scholarly journals Triage of hrHPV-positive women: comparison of two commercial methylation-specific PCR assays

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Carolin Dippmann ◽  
Martina Schmitz ◽  
Kristina Wunsch ◽  
Stefanie Schütze ◽  
Katrin Beer ◽  
...  
Keyword(s):  
Dna Methylation ◽  
False Positive ◽  
Pap Smear ◽  
Intraepithelial Neoplasia ◽  
Molecular Diagnostic ◽  
Cervical Lesions ◽  
Detection Rates ◽  
Diagnostic Assays ◽  
Specific Pcr

Abstract Aim High-risk human papillomavirus (hrHPV)-based screening is becoming increasingly important, either by supplementing or replacing the traditional cytology-based cervical Pap smear. However, hrHPV screening lacks specificity, because it cannot differentiate between transient virus infection and clinically relevant hrHPV-induced disease. Therefore, reliable triage methods are needed for the identification of HPV-positive women with cervical intraepithelial neoplasia (CIN) in need of treatment. Promising tools discussed for the triage of these patients are molecular diagnostic tests based on epigenetic markers. Here, we compare the performance of two commercially available DNA methylation-based diagnostic assays—GynTect® and the QIAsure Methylation Test—in physician-taken cervical scrapes from 195 subjects. Findings Both GynTect® and the QIAsure Methylation Test detected all cervical carcinoma and carcinoma in situ (CIS). The differences observed in the detection rates between both assays for the different grades of cervical lesions (QIAsure Methylation Test: CIN1 26.7%, CIN2 27.8% and CIN3 74.3%; GynTect®: CIN1 13.3%, CIN2 33.3% and CIN3 60%) were not significant. Concerning the false-positive rates, significant differences were evident. For the healthy (NILM) hrHPV-positive group, the false-positive rates were 5.7% for GynTect® and 26.4% for QIAsure Methylation Test (p = 0.003) and for the NILM hrHPV-negative group 2.2% vs. 23.9% (p = 0.006), respectively. When considering hrHPV-positive samples only for comparison (n = 149), GynTect® delivered significantly higher specificity compared to the QIAsure Methylation Test for CIN2 + (87.6% vs. 67.4% (p < 0.001)) and CIN3 + (84.1% vs. 68.2% (p = 0.002)). Overall our findings suggest that DNA methylation-based tests are suitable for the triage of hrHPV-positive women. With the goal to provide a triage test that complements the limited specificity of HPV testing in HPV-based screening, GynTect® may be preferable, due to its higher specificity for CIN2+ or CIN3+ .

scholarly journals Loop Electrosurgical Excision Procedure in Cervical Intraepithelial Neoplasia

2016 ◽  
Vol 11 (1) ◽  
pp. 58-61
Author(s):  
Rima Maharjan ◽  
BK Thapa ◽  
Neershobha Chitrakar ◽  
Jitendra Pariyar ◽  
Isha Shrestha ◽  
...  
Keyword(s):  
Squamous Cell ◽  
Simple Procedure ◽  
Pap Test ◽  
Intraepithelial Neoplasia ◽  
Final Diagnosis ◽  
Invasive Squamous Cell Carcinoma ◽  
Adenocarcinoma In Situ ◽  
Cervical Lesions

Aims: To evaluate the treatment outcome and acceptance of LEEP in precancerous cervical lesions.Methods: This is a descriptive study performed in Gynecology Department of Civil Service Hospital, from August 2014 - December 2015 in 28 cases that underwent LEEP forCIN. LEEP was performed as day care procedure under intravenous anesthesia and patient was sent home six hours after procedure. Follow up and further treatment was done after final histopathological reports.Results: Highest percentage ofCIN, 32.14% (9) was seen among 30-39 years age with 16 (57.14%) of parity three and more. 17 (60.71%) presented clinic with symptoms (lower abdominal, backpain, pervaginal discharge) while 11 (39.28%) were diagnosed from routine Pap test. Histopathology revealed four (14.28%)CIN1, eight (28.57%)CIN2, 11(39.28%)CIN3, two adenocarcinoma in situ, one of invasive squamous cell carcinoma, chronic cervicitis and atrophic change with no dysplasia. Margins were negative (satisfactory) in 20 (71.42%) and positive in eight (28.57%) with endocervical involvement in two that required second LEEP while one underwent radical hysterectomy for final diagnosis of invasive squamous cell carcinoma.Conclusions: Hysterectomy is a radical procedure for preinvasive cervical lesions that can be treated with simple procedure like LEEP that saves time and financial resources.

