Analysis Of Cervical Cytology Research Articles

The performance of JAM3/PAX1 methylation in the diagnosis of high-grade squamous intraepithelial lesions for women with high-risk HPV infection

ObjectiveTo assess the clinical value of DNA methylation measurement in exfoliated cervical cells for distinguishing high-grade squamous intraepithelial lesions (HSIL) from other cervical abnormalities.MethodsA total of 276 patients were enrolled, and general clinical information was collected. Exfoliated cervical cells were obtained to assess human papillomavirus (HPV) infection, conduct ThinPrep cytology tests (TCT), and measure methylation levels of JAM3 (△CtJ) and PAX1 (△CtP). Logistic regression was performed to identify factors significantly associated with HSIL diagnosis. A conditional inference tree model and the area under the curve (AUC) were employed to evaluate the efficacy of JAM3 and PAX1 methylation in detecting HSIL.ResultsIndependent risk factors for HSIL diagnosis included △CtJ, △CtP, atypical squamous cells of undetermined significance (ASCUS), and HPV16 infection. The conditional inference tree indicated that 96.4% of patients were non-HSIL when △CtJ > 11.66, and 99.1% were non-HSIL when △CtP > 10.97. The diagnostic performance of △CtJ/△CtP surpassed that of TCT/HPV alone. Among six methods, the combination of △CtP, TCT, and high-risk HPV (hr-HPV) testing achieved the highest sensitivity (91.2%), positive predictive value (50.0%), negative predictive value (98.6%), and AUC (0.932).ConclusionIn women with hr-HPV infection, DNA methylation analysis of cervical cytology outperformed traditional TCT or HPV testing. The combination of △CtP with TCT and HPV may offer the most accurate screening approach for HSIL.

A Retrospective Analysis of Cervical Cytology Using Pap Smear among Symptomatic Women Attending Gynaecology OPD in a Secondary Care Hospital in Northern India

A Retrospective Analysis of Cervical Cytology Using Pap Smear among Symptomatic Women Attending Gynaecology OPD in a Secondary Care Hospital in Northern India

English

English

Mutational analysis of cervical cytology improves diagnosis of endometrial cancer: A prospective multicentre cohort study.

Endometrial carcinoma (EC) is traditionally diagnosed by a histopathological assessment of an endometrial biopsy, leaving up to 30% of patients undiagnosed due to technical failure or an inadequate amount of tissue. The aim of the current study is to assess whether mutational analysis of cervical cytology or pipelle endometrial biopsies improves the diagnostic accuracy of traditional histopathological diagnosis of EC. This prospective multicentre cohort study included patients surgically treated for EC or a benign gynaecological condition (control group). A Pap brush sample, cervicovaginal self-sample, pipelle endometrial biopsy and surgical specimen of either the EC or normal endometrium were obtained. A targeted next-generation sequencing panel was used to analyse these samples for mutations in eight genes. Sensitivity, specificity and predictive values were calculated. Fifty-nine EC patients and 31 control patients were included. In these patients, traditional histopathological diagnosis by pipelle had a sensitivity of 79% and a specificity of 100%. For EC patients, 97% of surgical specimens contained at least one mutation. Mutational analysis of Pap brush samples, self-samples and pipelle endometrial biopsies yielded a sensitivity of 78, 67 and 96% with a specificity of 97, 97 and 94%, respectively. Combining one of these three methods with histopathological pipelle endometrial biopsy evaluations yielded a sensitivity of 96, 93 and 96%, respectively. Our study has shown that mutational analysis of either cervical cytology or pipelle endometrial biopsies improves diagnosis of EC. Prospective validation will support implementation in clinical practice.

