ASCUS Cases Research Articles

Atypical squamous cells of undetermined significance cervical cytology in Bahrain: Reporting rates, high-risk HPV testing, and cytologic and histopathologic follow-up findings.

Atypical squamous cells of undetermined significance cytology (ASC-US) is a challenging and equivocal diagnosis for pathologists in cervical Pap smears. The data on ASC-US cervical cytology in Bahrain are deficient. This study reviewed and identified the reporting rates, high-risk human papillomavirus (HPV) testing results, histopathologic follow-up findings, and the cytologic progression of patients diagnosed with ASC-US in Bahrain. A retrospective chart review was conducted on the medical records of 23,888 women who had Pap smear test results between January 2019 and March 2022 at the main referral tertiary hospital in Bahrain to identify the ASC-US cases. High-risk HPV (hrHPV) genotype was identified, and the histopathological results of the cervical biopsy was recorded. In addition, cytologic follow-up Pap smear tests conducted within 1 year of ASC-US diagnosis were tracked to monitor the progression or regression of ASC-US. In this study, 259 out of 23,888 women reported to have ASC-UC cytology results with a reporting rate of 1.1%. The mean age of the ASC-US cases was 43 ± 11.6. Thirty percent of the ASC-US cases tested positive for hrHPV, and they were predominantly infected with the other hrHPV genotype (75%). When the histopathological changes of the cervix were analyzed, 82.1% had normal histopathologic findings. However, low-grade cervical intraepithelial neoplasia-1 was reported in 2 cases (7.1%), and high-grade cervical lesions (cervical intraepithelial neoplasia-2 and higher) were reported in 3 cases (10.7%). Regarding the cytologic follow-up, most of the ASC-US cases were negative for intraepithelial lesion or malignancy (NILM) (73.8%) or had persistent ASC-US (17.9%). The remaining minority of cases progressed into either low-grade squamous intraepithelial lesions (6%) or high-grade squamous intraepithelial lesions (2.4%). There was a statistically significant and relatively strong association between the cytology follow-up findings and the hrHPV test results (χ2 [2] = 8.869, P < 0.012, Cramer's V = 0.417). This is the first and largest study to characterize the ASC-US cytology cases in Bahrain. The reporting rates of ASC-US fell within the worldwide reported range. Although most of the ASC-US cases regressed into NILM, ASC-US showed progression into more advanced cervical cytologic diagnoses or contributed to the malignant transformation of cervical tissue, especially in the presence of hrHPV infection which was positive in 30% of the ASC-US cases. This emphasizes the role of cotesting (combination of hrHPV genotyping and Pap smear test) and the importance of colposcopic evaluation of those women with cytologic follow-up tests at 1 year of diagnosis. Implementing these recommendations in the cervical cancer screening practice in Bahrain will help in having a better management plan for women diagnosed with ASC-US cervical cytology.

Evaluation of P16/Ki67 (CINtecPlus) and L1-capsid compared with HPV-genotyping in cervical cytology in women ≥35 years old focusing on patients with atypical squamous cells of undetermined significance.

Cervical cancer is the third most common cancer in women worldwide. Conventional cytological examination as a screening method with Papanicolaou has been established to reduce the incidence of dysplasia and cervical cancer for years. In addition to the conventional screening, the introduction of immunocytochemical examinations, including CINtecPlus and L1-capsid, has been demonstrated to have a positive impact on screening results. In addition to morphological screening methods, human papillomavirus (HPV)-testing has also been demonstrated to possess an enormous potential in the cervical screening process. Additionally, different screening models ranging from conventional cytological screening to primary HPV-testing do exist in different countries. At the beginning of the year 2020, a combination of cytological screening and HPV-testing was introduced in Germany for women ≥35 years. The aim of the present study was to evaluate the role of morphological screening, including immunocytochemistry, and to compare it with HPV-genotyping. Immunocytochemistry was added to confirm the diagnosis but needs established infrastructure and well-trained personnel. Furthermore, there was a need to establish the HPV-screening method. In the Institute for Pathology and Cytology (Schuettorf, Leer, Germany), 146,800 samples of women (>35 years old) were examined between January 2020 and January 2021. The present study retrospectively analyzed 146,800 samples. Each sample was examined using a conventional cytological technique and HPV-high risk-Test (HPV-HR-Test) with Viper-BD. Immunocytochemistry with CINtecPlus and L1-capsid was added in some cases. A total of 555 cases were cytological diagnosed as atypical squamous cells of undetermined significance (ASC-US; IIp). After performing immunocytochemistry, 79% of cases were suspected to be positive and 1.48% of cases were definitely positive. The HPV-HR-Test was positive in 26.4% of cases. Among cases of ASC-US and HPV-HR-negativity, 33.7% were suspicious of immunocytochemical positivity and 0.5% were definitely positive. Among patients with HPV-16-negativity, 13.6% were patients with highly squamous intraepithelial lesion (HSIL) and 22.7% were patients with low-grade squamous intraepithelial lesion (LSIL) and HSIL. Among patients with HPV-18-negativity, 14.3% were patients with HSIL and 19.5% were patients with LSIL and HSIL. There were 107 cases in this group of cases with negativity of both HPV-16 and HPV-18. After performing the colposcopy and biopsy, there were 6.5% with cervical intra-epithelial neoplasia (CIN) I, 8.4% with CIN II and 5.6% with CIN III. In conclusion, there is still a need for conventional cytological examination and maybe the addition of immunocytochemistry to confirm the diagnosis and to exclude dysplasia of cervical epithelium. The HPV-HR-Test is not enough as a screening method and may be misleading.