scholarly journals CADM1, MAL and miR124-2 methylation analysis in cervical scrapes to detect cervical and endometrial cancer

2014 ◽  
Vol 67 (12) ◽  
pp. 1067-1071 ◽  
Author(s):  
Lise M A De Strooper ◽  
Marjolein van Zummeren ◽  
Renske D M Steenbergen ◽  
Maaike C G Bleeker ◽  
Albertus T Hesselink ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Dna Methylation ◽  
Endometrial Cancer ◽  
Gene Promoter ◽  
Intraepithelial Neoplasia ◽  
Promoter Hypermethylation ◽  
Methylation Analysis ◽  
Cervical Intraepithelial Neoplasia Grade ◽  
Specific Pcr ◽  
Dna Methylation Analysis

AimsGene promoter hypermethylation is recognised as an essential early step in carcinogenesis, indicating important application areas for DNA methylation analysis in early cancer detection. The current study was set out to assess the performance of CADM1, MAL and miR124-2 methylation analysis in cervical scrapes for detection of cervical and endometrial cancer.MethodsA series of cervical scrapes of women with cervical (n=79) or endometrial (n=21) cancer, cervical intraepithelial neoplasia grade 3 (CIN3) (n=16) or CIN2 (n=32), and women without evidence of CIN2 or worse (n=120) were assessed for methylation of CADM1, MAL and miR124-2. Methylation analysis was done by the PreCursor-M assay, a multiplex quantitative methylation-specific PCR.ResultsAll samples of women with cervical cancer (79/79, 100%), independent of the histotype, and 76% (16/21; 95% CI 58.0% to 94.4%) of women with endometrial cancer scored positive for DNA methylation for at least one of the three genes. In women without cancer, methylation frequencies increased significantly with severity of disease from 19.2% (23/120; 95% CI 12.1% to 26.2%) in women without CIN2 or worse to 37.5% (12/32; 95% CI 20.7% to 54.3%) and 68.8% (11/16; 95% CI 46.0% to 91.5%) in women with CIN2 and CIN3, respectively. Overall methylation positivity and the number of methylated genes increased proportionally to the lesion severity.ConclusionsDNA methylation analysis of CADM1, MAL and miR124-2 in cervical scrapes consistently detects cervical cancer and the majority of CIN3 lesions, and has the capacity to broaden its use on cervical scrapes through the detection of a substantial subset of endometrial carcinomas.

Feasibility and outcome of laser CO2 conization performed within the 18th week of gestation

2007 ◽  
Vol 17 (1) ◽  
pp. 127-131 ◽  
Author(s):  
M. Fambrini ◽  
C. Penna ◽  
M. G. Fallani ◽  
A. Pieralli ◽  
A. Mattei ◽  
...  
Keyword(s):  
Minimally Invasive ◽  
Intraepithelial Neoplasia ◽  
Figo Stage ◽  
Therapeutic Benefit ◽  
Outpatient Setting ◽  
Cervical Lesions ◽  
Histologic Diagnosis ◽  
Potential Therapeutic Benefit

