability of TP diagnoses of atypical cells of undetermined significance (ASC-US) and squamous intraepithelial lesions (SILs) to predict biopsy diagnoses of cervical intraepithelial neoplasia (CIN) was analyzed using chi2 and McNemar tests. RESULTS: The rate of agreement between diagnoses of SIL by TP and CIN by biopsy was 74.7%. ASC-US accounted for 16.0% of TP diagnoses. ASC-US had biopsy diagnoses of CIN 1 in 60% and CIN 2/3 in 12.8% of cases. For TP diagnosis of low grade SIL, biopsy diagnoses of CIN 2/3 were found in 13.5% of cases. For TP diagnoses of ASC-US and higher, the proportions of TP and cervical biopsies in comparable diagnostic categories were statistically significant (p < 0.001), with TP having sensitivity of 89.4% and positive predictive value of 89.7% for the detection of CIN. The false positive rate for TP was 8.1%, but rescreening confirmed the presence of abnormal cells in 51 of 63 (81.0%) cases of ASC-US or higher having negative biopsies. TP had a false negative rate of 8.3% and negative predictive value of 61.3%. Rescreening showed that most (77.6%) of the false negative TP specimens failed to have abnormal cells on the slides. CONCLUSION: For patients having previously detected cervical abnormalities by CP, concurrent TP demonstrated the following: (1) that it has high diagnostic accuracy for SIL, (2) that ASC-US was diagnostically equivalent to LSIL, and (3) that false negative TP for SIL can be attributed primarily to sampling rather than cytotechnologists' screening errors.