Routine Cervical Cytology Research Articles

Cervical cancer screening by cytology and the burden of epithelial abnormalities in low resource settings: a tertiary-center 42-year study

BackgroundCytological screening remains a high-impact practice, particularly in low-resource settings, for preventing cervical cancer. The examination of screening practices over time and the prevalence of epithelial abnormalities have not been investigated in longitudinal studies in one of the largest countries in the Middle East and Africa.MethodsRoutine healthcare data, between March 1981 and December 2022, were extracted from the database of the Early Cancer Detection Unit in a tertiary referral university hospital in the Greater Cairo Region, Egypt. Cervical smears were obtained using a standardized technique and sent to the cytopathology laboratory for conventional cytology examination by expert pathologists. The anonymous data were analyzed to determine the temporal trend of the number of women screened each year and the prevalence of epithelial abnormalities.ResultsData included the results of satisfactory smears from 95120 women. The mean age (SD) of the women at the time of screening was 38.5 (10.5). None of the included women received an HPV vaccine. Abnormal epithelial cells were reported in 5174 women (5.44%). Of these epithelial abnormalities, the majority were low-grade squamous intraepithelial lesions in 4144 women (4.36%). Other abnormalities included atypical squamous cells in 378 women (0.40%), high-grade squamous intraepithelial lesions in 226 women (0.24%), atypical glandular cells not otherwise specified in 184 women (0.19%), adenocarcinoma in 165 women (0.17%), squamous cell carcinoma in 70 women (0.07%), and atypical glandular cells favoring neoplasms in 7 women (0.01%). Women who were at an early age at first intercourse, those who opted for routine cervical cytology screening, and those who were older at screening were more likely to have epithelial abnormalities. The yearly number of screened women was positively associated with the detection of low-grade squamous intraepithelial lesions (correlation coefficient [95% CI] = 0.84 [0.72, 0.91]) and negatively associated with the detection of squamous cell carcinoma (correlation coefficient [95% CI] = -0.55 [-0.73, -0.29]).ConclusionsThe small number of annually screened Egyptian women and the temporal trend in epithelial abnormalities critically demonstrate the need for establishing and scaling up a structured population-based program to achieve the goal of eliminating cervical cancer.

BD SurePath Direct to Slide (DTS) cervical cytology: Migrating the benefits of liquid-based cytology to low-resource settings.

The benefits of liquid-based cytology (LBC) in routine cervical cancer screening are often associated with the availability of instrumented platforms and economic considerations. A low-cost alternative to LBC in low-volume settings remains an unmet need. A multisite evaluation of the BD SurePath (SurePath) LBC Direct to Slide (DTS) method was conducted. The DTS preparations were evaluated across 3 sites. Cytology features for DTS preparation included predetermined thresholds for total cellularity, cell distribution, cellular preservation, and stain quality. Rare event detection was evaluated using SiHa cells spiked into pools from negative cytology specimens. Concordance between Bethesda classification results was evaluated for SurePath LBC and DTS methods using routinely collected SurePath specimens in a split-sample study design. The DTS specimens met criteria for total cellularity, cell distribution, cellular preservation, and stain quality in more than 98% of all cases. Rare event detection was observed with an average detection of 5 SiHa cells per 2mL of specimen. Concordant cervical cytology classifications were observed between SurePath LBC and DTS methods. The results demonstrate that the DTS process is suitable for routine cervical cytology evaluation. The procedure is reproducible and detected abnormal cervical cells in concordance with standard SurePath LBC preparation.

Endometrial cancer diagnoses prompted by routine cervical cytology: a retrospective case study.

Endometrial cancer is the commonest gynaecological cancer in New Zealand. Some women have their diagnosis of endometrial cancer prompted by an abnormal cervical cytology screening test. When high-risk human papillomavirus (hr-HPV) testing becomes the primary test for cervical screening, this avenue of incidental diagnosis will be reduced. Therefore, our aims were to estimate the proportion of women whose diagnosis of endometrial cancer follows incidental detection on routine cervical cytology, and to understand the clinicopathologic characteristics of these cases. Retrospective analysis of patient medical records from women of cervical screening age diagnosed with endometrial cancer between 2015-2019 in the South Island of New Zealand. Of 334 women, 26 (7.8%) had endometrial cancer diagnosis prompted by abnormal cervical cytology. Most women had low-grade (17/26, 65.4%), low-stage (18/26, 69.2%) disease of endometrioid histologic subtype (21/26, 80.8%). The small cohort prevented significant correlations with clinicopathologic characteristics and outcomes. Overall, cervical cytology had low sensitivity (32.3%) for the detection of endometrial cancer in the 6 months before diagnosis. A small number of women currently have diagnoses of endometrial cancer prompted by routine cervical screening with cytology. However, the undefined clinical benefit from and poor sensitivity of cervical cytology for detecting endometrial cancer does not justify its use in screening, or opposition to hr-HPV cervical screening.