Impact of education on institutional and faculty rates of atypical squamous cells

Papanicolaou test quality metrics include the ASC rate, ASC:SIL ratio, and ASC HPV+ rate. What a laboratory should do when metrics show a worrisome trend is not well defined. In 2015, our laboratory noted a worrisome trend in our quality metrics and decided to implement a systemic education program in 2016; we monitored the effectiveness of our program. An educational intervention was designed for March/April 2016. Cytotechnologist education consisted of: group meeting on March 10 to discuss metrics, lecture, and written materials on ASC-US criteria, a quiz on challenging ASC-US cases, encouragement to seek consultation, and each cytotechnologist received quarterly individual metrics. The cytopathologist education consisted of: group meeting on April 16 to discuss metrics, encouragement to bring borderline cases to consensus conference, and each faculty received quarterly individual metrics. The ASC rate, ASC:SIL ratio, and ASC HPV+ rate was collected for the institution and each individual faculty in 2016 for January to March (pre-interventions, Q1), April to June (post-interventions, Q2), and July to September (post-interventions, Q3). ASC-H was included in the calculation of ASC %, ASC:SIL, and ASC HPV+ rates. There was a substantial decline in the lab ASC rate and ASC:SIL ratio, and the ASC HPV+ rate increased. Individual faculty changes in ASC:SIL ratio and ASC HPV+ rate also improved. In our institution, an educational program has been very effective in improving Papanicolaou test metrics. It is helpful to perform re-education at all levels within the department.

Comparison of Conventional Pap Smear, Colposcopy, and HPV Testing in Diagnosis of CIN

To access prevalence of repeated smears in routine health screening and comparison of its outcome with colposcopy, and HPV testing in early diagnosis of cervical neoplasia. Cross-sectional study. Cervical screening of 1200 healthy patients 21 years and above was carried out at health camp. Conventional Pap staining was done in all cases. Abnormal cases were subjected to further testing. The result of conventional Pap smear, repeat Pap smear, HPV test, and colposcopy was compared in repeated smears. Sensitivity specificity and area under curve (AUC) were calculated with 95% CI with standard histopathology. 31.08% (N = 373) cases were followed by a repeat Pap smear. Sensitivity for conventional Pap smear in detecting CIN was found to be 82.93% and specificity was 84.76%,while sensitivity and specificity for colposcopy were 99.8% and 96.19%, respectively. Sensitivity for HPV in detecting CIN was 48.94%. AUC for Pap was 0.851, 95% CI (0.783–0.905). AUC for colposcopy was 0.981, 95% CI (0.943–0.996). In a routine health camp, as many as 31.08% of cases were repeated. 12.4% of patient’s Pap was repeatedly abnormal which shows a high prevalence of undetected cervical pathology in population. Our study also shows colposcopy has more sensitivity and specificity in detecting CIN as compared to repeat Pap smear in cases of inflammatory reactive and ASCUS cases. HPV, however, has low sensitivity in comparison with both methods.

A study of papanicolaou stain and cervical acid phosphatase papanicolaou stain in the detection of cervical intra epithelial neoplasm a comparative study

Introduction: In order to increase the sensitivity of the routine PAP test, a new test was introduced called the CAP-PAP test. In this test, lysosomal enzyme and cervical acid phosphatase (CAP) enzyme are labeled with conventional PAP test which will help in detecting abnormal squamous cells of cervix. This enzyme can be used as a biomarker for cervical dysplasia when CAP positivity is detected inside abnormal squamous cells of cervix and can also be used as a surrogate in detection of CIN. Aims: To perform CAP-PAP and PAP staining on cervical smears. To compare CAP-PAP results with PAP results and correlate with cervical histopathology reports. Methods and Materials: 150 females undergoing cervical cancer screening at OBG Department, of our institute were studied. Two cervical smears each were collected from all patients for PAP and CAP-PAP staining. The results were compared and correlated with respective histopathology reports.| Statistical Analysis Used: Chi-square test, Kappa statistics, P value of Results: 75 PAP positive cases out of which 34 were LSIL, 17 were HSIL, 13 were ASCUS, 9 were ASC-H, and 2 were SCC cases. In the remaining 75 PAP negative smears, 38 cases were inflammatory smears and 37 cases were of NLIM smears. Among the PAP positive cases, CAP-PAP results were similar to PAP results in all the LSIL, HSIL, ASCUS, ASC-H and SCC cases. Among the PAP negative cases, CAP-PAP was negative in all the 37 NILM cases, but of the 38 inflammatory cases, CAP-PAP was negative in 30 cases but was positive in 8 cases. CAP-PAP results had good agreement with PAP results and correlated well with histopathology results. Conclusion: CAP positivity is identified by presence of res granules in abnormal squamous cells which helps in its early detection. In screening of cervical cancer on a large scale. CAP PAP acts as a quick and efficient method. The test promises a great future in health centers as the technicians can be easily trained for identification of abnorma

