Detection Of High-grade Lesions Research Articles

Diagnostic Performance of Host and Viral DNA Methylation Analysis in the Identification of Anal Intraepithelial Neoplasia and Cancer: Systematic Review and Meta-Analysis

Introduction: DNA methylation-based biomarkers have been investigated as useful tools in the carcinogenesis process, including the triage of HPV-associated cancers. In this context, we conducted a systematic review and meta-analysis focused on evaluating the changes in the level of DNA methylation in cases of pre-cancerous (i.e., anal intraepithelial neoplasia, AIN-1, -2., -3) and cancerous (i.e., squamous cell carcinoma, SCC) anal lesions. Methods: A research in the PubMed, Scopus, and Web of Science databases was carried out, following the PRISMA 2020 protocol, using the following keywords: “anal cancer”, “anal intraepithelial neoplasia”, “methylation”, and “epigenetic”. All observational studies that reported the level of DNA methylation by grade of anal lesions and for different target genes were included. The QUADAS-2 tool was used to assess the studies’ quality, whereas pooled prevalence, sensitivity, specificity, and diagnostic odds ratio (DOR) were employed to verify the accuracy of the test in the detection of high-grade lesions. Results: Eight studies met the inclusion criteria, involving a total of 1555 clinical samples. The prevalence of methylation-positive samples by histological grading was 27%, 45%, 54%, and 98% for AIN1, AIN2, AIN3, and SCC, respectively. Similar results were observed for the DOR, with higher ORs in more severe lesions. The pooled AUC (95%CI) for the diagnosis of ≥AIN2 was 0.68 (0.63–0.73). Conclusions: The present review and meta-analysis support the introduction of DNA methylation-based biomarkers in the triage of subjects with low-grade anal lesions and in the monitoring of treatment outcomes. Standardized protocols and a prospective study design are needed to implement methylation tests in clinical practice.

Evaluating Opt-In Vaginal Human Papillomavirus Self-Sampling: Participation Rates and Detection of High-Grade Lesions (CIN2+) among Unscreened Japanese Women Aged 30-39.

Cervical cancer incidence is increasing among Japanese women, which is partly attributed to low screening rates. This study examined the implementation of opt-in human papillomavirus (HPV) self-sampling among Japanese women aged 30-39 years who had not undergone cervical cancer screening, focusing on those requiring preconception care. The responses to the opt-in approach and effectiveness in detecting cervical squamous intraepithelial neoplasia 2 or worse (CIN2+) were evaluated. Participants used the Evalyn® Brush for self-sampling, with HPV testing conducted using the Cobas 4800 system (version 2.2.0). Out of 3489 eligible, unscreened women from four municipalities in Fukui Prefecture, only 10.6% (370/3489) requested the self-sampling kit. Of these, 77.3% (286/370) returned the kit (HPV testing rate: 8.2% (286/3489)). The HPV positivity rate was 13.7% (39/285), yet only 61.5% (24/39) of those with positive HPV results proceeded to cytology testing. Subsequently, three cases of CIN2+ were detected (10.5/1000). While this study demonstrated a reasonable kit return rate and indicated the capability of opt-in HPV self-sampling to detect CIN2+ cases in unscreened women, the low ordering rate of kits and suboptimal compliance for follow-up cytology testing highlight significant challenges. The findings suggest the need for more effective strategies to enhance participation in cervical cancer screening programs.

