Impact of liquid-based gynecologic cytology on an HIV-positive population

OBJECTIVE: To examine the imprint of liquid-based technologies for cervicovaginal cytology on HIV-positive women, who are at high risk for cervical intraepithelial neoplasia. STUDY DESIGN: We performed a retrospective search of the cytopathology files of Johns Hopkins Hospital for the cervicovaginal cytology of HIV-positive women to examine the effect of liquid-based technology on this population. RESULTS: Significant intraepithelial lesions (SILs) (low grade SIL or greater) were identified in 24% of the conventional smears and 23% of the liquid-based cytology. Atypical squamous cells of undetermined significance (ASCUS)/atypical glandular cells of undetermined significance was diagnosed in 15% of the conventional smears and 9% of the liquid-based preparations (P = .02). In patients with ASCUS diagnoses and tissue follow-up within 7 months, significant SILs were identified in 29% with conventional smears and in 65% with liquid-based cytology. CONCLUSION: There was no statistically significant difference in the rate of SILs between conventional smears and liquid-based cervicovaginal preparations in HIV-positive women. The diagnosis of ASCUS on liquid-based cytology may have an increased likelihood of representing a significant SIL in comparison to conventional smears. For the high-risk, HIV-positive population, immediate colposcopy and biopsy may be warranted following ASCUS diagnoses on liquid-based cytology.     

Feasibility of cytology-based cervical cancer screening in rural Cameroon

OBJECTIVE: To determine the prevalence of cervical cancer and its precursors in a rural population in Cameroon and to evaluate the feasibility of a cytology-based screening program in such areas. STUDY DESIGN: A prospective study was conducted in the rural town of Bafang. Following an advocacy campaign, 750 women were recruited. After a clinical examination, all women had a Pap smear with the Cervex Brush. Each sample had two preparations, conventional and liquid based. The conventional smears were interpreted in Bafang. Cytologically abnormal cases, those with clinical inflammation and/or macroscopic cervical lesions, had a colposcopic examination and directed biopsy. HSIL and colposcopically abnormal cases were treated with large loop excision of the transformation zone (LLETZ). The liquid-based preparations and histopathology were performed in Geneva and the results sent to Cameroon for patient follow-up. RESULTS: Mean age and parity of the women screened were 43.7 years and 7.8, respectively. The conventional smears showed 3.6% cervical abnormalities: 2% (15/740) ASCUS/LSIL and 1.6% (12/740) HSIL. The liquid-based preparations showed 12.6% (91/722) cervical abnormalities: 10.1% (73/722) ASCUS/LSIL and 2.5% (18/722) HSIL. Fifty percent of samples in both preparations showed evidence of inflammation. Histology was performed on 64 colposcopically directed punch biopsies and LLETZ specimens. The histologic diagnoses agreed with the cytologic findings in 60% (14/23) of conventional smears and 85% (12/14) of liquid-based preparations. CONCLUSION: There is a high rate of cervical intraepithelial neoplasia in the unscreened rural population of Cameroon. The situation is complicated by a high rate of cervical infection. A population-based cytologic screening program for cervical cancer would not be feasible in rural Cameroon because of high cost, low quality and limited technical facilities. Rural Africa requires an algorithm using a simple, low-cost technique of mass screening and an improved cytology service only to triage selected patients.     

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.     

Glandular and squamous atypia and intraepithelial lesions in atrophic cervicovaginal smears. One institution's experience