Cytological Evaluation of p16Ink4a in Precancerous Lesions of the Cervix: Conventional Papanicolaou Smears

Background: Cancer of the uterine cervix is the second most common cancer among women worldwide. More than three fourths of these patients are diagnosed at advanced stages, leading to poor prospects of long term survival and cure. Introduction of Papanicolaou (Pap test) cytological screening for cervical precancerous lesions has significantly reduced the incidence and mortality of cervical cancer. Human papillomavirus (HPV) DNA testing has been recently demonstrated to be efficient to be integrated into screening programs, so it can be used to triage women with equivocal cytological abnormalities and also identifies women at risk of residual or recurrent disease after treatment of cervical intraepithelial neoplasia. However, it fails into triage low grade lesions. HPV DNA test confirms infection by the virus, present in 99% of cases. However, it does not discriminate between transient and persistent infection as it is crucial because it is the persistent infection which progresses to neoplasia. Histological assessment of cervical biopsy that is considered as “gold standard” can be hampered by intra and inter observer variability. A more specific triage marker is required to identify women who would need colposcopy. Hence, p16INK4a has emerged as a new diagnostic and prognostic biomarker. Aims and objectives: This study was conducted to evaluate the utility of staining of p16INK4a on conventional Pap smears and its comparison with corresponding biopsies. Material and Methods: 50 cases of conventional Papanicolaou stained cervical smears cases were randomly selected from the archive of cytopathology laboratory. The cervical smears were re-evaluated for adequacy, preservation of cells, cytomorphology and various lesions were categorized according to The Bethesda system 2001 (TBS) classification. Consecutive such cases were selected for which both cytological and histological material were available. Immunostaining of cervical cytological specimens for p16 was performed using monoclonal murine antibody, clone 16P04, JC2. Ready to use antibody was used for immunostaining as per manufacturer's protocol. Results: Out of the 50 smears of preneoplastic and invasive lesions, ASCUS was seen in 5 cases, LSIL in 10 cases, HSIL in 20 cases, SCC in 20 cases and AGUS in 5 cases. Of the 5 cases of ASCUS, histopathology showed 3 chronic cervicitis and 1 each in CIN-1 and CIN-2. Histopathological diagnosis of 10 cases of LSIL showed 6 CIN-1 and 2 each in CIN-2 and chronic cervicitis. Similarly, for 10 cases of HSIL, 3 were CIN-2, 5 CIN-3 and 2 SCC. All 20 cases of carcinoma showed SCC while 5 cases of AGUS showed 4 chronic cervicitis and one adenocarcinoma. Immunohistochemical staining of p16INK4A showed weak positivity in 3 cases of chronic cervicitis and 4 cases of CIN-1. In CIN-2 cases, 66.67% showed strong positivity, CIN-3 showed 80% while both carcinoma and adenocarcinoma showed 100% strong positivity. The sensitivity of immunohistochemical staining of p16INK4A was 77.5%, specificity was 100%, PPV 100% and NPV 52.6%. The relation between histological and cytological immunostaining of p16INK4A. Conclusion: p16INK4A is a reliable marker for dysplastic squamous and glandular cervical cells both in tissue sections and in cervical smears. p16 immunostaining can be easily performed on CPS, and there is high concordance of positivity on smears and tissue sections.

Cervical Cancer Screening in Pregnancy and Postpartum: A North Indian Hospital Based Prospective Observational Study

Introduction: In India, cervical cancer stands as the 2nd most common female cancer and it is the 2nd most leading cause of deaths in women aged 15 to 44 years. The first visit to the gynecologist for most of the women in India is during pregnancy, thereby making it a fair opportunity for the screening of premalignant and malignant cervical disease. Methods: A prospective observational study was conducted in the Department of Obstetrics and Gynaecology, AIIMS, Rishikesh, Uttarakhand, India from January 2018 to January 2019. The Pap smear testing of 237 spontaneously conceived antenatal women, aging between 20 to 35 years was performed. The same women were followed up for postnatal testing after 6 weeks of delivery. Results: Out of 237, 8 women were reported positive for pre malignant lesions of cervix in the antenatal testing, 5 cases of ASCUS, 1 case of AGC, 1 case of ASC-H &amp; 1 case of HSIL. In the postnatal Pap smear testing, 37 women were lost to follow-up including 1 case of ASCUS. Postnatal Pap smear testing of the remaining 200 women showed that 193 women who were reported NILM in the antenatal period remained unchanged in the postnatal screening too. Out of the 7 women who tested positive, 4 cases of ASCUS, 1 case of AGC and 1 case of ASC-H showed regression, giving result as NILM in the postnatal screening test. Out of the 7 positive antenatal tests, 1 case which was reported as HSIL in the antenatal screening, remained unchanged in the postnatal period.Conclusion: The study concluded that there is significant regression (p&lt;0.01) of Positive Pap smear findings from antenatal to postnatal period. Hence, it is imperative to repeat Pap smear test in postnatal period.