Correlation Between Colposcopic Impression And Histologic Diagnosis Of Premalignant Lesions Of The Cervix

Background: Cervical cancer is the commonest cancer in sub-Saharan African with majority of the women presenting with an advanced disease stage. This is largely due to the unavailability of an established cervical cancer screening programme in most countries. This also includes the use of colposcopy which is still not available to many gynaecologists practicing in Nigeria.Aim: To review reports of colposcopy carried out at the University of Abuja Teaching Hospital, Abuja, Nigeria and to determine the degree of concurrence between colposcopic impression and histologic diagnosis.Methods: A retrospective analysis of the colposcopic findings of 84 patients was done. Subsequent correlation with histopathology report was carried out in 53 patients who had colposcopically directed biopsies between March 2012 and February 2014.Results: The commonest impression made on colposcopy was high grade CIN in 40(47.6%) patients. The concurrence rate between colposcopic findings and histology diagnosis was 64.2% (34/53) {K =0.302, 95%CI= -0.010-0.436}. The concurrence rate was higher for high grade CIN 29/40(72.5%) than for low grade CIN 5/12 (41.7 %). There was an overestimation of colposcopic diagnosis in 13(24.5%) patients and an underestimation in 6(11.3%) patients. The sensitivity of colposcopy for detecting high grade lesions or more was32/36(88.9%) while the specificity was 8/17(47.1%). False positive rate for high grade lesions was 9/17(52.9%) and false negative rates for low grade lesions was 4/36(11.1%). Positive predictive value (PPV) of high grade colposcopic diagnosis or more was 32/41(78.04%) while the negative predictive value (NPV) was 8/12(66.73%).Conclusion: The strength of agreement between colposcopic diagnosis and cervical pathology was fair and colposcopy performs better in the detection of high grade lesions.

Contribution of Colposcopy in the Diagnosis of Precancerous Lesions of the Uterine Cervix at the Douala Gynaeco-Obstetric and Pediatric Hospital, Cameroon

Introduction: Cervical cancer is a public health problem in Cameroon, due to low screening and late diagnosis. We sought to assess practice of colposcopy at the Douala Gyneco-Obstetric and Pediatric Hospital (DGOPH) in Cameroon and its contribution to the fight against cervical cancer in our context. Method: This is a retrospective cross-sectional study of 99 colposcopies after which 71 exploitable biopsies were retained at the Douala for a period of 1year (December 1, 2019-December 1, 2020). The nomenclature of the French Society of Colposcopy and Cervico-Vaginal Pathology (SFCPCV) was used. Results: Mean age of the participants was 44 years, mostly multiparous (80%). Cytological abnormalities were the main reference pattern. During the examination 22% of colposcopies were found to be normal, 37% of TAG 1-2A, 31% of TAG 2B-C, and 5% suspected of cancer. After histological analysis of biopsies guided by colposcopy, we found 42% (30/71) of Cervical Intraepithelial Neoplasia (CIN) 1, 15.5% (11/71) of CIN 2 - 3, and 24% (17/71) cancer. Upon analysis of the diagnosed CIN1/CIN2-3/Cancers, we noted a concordance with colposcopy in 62% (23/37), 37% (10/27) and 85% (6/7) respectively. Colposcopic performance in the detection of high-grade lesions and above was 36% (26/71), with a sensitivity of 92.86%, specificity 83.33%, PPV 78.79% and NPV 94.59%. Conclusion: Despite the difficult socioeconomic context, colposcopy retains all its importance in the diagnosis of precancerous lesions of the uterine cervix. With the imminent putting in place of a national health policy, the goals 90-70-90 by 2030 of the World Health Organization for the fight against cervical cancer can be achieved in our sub-Saharan African countries.

Low Grade Squamous Intraepithelial Lesion on Pap Test with High Grade Squamous Intraepithelial Lesion on Follow-Up Biopsy: Does Presence of Transformation Zone Affect Detection of High Grade Lesions?

Low Grade Squamous Intraepithelial Lesion on Pap Test with High Grade Squamous Intraepithelial Lesion on Follow-Up Biopsy: Does Presence of Transformation Zone Affect Detection of High Grade Lesions?