The purpose of this study is to evaluate the feasibility, safety, and potential therapeutic benefit of laser CO2 conization of the cervix for in situ and minimally invasive carcinoma diagnosed during pregnancy. Twenty-six pregnant patients with biopsy-proven carcinoma in situ/cervical intraepithelial neoplasia III but colposcopically suspicious for invasion underwent laser CO2 conization during the 18th week of gestation in an outpatient setting under local anesthesia. No major intraoperative or postoperative complications occurred, and cervical cerclage was not required in any case. Two cases (7.7%) of occult FIGO stage IA1 minimally invasive cervical cancers with free surgical margins were diagnosed. Both patients delivered vaginally at term and were free of disease at postpartum follow-up. Median length of gestation was 39.1 weeks with a median birth weight of 3450 g. All 1-min Apgar scores were 8 or greater. Twenty patients (76.9%) delivered vaginally, while six patients underwent cesarean section for indications not related to the prior conization. After a mean postpartum follow-up of 18 months (range 3–42), 92.3% of patients continued to have both cytologic and colposcopic evaluations negative for persistent or recurrent disease. Two cases of persistent intraepithelial disease were successfully managed by reconization. In summary, our data suggest that laser CO2 conization performed within the 18th week of gestation is safe for both the patient and the fetus, provides reliable histologic diagnosis, and can be curative. Further studies are required to confirm the favorable risk–benefit ratio of laser CO2 conization in the management of non-reassuring cervical lesions observed in the first half of pregnancy.

scholarly journals ABNORMAL FINDING OF PAP SMEAR AMONG WOMEN HOSPITAL VISITORS IN CITY OF MOSUL, IRAQ

2020 ◽  
Vol 8 (7) ◽  
pp. 174-178
Author(s):  
Sanaa Rajab ◽  
Wasnaa A Elias ◽  
Layla G Saeed ◽  
Thukaa T Yahya
Keyword(s):  
Epithelial Cell ◽  
Pap Smear ◽  
Precancerous Lesions ◽  
Intraepithelial Neoplasia ◽  
Cervical Cytology ◽  
Cervical Lesions ◽  
Abnormal Finding ◽  
Pap Smear Screening ◽  
Negative Findings ◽  
Glandular Cells

Objective: The research aims to test the use of the Pap smear screening system to identify precancerous lesions among women in City of Mosul, Iraq. Methods: This prospective study was carried out over 1 year at the Department of Obstetrics and Gynaecology in Mosul Teaching Hospital, city of Mosul, Iraq. We screened 100 sexually active women who were more than 21 years of age. Women with different complaints, including vaginal discharge, blood‑mixed discharge, foul-smelling discharge, postcoital bleeding, intermenstrual bleeding, postmenopausal bleeding, abdominal pain, infertility, and secondary amenorrhea, were included in this study. The glass slides had been sent for cytopathological review to the pathology department. The laboratory results have been reported by the new Bethesda Cervical Cytology Reporting System 2014. The device divided the lesions narrowly into certain negative ones for intraepithelial neoplasia and with epithelial cell abnormalities (ECA) that involve squamous and glandular cells. Upon pap smear, the patient was treated accordingly. Results: The study had enrolled a total of 100 cases. All of these patients had an abnormal Pap smear finding that fell according to TBS-2014 criteria in the category of Epithelial Cell abnormality. We interviewed all patients in Detail by proforma. The data reported were statistically analyzed and were collected following observations and tests. Among the study subject, the most common abnormal findings (68.9%) were negative findings. Inflammatory constitute (15.4), and Atypical squamous cells of undetermined significance (7%) followed by LSIL (5.9) and HSIL (2.9). Conclusion: Pap smear is an effective method for screening for Cervical Lesions Precancerous and cancerous. Nevertheless, a cervical biopsy must be performed which Is gold standard if any epithelial defects are found to be confirmed in cervical cytology.

scholarly journals Virtues and Weaknesses of DNA Methylation as a Test for Cervical Cancer Prevention

2016 ◽  
Vol 60 (6) ◽  
pp. 501-512 ◽  
Author(s):  
Attila T. Lorincz
Keyword(s):  
Dna Methylation ◽  
Large Population ◽  
Healthcare Delivery ◽  
Clinical Specimen ◽  
Intraepithelial Neoplasia ◽  
Population Based ◽  
Cervical Cancer Prevention ◽  
Open Reading Frames ◽  
Molecular Diagnostic ◽  
Human Genes

