Detection Of High-grade Cervical Intraepithelial Neoplasia Research Articles

CIN Extension at Colposcopy: Relation to Treatment and Blood Parameters.

To determine the colposcopic lesion size that predicts the presence of residual lesion in patients with cervical intraepithelial neoplasia (CIN) 2/3, to aid gynaecologists in selecting conservative management. Data from 51 patients with low- and high-grade squamous intraepithelial lesions were evaluated. Colposcopic images were captured and lesion areas were calculated. Polymerase chain reaction (PCR) for human papillomavirus was performed. Laboratory parameters were evaluated. Receiver operating characteristic (ROC) curves were used to obtain cut-off values for lesion area. The performance of PCR in the detection of high-grade CIN was assessed. A flowchart was created to compare the costs of related procedures in the Brazilian health system. For CIN 2/3 treated with excisional surgery, the best cut-off value for lesion area below which no residual lesion was present was 21019 pixels2 (58.87 mm2). The cut-off value that predicted compromised surgical margins was 155577.65 pixels2 (435.75 mm2). Among all patients with CIN, lesion area correlated inversely with neutrophil/lymphocyte ratio (NLR; r=-0.446, P=0.001), platelet/lymphocyte ratio (PLR; r=-0.438, P=0.001), and absolute number of leukocytes (r=-0.351, P=0.011). Conservative clinical management with semi-annual clinical follow-up was found to reduce direct costs to the Brazilian Health System by R $909.82 (US $169.42). CIN reflects systemic alteration, leading to altered NLRs, PLRs, and absolute numbers of leukocytes. Patients with high-grade CIN and colposcopic lesion areas <21019pixels2 could benefit from conservative management, which would result in cost savings for the Brazilian health system.

Comparative accuracy of Pap smear and HPV screening in Ubon Ratchathani in Thailand

We evaluate the potential for using high-risk human papillomavirus (hr-HPV) testing-based screening for cervical intraepithelial neoplasia (CIN) in routine health services in Thailand; its accuracy in comparison to that of conventional cytology (CC); and the utility of HPV16/18 positive results and liquid-based cytology (LBC) triage for HPV-positive women in the detection of high-grade CIN. Women aged 30–60 years in Ubon Ratchathani province, Thailand were screened with CC and hr-HPV testing and those abnormal on either tests were referred for colposcopy and/or directed biopsies. The final diagnosis using COBAS was based on histology or colposcopy when histology was not available. Estimation of test accuracy parameters was done using latent class analysis using Bayesian models. Of the 5004 women were enrolled, 20 (0.4%) had abnormal CC and 174 (3.5%) women were HPV-positive. Among 185 women abnormal on CC or HPV-positive, 176 (95.1%) underwent colposcopy, of whom 101 (57.4%) had abnormal colposcopy findings. Ninety-seven women with abnormal and 69 with normal colposcopy had biopsies performed. All 21 women with histological CIN2 or worse had hr-HPV and none were abnormal on CC. The estimated sensitivity, specificity and positive predictive value were respectively 71.8%, 97.0% and 13.0% of HPV testing; 53%, 98.7% and 20.3% for triage of HPV-positive women with LBC; and 70.4%, 98.2% and 16.9% when test positivity was taken as HPV16/18 irrespective of LBC result or positive for hr-HPV non 16/18 types and LBC triage. Our study findings indicate poor performance of cytology screening and demonstrate the potential and utility of using HPV testing in public health services in Thailand as well as the utility of primary HPV testing and LBC triage in screening for cervical neoplasia.

Age-specific performance of careHPV versus Papanicolaou and visual inspection of cervix with acetic acid testing in a primary cervical cancer screening

BackgroundHuman papillomavirus (HPV) is recommended as a primary screening tool for cervical screening. Assessment of age-specific performance of newer HPV careHPV DNA testing is important as risk of cervical intraepithelial...

Adjunct screening of cervical or vaginal samples using careHPV testing with Pap and aided visual inspection for detecting high-grade cervical intraepithelial neoplasia