Variations in Progression and Regression of Precancerous Lesions of the Uterine Cervix on Cytology Testing Among Women of Different Races

Although not incorporated into current cervical cancer screening guidelines, racial differences are known to persist in both occurrence of and outcomes related to cervical cancer. To compare the differences in progression and regression of precancerous lesions of the uterine cervix on cervical cytologic analysis among women of different races who adhered to cervical cancer screening recommendations and follow-up. Retrospective cohort study comparing differences in precancerous lesion diagnoses for patients receiving adequate evaluation according to the American Society for Colposcopy and Cervical Pathology guidelines. The authors fit Markov multistate models to estimate self-reported race-specific expected wait times and hazard ratios for each possible regression and progression and compared a race model with an intercept-only model using a likelihood ratio test. The sample included 5472 women receiving a Papanicolaou test between January 2006 and September 2016, contributing a total of 24,316 person-years of follow-up. Of 21 hazard ratios tested for significance, the following 4 hazard ratios (95% CIs) were statistically significant: atypical squamous cells of undetermined significance (ASC-US) progression to low-grade squamous intraepithelial lesion (LSIL) for Hispanic patients (0.72; 95% CI, 0.54-0.96); LSIL regression to ASC-US for Hispanic patients (1.55; 95% CI, 1.04-2.31), LSIL regression to ASC-US for Asian patients (1.91; 95% CI, 1.08-3.36), and high-grade squamous intraepithelial lesion regression to LSIL for black patients (0.39; 95% CI, 0.16-0.96). There is an observed trend that all racial groups other than white had a slower rate of progression from ASC-US to LSIL, with Hispanics having demonstrated the slowest rate from ASC-US to LSIL. Hispanics also demonstrated the fastest rate from LSIL to HSIL when compared with all other race categories. In regressions, blacks had the slowest rate of regression from HSIL to LSIL, and Asians had the fastest rate from LSIL to ASC-US. The Hispanic group demonstrated the fastest expected progression (17.6 months; 95% CI, 11.5-25.5), as well as the fastest regression (27.6 months; 95% CI, 21.5-35.6), and the black group has the slowest expected times for both progression (28.1 months; 95% CI, 14.6-47.2) and regression (49 months; 95% CI, 29.1-86.2). The number of visits (1 vs ≥2) in the study was differentially distributed both by race (P=.033) and by last diagnosis (P<.001). Variations in precancerous lesions of the uterine cervix are not uniform across races.

Highly active antiretroviral therapy and cervical cytologic abnormalities among women with HIV infection in a limited-resource setting.

To examine the relationship between highly active antiretroviral therapy (HAART) and cervical cytologic abnormalities among women with HIV infection. A cross-sectional prospective study was undertaken of 110 women attending an HIV clinic in Nnewi, Nigeria, between January 2016 and January 2017. A cervical smear was obtained. A bivariate analysis was undertaken, and multiple logistic regression models were used to identify factors independently associated with cervical cytologic analysis. Cervical cytologic abnormalities were identified in 31 (28.2%) participants. On bivariate analysis, use of HAART for 2-5years was associated with a reduction in the risk of cervical cytologic abnormalities (P=0.033), and this risk was further reduced when HAART was taken for more than 5years (P<0.001). Other factors that significantly reduced risk of cervical cytologic abnormalities included a CD4 count of 300 cells per mL or more (P<0.001), age 30years or older (P<0.001), and time since HIV diagnosis of more than 5years (P=0.021). On multivariate analysis, risk of cervical cytologic abnormalities among the women were significantly reduced by use of HAART for more than 5years (P=0.032) and CD4 count of 300 cells per mL or more (P<0.001). Long-term use of HAART and CD4 count of 300 cells per mL or more were associated with a reduced risk of cervical cytologic abnormalities.

Analysis of Cervical Cytology, Colposcopy and Biopsy Results

Analysis of Cervical Cytology, Colposcopy and Biopsy Results

Histology Verification Demonstrates That Biospectroscopy Analysis of Cervical Cytology Identifies Underlying Disease More Accurately than Conventional Screening: Removing the Confounder of Discordance

