High-grade Abnormalities Research Articles

Cytomorphological Features of Hyperchromatic Crowded Groups in Liquid-Based Cervicovaginal Cytology: A Single Institutional Experience.

BackgroundHyperchromatic crowed groups (HCGs) are defined as three-dimensional aggregates of crowded cells with hyperchromatic nuclei, and are frequently encountered in cervicovaginal liquid-based cytology (LBC). Here, we aimed to examine the prevalence of HCGs in cervicovaginal LBC and the cytomorphological characteristics of various epithelial cell clusters presenting as HCGs.MethodsWe first examined the prevalence of HCGs in a “routine cohort” of LBC cytology (n=331), consisting of all cervicovaginal LBCs accessioned over 3 days from outpatient clinics (n=179) and the screening population (n=152). Then we examined a second “high-grade epithelial cell abnormalities (H-ECA) cohort” (n=69) of LBCs diagnosed as high-grade squamous intraepithelial lesion (HSIL), squamous cell carcinoma (SCC), or adenocarcinoma during 1 year.ResultsHCGs was observed in 34.4% of the routine cohort and were significantly more frequent in the epithelial cell abnormality category compared to the non-neoplastic category (p=.003). The majority of HCGs represented atrophy (70%). Of the 69 histologically confirmed H-ECA cases, all contained HCGs. The majority of cases were HSIL (62%), followed by SCC (16%). Individually scattered neoplastic cells outside the HCGs were significantly more frequent in SCCs compared to glandular neoplasia (p=.002). Despite the obscuring thick nature of the HCGs, examining the edges and the different focal planes of the HCGs and the background were helpful in defining the nature of the HCGs.ConclusionsHCGs were frequently observed in cervicovaginal LBC and were mostly non-neoplastic; however, neoplastic HCGs were mostly high-grade lesions. Being aware of the cytomorphological features of different HCGs is important in order to avoid potential false-negative cytology interpretation.

Routine cervical screening by primary HPV testing: early findings in the renewed National Cervical Screening Program.

To report human papillomavirus (HPV) testing patterns and rates of oncogenic HPV-positivity for specimens submitted during the first 6 months after the National Cervical Screening Program switched from cytology- to primary HPV-based screening. Retrospective cross-sectional review of 195606 specimens submitted for HPV testing, 1 December 2017 - 31 May 2018. Large community-based general pathology laboratory in metropolitan Sydney. Prevalence of oncogenic HPV types (all, HPV16/18, non-HPV16/18) by reason for HPV test (primary screening, non-screening); for oncogenic HPV-positive women in the age band recommended for primary HPV screening (25-74 years), prevalence of cytologic abnormality and rates of 12-month follow-up and colposcopy recommendations. 195606 samples were received: 157700 (80.6%) for primary screening, 37906 (19.4%) for non-screening tests. Oncogenic HPV was detected in 8.1% of screening tests (95% CI, 7.9-8.2%) and 20.9% of non-screening tests (95% CI, 20.5-21.3%); 35.5% (95% CI, 34.7-36.4%) of women of recommended screening age with positive oncogenic HPV screening test results also had a cytologic abnormality. The proportion of HPV16/18-positive samples with high grade abnormality was 15.3% (95% CI, 14.2-16.6%); for samples positive for other oncogenic HPV types, the proportion was 6.3% (95% CI, 5.8-6.8%). Repeat HPV testing after 12 months was recommended for 5.4% (95% CI, 5.3-5.5%) and direct colposcopy for 2.6% (95% CI, 2.5-2.7%) of screened women aged 25-74 years. High grade cytologic abnormalities were more common in women positive for HPV16/18, supporting their higher risk classification. Colposcopy referral rates were higher than during primary cytology-based testing, as predicted by clinical trial and modelling data. The prevalence of HPV was much higher in non-screening than in primary screening samples. Our findings indicate the renewed program is performing as expected during the initial HPV screening round.

Undifferentiated Uterine Sarcomas Represent Under-Recognized High-grade Endometrial Stromal Sarcomas.