ObjectiveTo evaluate the performance of careHPV DNA testing for human papillomavirus (HPV) on cervical and vaginal samples (CHPV and VHPV respectively) in adjunct screening together with visual inspection of the cervix by acetic acid (VIA) or Papanicolaou (Pap) tests in the detection of high-grade cervical intraepithelial neoplasia (CIN). Subjects and methodsA cross-sectional study examined 4658 women 30–59 years of age by performing screening tests for HPV using careHPV on cervical and vaginal samples together with Pap and VIA. The CHPV and VHPV test results were presented as a ratio of viral load expressed in relative light units (RLUs) to the mean RLU from a positive control set at 1pg/mL cut-off (CO). Performances of various pairs of screening tests in parallel and sequential settings were computed through the detection rates of CIN, percentages of unnecessary colposcopic referrals of screen positives, and compared with stand-alone tests. ResultsThe screening positivity of CHPV, VHPV, Pap and VIA ranged from 2.4% to 5.5%. The highest sensitivity (72%) was observed for the combination of CHPV and VIA in parallel, followed by 65.6% for CHPV and Pap, and 59% for all other combinations (VHPV and Pap, VHPV and VIA, and VIA and Pap). The percentage of unnecessary colposcopic referrals in the parallel setting of CINII+ detection ranged from 2.8% to 6.0%. Sequential testing of CHPV or VHPV with other tests yielded very low sensitivities with a reduction in unnecessary colposcopic referrals. ConclusionCervical careHPV testing (CHPV) in parallel with VIA was the option that performed best in the detection of high-grade CIN and could be a feasible option for low-resource countries (LRCs).

Predicting High-Risk Human Papillomavirus Infection, Progression of Cervical Intraepithelial Neoplasia, and Prognosis of Cervical Cancer With a Panel of 13 Biomarkers Tested in Multivariate Modeling

Comprehensive multivariate models were used to disclose whether any of our previously analyzed 13 markers would be independent predictors of intermediate end point markers in cervical carcinogenesis. The expression of the following biomarkers, E-cadherin, extracellular signal-regulated kinase 1, 67-kd laminin receptor (LR67), matrix metalloproteinase 2, tissue inhibitor of metalloproteinase 2, nuclear factor-kappaB, nm23-H1, p16, proliferating cell nuclear antigen, survivin, human telomerase reverse transcriptase, topoisomerase 2alpha, and vascular endothelial growth factor (VEGF) C in 150 cervical cancer (CC) and 152 cervical intraepithelial neoplasia (CIN) lesions were determined immunohistochemically. Multivariate models were constructed to test predictive power of the markers for 3 outcomes: (1) high-grade CIN, (2) high-risk human papillomavirus (HR-HPV), and (3) CC survival. Performance indicators were calculated and compared by the areas under receiver operating characteristic (ROC) curve. Three marker panels were identified consisting of 5 independent predictors of CIN2 (E-cadherin, extracellular signal-regulated kinase 1, LR67, topoisomerase 2alpha, and VEGF-C), 3 predictors of HR-HPV (survivin, p16, and human telomerase reverse transcriptase), and 2 predictors of CC survival (nm23-H1 and tissue inhibitor of metalloproteinase 2). In predicting CIN2, the best balance between sensitivity (SE) and specificity (SP) was obtained by combining the 2 most powerful predictors in panel 1 (VEGF-C and LR67), giving the area under ROC curve, 0.897 (95% confidence interval [CI], 0.847-0.947); odds ratio, 86.27 (95% CI, 19.71-377.47); SE, 86.0%; SP, 93.3%; positive predictive value (PPV), 99.1%; and negative predictive value (NPV), 43.1%. In a hypothetical screening setting (10,000 women; CIN2 prevalence, 1%), this marker combination should theoretically detect CIN2 with 86.0% SE, 100% SP, 99.1% PPV, and 99.6% NPV, area under ROC curve of 0.930 (95% CI, 0.909-0.951), and odds ratio, 29998.0 (95% CI, 7,879.0-37,338.0). Combining 2 markers (LR67 and VEGF-C) enables accurate detection of high-grade CIN in a clinical setting. However, testing the performance of this marker combination in a screening setting necessitates their analysis in cytological samples.

LUMA™ Cervical Imaging System

For approximately 30 years colposcopically directed biopsy of the uterine cervix has been the gold standard for the detection of cervical intraepithelial neoplasia (CIN) and cancer following an abnormal Papanikolaou (Pap) smear. Recent technological advancements utilizing properties of fluorescence, reflectance and spectroscopy intrinsic to in vivo tissues, have led to the development of a useful adjunct to improve colposcopic detection of high-grade CIN. The addition of the LUMA™ (MediSpectra, Inc., MA, USA) cervical imaging system to colposcopy has been shown in two prospective, randomized controlled trials to result in a 25% or greater increase in the true positive biopsy rate of colposcopy for patients with atypical squamous cell or low-grade squamous intraepithelial lesions on Pap smear, with only a 4% increase in the false-positive rate, versus that of colposcopy alone. The US FDA approved this device in March 2006 to be used to enhance the sensitivity of colposcopic examinations of women with abnormal cervical cytology, in an effort to further reduce the incidence of cervical cancer.