Epigenetics is the study of heritable and non-heritable genetic coding that is additive to information contained within classical DNA base pair sequences. Differential methylation has a fundamental role in the development and outcome of malignancies, chronic and degenerative diseases and aging. DNA methylation can be measured accurately and easily via various molecular methods and has become a key technology for research and healthcare delivery, with immediate roles in the elucidation of disease natural history, diagnostics and drug discovery. This review focuses on cancers of the lower genital tract, for which the most epigenetic information exists. DNA methylation has been proposed as a triage for women infected with human papillomavirus (HPV) and may eventually directly complement or replace HPV screening as a one-step molecular diagnostic and prognostic test. Methylation of human genes is strongly associated with cervical intraepithelial neoplasia (CIN) and cancer. Of the more than 100 human methylation biomarker genes tested so far in cervical tissue, close to 20 have been reported in different studies, and approximately 10 have been repeatedly shown to have elevated methylation in cervical cancers and high-grade CIN (CIN2 and CIN3), most prominently CADM1, EPB41L3, FAM19A4, MAL, miR-124, PAX1 and SOX1. Obtaining consistent performance data from the literature is quite difficult because most methylation studies used a variety of different assay methodologies and had incomplete and/or biased clinical specimen sets, varying assay thresholds and disparate target gene regions. There have been relatively few validation studies of DNA methylation biomarkers in large population-based screening studies, but an encouraging development more recently is the execution of well-designed studies to test the true performance of the markers in real-world settings. Methylation of HPV genes, especially HPV16, HPV18, HPV31, HPV33 and HPV45, in disease progression has been a major focus of research. Elevated methylation of the HPV16 L1 and L2 open reading frames, in particular, is associated with CIN2, CIN3 and invasive cancer. Essentially all cancers have high levels of methylation for human genes and for driver HPV types, which suggests that quantitative methylation tests may have utility in predicting CIN2 and CIN3 that are likely to progress. It is still early in the process of development of methylation biomarkers, but already they are showing strong promise as a universal and systematic approach to molecular triage, applicable to all cancers, not just cancer of the cervix. DNA methylation testing is better than HPV genotyping triage and is competitive with or complementary to other approaches such as cytology and p16 staining. Genome-wide studies are underway to systematically expand methylation classifier panels and find the best combinations of biomarkers. Methylation testing is likely to show big improvements in performance in the next 5 years.

scholarly journals Enhanced Detection of Cervical Cancer and Precancer Through Use of Imaged Liquid-Based Cytology in Routine Cytology and HPV Cotesting

2018 ◽  
Vol 150 (5) ◽  
pp. 385-392 ◽  
Author(s):  
R Marshall Austin ◽  
Agnieszka Onisko ◽  
Chengquan Zhao
Keyword(s):  
Cervical Cancer ◽  
Pap Smear ◽  
Cervical Screening ◽  
Intraepithelial Neoplasia ◽  
Pap Smears ◽  
Adenocarcinoma In Situ ◽  
Hpv Testing ◽  
Liquid Based Cytology ◽  
Positive Results

AbstractObjectivesCervical screening strives to prevent cervical cancer (CxCa), minimizing morbidity and mortality. Most large US reports on cytology and human papillomavirus (HPV) cotesting of women aged 30 years and older are from one laboratory, which used conventional Papanicolaou (Pap) smears from 2003 to 2009.MethodsWe quantified detection of CxCa and precancer (cervical intraepithelial neoplasia 3/adenocarcinoma in situ [CIN3/AIS]) in 300,800 cotests at Magee Womens Hospital since 2005. Screening histories preceding CxCa and CIN3/AIS diagnoses were examined to assess the contribution of cytology and HPV testing. Cotesting utilized Food and Drug Administration-approved imaged liquid-based cytology (LBC) and from-the-vial HPV tests.ResultsLBC identified more women subsequently diagnosed with CxCa and CIN3/AIS than HPV testing. HPV-negative/cytology-positive results preceded 13.1% of CxCa and 7.2% of CIN3/AIS diagnoses.ConclusionsLBC enhanced cotesting detection of CxCa and CIN3/AIS to a greater extent than previously reported with conventional Pap smear and HPV cotesting.