Long-term clinical significance of benign endometrial cells identified on routine cervical cytology in women aged more or equal to 45 years

Within the Bethesda System, the recommendation of describing benign-appearing endometrial cells (BECs) has changed over recent years. Since the 2014 revision, their presence in cervical cytology reports has been deemed essential, beginning with age 45. Recent studies have suggested rising the reporting age to 50 years. Does the presence of these cells necessitate further assessment? This retrospective cohort study included patients aged between 45 and 65 years in whom BECs were present on cervical cytology between January 2001 and December 2010, with a follow-up at 5 and 10 years. Women who had abnormal cervical cells or atypical endometrial cells on cervical cytology were excluded, as well as women with a history of cervical or endometrial cancer, or a history of hysterectomy and incomplete follow-up data. One hundred seventy-six women were included. Of these, 31% were postmenopausal of which 65% used hormonal substitution therapy. Twenty-eight percent presented with abnormal uterine bleeding at inclusion. During the follow-up period of 10 years, 87.5% had a normal gynecological follow-up and 11.4% underwent a hysterectomy for benign pathology. One percent (2 patients) had been diagnosed with endometrial malignancy, both presenting with postmenopausal bleeding and aged over 60 years. Our study confirmed that the presence of BECs is not a reason for concern when no additional clinical indicator is recognized, especially with normal ultrasonographic examination. Further invasive exploration may be controversial. If reporting BECs in cervical cytology continues, we strongly agree on rising the reporting age to 50 years or postmenopausal state.

Correlations between Colposcopy Findings and Histopathological Results from Colposcopy Directed Biopsy in Cervical Pre-Cancerous Lesions

Introduction: Cervical Intraepithelial Neoplasia is a precancerous condition in which abnormal cells grow on the surface of the cervix. CIN is a symptomless illness that often goes undetected by the naked eye. In most cases, the afflicted cervix appears to be in excellent health. As a result, the illness is detected by chance during cervicological histology or as a result of programs for routine cervical cytology or colposcopy screening. Colposcopy is an extra and valuable technique for identifying cervix anomalies. This study aimed to analyze the correlations between colposcopy findings and histopathological results from colposcopy-directed biopsy in cervical pre-cancerous lesions. Methods: A prospective observational study was conducted at the Department of Gynecology and Obstetrics, Chittagong Medical College Hospital, Chittagong, from September 2014 to February 2015. VIA-positive 72 women fulfilling all inclusion criteria who attended at colposcopy clinic of CMCH were included in the study. Statistical analyses were done by using the Statistical Package for Social Sciences (SPSS) version 16.0 for Windows. The quantitative observations were indicated by frequencies and percentages. Result: In the present study, the majority of the participants were over the age of 30 years, with 43.1% being in the age group of 30-39 years. Another 30.6% were from the age group of 40-49 years, while only 15.2% were from the age group of 20-29 years. Colposcopy findings were normal in 9.7% of the participants. CIN I was observed in the majority of the participants (54.2%), while CIN II and CIN III were observed in 29.2% and 6.94% respectively. According to the colposcopy-directed biopsy results, 5.6% of patients had normal outcomes, 7.7% had inflammations, 45.8% had CIN I, 30.6% had CIN II and 8.3% had CIN III. The correlation was calculated by reporting the number of cases histologically confirmed to the number of cases of colposcopic diagnosis for each lesion group separately. The correlation was 71.8% (28 out of 39) in the CIN I category, 76.2% (16 out of 21) in the CIN II category, and 75% (3 out of 4) in the CIN III category. The sensitivity and specificity of colposcopy were calculated considering a colposcopy-directed biopsy. Colposcopy findings revealed 65 CIN positive cases and 07 CIN negative cases, while biopsy findings revealed 60 positive and 12 negative cases. The sensitivity of colposcopy was 96.7%, specificity was 41.6%, the false positive rate was 58.4% and the false negative rate was 03.3% according to this study. Conclusion: This study demonstrated high accuracy and correlation between colposcopy and histology. The sensitivity of colposcopy was 96.7%, specificity was 41.6%, the false positive rate was 58.4% and the false negative rate was 03.3%. Specificity was lower in this study probably because biopsies were performed in all cases during diagnostic workups.