OBJECTIVE: To review the cytologic features and follow-up histologic findings in atrophic cervicovaginal smears with the diagnoses of glandular or squamous atypia or intraepithelial lesion. STUDY DESIGN: A total of 228 cases were included in the study. The selection criteria included: age > 48 years and a diagnosis of either atypical glandular cells (AGC) (51 cases), cellular changes suggestive of human papillomavirus (HPV) infection (S/O HPV, 97 cases), low grade squamous intraepithelial lesion (LSIL) (60 cases) or high grade squamous intraepithelial lesion (HSIL) (20 cases). Follow-up biopsy information was available for 103 cases (45%). RESULTS: From the AGC group, 35 (69%) cases had tissue studies; 14 (40%) cases showed glandular lesions; 5 (14%) showed squamous intraepithelial lesion (SIL) and atypical cells. Follow-up information was available for 32 (33%) cases classified as S/O HPV; significant lesions (glandular/squamous) were found in 11 (34%). In the LSIL category, 22 (37%) cases had follow-up; 16 (73%) showed SIL. In the HSIL category, 14 cases (70%) underwent biopsy, and all showed SIL (four LSIL and nine HSIL) or squamous cell carcinoma. CONCLUSION: Even though atrophy-related epithelial changes often pose diagnostic difficulties in the interpretation of postmenopausal smears, application of reproducible and established cytologic criteria in diagnosing SIL and/or glandular lesions can improve diagnostic accuracy and result in selection of patients for follow-up tissue studies.     

Does liquid-based technology really improve detection of cervical neoplasia? A prospective, randomized trial comparing the ThinPrep Pap Test with the conventional Pap Test, including follow-up of HSIL cases

OBJECTIVE: To compare the sensitivity, specificity and specimen adequacy of the ThinPrep Pap Test (TP) with the conventional Pap Test (CV) in a low-risk population with subsequent follow-up of HSIL cases. STUDY DESIGN: A prospective, randomized, controlled design was chosen to compare the TP with CV. Cytologic diagnosis and specimen adequacy were evaluated and compared with histology data in high grade squamous intraepithelial lesion (HSIL) cases. Fifteen gynecologists in private practice, all trained in colposcopy, participated in the trial. Cytologic diagnosis, specimen adequacy and follow-up of the cytologic HSIL cases were compared in the two groups. In total, 1,999 patients were included, 997 in the TP group and 1,002 in the CV group. Randomization assignments were designated on cytology case report forms, which were placed in sealed envelopes. Each envelope had a sequential randomization number on the outside to allow tracking and authentication of randomization assignments. RESULTS: Comparison of results between CVs and TPs revealed no statistically significant differences in all diagnostic categories, ranging from "within normal limits" to HSIL. Specimen adequacy, however, was superior with CVs (P < .001). The cytologic diagnosis of HSIL correlated with the histologic diagnosis in 91% of the TP group and 100% of the CV group. CONCLUSION: Because there was no statistically significant difference in sensitivity and specificity of the two techniques, improved detection of cervical abnormalities and better specimen adequacy might not be a consequence of utilizing liquid-based preparations but of a better sampling technique. Removing mucus and cellular debris from the cervical surface with a cellulose swab before sampling cells with a proper sampling device results in the same sensitivity and specimen adequacy and is much less expensive than the liquid-based technique.     

Human papillomavirus DNA detection in women with primary abnormal cytology of the cervix: prevalence and distribution of HPV genotypes

OBJECTIVES: In this study, we focus on the prevalence and occurrence of different anogenital human papillomavirus (HPV) genotypes in a first abnormal cervical screening test, and correlate HPV genotyping with the cytological diagnosis on thin-layer liquid-based preparations in routine gynaecological screening. METHODS: Out of 780 abnormal smears, 513 tested positive for HPV. All 25 different HPV types were identified by Line Probe Assay. RESULTS: The prevalence of high-risk HPV types increased from 72% in atypical squamous cell of undetermined significance to 94.5% in high-grade intra-epithelial lesion (HSIL). Co-infection with multiple HPV types was predominantly found in HSIL (35.8%). In the HSIL group the most common HPV types were 16, 52, 51 and 31; type 18 was rarely present. CONCLUSION: The role of types 31, 51 and 52 should be considered in future studies on vaccine development.     