Human papillomavirus testing improves the accuracy of colposcopy in detection of cervical intraepithelial neoplasia

To assess the performance of human papillomavirus (HPV) testing and colposcopy in detection of cervical pathology. A series of 389 women referred for colposcopy due to an abnormal Pap smear had cervical swabs analyzed for oncogenic (high-risk [HR]) HPV types using Hybrid Capture II (HC2) assay. Loop electrical excision procedure cone biopsy (88%) or colposcopic biopsy (11%) was used as the gold standard. Of the atypical squamous cells of undetermined significance (ASCUS) smears, 48% were positive for HR HPV, as compared to 76.3% of low-grade squamous intraepithelial lesions (LSIL) smears. HR HPV was detected in 66.7% and 90% of patients with cervical intraepithelial neoplasia (CIN) 1 and CIN2 (or higher), respectively. The sensitivity of the Pap smear using an ASCUS threshold in detecting high-grade CIN was 94.5% (95% confidence intervals (CI): 91-97%) and that of colposcopy 98.5% (95% CI: 95-99%). The respective specificities were 30% (95% CI: 17-28%) and 35.6% (CI: 29-42%). HC2 test had comparable sensitivity, 90% (95% CI: 85-93%), but higher specificity, 54.3% (95% CI: 47-61%). Combining HC2 test with Pap increased specificity, 66.7% and 41.3% for ASCUS and LSIL cutoff, respectively. The minor-abnormality threshold together with HC2 increased specificity of colposcopy with no changes in sensitivity. High viral load (>100 relative light unit/positive control) was associated with significant disease. HPV DNA testing improves the accuracy of colposcopy in the detection of high-grade CIN in women with ASCUS or LSIL smears.

The efficacy of HPV DNA chip test in the atypical squamous cell of undetermined significance

Objective: This study was performed to investigate the efficacy of DNA chip method for detecting and genotyping of human papillomavirus (HPV) and screening of high-grade CIN (cervical intraepithelial neoplasia) or invasive cancer in the patients with atypical squamous cells of undetermined significance (ASC-US). Methods: This study was based on 131 cases to be revealed ASC-US by Pap smear for the cervical cancer screening from July 2004 to Octorber 2004. They were evaluated by HPV DNA chip test, Cervical colposcopy and directed biopsy, and cone biopsy. The results of type 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 54, 56, 58, 59, 66 and 68 in HPV DNA chip test were categorized as high risk HPV. We evaluate the detection rate of the high-grade CIN and invasive cancer by HPV DNA chip test. Results: The incidence of high risk HPV DNA was 51.1% (67/131). Twelve of 131 (9.2%) were diagnosed as high-grade CIN or CIS on histology. The detection rate of high risk HPV DNA in high-grade CIN and invasive cancer was 83.3% (10/12). The detection rate of high risk HPV DNA was 36.0% (31/86) in normal or reactive, and 83.3% (10/12) in CIN II or above on histology. Higher the grade of biopsy, more the detection rate of high risk HPV DNA by HPV DNA chip test. Conclusion: The use of HPV DNA chip test in patients with ASC-US may be useful in detection of high-grade CIN or invasive cancer.

Outcome of women with inadequate cervical smears followed up for five years

Background: The clinical and prognostic significance of “inadequate” cervical smear is unknown, even though women with repeated inadequate smears are referred for colposcopy in the National Health Service (NHS) Cervical...

Ki-67 Antigen Staining as an Adjunct to Identifying Cervical Intraepithelial Neoplasia

The purpose of the work was to determine the feasibility and predictive value of Ki-67 immunostaining of cervical cytology and the detection of cervical dysplasia. Air-dried cervical smears were stained with MIB-1 antibody to identify the Ki-67 antigen. Nuclear decoration in abnormal squamous nuclei determined immunoreactivity. One hundred twenty-four nonpregnant patients underwent colposcopy and directed biopsies for abnormal cytology. Sensitivity (0.89), specificity (0.65), positive predictive value (0.60), and negative predictive value (0.91) were found for Ki-67 immunostaining in detection of high-grade cervical intraepithelial neoplasia (CIN) in 124 patients and positive Ki-67 staining was a significant predictor of high-grade CIN in both univariate (odds ratio 15.5 (95% CI 5.5–43.8) and multivariable (odds ratio 21.5 (95% CI 5.0–92.0) analysis. In 101 patients with ASCUS and LGSIL, Ki-67 immunostaining demonstrated the following in detection of high-grade CIN: sensitivity (0.96), specificity (0.67), positive predictive value (0.49), and negative predictive value (0.98). Ki-67 immunostaining of cervical cytology is a predictor of significant cervical pathology with high sensitivity and negative predictive value. Ki-67 immunostaining of cervical cytology may represent a new and cost-effective triage tool for patients with minor abnormalities on cytology.