Abstract 1123: Simultaneous p16/ki-67 expression in detection of high-grade squamous intraepithelial lesions, in women with ASC in cervical smears

Abstract Background Immunocytochemical staining for overexpression of the cell-cycle regulatory protein p16INK4a has been shown to be an efficient approach to triage to colposcopy women with cervical smears categorized as Atypical Squamous Cells (ASC). Overexpression of p16 is associated with the transforming activity of the HR-HPV-E7 oncoprotein in cervical dysplasia. Ki-67 is a marker of cell proliferation of dysplastic epithelium. The efficiency of p16 and Ki-67 separately has been widely described. In high-grade squamous intraepithelial lesion (H-SIL) and cancer they can be co-expressed and the identification of cells with double staining reactivity (p16/Ki-67) can be used as an indicator of H-SIL. We aim to evaluate the diagnostic performance of double p16/Ki-67 staining in the detection of underlying H-SIL in cytological smears of women referred to colposcopy due to an ASC cervical smear result. Design Prospective diagnostic test study. It took 18 months to complete the representative number of cases considering the prevalence of ASC in the colposcopy consultation. Samples were included from patients referred to colposcopy with a cytological diagnosis of ASC. Liquid based cytology was taken and processed to obtain a blank cytological preparation. The p16/Ki-67 staining was performed using CINtec Plus™. The immunoreactivity for both markers evidenced by one or more cervical epithelial cells with brown cytoplasmic immunostaining for p16, and nuclear red for Ki-67, was evaluated by two pathologists blind to colposcopy or biopsy results. Biopsies and/or endocervical curettage were obtained when the colposcopist considered necessary and they were considered as gold standard. In cases where there was no visible lesion and no biopsy was taken, colposcopy was considered gold standard and it was classified as: satisfactory/unsatisfactory, negative/normal or positive/abnormal. A high-grade biopsy lesion (≥ CIN2) with H&amp;E was considered as a final diagnosis. Results There were 120 cases included of ASC (114 ASCUS and 6 ASC-H), from women between 18 and 82 years (mean=38.6). 90 (75.0%) cases had histological study: 62 (68.9%) biopsies and 28 (31.1%) endocervical curettages, of which 17 (14.28%) cases had ≥CIN2, and none were cases of invasive cancer. p16/Ki-67 staining was positive in 21 (17.5%) cases, (64.7% sensitivity for ≥CIN2). All the ASC-H cases (3, 100%), and 57.1% of ASCUS cases with ≥CIN2 as final diagnosis were positive to p16/Ki-67. The specificity of p16/Ki-67 dual staining was greater than 90%. Conclusions There was a p16/Ki-67 specificity that exceeded the values ​​published in other studies on this double staining, but, the positivity and sensitivity estimates were lower than reported previously. The variability of p16/Ki-67 staining in HSILs would reflect the heterogeneity of these lesions. Citation Format: Lia Barrios, Luis Alvis, Ines Benedetti. Simultaneous p16/ki-67 expression in detection of high-grade squamous intraepithelial lesions, in women with ASC in cervical smears [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1123.

Atipias de células escamosas de significado incierto (ASCUS) y lesión escamosa intraepitelial de bajo grado (LSIL). Control citológico evolutivo a 3 meses. Resultados

ObjectiveProspective study of 4 years (2015-2018) of the ASCUS and LSIL cases in the vaginocervical cytology, and your evolutive cytological control in 3 months. DesignStudy of: age, parity, nulligravides, menopausal, contraceptive methods, sexuality and sexual dysfunctions, pathologic antecedents, cytology and HPV (human papillomavirus) analysis, comparing the evolution in both groups. ResultsThe series are 146 cases of ASCUS and 82 cases of LSIL.In ASCUS, there were significant differences in age (P<.02), parity (P<.001), and abortions (P<.02). In LSIL, there were significant differences in nulligravides (P<.001).There were significant differences (P<.02) in condom use in LSIL. In both groups more of 50% of the cases dońt use any contraceptive method There were no significant differences in sexuality nor in sexual dysfunctions, neither in antecedents.ASCUS was associated with infections in 15,05%. LSIL was associated with infections in 9,74%, without differences.There were significant differences in negative HPV (P<.001) in ASCUS, 43,15% versus 20,73% in LSIL. There were significant differences in High Risk other viruses positive (P<.001) in LSIL.In the cytologic control at 3 monts, there were significant differences in ASCUS+BV (bacterial vaginosis) (P<.02) in LSIL. Also in LSIL group there were more LSIL in the cytologic control at 3 months, 26,82% (P<.01).In the follow-up at 1 year, there were no significant differences. The negative cytology was in 64,86% and 47,82%, respectively. ConclusionThe reiterative cytology in 3 months are value for detecting the associated infections, and treated; to run over and advance the cytologic normality.