Undifferentiated uterine sarcoma is a diagnosis of exclusion with limited molecular genetic data available. Recent recognition of high-grade endometrial stromal sarcomas with diverse genotypes suggests that some tumors classified as undifferentiated uterine sarcomas may represent misdiagnosed high-grade endometrial stromal sarcomas. Archival material from 10 tumors diagnosed as undifferentiated uterine sarcomas in 2009 to 2017 were collected. BCOR immunohistochemistry and fluorescence in situ hybridization (FISH) using break-apart probes flanking BCOR, ZC3H7B, CCNB3, YWHAE, NUTM2, JAZF1, and BCORL1 were performed. Tumors lacking or harboring gene rearrangement with no known fusion partner by FISH were subjected to targeted RNA sequencing. Morphology was correlated with FISH and sequencing results. BCOR expression was moderate to strong in ≥50% of cells in 8 tumors, while weak in <5% cells and negative in 2. FISH detected mutually exclusive ZC3H7B-BCOR and YWHAE-NUTM2 fusions in 3 uniform undifferentiated uterine sarcomas; 2 pleomorphic tumors harbored YWHAE rearrangement with no known partner. Targeted RNA sequencing of 5 FISH-negative uniform undifferentiated uterine sarcomas detected BRD8-PHF1 and YWHAE-NUTM2B fusions and BCOR internal tandem duplication in 4 of them. Tumors with YWHAE-NUTM2 fusions and BCOR genetic abnormalities showed morphology characteristic of high-grade endometrial stromal sarcomas. No fusions were detected by sequencing in the tumor with YWHAE rearrangement only by FISH. Most tumors classified as undifferentiated uterine sarcomas represent misdiagnosed high-grade endometrial stromal sarcomas. BCOR expression in ≥50% of cells may help triage tumors for molecular confirmation of high-grade endometrial stromal sarcoma-related genetic abnormalities. Novel YWHAE rearrangements may define a subset of true undifferentiated pleomorphic sarcomas.

Effectiveness on high-grade cervical abnormalities and long-term safety of the quadrivalent human papillomavirus vaccine in Japanese women

This study for the first time assessed quadrivalent human papillomavirus (qHPV) vaccine effectiveness against HPV6/11/16/18-related high-grade cervical disease in Japanese women (16–26 years old), as previously demonstrated in overseas trials, and vaccine safety in a longer term (48-month) open-label study (NCT01544478). Participants received three doses of qHPV vaccine (Day 1, Month 2, Month 6). Effectiveness endpoints, assessed in the per-protocol population, included incidence of HPV6/11/16/18-related cervical intraepithelial neoplasia (CIN) Grade 2 or worse (CIN Grade 2 and 3, adenocarcinoma in situ, and/or cervical cancer) as primary endpoint and incidence of external genital lesions (EGLs). Disease related to other high-risk HPV types was also assessed. Adverse events (AEs) and serious AEs (SAEs) were collected from Days 1–15 after any vaccination; vaccine-related SAEs, deaths, and new medical conditions were collected throughout the study. A total of 1030 women received at least one vaccination. No cases of CIN2 or worse or EGLs were reported in the per-protocol population. Injection site-related AEs were reported in 14.5% of participants; most were mild and resolved within 15 days. Vaccine-related systemic AEs occurred in 8.6% of participants, most commonly headache (2.3%), malaise (1.7%), and pyrexia (1.3%). There were no vaccine-related SAEs; one participant discontinued due to a vaccine-related AE of mild uticaria. Overall, qHPV vaccine effectiveness against HPV6/11/16/18-related high-grade cervical disease and EGLs was indicated in Japanese women. The vaccine was well-tolerated, without new safety signals throughout the 48-month study period. Findings are consistent with overseas qHPV vaccine pivotal trials. Clinical trial registryclinicaltrials.gov; NCT01544478.