BackgroundSubjective visual assessment of cervical cytology is flawed, and this can manifest itself by inter- and intra-observer variability resulting ultimately in the degree of discordance in the grading categorisation of samples in screening vs. representative histology. Biospectroscopy methods have been suggested as sensor-based tools that can deliver objective assessments of cytology. However, studies to date have been apparently flawed by a corresponding lack of diagnostic efficiency when samples have previously been classed using cytology screening. This raises the question as to whether categorisation of cervical cytology based on imperfect conventional screening reduces the diagnostic accuracy of biospectroscopy approaches; are these latter methods more accurate and diagnose underlying disease? The purpose of this study was to compare the objective accuracy of infrared (IR) spectroscopy of cervical cytology samples using conventional cytology vs. histology-based categorisation.MethodsWithin a typical clinical setting, a total of n = 322 liquid-based cytology samples were collected immediately before biopsy. Of these, it was possible to acquire subsequent histology for n = 154. Cytology samples were categorised according to conventional screening methods and subsequently interrogated employing attenuated total reflection Fourier-transform IR (ATR-FTIR) spectroscopy. IR spectra were pre-processed and analysed using linear discriminant analysis. Dunn’s test was applied to identify the differences in spectra. Within the diagnostic categories, histology allowed us to determine the comparative efficiency of conventional screening vs. biospectroscopy to correctly identify either true atypia or underlying disease.ResultsConventional cytology-based screening results in poor sensitivity and specificity. IR spectra derived from cervical cytology do not appear to discriminate in a diagnostic fashion when categories were based on conventional screening. Scores plots of IR spectra exhibit marked crossover of spectral points between different cytological categories. Although, significant differences between spectral bands in different categories are noted, crossover samples point to the potential for poor specificity and hampers the development of biospectroscopy as a diagnostic tool. However, when histology-based categories are used to conduct analyses, the scores plot of IR spectra exhibit markedly better segregation.ConclusionsHistology demonstrates that ATR-FTIR spectroscopy of liquid-based cytology identifies the presence of underlying atypia or disease missed in conventional cytology screening. This study points to an urgent need for a future biospectroscopy study where categories are based on such histology. It will allow for the validation of this approach as a screening tool.

The Role Treatment for Cervical Intraepithelial Neoplasia Plays in the Disappearance of Human Papilloma Virus

To explore the role played by excision of the transformation zone in women diagnosed with cervical intraepithelial neoplasia (CIN) in the disappearance of human papillomavirus (HPV). In a retrospective, cohort study, women with CIN who were treated by loop electrosurgical excision procedure of the transformation zone were compared with another group of women with CIN who were managed expectantly. The decision to treat or manage expectantly was made by one of the authors on clinical grounds. All patients were evaluated with cervical cytologic analysis, pathologic examination of excised tissue, and HPV DNA testing, which was considered positive when high-risk HPV types were detected. Among women treated with loop electrosurgical excision procedure, the median lag time was calculated from diagnosis of CIN to treatment. The median time for conversion from HPV-positive to HPV-negative status in both groups was compared, as well as the 1- and 2-year cure rates (defined as converting to HPV-negative status) in the treated and untreated groups. In the treated group, 12% had CIN 1, 83% had CIN 2,3, 2% had cancer, and 3% had normal pathologic results. In the untreated group, 82% had CIN 1, 16% had CIN 2,3, and 2% had normal pathologic results (p < 0.0001). The lag time from the initial diagnosis of CIN to treatment was less than 1 month. The median follow-up time was 7 months (range, 1-121 months) in the treated group and 13 months (range, 1-70 months) in the untreated group. The 1-year rates of conversion to HPV-negative status, defined as the cure rates in the treated and untreated groups, were 65% (+/- 6%) and 23% (+/- 7%), respectively, and the 2-year cure rates in the treated and untreated groups were 90% (+/- 4%) and 56% (+/- 11%), respectively (p < 0.0001). Median time to conversion to a negative HPV status was 7.7 months for the treated patients compared with 19.4 months in the untreated patients (p < 0.0001). Women treated by loop electrosurgical excision procedure are more likely convert to HPV-negative status at 1 and 2 years and do so significantly sooner than those managed expectantly.