Eliminating the diagnosis atypical squamous cells of undetermined significance: impact on the accuracy of the Papanicolaou test

OBJECTIVE: To assess eliminating the diagnosis "atypical squamous cells of undetermined significance" (ASCUS) from the Bethesda System for Reporting Cervical/Vaginal Cytological Diagnoses and analyze its impact on the sensitivity and positive predictive value of Pap smears. STUDY DESIGN: A total of 166 previously diagnosed ASCUS cases with follow-up biopsy results available were prospectively downgraded to within normal limits/benign cellular changes or upgraded to specific squamous intraepithelial lesions (SILs) or the malignant category. These review cytodiagnoses were compared with the histologic outcome. The impact on the sensitivity and positive predictive value of Pap smears was also assessed. RESULTS: Though there was a decrease in the sensitivity of the Pap smear from 100% to 76.3% for SIL overall and from 100% to 80% for high grade SIL (HSIL) alone, there was an improvement in the positive predictive value of diagnosing SIL from 46% to 85% and from 6% to 15% for HSIL alone. CONCLUSION: The ASCUS diagnosis can be minimized to a great extent, if not eliminated completely. The "ASCUS-favor reactive" group can be eliminated, while the diagnoses "ASCUS favor SIL" and "ASCUS-not otherwise specified" should be used sparingly.     

Performance of the AutoPap Primary Screening System in the detection of high-risk cases in cervicovaginal smears

OBJECTIVE: To assess the performance of the AutoPap Primary Screening System (APSS) (TriPath Imaging, Inc., Burlington, North Carolina, U.S.A.) for the detection of high grade cervical squamous intraepithelial lesions and invasive cervical cancer. STUDY DESIGN: A total of 14,779 consecutive conventional Pap smears were processed by the APSS. All slides designated as "Review" by the device were manually screened according to the Bethesda System. The ranking scores obtained from the device were compared with the cytologic interpretations in all cases and with the final histologic diagnoses in the cases with cytologic severe abnormalities. RESULTS: The device classified 10,349 slides as Review (78%) and 2,912 (22%) as "No Further Review." In the 78% Review cases, the samples were ranked in descending order of potential abnormality, broken into quintiles. The correlation between the slide quintile ranks and the manual cytologic diagnosis indicated that 90% of abnormal smears were categorized by the device as in the first and second quintile rank, and the correlation between the rank report of the device and the histologic diagnosis showed that all cases of HSIL or invasive carcinoma were in the top two ranks. No significant abnormalities were observed in any of the smears categorized as No Further Review. CONCLUSION: This study confirmed the effectiveness of APSS for the detection of Pap smears with severe abnormalities.     

Evaluation of p16INK4a in cervical lesion of premenopausal and postmenopausal women

Pap smears of postmenopausal women are often misdiagnosed because of the difficulty in distinguishing atrophic epithelial cells groups only by morphological criteria. In this study we investigated the diagnostic application of immunocytochemical staining of p16INK4a on conventional Pap smear. A total of 137 cervical specimens were enrolled in this study, of which 77 and 60 cervical smears were taken from premenopausal and postmenopausal women, respectively. Two cervical smears were taken simultaneously in 68 women, one for conventional cytology and the other for immunostaining. Additional 69 cervical smears were taken from the archive, decolorized and then used for immunostaining. In premenopausal women 1 out of 14 (7.1%) with negative cytology, 7 out of 24 (29.2%) with low grade squamous intra-epithelial lesion (LSIL), all 35 (100%) with high grade squamous intraepithelial lesion (HSIL) and all 4 (100%) with squamous cell carcinoma (confirmed by histopathology) had positive staining to p16INK4a. In postmenopausal women p16INK4a positivity was observed in 4 out of 7 (57.1%) cases of LSIL, 12 out of 14 (85.7%) cases of HSIL and all 4 out of 5 (80%) different cases of carcinoma (1 cervical adenosquamous carcinoma and 3 cervical squamous cell carcinoma in situ confirmed by histopathology), but none of 34 smears with normal cytology. Twenty smears with normal cytology chosen for the negative control in this study were from the group of postmenopausal women and were as expected negative for p16INK4a immunostaining. In the group of postmenopausal women, 16 out of 60 (26.7%) cases the cytological diagnosis was established on the basis of pl6lNK4a immunostaining as being HSIL. From our preliminary study on a limited number of samples, we can however conclude that pl6INK4a immunostaining is a very useful tool for cytological diagnosis enabling to distinguish HSIL from normal, reactive or inflammatory changes.     