RESULTS OF PROSAFE PAP IN CERVICAL CYTOLOGY

Papanicolaou staining is recommended for routine cervical cytology and cervical cancer screening. Our study was conducted by adapting modied staining technique which involves replacement of use of descending grades of alcohol with one step of 80% isopropyl alcohol. Prosafe papanicolaou staining was intended to reduce the staining time and cost of staining without compromising the quality or cytodiagnosis of the smear.

Utility of routine cytology in detecting asymptomatic cervical cancer recurrence.

The objective of this study was to examine the utility of routine cervical cytology after cervical cancer treatment. We performed a retrospective study from 2004 to 2020, which identified 581 cervical cancer patients. Of the 581 patients, 233 were included in the analysis. The remaining 348 were excluded because of failure to enter the surveillance period, loss to follow-up, or treatment at an outside facility. The continuous data were summarized using the median and interquartile range for non-normally distributed data. The categorical data were summarized using frequencies and proportions. Comparisons between the categorical data were performed using the Fisher exact test. Of the 233 included patients, 78 (33.5%) had had ≥1 abnormal Papanicolaou (Pap) test during surveillance. Of these 78 patients, 22 (28.2%) underwent biopsy, with all biopsies negative for malignancy. Local recurrence was identified in 15 patients. Of these 15 patients, 14 (93.3%) were symptomatic at diagnosis, 7 (46.7%) had had visible disease on the physical examination, and 6 (40.0%) had normal cytology findings throughout surveillance. Only 1 case of local, asymptomatic cervical cancer recurrence was detected by Pap test alone. A subset analysis was performed to compare the rate of abnormal Pap tests between the radiation therapy and non-radiation therapy groups. Of the 233 patients, 154 (66.1%) underwent primary radiation therapy, 64 (41.6%) of whom had abnormal cytology during surveillance. Of 82 patients who did not undergo radiation therapy, only 14 (17.1%) had had abnormal cytology (P < 0.01). None of the patients in either group had underlying recurrent disease at the time of abnormal cytology. The results of our study show that routine Pap tests have limited clinical utility in the surveillance of cervical cancer recurrence. Consideration should be given to removing routine cytology from the surveillance recommendations.

Detection of HIV mRNA in routine liquid-based cytology specimens of HIV-infected women.

Human immunodeficiency virus-infected women have a high incidence of HPV infection, and HIV and HPV coinfection is associated with high incidence of cervical intraepithelial lesions and cervical cancer. This study investigated the ability to detect HIV mRNA in routine screening cervical liquid-based cytology (LBC) samples and its correlation with HPV coinfection and cervical intraepithelial lesions. Liquid-based cytology samples from 80 HIV-infected women under combined antiretroviral therapy (cART) were studied for detection of HIV and HPV mRNA using Aptima® tests and for cytology diagnosis according to the 2014 Bethesda System for Reporting Cervical Cytology. Peripheral blood (PB) HIV mRNAs were assessed by real-time polymerase chain reaction (RT-PCR). Statistical analysis used Fisher's exact or Chi-square test to compare frequencies among groups and the Mann-Whitney U test to compare continuous variables. Human immunodeficiency virus mRNA was present in 21.3% of routine LBC samples in HIV-infected women, 12.5% of which had no detectable PB viral load. Among 10 patients diagnosed with high-grade squamous intraepithelial lesion (HSIL), 50% had detectable HIV viral load. The occurrence of HSIL vs low-grade intraepithelial lesion/negative intraepithelial lesion or malignancy in LBC samples was significantly higher in women with detectable HIV viral load (P=.029). Human immunodeficiency virus mRNA was present in routine LBC samples in HIV-positive women under cART. Detection of HIV viral load in LBC is significantly associated with cervical HSIL. This suggests the relevance of HIV mRNA viral load assessment in routine LBC, to evaluate patients' infectious potential and monitor efficacy of the cART scheme.