The Clinical Usefulness of Human Papillomavirus Testing in the Follow-up of Women after Treatment for Cervical Intraepithelial Neoplasia

To compare the effectiveness of human papillomavirus (HPV) testing and cervical cytologic analysis in monitoring patients after treatment for cervical intraepithelial neoplasia. A retrospective study comparing cytologic analysis and HPV testing using the follow-up protocol recommended by the American Society for Colposcopy and Cervical Pathology Consensus Conference. Sixty-one patients were seen for a total of 193 follow-up patient visits. In 120 visits, both cytologic and HPV results were available. Specificity, sensitivity, positive and negative predictive values, and the rate of referral to colposcopy were calculated. In 68 visits, both HPV and cytologic results were negative, and in 19, both were positive. In 21 visits, cytologic results were positive and HPV results were negative, and in 12 visits, cytologic results were negative and HPV results were positive. The specificity of cytologic analysis and HPV testing was 68.3% and 75.8%, respectively (p = .16). The positive predictive value for cytologic analysis and HPV testing was 6.5% and 7.5%, respectively, and the negative predictive value was 100% and 98.9%, respectively. Had either test been used alone, cytologic analysis would have referred 40 patients to colposcopy and HPV testing would have referred 31 patients. Had both been used in combination, 52 patients would have required colposcopy with no significant improvement in the amount of disease detected. Both cytologic analysis and HPV testing are equally effective in monitoring patients after treatment for cervical intraepithelial neoplasia. The simultaneous use of cytologic analysis and HPV testing significantly increased colposcopy referrals without increasing the amount of disease detected.

Pitfalls in the Diagnosis of Cervical Intraepithelial Neoplasia 1

This review article outlines the issues involved in (1) the cytologic diagnosis of low-grade squamous intra-epithelial lesion (cervical intraepithelial neoplasia [CIN] 1), (2) histologic diagnosis of CIN 1, (3) the advantages and disadvantages of various management strategies for CIN 1 confirmed by biopsy, and (4) the evolving technology that may be useful for predicting the course of the disease. A MEDLINE search was conducted using the search terms cervical intraepithelial neoplasia, low-grade dysplasia, mild dysplasia, low-risk squamous intraepithelial lesion, mild dyskaryosis, HPV, colposcopy, histology, and cytology. RESULTS.: Using a loop electrosurgical excision procedure or cone biopsy assessment of the cervix as the gold standard, a cytologic assessment of CIN 1 alone results in a high false-positive rate (51.5%) and a false-negative rate (24%) for CIN 3. The appropriate second test after low-grade squamous intraepithelial lesion (CIN 1) cytologic results includes repeat cervical cytologic analysis. Subsequent human papillomavirus testing provides no advantage and increases the cost of care. Immediate referral to colposcopy is costly but minimizes the percent of women lost to follow-up. Using a loop electrosurgical excision procedure or cone biopsy assessment of the cervix as the gold standard, the colposcopically directed biopsy may give a false-positive result (11.7%) or false-negative result (up to 31%) for CIN 3. One contributing issue is the moderate interobserver reliability of histologic analysis (kappa= 0.46). There are advantages and disadvantages to both the immediate and expectant management strategies. The most crucial concern for immediate treatment is overtreatment, and that for expectant management the high rate of patients lost to follow-up. Novel technologies, including MIB-1, p16(INK)4a, and genetic assessments, may be helpful in predicting those CIN 1 lesions destined to progress or to persist. The cytologic and histologic diagnosis of CIN 1 is fraught with problems related to the subjectivity of the diagnosis. Both management options are also fraught with concerns. Any technique that can better predict disease course would be an advantage to the care of women with this abnormality.