HPV genotyping and E6/E7 transcript assays for cervical lesion detection in an Asian screening population—Cobas and Aptima HPV tests

BackgroundHigh-risk human papillomavirus (hrHPV) detection and genotyping by Cobas HPV test has become an important technical platform in cervical cancer screening. It may be used as a co-test with cervical cytology or as a standalone test. Aptima HPV assay (AHPV) is another hrHPV test detecting 13 genotypes through qPCR based amplification of viral E6/E7 transcripts. Partial genotyping with Aptima HPV 16 18/45 genotype assay (AHPV GT) on positive samples is possible. Evidence supporting the performance of AHPV in Asian populations is scarce. ObjectiveTo compare the performances of Cobas and AHPV in detection of cervical squamous intraepithelial lesions (SIL) and triage of cytologically equivocal smears in a cohort of Hong Kong women. Study design442 liquid based cytology (LBC) residues with biopsy confirmed diagnoses were evaluated by both AHPV and Cobas HPV tests. ResultsOverall, there was a moderate agreement between AHPV and Cobas (κ = 0.5082, 95% CI: 0.492–0.672). The sensitivities of AHPV and Cobas for detecting biopsy confirmed HSIL or worse lesions (HSIL+) were 96.71% (95% CI: 92.49%–98.92%) and 97.37% (95% CI: 93.40%–99.28%) respectively. AHPV demonstrated significantly higher specificity than Cobas (37.85% vs 23.96%, p < 0.0001). Both tests could identify all ASC-US and AGC cases with HSIL + in follow-up biopsies, but AHPV showed a significantly higher specificity in both settings (ASC-US: 28.81% vs 11.86%, p < 0.0001; AGC: 55.00% vs 20.00%, p = 0.0233). ConclusionsBoth AHPV and Cobas were equally sensitive in detecting high-grade SIL in both scenarios of screening and ASC-US or AGC triage but AHPV showed a higher specificity.

High-risk human papillomavirus, thin-prep cytologic test combined with digital colposcopy cervical biopsy in the diagnosis of cervical intraepithelial neoplasia and cervical cancer

Objective To analyze the application of the HR-HPV, TCT combined with digital colposcopy cervical biopsy in diagnosis of CIN and cervical carcinoma. Methods From 2014 to 2016, 250 cases diagnosed as ASCUS and above the level of disease were selected in Shanxi Cancer Hospital, including 148 cases of ASCUS, 68 cases of LSIL, 27 cases of HSIL and 7 cases of SCC.The HR-HPV copy number was detected by using PCR fluorescence measurement, the Reid colposcopy scores were measured by using digital colposcopy, and the cervical histopathological diagnosis was regarded as a measurement rule. Results The diagnostic rate of simple use of TCT for the diagnosis of CIN and above lesions was 41.20%(103/250), HR-HPV & TCT in diagnosis of CIN and above lesions was 58.78%(77/131), TCT & digital colposcopy for the diagnosis of CIN and above lesions was 67.42%(89/132), which were significantly increased(χ2=35.87, P=0.00; χ2=59.01, P=0.00). The diagnostic rate of HR-HPV & TCT combined with electronic colposcopy in diagnosis of lesions above CIN was 79.82%(91/114), which was significantly higher than that of HR-HPV & TCT[58.78%(77/131)], and the diagnostic rate of TCT & digital colposcopy was 67.42%(89/132)(χ2=15.54, P=0.01; χ2=8.05, P=0.02). The incidence of CIN and cervical cancer were closely related with HR-HPV infection and the rate of HR-HPV infection showed an increasing trend with the aggravating degree of disease(the HR-HPV infection rate of ASCUS was 39.86%, the HR-HPV infection rate of LSIL was 61.76%, the HR-HPV infection rate of HSIL was 88.89%, while the HR-HPV infection rate of SCC was 100.00%). Conclusion HR-HPV, TCT combined with digital colposcopy can effectively improve the diagnosis rate of CIN and above the level of disease.At the same time, with the deterioration of the disease, HR-HPV infection rate increases significantly, which can provide diagnostic information and significance in the clinical diagnosis of CIN and cervical cancer. Key words: Human papillomavirus; Cytological techniques; Colposcopy; Biopsy; Cervical intraepithelial neoplasia

Team Reading (Peer Review) of Suspicious/Positive Slides for Continuous Quality Improvement in Cervical-Vaginal Cytology: A Comparison between Methods and Indicators

Aim: In 2013, the Local Health Unit Roma 2 ex C screening laboratory introduced a new set of indicators for quality assurance. We compare 2 sets of indicators based on routine multiple readings (peer review) for their ability to identify problems in single-reader accuracy. Methods: All suspect slides were blindly reviewed by all the cytologists of the laboratory. The standard set of indicators includes interreader Cohen's kappa, positivity rate and atypical squamous cell of undetermined significance/squamous intraepithelial lesion (ASC-US/SIL) ratio. The new set included sensitivity for cervical intraepithelial neoplasia of grade 2 or worse (CIN2+), positive predictive value (PPV) and percentage of positive high-risk (HR)-HPV cases among ASC-US. In order to estimate sensitivity and PPV, we considered all women for whom there was a consensus of negative cytology, negative HR-HPV test, negative colposcopy or negative histology true negative. Results: Kappa values ranged from 0.521 to 0.753, with narrow 95% confidence intervals (CIs). Positivity rate ranged from 73.9 to 85.7 and the ASC-US/SIL ratio from 0.61 to 0.81. Sensitivity for CIN2+ at the low-grade SIL threshold ranged from 85.8 to 94.2, PPV ranged from 14.8 to 19.4, and both had a broad 95% CI. Readers with low sensitivity did not show low kappa values. The percentage proportion of HR-HPV-positives (HR-HPV+) among ASC-US ranged from 39.9 to 43.8% with a narrow 95% CI. Conclusion: The proportion of HR-HPV+ among ASC-US cases is a powerful indicator to address in training.