Comparison Between HPV OncoTect and Nuclisens EasyQ Assay and Its Potential Role in Detecting Preneoplastic Lesions of the Cervix

Objectives: This study compare the performance of NucliSENS EasyQ test (bioMerieux), a RT-PCR based method, or HPV OncoTect (IncellDx) a flow cytometry-FISH based method, in the detection of the E6/E7 mRNA expression of hrHPV. Moreover, we investigated the potential role, for the detection of high-grade lesions, of the HPV OncoTect …

Value of PAX1 Methylation Analysis by MS-HRM in the Triage of Atypical Squamous Cells of Undetermined Significance.

Detection of cervical high grade lesions in patients with atypical squamous cells of undetermined significance (ASCUS) is still a challenge. Our study tested the efficacy of the paired boxed gene 1 (PAX1) methylation analysis by methylation-sensitive high-resolution melting (MS-HRM) in the detection of high grade lesions in ASCUS and compared performance with the hybrid capture 2 (HC2) human papillomavirus (HPV) test. A total of 463 consecutive ASCUS women from primary screening were selected. Their cervical scrapings were collected and assessed by PAX1 methylation analysis (MS-HRM) and high-risk HPV-DNA test (HC2). All patients with ASCUS were admitted to colposcopy and cervical biopsies. The Chi- square test was used to test the differences of PAX1 methylation or HPV infection between groups. The specificity, sensitivity, and accuracy for detecting CIN2 + lesions were: 95.6%, 82.4%, and 94.6%, respectively, for the PAX1 MS-HRM test; and 59.7%, 64.7%, and 60.0% for the HC2 HPV test. The PAX1 methylation analysis by MS-HRM demonstrated a better performance than the high-risk HPV-DNA test for the detection of high grade lesions (CIN2 +) in ASCUS cases. This approach could screen out the majority of low grade cases of ASCUS, and thus reduce the referral rate to colposcopy.

S17.1 Cervical cancer prevention in hiv-infected women

HIV-infected women are living longer and are at a higher risk of acquiring cervical cancer. More data comparing cervical cancer screening and treatment strategies in these women are urgently needed. WHO guidelines on optimal methods to screen and treat cervical cancer are available, but there are limited data to inform their potential modification for HIV-infected women. Even fewer data are available which compare the efficacy of treatment methods (loop electrosurgical excision procedure (LEEP) and cryotherapy) and differences in cervical disease recurrence between HIV-infected and HIV-uninfected women. HPV testing appears to be the most sensitive, although less specific for CIN-2+ detection than either VIA and cytology screening. Several studies of HIV-infected women have shown equivalent sensitivity of VIA and of cytology screening for CIN-2+, although there is variation in results. Consistently across studies, the specificity of cytology appears higher than either VIA or for high-risk HPV testing. Two studies in South Africa and Kenya have suggested that the specificity of HPV testing and VIA for detection of high grade lesions is lower in HIV-infected women with lower CD4 counts; more research is needed to examine if screening test performance varies for HIV-infected women with higher versus lower CD4 counts. More research in HIV-infected women is needed to examine if LEEP and cryotherapy treatment methods are associated with differences in HIV-viral shedding and in HIV transmission during or shortly after treatment. HIV-infected adolescents have found to induce high-levels of neutralizing antibody titers following prophylactic HPV vaccination in bridging studies. Studies are not yet available on HPV vaccine efficacy in HIV infected women against either HPV-infection or clinical disease endpoints.

Single-center early experience of optical coherence tomography (OCT) for evaluation of high-grade dysplasia or early cancer in Barrett's esophagus.