Performance of 3 methods for quality control for gynecologic cytology diagnoses

OBJECTIVE: To evaluate performance and viability of internal quality control (QC) strategies in a public health laboratory of the state of S?o Paulo. STUDY DESIGN: A retrospective study was performed with 3 QC strategies to improve internal cytologic diagnoses: morphologic guided-list criteria (MGLC), 100% rapid-rescreening (100% RR) of negative slides ("turret" method) and 10% rescreening (10% R) of negative slides. Cases were examined at Adolfo Lutz Institute, S?o Paulo, Brazil, from 2002 to 2004. Histopathologic results, when available, were considered gold standard; cytologic consensus diagnosis was by 2 pathologists when histologic results were unavailable. RESULTS: MGLC selected 20.7% samples with cytologic atypias, 10% R selected 0.6% and RR selected 2.5%. Cytologic/histologic initial concordance was 57.4%, low-grade squamous intra-epithelial lesion false negative rate was 34.9% and high-grade squamous intraepithelial lesion false negative rate was 12.2%. After diagnosis, consensus concordance was 97.2%. CONCLUSION: The 100% RR and 10% R QC strategies detected more false negative cases in liquid-based cytology than in conventional Pap smears. The 100% RR strategy reduced the false negative results and allowed evaluation of individual staff performance. The 10% R strategy did not offer significant results. We concluded that association of MGLC and 100% RR strategies might improve cytologic diagnostic quality.     

Vaginal intraepithelial neoplasia and the Pap smear

OBJECTIVE: To assess the sensitivity of the vaginal smear cytologic examination in detecting vaginal intraepithelial neoplasia (VAIN) and to evaluate the cytologic findings of cases of VAIN. STUDY DESIGN: Cases with a histologic diagnosis of VAIN were identified from the Barnes-Jewish Hospital South and North Campus over a period of five and nine years, respectively. Only posthysterectomy patients with a tissue biopsy diagnosis of VAIN and with a vaginal smear obtained within three months of the biopsy were included in the study. Pertinent clinical information was obtained by reviewing the medical records. Two pathologists reviewed the pathologic samples. RESULTS: Thirty-five vaginal smears from 31 posthysterectomy patients were included in the study. The mean age was 57 years (range, 29-84). The cytologic diagnoses of smears from patients with VAIN included: high grade squamous intraepithelial lesion (19 cases), low grade squamous intraepithelial lesion (10 cases), atypical squamous cells of uncertain significance (5 cases) and negative for malignancy (1 case). CONCLUSION: The sensitivity of the vaginal smear cytologic examination in detecting VAIN is 83%. Obscuring inflammation contributed to false negative diagnoses in two cases.     

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.     

Endocervical glandular cell abnormalities in conventional cervical smears: evaluation of the performance of cytomorphological criteria and HPV testing in predicting neoplasia

Objective:  To analyse the correlation between cytomorphological criteria in smears with atypical glandular cells (AGC) or adenocarcinoma in situ (AIS) and human papillomavirus (HPV) reflex test results with different neoplastic histological diagnoses, particularly to distinguish between glandular and squamous neoplasia.
Methods:  A series of 155 women with glandular abnormalities in their conventional cervical smears was included: 106 with AGC, 35 with AGC associated with high-grade squamous intraepithelial lesion (HSIL) and 14 with AIS. Two reviewers evaluated 35 cytomorphological criteria and hybrid capture II (HCII) was performed in all cases. Colposcopy was carried out in all cases and biopsy in 126/155. For statistical purposes, predictive values and odds ratio (OR) were calculated, followed by chi-square automatic interaction detection.
Results:  Histology detected 56 cases of squamous and 17 of glandular intraepithelial or invasive neoplasia. Predictive values of the papillary groups and feathering criteria for glandular neoplasia were, respectively, 80.0% and 73.3%. Feathering was the criterion with the highest OR for distinguishing glandular from squamous neoplasia and also for distinguishing between glandular and non-neoplastic diagnosis. Rosettes and pseudostratified strips did not perform as well. Multivariant Classification and Regression Trees analysis identified feathering as the best criterion for distinguishing between glandular, squamous and non-neoplastic diagnoses regardless of HPV status.
Conclusions:  Feathering was the best criterion for predicting glandular neoplasia.     