Immunocytochemical staining of cervical smears – A comparative study with routine cytology for confirmation of precancerous and cancerous lesions of cervix

Introduction: Carcinoma cervix is one of the leading causes of morbidity and mortality. The most effective method of screening is based on Pap smear study. However, Pap smear has relatively low sensitivity and irreducible false negative & false positive rates. In countries like India, it is not always feasible to follow the patient for confirmation by histology. In the present study, we have tried to fill this gap by staining the cervical smears with, epithelial cell markers including CK17 and CEA expressed by dysplastic squamous cells. Materials & Method s: 50 cervical smears reported as precancerous or cancerous were stained with anti CK17 and anti CEA. The patients were followed for histopathology. Results: Out of 20 cases of ASCUS, three were positive both for anti-CK17 and anti-CEA and six were positive for anti-CK17 only. Out of 18 cases of LSIL, nine were positive for both anti-CK17 and anti-CEA and fifteen were positive for anti-CK17 only. Out of eight cases of HSIL, three were positive for both anti-CK17 and anti-CEA and six were positive for anti-CK17 only. Out of 4 cases of SCC, three were positive for both anti-CK17 and anti-CEA and all four were positive for anti-CK17. Conclusion: Positive result in staining was higher in high grade lesions. CK 17 was found to be better marker than CEA. CK17 and CEA can be used as adjunct to Pap smear screening but its high cost may restrict its use in routine.

The Impact of Pressurization on Anode-Supported and Electrolyte-Supported Planar Solid Oxide Fuel Cells at 750oC ~ 850oC

How to reduce effectively the severe impact of various environmental and energy problems is one of the most important issues in our human society. This continues to drive the development of hybrid power generation systems aiming to achieve much higher efficiencies together with much lower emissions than conventional power systems. Among only a few available hybrid energy conversion systems, a pressurized solid oxide fuel cells (PSOFC) integrating with a gas turbine (GT) or micro gas turbine (MGT), the hybrid PSOFC-GT or -MGT power system, has the highest efficiency up to 70%. Moreover, the development of such hybrid PSOFC-GT or –MGT power system is not only beneficial for the environment, but also it is important to the consolidation of the fuel cell industry and the expansion of the gas turbine industry. Although several demos of the hybrid PSOFC-MGT power system have been established, many technical challenges existing in the design of such hybrid power system and its control still need to be solved in order to assure a stable operation among different components of the hybrid system. One of the most important technical challenges is the detail experimental information on electrochemical impedance spectra (EIS) of PSOFC, which is still rare in literatures. This motivates us to measure experimentally the effect of pressurization on EIS of PSOFC. In this work, we measure the pressurization influence on power generating characteristics and EIS for both anode-supported and electrolyte-supported cells (ASC and ESC) using a recently-established high-pressure SOFC facility. It is worth of noting that the present study has an important advantage due to the fact that both ASC and ESC use the same single-cell setup, a planar full cell having 40 × 40 mm2 effective reactive area sandwiched by a pair of rib-channel flow distributors (interconnectors) on both anode and cathode, under exactly the same experimental conditions. Specifically, both ASC and ESC apply exactly the same flow rates (Q anode = 0.5 slpm H2 + 0.4 slpm N2 and Q cathode = 0.9 slpm air) at three operating temperatures (T = 750 oC, 800 oC, 850oC), each T under five different pressures (p = 1, 2, 3, 4, 5 atm), having a total of 30 data sets for comparison. Hence, a direct comparison of experimental EIS data and power generating characteristics between ASC and ESC at elevated pressures can be clearly made. To the best knowledge of the authors, the present measured EIS comparison between ASC and ESC is new, and experimental EIS data of pressurized electrolyte-supported planar SOFC are still not available in literatures. These ASC and ESC measurements under the same experimental conditions suggest the following points: (1) At T = 850oC and 0.7 V, power densities of ASC/ESC increase from 309/193 mW cm-2 to 476/250 mW cm-2, as p increases from 1 atm to 5 atm. As T increases from 750oC to 850oC at 0.7 V, power densities of ASC/ESC increase from 175/97 mW cm-2 to 309/193 mW cm-2 at p = 1 atm, while at p = 5 atm, the corresponding increases of power densities are 281/137 mW cm-2 to 476/250 mW cm-2. It is found that ASC is more sensitive to pressurization than ESC, while the latter is more temperature-sensitive than the former. (2) The ohmic resistance is not varied with the loaded current density and it is independent of pressure for both ASC and ESC cases. Furthermore, ESC has higher values of the ohmic impedance, about 16 % larger, than that of ASC. The thicker the electrolyte thickness is, the larger the ohmic impedance is. (3) The polarization impedance decreases noticeably with increasing p for both ASC and ESC cases at either unloaded or loaded conditions. This explains why power densities increase with increasing pfor both ASC and ESC. (4) These measurements reveal that the better cell performance of ASC than that of ESC is not simply due to the larger ohmic overvoltage of ESC as previously predicted by numerical simulations. The variation of the polarization overvoltage between ASC and ESC also plays an important role. We hasten to note that it is not sure whether the present conclusions can be extended to all ASCs and ESCs due to different electrolytes and anodes used in the present ASC and ESC, but these results should be of help in the further development of PSOFC integrating with micro gas turbines for future stationary power generation. Figure 1

Does high-risk human papilloma virus genotyping of abnormal anal cytology improve detection of high-grade anal intraepithelial neoplasia?