Sensitivity of cervico-vaginal cytology in endometrial carcinoma: A systematic review and meta-analysis.

Cervico-vaginal cytology is primarily a cervical cancer screening test. The anatomical continuity of the uterine cavity with the cervix makes the Papanicolaou (Pap) test accessible to evaluate signs of disease shed from the endometrium. Our aim was to determine the sensitivity of routine Pap test in endometrial carcinoma detection and its relationship with clinico-pathologic factors. We performed a systematic review of studies reporting Pap test results prior to diagnosis of or surgery for endometrial carcinoma between 1990 and 2018 in PubMed or Web of Science. Two independent reviewers extracted data and assessed study quality using an adapted Newcastle-Ottawa Quality Assessment Scale and Quality Assessment of Diagnostic Accuracy Studies tool. We identified 45 studies including a total of 6599 women with endometrial cancer. Abnormal Pap test results prior to diagnosis of or surgery for endometrial carcinoma were observed in 45% (95% CI, 40%-50%) of study participants. This percentage was significantly higher among those of non-endometrioid histology compared with endometrioid subtypes (77% [95% CI, 66%-87%] vs 44% [95% CI, 34%-53%], respectively; P heterogeneity <.001). Several clinico-pathologic factors were related to a higher percentage of abnormal Pap test results, including high-stage, myometrial invasion >50%, high histological grade, positive peritoneal cytology, presence of lymph node metastasis, cervical involvement, and lymphovascular invasion (P heterogeneity <.05 for all variables). Routine cervical cytology can detect endometrial cancer in almost half of patients, whereas sensitivity is higher among individuals with non-endometrioid histology or more advanced cancers. This review summarizes the current clinical and prognostic value of cervical cytology in endometrial carcinoma. Recent technological developments using molecular biomarkers may improve accuracy for early cancer detection.

Diffuse Large B-Cell Lymphoma of the Cervix Diagnosed on Cervical Screening Cytology

Abstract Case Presentation Primary lymphoma of the cervix is an uncommon entity and far more rarely diagnosed on routine screening cervical cytology. We present a case of a 38-year-old female with a 1-year history of heavy cyclical menstrual bleeding and interval spotting. She had no other significant past medical or obstetric history. On cervical exam, obscuring blood was noted without distinct abnormalities of the visualized cervix. Pathologic Findings Cervical cytology by ThinPrep (Hologic, Marlborough, MA) liquid-based cytology preparation demonstrated atypical squamous cells of undetermined significance as well as an abundant population of atypical lymphoid-appearing cells. Morphology of this second population was characterized by large cells (2-3 times the size of background inflammatory cells) with high nuclear-to-cytoplasm ratio, vesicular chromatin, occasional nucleoli, marked nuclear membrane irregularities, and scant cytoplasm. A cell block of the specimen was performed and demonstrated a mature but cytologically large and atypical lymphoid population. Immunohistochemistry on the cell block specimen was consistent with a B-cell immunophenotype with strong CD45 and CD20 immunolabeling. Subsequent radiologic workup showed a diffusely enlarged cervix with increased metabolic uptake, as well as bilateral metabolically active pelvic lymph nodes. Conclusion Cervical and endometrial curettings obtained at an outside facility confirmed the diagnosis of lymphoma that was further categorized as diffuse large B-cell lymphoma, germinal center B-cell type. This case highlights an uncommon diagnosis found on screening cervical cytology. It reinforces awareness of the potential for lymphoid neoplasms on cervical cytology and the differential diagnosis associated with such cases.

HPV testing compared with routine cytology in cervical screening: long-term follow-up of ARTISTIC RCT.