Population-level impact and herd effects following HPV vaccination programs: a global view

Prophylactic HPV-vaccination programs constitute major public-health initiatives worldwide. HPV vaccines have been introduced into national immunization programs in over 80 countries, although most are in high income countries. Now that these vaccines have been implemented just over 10 years, the impact and effectiveness on HPV infection and disease has been reported in various observational studies. Underpinning outcomes, is high coverage of target populations before HPV exposure, as well as those where catchup programs have been initiated. Recently reported are maximal reductions of ∼90% for HPV related infections such as 6/11/16/18, ∼90% for genital warts, ∼45% for low-grade cytological cervical abnormalities, ∼60% for high-grade histologically-proven cervical abnormalities (HSIL), in addition to reductions in colposcopic referrals, plus ablative therapy. With these reductions in HSIL, the positive predictive value of cervical cytology for underlying precancer has reduced: thus countries are adopting more sensitive HPVDNA screening methods. Where catchup programs have extended to high coverage and to up to 26 years of age, herd protection for vaccine-related infections and disease has been seen in unvaccinated women, as well as in similar age males, all from the female only vaccine programs. Modelling suggests that the incremental benefit of vaccinating boys where female coverage is high will be small. However, that does not address gender neutral (male) vaccination.

Neuroimaging findings in midlife and risk of late-life dementia over 20 years of follow-up.

To examine the association between neuroimaging features in a predominantly middle-aged cohort and risk of late-life dementia. Cerebral MRI was performed on 1,881 individuals with no history of stroke from the Atherosclerosis Risk in Communities Study cohort in 1993 to 1995. White matter hyperintensities (WMH), ventricular size, and sulcal size were graded on a semiquantitative scale, and presence of silent cerebral infarcts was identified. In 2011 to 2013, dementia was determined from neuropsychological testing, informant interview, hospital ICD-9 codes, and death certificate dementia codes. Cox regression was used to evaluate associations between MRI findings and dementia. Over 20 years of follow-up, dementia developed in 279 participants (14.8%). High-grade WMH and high-grade ventricular size were independently associated with increased dementia risk (hazard ratio [HR] for WMH 1.62, 95% confidence interval [CI] 1.14-2.30; HR for ventricular size 1.46, 95% CI 1.06-2.03). There was an increased risk of dementia for diabetic participants with silent infarcts (HR 2.56, 95% CI 1.23-5.31) but not among nondiabetic participants (HR 0.87, 95% CI 0.56-1.37). Each 1-unit increase in the total number of high-grade cerebral abnormalities at baseline (count values range 0-4) showed increased dementia risk, with a considerably higher risk among diabetic participants (HR for diabetes mellitus 1.97, 95% CI 1.44-2.69; HR for no diabetes mellitus 1.20, 95% CI 1.03-1.39). In adults without evidence of clinical stroke, MRI-detected WMH and ventricular enlargement in midlife may represent markers of brain injury that increase risk for later-life cognitive impairment. The presence of diabetes mellitus may modify the association between silent infarcts and dementia.

Detection of HPV mRNA in Self-collected Vaginal Samples Among Women at 69-70 Years of Age.

Cervical cancer is associated with poorer diagnosis among the elderly and pap-smear screening has a lower sensitivity. Self-sampling for detection of high-risk human papillomavirus (hr-HPV) may be an alternative screening method. The aim of this study was to analyze the response rate to vaginal HPV self-sampling and the HPV mRNA prevalence among women 69-70 years. An HPV self-sampling kit was sent to 1,000 women 69-70 years whom had not taken a cervical smear in ≥5 years. The samples were analyzed by the Aptima HPV mRNA assay. HPV-positive women were recalled for a follow-up examination. The self-sample response rate was 43.3%. The HPV mRNA prevalence was 6.2%. All HPV-positive women attended follow-up. HPV self-sampling was accepted among older women. Although the HPV mRNA prevalence was 6.2%, no high-grade cytological abnormalities were found. Larger studies are needed to elucidate hr-HPV self-sampling as a tool to identify older women at risk of cervical cancer.