Direct Visual Inspection of the Cervix for the Detection of Premalignant Lesions

To assess the feasibility and performance of direct visual inspection (DVI) of the cervix as a primary tool for the detection of premalignant lesions of the cervix (HPV/CIN 1 and CIN 2,3). The early cancer detection unit at the Ain Shams University Maternity Hospital in Cairo, Egypt. The study included 2049 women. Cervical smears were obtained from all women for cytologic evaluation followed by direct visual inspection (DVI) of the cervix after painting with 5% acetic acid. Women whose smear reports showed abnormal cells suggestive of squamous intraepithelial lesion (SIL) or human papillomavirus (HPV) infection or those who showed abnormalities or acetowhite areas on direct visual inspection subsequently were referred for colposcopy and biopsy when appropriate. Colposcopy also was performed for women with negative DVI and negative smears if they had contact bleeding or chronic per vaginal discharge. Mean (SD) age of women included in the study was 39.9 (10.2) years with their mean (SD) parity 2.9 (1.1). Results of DVI were normal in 1916 women (93.4%) and showed abnormal acetowhite appearance in 133 (6.6%) women. There were 458 (22.4%) colposcopic examinations and 130 biopsies (6.34%) were carried out, picking up 83 cases of premalignant lesions (4.0%). Premalignant lesions were 80 HPV/CIN 1 and CIN 2,3. Direct visual inspection detected 71 of the 83 premalignant lesions (sensitivity, 85.5%; specificity, 96.8%; positive predictive value, 52.6%). Direct visual inspection missed one of the three samples showing CIN 2,3. Cervical cytologic analysis showed abnormal cells in 60 (2.9%) and identified only 14 of the premalignant lesions (sensitivity, 16.9%; specificity, 97.8%; positive predictive value, 23.3%). Twelve of the premalignant lesions had positive smear results and a negative DVI, with none of them being of a high grade. Direct visual inspection is feasible and had superior sensitivity compare with cervical cytologic analysis in detecting premalignant lesions of the cervix. Direct visual inspection can be used as a primary screening tool with a satisfactory low biopsy rate in low-resource settings or where cytologic services are suboptimal.

The Significance of ASCUS Cytology in HIV-Positive Women

Objective. The aim of this study was to determine the incidence and severity of dysplasia associated with a cytologic diagnosis of atypical cells of undetermined significance (ASCUS) in women infected with the human immunodeficiency virus (HIV).Methods. A cross-sectional analysis of cervical cytology, colposcopic impression, and cervical biopsy results was performed on 261 HIV-positive women diagnosed with ASCUS. The prevalence and grade of histologically documented cervical intraepithelial neoplasia (CIN) was determined. Patients with CD4 counts above and below 200 cells/mm3 were compared using χ2 analysis to determine any effect of worsening immunosuppression on the rates of associated dysplasia.Results. Seven hundred sixty-one Pap smears were performed during the study period. Two hundred nine (27%) were diagnosed as ASCUS. All patients (pts) received colposcopic evaluation. The incidence of human papilloma virus (HPV) effect, low-grade CIN (I), and high-grade CIN (II, III, and carcinoma in situ) documented by cervical biopsy, cervical conization or endocervical curettings was 40, 17, and 15%, respectively. No cases of invasive cancer were found. These results are similar to those of previous cytohistologic studies of ASCUS in HIV-untested populations. There was no significant difference in frequency or severity of CIN in pts with severe immunosuppression (P = 0.4).Conclusion. A cytologic diagnosis of ASCUS in HIV-positive women identifies a group at significant risk for histologic abnormalities. The majority of pts will be diagnosed with HPV or low-grade CIN. HIV infection and severe immunosuppression do not appear to increase the frequency or severity of CIN associated with ASCUS. Given the 32% risk of associated CIN, all HIV-positive women with ASCUS cytology should undergo colposcopic evaluation.

Preoperative Cervical Cytology in Endometrial Carcinoma and Its Clinicopathologic Relevance

Objective.The aim of this study was to assess the significance of malignant or suspicious cervical cytology in preoperative identification of poor prognostic factors in endometrial carcinoma and to determine whether preoperative abnormal cervical cytology is an independent prognostic factor for endometrial carcinoma.Methods.We evaluated the correlation between preoperative cervical cytology and postoperative clinicopathologic findings, sites of metastasis, and receptor status from 99 surgically staged patients with endometrial carcinoma.Results.Sixty-eight patients (68.7%) had normal cervical cytology, 1 (1.0%) had atypical cytology suspicious for malignancy, and 30 (30.3%) had malignant cytology on preoperative cervical cytology. Malignant and suspicious cervical smears were statistically correlated with surgical stage (P= 0.001), histopathology (P= 0.010), tumor grade (P= 0.012), depth of myometrial tumor invasion (P= 0.001), cervical involvement (P= 0.01), lymph node metastases (P= 0.002), adnexal metastases (P= 0.012), progesterone receptor (P= 0.007), and estrogen receptor (P= 0.031). No association was found between preoperative cervical cytology and patients' age or peritoneal cytology. Univariate analysis showed that cervical cytology was related to survival (P= 0.018). However, multivariate analysis of cervical cytology, stage, grade, and myometrial invasion showed that preoperative cervical cytology was not a significant prognosticator for survival.Conclusion.Patients with endometrial carcinoma who have malignant or suspicious cytology detected by preoperative cervical cytology are at increased risk of having known poor prognostic factors. However, positive preoperative cervical cytology itself does not appear to be an independent prognostic factor and probably should not influence treatment decisions in endometrial cancer.