56 Background: Barrett’s esophagus is a well-known risk factor for esophageal cancer. Surveillance esophagogastroduodenoscopy (EGD) and procedures like endoscopic mucosal resection (EMR) and radio frequency ablation (RFA) are adopted to mitigate risk of evolution to high grade dysplasia and cancer. Newer imaging modalities are expected to improve diagnostic accuracy and guide management. Here we describe our early experience with optical coherence tomography (OCT) which is an near infra-red light imaging technique for diagnosing high grade dysplasia and early stage cancer in patients with Barrett’s esophagus. Methods: Patients who underwent EGD and diagnosed with Barrett’s esophagus and endoscopic features worrisome for high grade dysplasia or early cancer were selected for the procedure. Patients underwent OCT for further characterizations of these lesions. Clinical and endoscopic findings, imaging studies and OCT findings were recorded and analyzed. Results: 5 patients were studied in this early series and details are tabulated below. (OCT images will accompany final presentation.) Conclusions: Early detection of high grade lesions and early cancer with image directed therapy in Barrett’s esophagus may positively impact survival. Our early experience suggests OCT is helpful in detecting cryptic dysplastic changes, especially in the aftermath of previous ablation and can guide additional endoscopic treatment. Further studies are necessary to determine efficacy of such an approach. [Table: see text]

Utility of molecular tests in cytopathology.

With the popularity of interventional radiology, diagnostic material obtained can be limited requiring critical decisions on making the best use of it. Molecular testing using nanogram amounts of tissue can add useful diagnostic information by improving sensitivity and/or specificity of the diagnosis. This review examines the use of molecular tests in cervical cytology, “indeterminate” thyroid cytology specimens, pancreatic cyst fluid, urinary tract and pulmonary adenocarcinoma cytologic material. Molecular human papillomavirus (HPV) testing combined with cervical cytology increases sensitivity of detection of high grade lesions. In cytologically negative cases, the HPV negative predictive value endorses longer screening intervals. With the high prevalence of benign thyroid nodules, cytology plays a vital role in screening. However, 10-40% of the specimens obtained are cytologically indeterminate. Molecular analysis of these specimens can predict the malignant risk in these cases. Increased detection of pancreatic cysts has necessitated accurate pre-operative diagnosis delineating non-mucinous from mucinous cysts, which have a potential for progression to adenocarcinoma. Multimodal diagnosis of pancreatic cysts and molecular analysis help to clarify neoplastic risk; and in cases of limited fluid, may be the only available diagnostic information. Urothelial carcinoma (UC) of the bladder, a common cancer with frequent recurrences, requires lifelong surveillance. The UroVysion ™ test kit can increase the sensitivity of detection of UC especially in cases of residual/recurrent carcinoma after therapy. Subsets of lung adenocarcinomas are now commonly targeted by therapies based on molecular mutation results of epidermal growth factor receptor, KRAS or echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase re-arrangements. The move toward standardization of reporting of cytology specimens commencing with cervical smears and more recently, thyroid cytology specimens is also changing the practice of cytopathology. Combining the stringent cytology criteria with ancillary molecular testing is expected to yield more discrete and diagnostic categories for research and reporting. The profession is at an exciting point of implementing novel molecular markers to refine diagnostic criteria and create clinically relevant classification systems.

PAX1 Methylation Analysis by MS-HRM is Useful in Triage of High-grade Squamous Intraepithelial Lesions

This study is aimed to investigate the role of paired boxed gene 1 (PAX1) methylation analysis by methylation- sensitive high-resolution melting (MS-HRM) in the detection of high grade lesions in atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion (ASC-H) and compared its performance with the Hybrid Capture 2 (HC2) human papillomavirus (HPV) test. In our study, 130 cases with a diagnosis of ASC-H from the cervical cytological screening by Thinprep cytologic test (TCT) technique were selected for triage. Their cervical scrapings were collected and evaluated by using PAX1 methylation analysis (MS-HRM) and high-risk HPV DNA test (HC2), followed by colposcopy and cervical biopsy. Chi-square test were used to test the differences of PAX1 methylation or HPV infection between groups. In the detection of CIN2+, the sensitivity, specificity, the PPV, NPV and the accuracy of PAX1 MS-HRM assay and high-risk HPV (HR-HPV) tests were respectively 80.6% vs 67.7%, 94.9% vs 54.5%, 83.3%, vs 31.8%, 94.0% vs 84.4%, and 91.5% vs 57.7%. The PAX1 MS-HRM assay proved superior to HR-HPV testing in the detection of high grade lesions (CIN2+) in ASC-H. This approach could screen out the majority of high grade lesion cases of ASC-H, and thus could reduce the referral rate to colposcopy.