The National Screening Committee (NSC) based its recommendation that human papillomavirus (HPV) testing should replace cytology in primary cervical screening largely on the 2009 follow-up results of the ARTISTIC trial (A Randomised Trial In Screening To Improve Cytology). The NSC must now decide on screening intervals and triage policy. Options include extending the screening interval up to 10 years for human papillomavirus-negative (HPV-) women, delaying recall for human papillomavirus-positive (HPV+) women with normal cytology (as their infections are usually transient), and basing triage on full HPV typing. In ARTISTIC, 24,510 women were recruited who were attending routine cervical cytology in Greater Manchester in 2001-3. The women were randomly allocated between revealing and concealing their HPV test results and were recalled every 3 years. After 2009, the women returned to routine cytological screening with recall every 3 years for those aged < 50 years, and every 5 years for those aged 50-64 years. We have followed the cohort to 2015 through national cancer registration for CIN3 (cervical intraepithelial neoplasia grade 3) and cancer, and through linkage to the cervical screening call-recall system to obtain lifetime cytology records. The analysis comprised 24,496 women at round 1 and 13,591 women at round 2 (which was 30-48 months later). Follow-up via local histology laboratories and national cancer registration identified 505 cases of cervical intraepithelial neoplasia grade 3 or cervical cancer (CIN3+) (including 22 invasive cervical cancers). The cumulative CIN3+ risk 10 years after a negative HPV test [0.31%, 95% confidence interval (CI) 0.18% to 0.49%, in the revealed arm] was similar to that 3 years after negative cytology (0.30%, 95% CI 0.23% to 0.41%, in the concealed arm) and fell sharply with age, from 1.1% (95% CI 0.7% to 1.8%) in those women aged < 25 years to 0.08% (95% CI 0.03% to 0.20%) in those women aged > 50 years. The 10-year cumulative CIN3+ risk following a new HPV infection at round 2 was 3.4% (95% CI 2.1% to 5.4%). The highest risks were associated with type-specific persistent infections that, overall, resulted in a 10-year cumulative CIN3+ risk of 20.4% (95% CI 15.6% to 26.4%). We found a similar level of protection 10 years after a negative HPV test and 3 years after negative cytology. These data support a considerably longer screening interval after a negative HPV test than after a negative cytology test. About three-quarters of women with HPV infection and normal cytology clear their infections within about 3 years. Their risk of CIN3+ within this time frame is low (1.5%), suggesting that the current policy of annual repeat testing and referral after 2 years may be unnecessarily cautious. Approximately 40% of women who remained HPV+ had cleared their initial infection and acquired a new HPV type. The cumulative CIN3+ risks in women with type-specific persistent infections are about six times higher than in women with new infections. Triage strategies based on HPV persistence would, therefore, reduce unnecessary referral of women with new (and largely transient) infections. HPV assays that identify HPV types 31, 33, 45, 52 and 58 in addition to 16 and 18 could be useful in triage as well as in primary HPV testing. Similar results in recent routine HPV screening suggest that our results are generalisable despite changes in cytology and HPV assay methods. We are continuing to follow the ARTISTIC cohort into the new era of primary HPV screening. Future work will focus on the implications of more sensitive HPV testing for primary HPV screening policy and triage of HPV-positive women. Our results suggest that a more sensitive test is needed to detect occult CIN3 at high risk of progression to cancer, but this would substantially increase the overall HPV detection rate. Tests such as DNA (deoxyribonucleic acid) methylation for distinguishing HPV infection from neoplasia will be evaluated on stored samples and on further samples now being collected from women in the cohort who are still being screened. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 28. See the NIHR Journals Library website for further project information.

Evaluation of Loop-Mediated Isothermal Amplification Assay for Detection and Typing of Human Papilloma Virus 16 and 18 from Endocervical Samples