Spatial variation in cervical cancer screening participation and outcomes among Indigenous and non‐Indigenous Australians in Queensland

AbstractIndigenous women continue to experience a disproportionately higher burden of cervical cancer than non‐Indigenous women in Australia. The National Indigenous Cervical Screening Project used probabilistic record linkage to combine population‐based administrative databases and identify Indigenous women on Pap Smear Registers. This study aimed to quantify the spatial variation by local government areas (LGAs) for Indigenous and non‐Indigenous women in Queensland in cervical screening participation rates and related outcomes. Empirical Bayes local geostatistical smoothing was performed to reduce the likelihood of spurious variation between small areas. The cohort included 1,091,260 women (2 per cent Indigenous) aged 20 to 69 with 2,393,708 Pap smears between 2006 and 2011. Indigenous women had smoothed LGA‐specific 5‐year participation rates (interquartile range (IQR) 38.9–53.3 per 100 eligible women) consistently lower than non‐Indigenous women (IQR 80.7–85.3). The non‐overlapping confidence intervals of these rates suggest that the Indigenous differential was significant. Compared with Indigenous women, non‐Indigenous women had consistently lower and more stable prevalence rates of histologically confirmed high grade abnormalities (IQR 8.0–10.1 versus 15.0–21.3 per 1,000 screened women). Although the LGA‐specific rates also suggest that a higher proportion of non‐Indigenous women were followed‐up within two months of an abnormal screening result, the wide confidence intervals for these estimates limit our ability to draw definitive conclusions about spatial patterns for this outcome. These findings highlight the importance of continued monitoring and ongoing efforts to identify drivers of these patterns and develop effective strategies to improve participation and potentially reduce the cervical cancer burden among Indigenous women.

Cervical HPV prevalence and genotype distribution in immunosuppressed Danish women.

Women receiving immunosuppressive treatment due to organ transplantation are at increased risk of Human papilloma virus (HPV)-related diseases, including cervical neoplasia. This pilot study aimed to describe the cervical HPV prevalence and genotype distribution in immunosuppressed Danish women. We included women who underwent renal (RTR) or bone marrow transplantation (BMTR) in 2009-2012 or 2014 at Aarhus University Hospital, Denmark. Women undergoing transplantation in 2009-2012 had one cervical cytology performed, whereas women undergoing transplantation in 2014 had three, one before and two after transplantation. The samples were examined for cytological abnormalities and tested for HPV using Cobas® HPV Test and CLART® HPV2 Test. Of 94 eligible cases we included 60 RTR and BMTR. The overall prevalence of high-risk HPV was 15.0 [95% confidence interval (CI) 7.1-26.6] and the prevalence was higher among BMTR (29.4; 95% CI 10.3-56.0) than RTR (9.3%, 95% CI 2.6-22.1), although this was not statistically significant (p=0.10). The distribution of high-risk HPV was broad, with HPV 45 as the most common genotype (3.3%). The prevalences of high-risk HPV types included in the bivalent/quadrivalent and the nonavalent vaccines were 1.7 and 8.3%, respectively. The prevalence of low-grade and high-grade cytological abnormalities was 6.7 and 5.0%, respectively. Immunosuppressed women were infected with a broad range of high-risk HPV genotypes and the prevalence of cytological abnormalities was higher than found in previous studies of the general population. The nonavalent HPV vaccine will offer immunosuppressed individuals a greater protection against HPV-related diseases compared with the bivalent/quadrivalent HPV vaccines.

Does CIN2 Have the Same Aggressive Potential As CIN3? A Secondary Analysis of High-Grade Cytology Recurrence in Women Treated with Cold-Coagulation Cervical Treatment.