scholarly journals High risk human papillomavirus type 16 and 18 infection in the cervical lesions of women with epithelial cell abnormality in Pap smear: A cytohistomorphologic association in Bangladeshi women

CytoJournal ◽  
2013 ◽  
Vol 10 ◽  
pp. 14 ◽  
Author(s):  
Urmila Banik ◽  
M. Shahab Uddin Ahamad ◽  
Pradip Bhattacharjee ◽  
Arun Kumar Adhikary ◽  
Zillur Rahman
Keyword(s):  
Human Papillomavirus ◽  
High Risk ◽  
Epithelial Cell ◽  
Pap Smear ◽  
Intraepithelial Neoplasia ◽  
Cervical Lesions ◽  
Cervical Intraepithelial Neoplasia Grade ◽  
Cross Sectional ◽  
Hpv 16 ◽  
Hrhpv Type

Background: The aim of this study was to find out the extent of high-risk human papillomavirus (hrHPV) type 16/18 infection in the cervical tissue of women with epithelial cell abnormality in Pap smear and to establish an association between hrHPV type 16/18 infection and cytohistomorphology. Materials and Methods: A cross-sectional descriptive study was carried out in 1699 patients who went through Pap smear examination. Prevalence of epithelial cell abnormality was calculated. Forty eight of these women underwent routine histopathology and 47 were evaluated for human papillomavirus (HPV) type 16/18 by polymerase chain reaction assay. Results: Total 139 women revealed epithelial cell abnormality. Histopathology showed simple inflammation to malignancy. HPV type 16/18 infection was detected in 40.42% (19/47) of the patients. Individually type 16 and 18 were positive in 7 (14.9%) cases each and dual infection with type 16 and 18 were seen in 5 (10.6%) cases. While cervical intraepithelial neoplasia grade 1 (CIN 1) and < CIN 1 lesions showed 18.75% (3 out of 16) and 35% (7 out of 20) positivity respectively, ≥CIN 2 lesions revealed positivity of 81.82% (9 out of 11). Eighty percent HPV 16/18 positivity was seen in women of < 30 years of age. Conclusion: The findings of this study will contribute to HPV 16/18 knowledge in Bangladesh that will be useful in assessing the success of current vaccines with limited type spectra and augmenting cervical cancer screening strategies.

scholarly journals Visual Inspection with Acetic Acid (VIA) in cervical cancer screening in low resource settings

2014 ◽  
Vol 13 (4) ◽  
pp. 454-459
Author(s):  
Shaheen Shaheen ◽  
Rajyashri Sharma ◽  
Rashi Rashi
Keyword(s):  
Acetic Acid ◽  
Visual Inspection ◽  
Pap Smear ◽  
Screening Program ◽  
Low Cost ◽  
Medical Science ◽  
High Sensitivity ◽  
Intraepithelial Neoplasia ◽  
Screening Methods ◽  
Cervical Lesions

Objective: To evaluate the feasibility and validity of visual inspection of the cervix with acetic acid (VIA) for screening cervical intraepithelial neoplasia. Materials and Methods: In this study, 942 women recruited from gynecology outpatient clinic, were screened using the Papanicolaou (PAP) smear, and VIA. The sensitivity and specificity of both the screening methods were analyzed. Results: VIA was positive in 29.3%. The sensitivity of VIA (74.16%) was much higher than that of the Pap smear (47.83%). The specificity of VIA (50.00%) was lower than that of the Pap smear (74.16%), resulting in high false-positive rates for VIA. Conclusion: Visual inspection of the cervix with acetic acid is sensitive for ecto-cervical lesions. The advantage of the VIA method lies in its easy technique, low cost and high sensitivity which are important factors for determining the efficacy of any screening program in developing countries. DOI: http://dx.doi.org/10.3329/bjms.v13i4.15019 Bangladesh Journal of Medical Science Vol.13(4) 2014 p.454-459