Expression of p16INK4A in Pap smears containing atypical glandular cells from the uterine cervix

OBJECTIVE: To verify one of the diagnostic dilemmas concerning atypical glandular cells (AGC) by immunocytochemical detection of p16INK4A (p16) applied to routine Pap smears with correlation of follow-up biopsies for improvement of cytologic diagnoses. STUDY DESIGN: The study included 36 Pap smears in AGC diagnostic categories, all of which were correlated histologically. The cytologic diagnoses of AGC were further classified according to the 2001 Bethesda System. All Pap smears were decolorized and immunostained with the primary anti-p16 antibody, clone E6H4. Immunoreactivity for p16 was correlated with histologic sections in a semiblind fashion. RESULTS: Of the 36 smears containing AGC, 22 (61%) were reclassified as general AGC and 14 (39%) as AGC--favor neoplasia. Follow-up biopsies revealed that 15 (42%) cervixes had no obvious abnormalities and that 21 (58%) cases had different cervical lesions. More than half the cases (19/36, 53%) of follow-up biopsies concerning AGC-containing smears represented significant lesions. There was a much higher proportion of significant lesions (13/14, 93%) in AGC--favor neoplasia than those (6/22, 27%) in general AGC cases. Fifteen of 36 (36%) AGC-containing cases were actually squamous abnormalities on follow-up biopsies. p16 Immunocytochemical stain was reactive in 22 (61%) of 36 smears, either weakly/sporadically (2 cases, 6%) or strongly positively (20 cases, 55%). Conversely, 14 (39%) of the smears were negative for p16 and displayed predominantly reactive changes. However, there was 1 case of high grade squamous intraepithelial lesion showing negative immunostaining for p16. From the view-point of clinical significance, this analysis was highly sensitive (sensitivity, 95%) and specific (specificity, 88%) and had favorable positive (90%) and negative (94%) predictive values. CONCLUSION: On the basis of both morphologic and immunostaining patterns, there was a clear association between strong p16 immunostaining of atypical cells in smears and the presence of significant lesions in the cervix except in 1 patient. Similarly, there was a clear association between lack of p16 expression and absence of cervical lesions. p16 Immunocytochemical stain can be applied successfully to conventional Pap smears and may serve as a useful biomarker in diagnoses of AGC-containing smears. This may offer a more objective parameter to help clarify this ambiguous area of gynecologic cytopathology.     