Introduction To determine whether women with CIN2 versus CIN3 on pretreatment cervical punch biopsy have less high-grade cytology recurrence following cold-coagulation cervical treatment. Materials and Methods This was a retrospective study of women having had cold coagulation between 2001-2011 in our colposcopy unit. Women with previous cervical treatment were excluded. Results We identified 402 women with 260 (64.7 %) cases of CIN2 and 142 (35.3 %) cases of CIN3 on pretreatment cervical punch biopsy. In the total sample, the mean age of women was 27.5 years (SD = 4.9), 75.1 % were nulliparous and 36.6 % were smokers. Referral cytology and pretreatment colposcopic appearance were high-grade in 62.7 % and 57.1 %. The mean follow-up period was 2.8 years (SD = 2.1). Women with CIN2 on pretreatment cervical biopsy when compared to those with CIN3 had less frequently high-grade referral cytology and high-grade pretreatment colposcopic appearances, and had less pretreatment cervical biopsies taken. During the follow-up period, women with CIN2 on pretreatment cervical biopsy had less high-grade cytology recurrence when compared to those women with CIN3 (1.9 vs. 5.6 %, p = 0.046). Multiple stepwise Cox regression analysis showed that women with CIN3 on pretreatment cervical biopsy had 3.21 times greater hazard for high-grade cytology recurrence (HR = 3.21, 95 % CI: 1.05-9.89; p = 0.041) in comparison with CIN2 cases. Conclusion We found that women with CIN2 on pretreatment cervical punch biopsy had less high-grade cytology recurrence following cold-coagulation treatment in comparison to those with CIN3. This finding lends support to the theory that CIN2 even though a high-grade abnormality might not have the same aggressive potential as CIN3.

The prevalence of HIV among women with high-grade cervical smear abnormalities in Birmingham, United Kingdom: A prospective cohort study

ObjectiveThe aim of the study was twofold: 1. To assess the acceptance for HIV screening in women attending Colposcopy clinic 2. To determine the prevalence of HIV in women presenting with high-grade cervical smear abnormalities. DesignA prospective study. SettingColposcopy clinic, Birmingham Women’s Hospital, UK. PopulationPatients attending colposcopy clinic. Main outcome measuresTo determine acceptance of HIV testing and prevalence in colposcopy patients with High-grade cervical smear abnormalities. ResultsOf the 252 patients who were offered the HIV test, 244(96.5%) accepted the test. None of 244 cases tested for HIV were found positive. ConclusionsHIV testing is feasible and acceptable in colposcopy clinics

Time to clinical investigation for Indigenous and non-Indigenous Queensland women after a high grade abnormal Pap smear, 2000-2009.

To investigate time to follow-up (clinical investigation) for Indigenous and non-Indigenous women in Queensland after a high grade abnormality (HGA) being detected by Pap smear. Population-based retrospective cohort analysis of linked data from the Queensland Pap Smear Register (PSR), the Queensland Hospital Admitted Patient Data Collection, and the Queensland Cancer Registry. 34 980 women aged 20-68 years (including 1592 Indigenous women) with their first HGA Pap smear result recorded on the PSR (index smear) during 2000-2009 were included and followed to the end of 2010. Time from the index smear to clinical investigation (histology test or cancer diagnosis date), censored at 12 months. The proportion of women who had a clinical investigation within 2 months of a HGA finding was lower for Indigenous (34.1%; 95% CI, 31.8-36.4%) than for non-Indigenous women (46.5%; 95% CI, 46.0-47.0%; unadjusted incidence rate ratio [IRR], 0.65; 95% CI, 0.60-0.71). This difference remained after adjusting for place of residence, area-level disadvantage, and age group (adjusted IRR, 0.74; 95% CI, 0.68-0.81). However, Indigenous women who had not been followed up within 2 months were subsequently more likely to have a clinical investigation than non-Indigenous women (adjusted IRR for 2-4 month interval, 1.21; 95% CI, 1.08-1.36); by 6 months, a similar proportion of Indigenous (62.2%; 95% CI, 59.8-64.6%) and non-Indigenous women (62.8%; 95% CI, 62.2-63.3%) had been followed up. Prompt follow-up after a HGA Pap smear finding needs to improve for Indigenous women. Nevertheless, slow follow-up is a smaller contributor to their higher cervical cancer incidence and mortality than their lower participation in cervical screening.