AbstractBackground: Many human papillomavirus (HPV) types are associated with cervical cancer (CC). Therefore, HPV genotyping has both clinical and epidemiological importance. HPV 16 and 18 are two principal high-risk types responsible for more than 70% of all CC cases. Although several commercial and non-commercial genotyping assays are available, there is a need for a cost-effective and sensitive genotyping method for low- and middle-income countries. Methods: The study was aimed at evaluation of loop-mediated isothermal amplification (LAMP) assay for HPV genotyping in cervical samples. A total of six primer sets for each HPV type were selected for the assay. The LAMP assay was standardised and validated with HPV control panel. Cervical biopsies were subjected to nested multiplex polymerase chain reaction (NM-PCR; as a part of routine diagnostic workup) and LAMP (HPV 16 and 18) simultaneously. Results: A total of 225 clinical samples were processed during the study period. The sensitivity of the assay was determined using the 10-fold dilutions of positive controls. Both the HPV 16-LAMP and HPV 18-LAMP assays were shown to detect as low as 10 viral copies per reaction, which is similar to that of NM-PCR. The LAMP assay had a good agreement (new cases; 92%, post-chemoradiotherapy [post-CRT]; 89.1%) with NM-PCR for the detection of both HPV 16 and 18. As compared to histology (new cases; 79.8%, post-CRT; 51.3%), LAMP had better agreement with NM-PCR for detection of HPV from post-CRT cases. Conclusions: We evaluated the LAMP assay for simultaneous detection and typing of HPV 16 and 18. The assay had good agreement with NM-PCR for detection of both HPV 16 and 18. The LAMP assay is a promising tool for HPV genotyping along with routine cervical cytology, especially in resource-constrained settings.

Discriminating Performance of Early Uterine and Cervical Artery Pulsatility and Resistivity In Pre-Invasive Cervical Lesions.

Objectives:The aim of the present study was to investigate the diagnostic effectiveness of uterine and cervical vascularity alone or in combination with human papillomavirus (HPV) DNA testing and with cytology.Methods:Data were prospectively collected from 129 patients in an outpatient clinic of a secondary setting. Routine liquid-based cervical cytology and HPV-DNA testing were obtained. An abnormal result of any of these high-risk types was viewed as positive. Pulsatility (PI) and resistance (RI) indices of uterine (UA) and cervical (CA) arteries were assessed by Doppler sonography. Pathological diagnosis was considered as the gold standard for assessment. Diagnostic efficiency of alone and joint screening of the three indices for discriminating cervical intraepithelial neoplasia (CIN-I) or above from below was assessed.Results:UA-RI and CA-RI were significantly lower in the HPV (+) group than in the controls (p=0.02 and p=0.03, respectively). In subsequent sub-analysis among patients with positive HPV-DNA, UA-PI was significantly higher in the HPV-16 (+) group than in the HPV-18 (+) group (p=0.04). High-risk HPV (Hr-HPV) testing had the highest sensitivity compared with Doppler and cytology (76.5%, 64.7%, and 58.5%, respectively). Combining CA-RI with cytology or Hr-HPV significantly reduced the sensitivity (23.5% and 29.4, respectively) but improved the specificity from 54.4% to 69.8% and 40.9% to 70.7%, respectively. Combining UA-PI with Hr-HPV slightly increased the positive predictivity when compared with testing Hr-HPV alone (36.1% vs. 33.3%).Conclusion:The potential of the Doppler indices of UA and CA was doubtful in discriminating CIN-I or above lesions in the early period. In addition, RI of UA and CA differed with regard to the presence of HPV infection, whereas CA-RI differed in high-risk HPV cases.

Adherence to Recommended Cervical Cancer Screening Based on Human Papillomavirus Vaccination Status [17OP

INTRODUCTION: Human Papillomavirus (HPV) vaccination and routine cervical cytology both aim to prevent cervical cancer, however limited data exists for how vaccination affects patient behavior. The objective of this study is to examine if adherence to cervical cancer screening is affected by HPV vaccination. METHODS: Retrospective chart review was completed using billing data for cervical cytology and HPV vaccination from 2006 to 2010. These years were chosen because the HPV vaccine was released in 2006, and annual cervical cytology was recommended until 2010. Participants were included based on birth year, ensuring participants were old enough to obtain cervical cancer screening and young enough to receive the HPV vaccine. For inclusion two or more cervical cytology samples were needed, and vaccination status confirmed via billing data or chart review. Adherence to cervical cancer screening was assessed using a ratio of appropriately timed pap smears to all pap smears in the study period. RESULTS: 2,397 charts were reviewed, 943 were included, of these 350 were vaccinated and 593 were unvaccinated. Adherence to screening was not affected by overall vaccination status. For the sub-group of women vaccinated mid-study, adherence was compared before and after vaccination and it was found that these women were significantly less likely to be adherent after vaccination (N=140, adjusted OR 0.19, CI 0.08 - 0.49). CONCLUSION: Comparing patterns of adherence to cervical cancer screening before and after vaccination shows that women were less likely to adhere to screening guidelines after HPV vaccination. This may represent an unintended consequence of the HPV vaccination program.