Human papillomavirus DNA and genotypes: prognostic factors for progression of cervical intraepithelial neoplasia

1994 ◽  
Vol 4 (2) ◽  
pp. 73-78 ◽  
Author(s):  
K. N. Gaarenstroom ◽  
P. Melkert ◽  
J. M.M. Walboomers ◽  
A. J.C. Van Den Brule ◽  
P. F.J. Van Bommel ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Cervical Intraepithelial Neoplasia ◽  
Intraepithelial Neoplasia ◽  
Cervical Lesions ◽  
Histologic Diagnosis ◽  
Hpv Dna ◽  
Specific Pcr ◽  
Abnormal Cervical Cytology ◽  
Primer Polymerase Chain Reaction ◽  
Dna Types

A retrospective study of 227 patients presenting with abnormal cervical cytology was conducted to investigate the relationship between human papillomavirus (HPV) and progression of untreated cervical intraepithelial neoplasia (CIN) lesions. All patients had colposcopically directed biopsies for histologic diagnosis. The patients were followed cytologically and colposcopically for a mean of 19 months (range 6–42 months). Progression of a cervical lesion was defined as progression to a higher CIN grade confirmed histologically by directed biopsy. HPV DNA detection was done on material remaining from the cervical swabs by the general primer polymerase chain reaction (PCR) and type-specific PCR method, which made the detection of HPV types 6, 11, 16, 18, 31, 33 and not yet sequenced DNA types (X) possible. The presence of HPV DNA increased with the severity of the lesion (P< 0.001). In CIN III, a 100% HPV DNA prevalence was found, with HPV type 16 being the most prevalent type in 75%. Progression was significantly related to the presence of HPV DNA, in particular HPV type 16. The percentage of progressive disease was 21% in the case of HPV DNA positive lesions (n= 130) and 29% in the presence of HPV type 16, whereas HPV DNA negative lesions (n= 97) showed no progression. The detection of HPV DNA and HPV genotype can be used to identify patients with high-risk cervical lesions, since the presence of HPV DNA and genotype 16 in particular are closely related to CIN progression.

scholarly journals Changes in the vaginal microbiota in women with cervical diseases

2012 ◽  
Vol 93 (1) ◽  
pp. 76-79
Author(s):  
L D Andosova ◽  
O V Kachalina ◽  
A V Belov ◽  
S Yu Kudel’kina
Keyword(s):  
Intraepithelial Neoplasia ◽  
Vaginal Microbiota ◽  
Stage Iii ◽  
Cervical Lesions ◽  
Chain Reaction ◽  
Number Of Patients ◽  
Polymerase Chain ◽  
Cervical Diseases ◽  
The Relationship

Aim. To study the relationship between the condition of the vaginal microbiota and the severity of pathological changes of the cervical epithelium. Methods. Studied were 99 female patients aged from 18 to 56 years with secondary and precancerous cervical processes: the first group - 20 women with cervical ectopias; the second group - 20 females with cervical intraepithelial stage I neoplasia; the third group - 19 women with stage II neoplasia; the fourth group - 20 patients with cervical intraepithelial stage III neoplasia (cancer in situ); the fifth group - 20 women with invasive cancer. The investigation of the vaginal biocenosis was conducted by the real-time polymerase chain reaction technique. Results. Established was a correlation between the dysbiotic vaginal changes and cervical lesions. In the first group normocenosis was reported in 4 women (20%), in the groups with cervical intraepithelial stage III neoplasia (cancer in situ) and with cervical cancer - only in 1 woman, accounting for 5% of the total number of patients in the group. In the first group in 16 women out of 20 (80%) noted was the dominance of Lactobacillus, in the groups with cervical intraepithelial neoplasia the proportion of such patients decreased, reaching for the fourth and fifth groups - 45 and 50% respectively. Conclusion. Imbalance of the urogenital tract microbiota may contribute significantly to the development and progression of cervical lesions.

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