Loop electrosurgical excision procedure versus expectant management to treat high-grade squamous intraepithelial lesion in women up to 25 years

considerably.Aim: To determine outcome of regression in a cohort of women younger than 25 years old with cervical intraepithelial neoplasia grade 2 and 3 (CIN2/3) undergoing treatment with Loop Electrosurgical Excision Procedure (LEEP) or observational management.Methods: Prospective cohort study was carried out between April 2015 and January 2017 with all newly diagnosed biopsy-proven CIN2/3 outpatients. Analysis was performed that compared women who had immediate surgical treatment with women who chose expectant management. The primary outcome was development of high-grade changes (defined as cytological evidence of atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H), HSIL, adenocarcinoma in situ, atypical glandular cells (AGC), or worse) from at least one Pap Smear (PS) collected every 6 months in the minimum follow-up of 1 year. Comparisons were made using Cox proportional hazards regression analysis.Results: Sixty-four women were diagnosed through cervical biopsy with CIN 2/3 and could choose between conservative or surgical treatment. In the group up to 19 years of age, 6 (37.5%) with CIN2 chose the expectant management and 10 (62.5%) LEEP. While among 20-25-year-old women, 38 (79.2%) chose surgery and 10 (20.8%), being just 4 with CIN3, chose only follow-up for 1 year. The risk of cytological high-grade abnormality over the follow-up period was 62.5% for expectant management and 4.2% for LEEP group (p=0.001).Conclusion: Women aged up to 25 years with CIN2/3 undergoing treatment with LEEP had a significantly lower risk of cytological high-grade abnormality at 12 months follow-up compared with those who remained only under clinical observation.

Effect of human papillomavirus vaccination on cervical cancer screening in Alberta.

A school-based program with quadrivalent human papillomavirus (HPV) vaccination was implemented in Alberta in 2008. We assessed the impact of this program on Pap test cytology results using databases of province-wide vaccination and cervical cancer screening. We conducted a nested case-control study involving a cohort of women in Alberta born between 1994 and 1997 who had at least 1 Pap test between 2012 and 2015. Women with negative cytology results were controls. Women with low-grade (atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion) and high-grade (atypical squamous cells, cannot rule out a high-grade lesion; or high-grade squamous intraepithelial lesion) cervical abnormalities were cases. Exposure status was assigned according to records of HPV vaccination. Odds ratios (ORs) for abnormal cytology results by vaccination status were adjusted for neighbourhood income, laboratory service, rural versus urban residency, and age. The total study population was 10 204. Adjusting for age, vaccinated women had a higher screening rate than unvaccinated women (13.0% v. 11.4%, p < 0.001). Among women who received full vaccination (≥ 3 doses), the adjusted OR for cervical abnormalities was 0.72 (95% confidence interval [CI] 0.63-0.82). For high-grade lesions, the adjusted OR was 0.50 (95% CI 0.30-0.85). With 2-dose HPV vaccination, the adjusted OR for cervical abnormalities was 1.08 (95% CI 0.84-1.38). Quadrivalent HPV vaccination significantly reduced high-grade cervical abnormalities but required 3 doses. Vaccination against HPV was associated with screening uptake. Population-based vaccination and screening programs should work together to optimize cervical cancer prevention.

Findings and Outcomes in a Prevaccination Cohort of Women Younger Than 25 Years Attending a Tertiary Colposcopy Service.

To describe clinical presentation and treatment in women younger than 25 years referred to the Royal Women's Hospital colposcopy clinic, before implementation of the National Human Papillomavirus Vaccination Program. Retrospective cohort analysis of women younger than 25 years referred to a tertiary hospital colposcopy clinic between 1998 and 2007. Clinical presentation and correlation between cervical cytology, biopsy, and histology at treatment was examined. Approximately 14,635 colposcopies were undertaken in 4104 women (median age, 22 years); 3051 had abnormal referral cytology, of whom, 23.8% had high-grade disease on punch biopsy. High-grade disease was found in 15.1% of those with possible low-grade or low-grade cytology (293/1932), 42.4% of those with possible high-grade or high-grade cytology (474/1119). Sensitivity and specificity of colposcopy for high-grade disease (high-grade epithelial abnormality, adenocarcinoma in situ, cervical cancer up to 2 years follow-up) was 60.0% and 82.3%, respectively. Thirty-nine percent (n = 1180) with abnormal cytology had treatment, of which, 66.6% was ablative. Histological CIN3+ was found in 53.8% of those with a previous high-grade punch biopsy (126/234) at excisional treatment, and 23.0% of those with a previous low-grade punch biopsy (20/87) (relative risk, 2.3 [CI, 1.6-3.5]). Four cancers were detected (0.1% of the total cohort, 0.5% of those with a high-grade biopsy, and 1.7% of those with a high-grade biopsy who underwent excisional treatment.) Before vaccination, young women experienced a high real-time burden of high-grade disease and high rates of intervention. These baseline data contribute to monitoring of HPV vaccination and revised cervical screening strategies.