Primary Carcinosarcoma of the Uterine Cervix: Report of a Case and Review of the Literature

Abstract Background: Cervical carcinosarcoma is extremely rare. A case of cervical carcinosarcoma is presented and the literature is reviewed. Case: A multiparous woman in her mid-40s, with multiple medical comorbidities, including a body mass index of 48, had an adenocarcinoma identified on routine cervical cytology testing. The cytology was human papilloma virus p16/18–negative, raising suspicion of a primary endometrial rather than a cervical carcinoma but a cervical mass was detected. This patient underwent a robotic-assisted radical hysterectomy and pelvic lymph-node dissection for stage IB1 cervical carcinosarcoma. Results: This patient's postoperative course was complicated by ileus, which resolved spontaneously. Conclusions: Because of the rarity of this lesion, there are no specific treatment protocols. Spread from a uterine primary needs to be ruled out. (J GYNECOL SURG 32:354)

Automated Extraction of Formalin-Fixed, Paraffin-Embedded Tissue for High-Risk Human Papillomavirus Testing of Head and Neck Squamous Cell Carcinomas Using the Roche Cobas 4800 System.

-Testing for high-risk human papillomavirus (HR-HPV) in head and neck squamous cell carcinomas (HNSCCs) is important for both prognostication and clinical management. Several testing platforms are available for HR-HPV; however, effective alternative automated approaches are needed. -To assess the performance of the automated Roche cobas 4800 HPV real-time polymerase chain reaction-based system on formalin-fixed, paraffin-embedded HNSCC specimens and compare results with standard methods of in situ hybridization (ISH) and p16 immunohistochemistry. -Formalin-fixed, paraffin-embedded samples of HNSCC were collected from archival specimens in the Department of Pathology, Massachusetts General Hospital (Boston), and prepared using the automated system by deparaffinization and dehydration followed by tissue lysis. Samples were integrated into routine cervical cytology testing runs by cobas. Corresponding formalin-fixed, paraffin-embedded samples were evaluated for HR-HPV by ISH and p16 by immunohistochemistry. Discrepant cases were adjudicated by polymerase chain reaction. -Sixty-two HNSCC samples were analyzed using the automated cobas system, ISH, and immunohistochemistry. Fifty-two percent (n = 32 of 62) of formalin-fixed, paraffin-embedded tumors were positive for HR-HPV by cobas. Eighty-eight percent (n = 28 of 32) of cases were the HPV 16 subtype and 12% (n = 4 of 32) were other HR-HPV subtypes. Corresponding testing with ISH was concordant in 92% (n = 57 of 62) of cases. Compared with the adjudication polymerase chain reaction standard, there were 3 false-positive cases by cobas. -Concordance in HNSCC HR-HPV status between cobas and ISH was more than 90%. The cobas demonstrated a sensitivity of 100% and a specificity of 91% for detection of HR-HPV. Advantages favoring cobas include its automation, cost efficiency, objective results, and ease of performance.

Raman spectroscopy for cytopathology of exfoliated cervical cells.

Cervical cancer is the fourth most common cancer affecting women worldwide but mortality can be decreased by early detection of pre-malignant lesions. The Pap smear test is the most commonly used method in cervical cancer screening programmes. Although specificity is high for this test, it is widely acknowledged that sensitivity can be poor mainly due to the subjective nature of the test. There is a need for new objective tests for the early detection of pre-malignant cervical lesions. Over the past two decades, Raman spectroscopy has emerged as a promising new technology for cancer screening and diagnosis. The aim of this study was to evaluate the potential of Raman spectroscopy for cervical cancer screening using both Cervical Intraepithelial Neoplasia (CIN) and Squamous Intraepithelial Lesion (SIL) classification terminology. ThinPrep® Pap samples were recruited from a cervical screening population. Raman spectra were recorded from single cell nuclei and subjected to multivariate statistical analysis. Normal and abnormal ThinPrep® samples were discriminated based on the biochemical fingerprint of the cells using Principal Component Analysis (PCA). Principal Component Analysis - Linear Discriminant Analysis (PCA-LDA) was employed to build classification models based on either CIN or SIL terminology. This study has shown that Raman spectroscopy can be successfully applied to the study of routine cervical cytology samples from a cervical screening programme and that the use of CIN terminology resulted in improved sensitivity for high grade cases.