High-risk (HR) human papillomavirus (HPV) testing is accepted as the standard of care for surveillance of cervical cancer. Its role in anal cancer is not clear. This study was therefore designed to determine if HR HPV genotyping is a useful adjunct in management of abnormal anal Papanicolaou (Pap) tests. HR HPV genotyping and virus quantification was performed on 101 residual anal Pap test samples (28 negative, 25 atypical squamous cells of undetermined significance [ASC], 34 low-grade squamous intraepithelial lesion [LSIL], 6 atypical squamous cells of undetermined significance, cannot exclude high-grade squamous intraepithelial lesion, and 8 high-grade squamous intraepithelial lesion) using multiplex real-time polymerase chain reaction. Results were correlated with cytodiagnosis and follow-up. HR HPV was detected in 82% (50% negative, 84% ASC, and 100% LSIL and above) cases. Multiple genotypes were present in 71% of cases. Genotype number and viral load correlated with the degree of anal cytologic abnormality. HPV 16, 18, and 45 were the most frequent genotypes detected. The high frequency of HR HPV in abnormal anal cytologies limits its use as an adjunct test. Anal Pap test samples with anal intraepithelial neoplasia 2/3 (AIN 2/3) on follow-up were positive for HPV 16 and/or 18 (HPV 16/18+) in 80% of cases. We hypothesize that testing for HPV 16/18 on the ASC and LSIL cases would have detected AIN 2/3 with a sensitivity of 81%, specificity of 43%, positive predictive value of 39%, and negative predictive value of 83%. Our results with a small cohort suggest that genotyping for HPV 16/18 may be effective in identifying patients at high risk for anal cancer and in reducing the number of anoscopy referrals. Prospective studies with follow-up are warranted.

Ring-enhancement pattern on contrast-enhanced CT predicts adenosquamous carcinoma of the pancreas: A matched case-control study

ObjectivesAdenosquamous carcinoma of the pancreas (ASC) is a rare malignant neoplasm of the pancreas, exhibiting both glandular and squamous differentiation. However, little is known about its imaging features. This study examined the imaging features of pancreatic ASC. MethodsWe evaluated images of contrast-enhanced computed tomography (CT) and endoscopic ultrasonography (EUS). As controls, solid pancreatic neoplasms matched in a 2:1 ratio to ASC cases for age, sex and tumor location were also evaluated. ResultsTwenty-three ASC cases were examined, and 46 solid pancreatic neoplasms (43 pancreatic ductal adenocarcinomas, two pancreatic neuroendocrine tumors and one acinar cell carcinoma) were matched as controls. Univariate analysis demonstrated significant differences in the outline and vascularity of tumors on contrast-enhanced CT in the ASC and control groups (P < 0.001 and P < 0.001, respectively). A smooth outline, cystic changes, and the ring-enhancement pattern on contrast-enhanced CT were seen to have significant predictive powers by stepwise forward logistic regression analysis (P = 0.044, P = 0.010, and P = 0.001, respectively). Of the three, the ring-enhancement pattern was the most useful, and its predictive diagnostic sensitivity, specificity, positive predictive value and negative predictive value for diagnosis of ASC were 65.2%, 89.6%, 75.0% and 84.3%, respectively. ConclusionsThese results demonstrate that presence of the ring-enhancement pattern on contrast-enhanced CT is the most useful predictive factor for ASC.

Evaluation of the Oncogenic Human Papillomavirus DNA Test with Liquid-Based Cytology in Primary Cervical Cancer Screening and the Importance of the ASC/SIL Ratio: A Belgian Study

Objectives. In Belgium, very few studies have focused on cervical high-risk human papillomaviruses (hrHPV) prevalence and the relationship between HPV and cervical cytological abnormalities. The aim of this study was to investigate hrHPV prevalence and its relationship with cytological screening and histological results in the French-speaking community in Belgium (Brussels and Wallonia). Methods. A total of 58,265 liquid-based cytology tests were performed during this period. All cases of ASC-US, ASC-H, LSIL, and HSIL were tested by Hybrid Capture 2 for hrHPV screening. Results. The prevalence of cytological abnormalities was 3.1% for ASC-US, 0.3% for ASC-H, 1.5% for LSIL, and 0.3% for HSIL. The frequency of hrHPV infection was 47% in ASC-US, 90% in ASC-H, 86% in LSIL, and 98.4% in HSIL. CIN 2+ lesions were found in 12.2% of smears with an ASC-US result, in 54% of smears with an ASC-H result, in 12.5% of smears with a LSIL result, and in 89.3% of smears with a HSIL result. The ASC/SIL ratio was 1.9%. Conclusions. This study provides a good representation of cytological abnormalities and HPV status in patients living in Belgium's French-speaking community. The prevalence in our study was similar to that derived from meta-analyses of European studies. Our ASC/SIL ratio was 1.9%, being within the lower and upper limits proposed in the literature, which tends to prove the good quality diagnosis of cervical smears in our laboratory.