An Audit on Adequacy of Pap Smears

Conventional Pap smear is a commonly done screening test for cervical cancer. Accurate interpretation depends upon the specimen adequacy which is considered to be the single most important quality indicator of “The Bethesda System (TBS)”. To audit specimen adequacy and compare results based on 2014 TBS. Retrospective audit from 1 April to 31 December 2015. Data was collected from case notes and Pap smear reports. A total of 146 Pap smears were done during the study period. Majority of the women (34 %) were between 41 and 50 years. Fifty-five per cent had a small family size of two children. Seventy-six per cent were premenopausal while 34 % were post-menopausal. Transformation zone/endocervical component (TZ/EC) was seen in 87 % of smears. Blood was seen in 2.7 % and inflammatory cells in 59.6 % of smears. All smears were satisfactory for interpretation by the cytologist. In the final interpretation, atrophic smears were seen in 2/146 (1.4 %), low-grade epithelial abnormality and high-grade abnormality were seen in one smear each (0.7 %). Colposcopy and directed biopsy were normal in both. A total of 43.8 % were normal. A total of 53.4 % were inflammatory. In this audit, 100 % smears were satisfactory for interpretation and above the literature standard of 99.5 %.

Study of Correlation of Cervical Epithelial Thickness With the Grade of Colposcopic Abnormality.

Low epithelial thickness has been identified as the cause for nonvisualization of high-grade cervical intraepithelial neoplasia (CIN) on colposcopy in an earlier study. Multiple random biopsies are recommended by some authors to detect these "thin" CIN lesions in absence of colposcopic abnormalities. The present study was conducted to evaluate the correlation between the severity of colposcopic impression and the thickness of the epithelium so that the results of previous study could be validated. The cross-sectional study examined 209 histopathology slides with normal, human papillomavirus, or CIN diagnosis from a population-based study. Average epithelial thickness was measured by obtaining mean of the thicknesses at thinnest and thickest areas. Average thickness of dysplastic layer was also measured. These values were correlated with age, human papillomavirus status, colposcopic appearance and histopathology. Mean epithelial thicknesses were 212.8 μm for normal (N=28), 297.3 μm for human papillomavirus changes (N=48), 245.3 μm for CIN1 (N=46), 191.4 μm for CIN2 (N=50), and 218.5 μm for CIN3 (N=37). Within each histologic category, no correlation was observed between epithelial thickness and severity of colposcopic appearance. Mean epithelial thickness of CIN1/CIN2 lesions with normal colposcopy was more than that of CIN1/CIN2 lesions with high-grade appearance on colposcopy. Thickness of CIN3 lesions with high-grade abnormalities was higher than those without visible colposcopic abnormality but the difference was not statistically significant. Thickness of dysplasia increased with higher grades of CIN but did not have any relation to colposcopic appearance. Colposcopic appearance does not depend on the thickness of the epithelium affected by CIN. False-negative colposcopy in presence of high-grade CIN is likely due to failure of detecting small or predominantly endocervical lesions rather than "thin" CIN.