Prevalence, Risk Factors, and Accuracy of Cytologic Screening for Cervical Intraepithelial Neoplasia in Women with the Human Immunodeficiency Virus

Abstract Objectives. The objective was to evaluate the sensitivity and specificity of cervical cytology in women infected with the human immunodeficiency virus (HIV), risk factors for abnormal cytology in HIV-infected and uninfected women, and risk factors for histologic diagnosis of cervical intraepithelial neoplasia (CIN) in HIV-infected women. Methods. Methods included a cross-sectional analysis of cervical cytology, colposcopic impression, and histology in 248 HIV-infected women and multivariate analyses of risk factors for abnormal cytology in 253 HIV-infected and 220 uninfected women and risk factors for CIN in 186 HIV-infected women. Results. The sensitivity and specificity of cytology for all CIN grades were 0.60 and 0.80 and, for high-grade CIN, 0.83 and 0.74. The prevalence of abnormal cytology was 32.9% in HIV-infected and 7.6% in HIV-negative women. Independent risk factors for abnormal cytology were immunodeficiency [odds ratio (OR) 8–17, P P P = 0.005). Conclusion. Given the high prevalence of abnormal cytology and CIN in HIV-infected women, cytologic screening has significant limitations. Both immunodeficiency and type of HPV infection are important risk factors.

Prevalence, Risk Factors, and Accuracy of Cytologic Screening for Cervical Intraepithelial Neoplasia in Women with the Human Immunodeficiency Virus

Objectives.The objective was to evaluate the sensitivity and specificity of cervical cytology in women infected with the human immunodeficiency virus (HIV), risk factors for abnormal cytology in HIV-infected and uninfected women, and risk factors for histologic diagnosis of cervical intraepithelial neoplasia (CIN) in HIV-infected women.Methods.Methods included a cross-sectional analysis of cervical cytology, colposcopic impression, and histology in 248 HIV-infected women and multivariate analyses of risk factors for abnormal cytology in 253 HIV-infected and 220 uninfected women and risk factors for CIN in 186 HIV-infected women.Results.The sensitivity and specificity of cytology for all CIN grades were 0.60 and 0.80 and, for high-grade CIN, 0.83 and 0.74. The prevalence of abnormal cytology was 32.9% in HIV-infected and 7.6% in HIV-negative women. Independent risk factors for abnormal cytology were immunodeficiency [odds ratio (OR) 8–17,P< 0.001] and human papillomavirus (HPV) infection (OR = 5,P< 0.001). The prevalence of CIN on histology was 32% in HIV-infected women, and the only independent risk factor for CIN was oncogenic HPV type (OR = 5,P= 0.005).Conclusion.Given the high prevalence of abnormal cytology and CIN in HIV-infected women, cytologic screening has significant limitations. Both immunodeficiency and type of HPV infection are important risk factors.

Automated quantitative fluorescent image analysis of cervical cytology

Cervical cytology from 122 patients with histories of one or more abnormal Pap smears were studied using slide-based automated quantitative fluorescence image analysis (QFIA) in order to determine the usefulness of the QFIA technique in detecting neoplasias. The purpose of the study was to evaluate the accuracy and validity of QFIA as a cytological method for the early detection of cervical cancer, based on comparisons with the conventional Pap smear and histopathology. The results of the analysis demonstrated that the sensitivity of the automated QFIA cytology was 100% for high-grade neoplasms (CIN III and invasive carcinoma), compared with 82% for the Pap smear. Evaluation of lower grade neoplasms was also performed. Initial analyses of the data indicate that QFIA, which uses objective biochemical criteria to identify cells with increased nuclear nucleic acid content, is a more sensitive detector of cervical neoplasia of all grades than is conventional Pap cytology.