P16INK4A as an adjunct test in liquid-based cytology

OBJECTIVE: To assess the utility of P16INK4A as an adjunct test in liquid-based cytology in cases with equivocal morphologic changes of high grade squamous intraepithelial lesion (HSIL). STUDY DESIGN: P16INK4A immunoreactivity was investigated in residual ThinPrep material (Cytyc Corp., Boxborough, Massachusetts, U.S.A.) from 30 cases with equivocal diagnoses of HSIL that had corresponding follow-up biopsies. Two control ThinPrep cases were included: 1 HSIL with biopsy-confirmed cervical intraepithelial neoplasia (CIN) 3 and a negative specimen with a corresponding biopsy of squamous metaplasia. The expression of P16INK4A in ThinPrep specimens and corresponding biopsies was scored as previously described. A ThinPrep case was scored positive if it contained > 10 abnormal cells with nuclear and cytoplasmic immunocytochemical staining. Corresponding biopsies were scored as having negative, sporadic, focal or diffuse staining. RESULTS: The P16INK4A antibody assay was positive in 19 of 30 ThinPrep cases (63.3%). Seventeen of the 19 (89.4%) biopsies corresponding to the positively stained ThinPreps also were positive, with a score of at least focal positivity in the dysplastic regions (2 CIN 1, 4 CIN 2, 11 CIN 3; 2 lesions lost in the tissue recut). The assay was negative in 11 ThinPreps (36.6%) and 10 biopsies (33.3%) with tissue confirmation of chronic cervicitis (5), squamous metaplasia (2), CIN 1 (3) and 1 lesion lost in the tissue recut. Seventeen of 18 (94.4%) ThinPreps confirmed as high grade lesions upon biopsy showed P16INK4A positivity. The control HSIL case with a CIN 3 biopsy was diffusely positive for P16INK4A, and the control negative case with biopsy diagnosis of squamous metaplasia was negative. Nondysplastic squamous and metaplastic epithelium in 7 biopsies and nondysplastic squamous or metaplastic cells in ThinPrep cases were negative. Sporadic staining of bacteria, inflammatory cells and endocervical cells was noted. CONCLUSION: ThinPrep cases in the equivocal cytologic category with the corresponding tissue biopsy assayed for P16INK4A expression showed that there was utility for this type of testing. A larger series comparing corresponding ThinPrep and tissue biopsies will be undertaken. The role of HPV infection in these cases will also be explored.     

Cervical smear abnormalities in the United Arab Emirates: a pilot study in the Arabian Gulf

OBJECTIVE: To gather epidemiologic data on cervical abnormalities and make recommendations pertaining to a national cervical screening policy in the United Arab Emirates (UAE). STUDY DESIGN: A cross-sectional survey of patients and physicians in the UAE with regard to cervical cytology was carried out. Knowledge, attitudes and practices (KAP) of a group of female primary care physicians on cervical cytology were assessed by a self-administered questionnaire. Pap smears and Chlamydia testing were offered to women attending selected primary care centers and secondary health care facilities. RESULTS: Results of Chlamydia prevalence and KAP were published elsewhere; this report addresses the cytologic aspects of this study. There were 2,013 smears collected from primary health centers and 2,042 from secondary care. The overall rate of cervical screening among women in this survey was 85.5% in primary care and 77% in secondary care. The proportion of unsatisfactory smears was < 5%. The prevalence of cervical abnormalities according to the Bethesda System 2001 was 3.6%. There were 9 (primary care) and 21 (secondary care) cases of low grade squamous intraepithelial lesion (LSILs), for a prevalence of 0.77%. There were 4 primary care and 17 secondary care cases of high grade squamous intraepithelial lesion (HSIL), for a prevalence of 0.54%. The combined prevalence for LSIL and HSIL is 1.32%. There were 3 cases of glandular abnormalities. The atypical squamous cells of undetermined significance/SIL ratio was 1.71. No cases of squamous cell carcinoma were detected. No tissue follow-up information is available. The prevalence of cervical abnormalities is low in the UAE. We first recommend the institution of a more organized approach to opportunistic screening in the UAE with appropriate clinical follow-up rather than the immediate launch of a cervical mass screening program.     