Smear Tactics

INTRODUCTION: Cervical cancer holds significant social and financial implications not only on Irish society, but across the globe, as it is the fourth most common cancer affecting women worldwide (IARC). This project identified the incidence, presentation, time to diagnosis and association of risk factors with cervical cancer in women referred to colposcopy in Dublin, Ireland over the last 6 years. Special attention was given to analysis of women presenting to colposcopy with initial low-grade smears as recent literature has advocated for stricter guidelines referring only those women presenting with high-grade smears to colposcopy. METHODS: A retrospective study (n=148) spanning 1/1/2009–3/15/15 was conducted in the colposcopy clinic of Tallaght Hospital, serving Dublin, Ireland. Statistical analyses utilized SPSS (22.0). RESULTS: The median time to identification of cervical cancer in women presenting with abnormal smears is 64.5 days. It was found 23.6% of patients presenting with low-grade smears had cervical cancer. More women using contraceptives were found to have adenocarcinoma than squamous cell carcinoma. Associations between squamous cell carcinoma and high parity, smoking and abnormal bleeding were also observed. CONCLUSION: Nearly 24% of women presenting with initial low-grade cytology developed cervical cancer. Early treatment of these cases resulted in over €7,000,000 saved, strengthening the argument against recent European and American proposals to enforce stricter guidelines allowing only women with severe or high-grade abnormalities to be referred to colposcopy clinics. Instead, evidence put forth in this study indicates that a referral to colposcopy following a low-grade smear is indeed an appropriate clinical action with immense economic benefits.

EUROarray human papillomavirus (HPV) assay is highly concordant with other commercial assays for detection of high-risk HPV genotypes in women with high grade cervical abnormalities.

The purpose of this study was to evaluate the performance of the EUROIMMUN EUROArray HPV genotyping assay against the Roche Cobas 4800, Roche HPV Amplicor, Roche Linear Array and Qiagen Hybrid Capture 2 assays in the detection of high-risk HPV (HR-HPV) from liquid based cervical cytology samples collected from women undergoing follow-up for abnormal cervical cytology results. Cervical specimens from 404 women undergoing management of high-grade cytological abnormality were evaluated by EUROarray HPV for detection of HR-HPV genotypes and prediction of histologically-confirmed cervical intraepithelial neoplasia grade 2 or higher (≥CIN2). The results were compared to Hybrid Capture 2, Cobas 4800 HPV, Amplicor and Linear Array HPV. Positivity for 14 HR-HPV types was 80.0% for EUROarray (95% CI; 75.7-83.8%). Agreement (κ, 95% CI) between the EUROarray and other HPV tests for detection of HR-HPV was good to very good [Hybrid Capture κ = 0.62 (0.54-0.71); Cobas κ = 0.81 (0.74-0.88); Amplicor κ = 0.68 (0.60-0.77); Linear Array κ = 0.77 (0.70-0.85)]. For detection of HR-HPV, agreement with EUROarray was 87.90% (Hybrid Capture), 93.58% (Cobas), 92.84% (Amplicor) and 92.59% (Linear Array). Detection of HR-HPV was not significantly different between EUROarray and any other test (p < 0.001). EUROarray was concordant with other assays evaluated for detection of high-risk HPV and showed sensitivity and specificity for detection of ≥ CIN2 of 86% and 71%, respectively.

Choropleth Mapping of Cervical Cancer Screening in South Africa Using Healthcare Facility-level Data from the National Laboratory Network.

BackgroundIn South Africa, cervical cancer remains among the most common cancers and a leading cause of cancer death. Co-infection with HIV increases the risk of developing cervical pre-cancer and cancer. We analysed National Health Laboratory Service cervical cytology data to investigate geographic variations of Pap smear coverage, quality, and high grade lesions.MethodsFacility-level data were extracted from the NHLS for April 2013–March 2014. We present results and choropleth maps detailing coverage, adequacy and high-grade Pap smear cytology abnormalities defined as Pap smears suspicious for invasive carcinoma, high-grade squamous intraepithelial lesions (HSIL) or atypical squamous cells: cannot exclude HSIL (ASC-H).Results4,562 facilities submitted 791,067 cytology slides. The interquartile range (IQR) for Pap smear coverage among HIV-infected women was 26–41%; similar to coverage in women aged 30 and older (IQR: 26–42%). 6/52 districts had adequacy rates above the national standard (70%) and 2/52 districts had adequacy rates below 35%. We observed marked variation in Pap smear abnormalities across the country, with the proportion of high-grade cytology abnormalities ≥0.3% in 17/52 districts.ConclusionUsing district-level choropleth maps, we are able to display variations in Pap smear coverage, quality, and results across South Africa. This approach may be used to improve resource allocation, achieving better equity in cervical cancer prevention.