High grade lesion of ASCUS and ASCH cases in Chaopraya Abhaibhubejr Hospital

The aim was to determine the high grade lesion in ASCUS and ASCH cases in cervical cancer screening of Chaopraya Abhaibhubejr Hospital from September 2007 to December 2012 and comparison with histopathology. From 30,301 cases of the conventional Pap smears, 60 cases (0.198%) were ASCUS and 28 of these cases (6.62%) underwent tissue biopsy: 8 (28.57%) cases were chronic cervicitis with koilocytic change, 7 cases (25%) were CIN I, 2 cases (7.14%) were CIN II, 10 cases (35.71%) of CIN III/CIS, and 1 case (3.57%) of adenocarcinoma. Ten cases (0.033%) were ASCH and 3 of these cases underwent tissue biopsy: 1 case (33.33%) was chronic cervicitis with koilocytic change, 1 case (33.33%) was CIS, and 1 case (33.33%) was squamous cell carcinoma. The possibility for high grade lesion of ASCUS is 46.43% and ASCH is 66.67% and both categories were 48.38%. Work up for the suspicious groups to determine the final result should be performed. The aim was to determine the high grade lesion in ASCUS and ASCH cases in cervical cancer screening of Chaopraya Abhaibhubejr Hospital from September 2007 to December 2012 and comparison with histopathology. From 30,301 cases of the conventional Pap smears, 60 cases (0.198%) were ASCUS and 28 of these cases (6.62%) underwent tissue biopsy: 8 (28.57%) cases were chronic cervicitis with koilocytic change, 7 cases (25%) were CIN I, 2 cases (7.14%) were CIN II, 10 cases (35.71%) of CIN III/CIS, and 1 case (3.57%) of adenocarcinoma. Ten cases (0.033%) were ASCH and 3 of these cases underwent tissue biopsy: 1 case (33.33%) was chronic cervicitis with koilocytic change, 1 case (33.33%) was CIS, and 1 case (33.33%) was squamous cell carcinoma. The possibility for high grade lesion of ASCUS is 46.43% and ASCH is 66.67% and both categories were 48.38%. Work up for the suspicious groups to determine the final result should be performed.

HPV Prevalence and Detection of Rare HPV Genotypes in Hong Kong Women from Southern China with Cytological Abnormalities

Human papillomavirus (HPV) has been identified as the primary cause of cervical squamous intraepithelial lesion and invasive cervical cancer. The emergence of various commercial HPV genotyping kits with different characteristics facilitates the detection of most high-risk and low-risk HPV genotypes, but the rare HPV types are usually underdiagnosed. In the present study, HPV detection was performed using the GenoFlow HPV Array Test kit (DiagCor Bioscience), which can identify 33 HPV subtypes by specific probes. Besides, a HPV consensus probe (universal probe) was designed to capture not only the 33 genotypes but also rare subtypes. Of the 1643 Southern Chinese women tested between 2012 and 2013, the HPV prevalence was 42.3%, with HPV 52 (139/1643, 8.5%), HPV 81 (89/1643, 5.4%), and HPV 16 (63/1643, 3.8%) being the most frequent subtypes detected. Among all 695 HPV-positive cases, 56 (8.1%) cases were only detected by the universal probe, in which 5 were either ASCUS or LSIL cases. Sequencing results confirmed HPV types 30, 91, and 74, and the intratypic variants of HPV 72 and 82 were present in the 5 cases. The result suggests that some rare HPV subtypes might be involved in cervical lesions.

Significance of DNA Quantitative Cytology and High-risk HPV-DNA Test in ASCUS Triage Diagnosis

Objective To explore the significance of DNA quantitative cytology and High-risk HPV-DNA testing in ASCUS riage diagnosis.Methods The DNA quantitative cytology group included 193 cases and the high-risk HPV-DNA comprises 134 cases.ASCUS diagnosed by TBS undergone with automatic cell tumour check analysis system or High-risk HPV-DNA test later,were both done colposcopy directed biopsy soon.There was a comparison between these two cases in pathological results.Results Of the 327 ASCUS cases,204 cases were histologically diagnosed as inflammation(62.39%),70 cases were CIN Ⅰ(21.41%),13 cases were CINⅡ(3.98%),30 cases were CIN Ⅲ(9.17%),and 10 cases were cervical invasive cancer(3.05%).The histological diagnosis were no statistical distinction between HR-HPV-DNA and DNA Quantitative cytology groups.The negative predictive values of HPV-DNA and DNA Quantitative cytology were 94.74% and 98.93%,respectively.Compared with the percentage of DNA amount greater than 5C(DNA Index>2.5) cells,the histological diagnosis were significantly different between <0.1% and ≥0.1%.DNA heteroploid more than or equal to three were used to predict CINⅡor more severe pathological changes,and its sensitivity,specificity,positive predictive values and negative predictive values were 80.64%,47.06%,40.99%,84.21%,respectively.Conclusion DNA Quantitative cytology and High-risk HPV-DNA test can be used for ASCUS triage,but the cost of DNA Quantitative cytology is cheaper than High-risk HPV-DNA test.