Clinical Performance of HPV OncoTect Compared to NucliSENS EasyQ Assay and its Potential Role Over Papanicolaou Test in Detecting Preneoplastic Lesions of the Cervix

The purpose of this study was to compare the performance in the detection of the E6/E7 mRNA expression of hrHPV, using the NucliSENS EasyQ test (bioMerieux), a RT-PCR based method, or HPV OncoTect (IncellDx) a test based on the flow cytometry-FISH method. Moreover, we investigated the potential role, for the detection of high grade lesions, …

FemCerv – Single Pass Device for Targeted Endo-Cervical – In-Office Sampling

Demonstrate use of the FemCerv Endocervical Sampler (FemCerv) prototype as a single-pass 360 degree alternative to the multi- pass Kevorkian device. Evaluate adequacy of sample size for pathological evaluation and tissue type specificity. Design Feasitility Study. Extirpated Uterus in Operating Room under institutional IRB approval. Undergoing hysterectomy for benign disease. The FemCerv single use device (Femasys Inc.) is placed transvaginally into the cervical canal utilizing its self-dilating tapered tip is advanced to the placement marker for targeted sampling of the endocervix. The device collection chamber which measures 2.0 cm is opened only within the endo-cervical canal. With the chamber open, it is rotated clockwise 360 degrees and then counter-clockwise to its original position. During the rotation process the laser cut edges gather tissue into the chamber. It is then closed while in the endo-cervix avoiding ecto-cervical sample contamination during device removal. Sample submitted was 1cm in aggregate dimension and upon histopathological evaluation found to contain only endo-cervical tissue. A single pass endo-cervical sampling device that provides an adequate site specific specimen for pathologic evaluation should reduce false positive findings and in turn decrease the number of unnecessary LEEP and Cone-Biospy procedures. With its ease of use and anticipated decreased patient discomfort, health care providers might be less reluctant to sample the endo-cervix and thus with increased use may improve the early detection of high grade lesions. The device's encouraging initial results warrants a more robust extirpated study leading to an in-office evaluation used to assess its applicability in clinical practice.

Relative Accuracy of Cervical and Anal Cytology for Detection of High Grade Lesions by Colposcope Guided Biopsy: A Cut-Point Meta-Analytic Comparison

BackgroundWe recently reported, using a receiver operating characteristic area metric, the first meta-analytic comparison of the relative accuracy of cervical and anal cytology in detecting moderate or severe histopathologic lesions by magnification directed punch biopsy. The aim of the present research was to meta-analytically examine cut-point specific operating characteristics (sensitivity, specificity) of cervical and anal cytology in detecting high grade squamous intraepithelial lesion (HSIL) histopathology by colposcope directed punch biopsy.Methodology/Principal FindingsThe primary eligibility requirement was availability of tabulated cytology (normal, atypical cells of unclear significance [ASCUS], low grade squamous intraepithelial lesion, HSIL or atypical squamous cells cannot rule out high grade [ASC-H]) and biopsy (<HSIL, ≥ HSIL) counts. Meta-analysis and meta-regression of diagnostic accuracy was performed with examination of study quality criteria and heterogeneity. Thirty-three cervical and 11 anal publications were eligible between 1990 and 2010. Meta-analytically cut-point analysis showed that using a cut-point of ASCUS the sensitivity in both settings is similar while anal cytology is less specific than cervical cytology (specificity [95% confidence interval] 0.33 [0.20–0.49] vs. 0.53[0.40–0.66], p = 0.04) for the detection of HSIL histopathology by colposcope directed punch biopsy.Conclusions/SignificanceUsing a cytology cut-point of HSIL or ASC-H, anal cytology is less sensitive but comparably specific to cervical cytology. However, using a cut-point of ASCUS, differences in accuracy were of borderline significance.