AgNOR counts in cervical smears under normal and other cytopathologic conditions

OBJECTIVE: To investigate the diagnostic value of AgNOR counts in cervical smears in the process of cervical carcinogenesis and in discriminating the different grades of squamous intraepithelial lesion (SIL). STUDY DESIGN: Silver nitrate staining for AgNOR counts was performed in 50 cervical smears of cytologically diagnosed normal, inflammatory, low grade SIL (LSIL) (mild dysplasia), high grade SIL (HSIL) (moderate and severe dysplasia) and squamous cell carcinoma. The smears were derived from the ongoing routine outpatient cytology screening at Queen Mary's Hospital, Lucknow, India. RESULTS: In normal and inflammatory smears, the number of AgNOR dots varied from 1 to 2, in mild dysplasia from 2 to 4, in moderate dysplasia from 4 to 6 and in severe dysplasia from 6 to 8. Frank cervical carcinoma cases revealed 8-10 dots. Thus, a progressive increase in AgNOR counts was observed when the severity of pathologic lesions increased. Statistical analysis revealed a significant difference in AgNOR counts between normal and inflammatory smears, but it was highly significant between inflammatory and LSIL cases, between LSIL and HSIL, and between severe dysplasia and frank malignancy. CONCLUSION: This study underscored the diagnostic importance of AgNOR counts, especially in discriminating between LSIL and HSIL of the cervix. Another study is under way to assess the potentiality of AgNOR counts as tumor markers in cervical carcinogenesis.     

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.     

Effect of cellularity on the sensitivity of detecting squamous lesions in liquid-based cervical cytology

OBJECTIVE: To evaluate the effect of cellularity on the sensitivity of both screening and diagnosis in a liquid-based cervical sample. STUDY DESIGN: SurePath samples (TriPath Imaging Inc., Burlington, North Carolina, U.S.A.) with known diagnoses were selected, including 18 negative, 16 low grade squamous intraepithelial lesion (LSIL) and 12 high grade squamous intraepithelial lesion (HSIL) cases. Through a serial dilution technique, samples of varying cellularity were prepared. The 275 slides were assigned random numbers and were routinely screened by 1 of 2 senior cytotechnologists, blinded to the reference diagnosis. Specimens with a screening diagnosis of atypical squamous cells of undetermined significance (ASCUS) or higher were reviewed by two pathologists, resulting in a final consensus diagnosis. Using a grid counting system, cellularity was determined for each slide. RESULTS: There was a clear demarcation in sensitivity between specimens with a cellularity of < 5,000 or > or = 5,000 squamous cells. This applied to both the sensitivity for screening and to the final consensus diagnosis. For cases with a reference diagnosis of LSIL+, at a cytotechnologist screening level of ASCUS or greater, sensitivity increased from 72.8% (< 5,000 cells) to 98.1% (> or = 5,000 cells) and for a reference diagnosis of HSIL from 85.7% to 100%, respectively. Similarly, for the consensus diagnosis, sensitivity rose from 78.5% (< 5,000 cells) to 96.6% (> or = 5,000 cells) for LSIL+ and from 82.9% to 100%, respectively, for HSIL. These differences were statistically significant (P < .001). CONCLUSION: A minimum cellularity of 5,000 squamous cells is recommended for SurePath liquid-based cervical preparations.     

Comparison of two preparation methods for endocervical evaluation

OBJECTIVE: To assess the validity of SurePath liquid-based preparation method for examination of endocervical brush specimens as a substitute for conventionally prepared cytology methods for evaluating the endocervical canal during colposcopic examination and biopsy. STUDY DESIGN: Paired SurePath liquid-based test slides and conventional smears were obtained using an endocervical brush in a split sample protocol before biopsy at the time of colposcopy. The level of agreement between cytologic results obtained was assessed. Accuracy and operating characteristics were evaluated compared to histologic follow-up. RESULTS: Agreement between cytology results for the methods was excellent. The overall kappa was 0.924 (p = 0.0000). There was exact agreement on interpretation between the methods in 283 of 299 cases (94.6%). Cytohistologic follow-up results correlation were: SurePath liquid-based Pap test results and conventional smear results agreed with histology results in 47.8% and 49.2% of cases, respectively. Allowing for a discrepancy within 1 level of severity of cytologic grade, agreements were 76.6% and 77.2%, respectively. CONCLUSION: This study demonstrates that the SurePath method is equivalent to conventional endocervical brush cytology preparation and performs well for detection of cervical intraepithelial lesions and cancer. SurePath is acceptable for endocervical evaluation as a substitute for endocervical curettage at colposcopic biopsy.