Single life time cytological screening in high risk women as an economical and feasible approach to control cervical cancer in developing countries like India.

In view of funding crunches and inadequate manpower in cytology in developing countries like India, single lifetime screening for cervical cancer has been suggested. In this study, an attempt was made to identify high risk groups of women for this screening to make it more effective for early detection. Cytological data were derived from the ongoing routine cervical cytology screening program for women attending Gynaecology Out Patient Department of Queen Mary's Hospital of K.G.Medical University, Lucknow, India during a span of 35 years (April 1971 - December 2005). Cervical smears in a total of 38,256 women were cytologically evaluated. The frequencies of squamous intraepithelial lesions of cervix (SIL) and carcinoma cervix were found to be 7.0% and 0.6%, respectively, in the series. Predisposing factors related to cervical carcinogenesis were analyzed in detail to establish the most vulnerable groups of women for single life time screening. The incidence of SIL and carcinoma cervix was found to be maximal in women above the age of 40 years irrespective of parity and in multiparous women (with three or more children) irrespective of age. The incidence of cervical cytopathologies was significantly higher in symptomatic women, the frequency of SIL being alarmingly higher in women complaining of contact bleeding and that of carcinoma cervix in older women with postmenopausal bleeding. It is consequently felt that single life time screening must include the three groups of women delineated above. Such selective screening appears to be the most economical, cost effective and feasible approach to affordably control the menace of cervical cancer in developing countries like India.

HPV Adjunct Testing to VIA as an Alternative to Cytology for Cervical Cancer Screening in Pakistan

Background: Developing countries often lack sufficient resources to use the Pap smear as a screening tool for cervical abnormalities. Visual inspection with acetic acid (VIA) is similar to Pap smears in terms of sensitivity for highgrade CIN. However, it is not very specific and adjunct testing with HPV can improve the test characteristics of VIA. Aim: To evaluate VIA with adjunct Human Papilloma Virus (HPV) testing as an alternative to routine cervical cytology for cervical cancer screening in a low resource setting. Methods: We conducted a cross-sectional study among the attendees of the gynecology clinics attached to our hospital. Each patient underwent three screening tests, viz., Pap smear, HPV DNA testing and VIA, sequentially. The patients who tested positive by any of these methods underwent colposcopy. Trained colposcopists, blinded to the results of initial screening tests collected biopsies from patients with colposcopic abnormalities. We tested the specimens for HPV by Polymerase Chain Reaction (PCR) using the general primers GP5+/GP6+, and checked for high risk HPV types in positive samples. Results: The median age of participants was 38 years. Out of the 857 patients screened, 46 (5.36%), 4 (0.47%) and 13 (1.53%) tested abnormal/positive by VIA, Pap smear and HPV PCR, respectively. Sequential VIA and HPV PCR yielded a sensitivity and specificity of 80% and 93%, respectively. Conclusions: We propose that sequential testing involving the use of VIA followed by HPV PCR could improve the test characteristics, in low-resource settings.

Human Papillomavirus: Flow Cytometry Detection and PCR Analysis, A Comparison Study

Recent reports have shown that during persistent HPV infections of the cervical epithelium the viral genome, of high risk HPV types, often integrate into the host chromosome, which results in an over expression of the viral proteins E6 and E7 of human papillomavirus. These oncoproteins induce immortalization and malignant transformation of cells conferring a certain growth advantage to the infected cells. A total of 100 women undergoing routine cervical cytology samples joined this cohort study. A Thin Prep Pap Test sample was taken following consent for study participation and was tested for HPV. Cytological screening of the samples was done by trained cytologists. After sample collection, 1 ml aliquot was removed and prepared for flow cytometric analysis and the rest of the sample was sent for PCR analysis. In the total of 100 cases, 4 specimens were characterized as unsatisfactory. For the rest 96 specimens, 82 specimens were found to be positive, for the HPV virus and 14 negative. In the total of 100 cases the analysis of flow cytometry and PCR detection gives the same results in most cases. As a conclusion, our results showed that the use of flow cytometry in the detection of HPV virus is a feasible method and requires only 1ml of sample specimen to give accurate results for the diagnosis.