Detection of High-Grade Lesions on Cell Blocks from Residual Fluids of Pap Smears Diagnosed as Low-Grade Abnormalities: A Preliminary Pilot Study

Objective: To investigate the feasibility of the technique of cell blocks (CBs) from residual fluids of Papanicolaou (Pap) smears diagnosed as low-grade abnormalities in the detection of high-grade lesions on biopsies. Study Design: In the present pilot study, we evaluated the sensitivity and specificity of 70 CBs from liquid-based cervicovaginal smears of women with atypical squamous cells (ASCs) of undetermined significance (ASCUS; n = 39), ASCs that cannot exclude high-grade squamous intraepithelial lesion (ASC-H; n = 17) and low-grade squamous intraepithelial lesions (LSILs; n = 14) in the detection of cervical intraepithelial neoplasia (CIN) type 2+ lesions. Results: Of the 70 CBs, 22 were diagnosed as negative, 27 as CIN1 and 21 as CIN2+. The sensitivity and specificity of CB preparation for the diagnosis of CIN2+ lesions were 50 and 100%, respectively, in ASCUS, 92 and 100%, respectively, in ASC-H, 100 and 100%, respectively, in LSILs. Conclusions: Our study confirms that CB preparation is a simple and reproducible technique with a good specificity that could be added advantageously to Pap smears to detect CIN2+ lesions in women with ASCs and LSILs.

Visual inspection with acetic acid for detection of high grade lesion in atypical squamous cells and low grade squamous intraepithelial lesions from cervical Pap smear

ObjectiveTo evaluate the value of visual inspection with acetic acid (VIA) test to detect high grade lesion in women with atypical squamous cells or low grade squamous intraepithelial lesions cervical cytology.MethodsWomen with atypical squamous cells or low grade squamous intraepithelial lesions who were scheduled to undergo colposcopy at Vajira Hospital and met inclusion criteria were included. All participants underwent VIA test prior to usual steps of colposcopy. The VIA results were interpreted as positive or negative using the criteria by the International Agency for Cancer Research. The standard colposcopic examination and appropriate investigations for cervical pathology were then continued. The diagnostic values of VIA test including sensitivity, specificity, positive predictive value, and negative predictive value were determined using high grade lesion including cervical intraepithelial neoplasia 2-3 and squamous cell carcinoma as a threshold.ResultsTotal of 106 women was included. The VIA test was positive in 33 women (31.1%) and negative in 73 women (68.9%). Among the women with VIA test positive, 14 had high grade lesion (42.4%) while 19 had no significant lesions. Only 2/73 (2.7%) cases with negative VIA test had high grade lesion (both had cervical intraepithelial neoplasia 2). The sensitivity, specificity, positive predictive value and negative predictive value with 95% confidence interval were 87.5% (81.2 to 93.8%), 78.8% (71.1 to 86.7%), 42.4% (33.0 to 51.8%), and 97.2% (94.2 to 1.0%) respectively.ConclusionVIA as the intermediate test in atypical squamous cells and low grade squamous intraepithelial lesions cytology may reduce the necessity to refer some women for colposcopy.

Complementary Utility of Multislice Computed Tomographic Coronary Angiography for Detection of High-Grade Lesions in Patients with Negative Stress Myocardial Perfusion Imaging

Myocardial perfusion imaging (MPI) is a highly sensitive and specific test for noninvasive detection of coronary artery disease. Therefore, in patients with negative MPI results, further noninvasive testing is usually not pursued. We report a series of patients with negative MPI results in whom 64-slice computed tomographic coronary angiography accurately predicted flow-limiting coronary lesions requiring subsequent revascularization.

HPV DNA Testing in Cervical Cancer Screening: Results From Women in a High-Risk Province of Costa Rica

ContextHuman papillomaviruses (HPVs) are known to cause most cervical cancer worldwide, but the utility of HPV DNA testing in cervical cancer prevention has not been determined.ObjectiveTo provide comprehensive data on the screening performance of HPV testing for the most common carcinogenic types, at different levels of analytic sensitivity.DesignLaboratory analysis conducted during 1993-1995, using 3 cytologic techniques and cervicography, followed by colposcopic examination of women with any abnormal cervical finding, to detect all high-grade intraepithelial lesions and cancer (reference standard of clinically significant disease). The HPV testing was performed subsequently with masking regarding clinical findings.SettingGuanacaste Province, Costa Rica, a region with a high age-adjusted incidence of cervical cancer.ParticipantsOf 11,742 randomly selected women, 8554 nonpregnant, sexually active women without hysterectomies underwent initial HPV DNA testing using the original Hybrid Capture Tube test; a stratified subsample of 1119 specimens was retested using the more analytically sensitive second generation assay, the Hybrid Capture II test.Main Outcome MeasuresReceiver operating characteristic analysis of detection of cervical high-grade intraepithelial lesions and cancer by HPV DNA testing based on different cut points of positivity.ResultsAn analytic sensitivity of 1.0 pg/mL using the second generation assay would have permitted detection of 88.4% of 138 high-grade lesions and cancers (all 12 cancers were HPV-positive), with colposcopic referral of 12.3% of women. Papanicolaou testing using atypical squamous cells of undetermined significance as a cut point for referral resulted in 77.7% sensitivity and 94.2% specificity, with 6.9% referred. Specificity of the second generation assay for positivity for high-grade lesions and cancer was 89.0%, with 33.8% of remaining HPV DNA–positive subjects having low-grade or equivocal microscopically evident lesions. The higher detection threshold of 10 pg/mL used with the original assay had a sensitivity of 74.8% and a specificity of 93.4%. Lower levels of detection with the second generation assay (<1 pg/mL) proved clinically nonspecific without gains in diagnostic sensitivity.ConclusionsIn this study population, a cut point of 1.0 pg/mL using the second generation assay permitted sensitive detection of cervical high-grade lesions and cancer, yielding an apparently optimal trade-off between high sensitivity and reasonable specificity for this test. The test will perform best in settings in which sensitive detection of high-grade lesions and cancer is paramount. Because HPV prevalence varies by population, HPV testing positive predictive value for detection of high-grade lesions and cancer will vary accordingly, with implications for utility relative to other cervical cancer screening methods.

Hybrid capture II, a new sensitive test for human papillomavirus detection. Comparison with hybrid capture I and PCR results in cervical lesions.

AIM: To test a new assay for the detection of human papillomavirus (HPV) DNA, hybrid capture II (HC II), compared with the previous commercialized hybrid capture I (HC I) and...

Grading of precancerous laryngeal lesions by multiparameter image analysis at separate epithelial layers

In order to detect early precancerous changes which do not involve the whole thickness of the epithelium, we used a novel image analysing program based on an IBAS system (Kontron, Germany) to determine nuclear DNA content (NC) as well as average nuclear area (NA) and variation of nuclear area (VA), in the entire epithelium and in three sublayers, parabasal, intermediate, and superficial. DNA aneuploidy was found in only half of the cases classified as 'high-grade' (HG) lesions, comprising carcinoma in situ (CIS) and severe epithelial dysplasias (EDIII), and was chiefly demonstrable in the parabasal third of the epithelium. The other lesions were DNA euploid. HG lesions showed highly significant increases of NA and VA at the lower levels of the epithelium when compared with 'low-grade' (LG) lesions comprising moderate and mild epithelial dysplasias (EDII and EDI). Our data show that the combination of multiparameter image analysis with conventional morphology assists in the objective grading of precancerous lesions and permits the reliable detection of high-grade lesions.