Conventional Direct Smear Yields Diagnostic Indicators of Gastric-Type Mucinous Carcinoma Compared with Cytomorphological Features Identified by Liquid-Based Cervical Cytology

2020 ◽  
pp. 1-8
Author(s):  
Ayumi Ryu ◽  
Shigenori Nagata ◽  
Chiaki Kubo ◽  
Yuko Ueda ◽  
Satoshi Tanada ◽  
...  
Keyword(s):  
Cervical Screening ◽  
Mucinous Carcinoma ◽  
Neoplastic Cell ◽  
Nuclear Chromatin ◽  
Ki 67 ◽  
Distinct Cell ◽  
Hpv Test ◽  
Gastric Type ◽  
Gastric Phenotype ◽  
Histological Confirmation

<b><i>Introduction:</i></b> Gastric-type mucinous carcinoma (GAS) of the uterine cervix is an adenocarcinoma subtype with a gastric phenotype that poses diagnostic pitfalls in cervical screening cytology because of its blunt morphologic atypia and the limited utility of human papillomavirus testing and ancillary immunochemical staining. Despite the recent widespread uptake of liquid-based cytology (LBC) systems, the cytomorphological features of GAS in LBC samples and the differential features between GAS and usual-type endocervical adenocarcinoma (UEA) remain unclear. <b><i>Methods:</i></b> Eight GAS cases, all of which were surgically treated following histological confirmation, were examined. Direct Papanicolaou-stained smears and LBC samples were reviewed and compared with 10 UEA cases as controls. Featured cytomorphological findings were as follows: background (mucinous, inflammatory, or necrotic), cell crowding (size of neoplastic cell clusters), cytoplasm (golden mucin and cell border), and nuclei (nuclear chromatin and nucleoli). <b><i>Results:</i></b> Of 18 adenocarcinomas, 16 were detected against a non-mucinous background in LBC samples, most of which were accompanied by mild to moderate inflammation. Clusters comprising &#x3e;300 neoplastic cells were identified in both GAS and UEA in conventional smears (CSs), while no LBC samples harboured clusters as large as these. Cell borders of GAS were more distinct than those of UEA in CSs (<i>p</i> &#x3c; 0.001), although fewer populations of neoplastic clusters revealed distinct cell borders in both GAS and UEA in LBC samples. Three of 8 and 2 of 8 GAS cases had golden mucin in CSs and in LBC samples, respectively, which was not detected in UEA at all. Nucleoli against fine nuclear chromatin were more pronounced in GAS than in UEA on CS (<i>p</i> = 0.03), although the difference between GAS and UEA was not apparent in LBC samples. <b><i>Discussion/Conclusion:</i></b> This study demonstrated that the diagnostic clues to detect GAS using the conventional approach, namely distinct cell borders and prominent nucleoli, are not useful for excluding UEA in LBC samples. Conventional cervical smears may indicate a diagnosis of GAS; however, specific high-risk HPV detection approaches, such as HPV test or immunocytochemical p16/Ki-67 dual staining, are desirable to differentiate GAS from UEA in the setting of LBC with ambiguous cytomorphological features.

scholarly journals Role of Protein Biomarkers in the Detection of High-Grade Disease in Cervical Cancer Screening Programs

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Charlotte A. Brown ◽  
Johnannes Bogers ◽  
Shaira Sahebali ◽  
Christophe E. Depuydt ◽  
Frans De Prins ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Screening ◽  
Cervical Cancer Screening ◽  
Cervical Screening ◽  
False Negative ◽  
Pap Test ◽  
Developed Countries ◽  
Protein Biomarkers ◽  
Ki 67 ◽  
Screening Programs

Since the Pap test was introduced in the 1940s, there has been an approximately 70% reduction in the incidence of squamous cell cervical cancers in many developed countries by the application of organized and opportunistic screening programs. The efficacy of the Pap test, however, is hampered by high interobserver variability and high false-negative and false-positive rates. The use of biomarkers has demonstrated the ability to overcome these issues, leading to improved positive predictive value of cervical screening results. In addition, the introduction of HPV primary screening programs will necessitate the use of a follow-up test with high specificity to triage the high number of HPV-positive tests. This paper will focus on protein biomarkers currently available for use in cervical cancer screening, which appear to improve the detection of women at greatest risk for developing cervical cancer, including Ki-67,p16INK4a, BD ProEx C, and Cytoactiv HPV L1.

scholarly journals Clinical Validation of the cobas 4800 HPV Test for Cervical Screening Purposes

2011 ◽  
Vol 49 (11) ◽  
pp. 3983-3985 ◽  
Author(s):  
D. A. M. Heideman ◽  
A. T. Hesselink ◽  
J. Berkhof ◽  
F. van Kemenade ◽  
W. J. G. Melchers ◽  
...  
Keyword(s):  
Cervical Screening ◽  
Clinical Validation ◽  
Hpv Test

Οικονομική αξιολόγηση της δοκιμασίας HPV DNA ως πρωταρχικής μεθόδου προσυμπτωματικού ελέγχου για καρκίνο τραχήλου της μήτρας στην Ελλάδα

2021 ◽  
Author(s):  
Αναστάσιος Σκρουμπέλος
Keyword(s):  
Purchasing Power Parity ◽  
Price Index ◽  
Cervical Screening ◽  
Consumer Price Index ◽  
Real Life ◽  
Sensitivity Analyses ◽  
Purchasing Power ◽  
Power Parity ◽  
Hpv Dna ◽  
Hpv Test

Ο καρκίνος του τραχήλου της μήτρας αποτελεί την 7η συχνότερη μορφή καρκίνου στις γυναίκες στην Ελλάδα. Η αποτελεσματική διαχείριση της νόσου βασίζεται στην πρόληψη και δει στον προσυμπτωματικό έλεγχο ο οποίος έως πρόσφατα βασιζόταν στην κυτταρολογική εξέταση. Η σύνδεση του καρκίνου του τραχήλου της μήτρας με τον ιό των ανθρωπίνων θηλωμάτων οδήγησε στην ανάπτυξη της δοκιμασίας HPV DNA, η κλινική αποτελεσματικότητα της οποίας αποδεικνύεται πως υπερέχει της καθιερωμένης πρακτικής της κυτταρολογικής εξέτασης. Παρά την κλινική του υπεροχή η εισαγωγή του σε εθνικά προγράμματα προσυμπτωματικού ελέγχου απαιτεί τον έλεγχο της οικονομικής του αποδοτικότητα καθώς υπό τον περιορισμό των σπανίων πόρων η χρηματοδότησή του οφείλει να μεγιστοποιεί την αξία της επένδυσης. Στο πλαίσιο αυτό, σκοπό της παρούσας διατριβής αποτελεί η διερεύνηση της οικονομικής αποδοτικότητας εναλλακτικών στρατηγικών προσυμπτωματικού. Η προσέγγιση της υπόθεσης εργασίας επιτευχθεί με την ανάπτυξη μαρκοβιανών υποδειγμάτων τα οποία εξέτασαν την αποτελεσματικότητα και το κόστος εννέα εναλλακτικών στρατηγικών προσυμπτωματικού ελέγχου στην Ελλάδα. Οι στρατηγικές ελέγχθηκαν με ενναλακτικές προσεγγίσεις των βασικών παραμέτρων τους όπως η πρωταρχική μέθοδος, το διάστημα επανελέγχου, τα ηλικιακά όρια του πληθυσμού-στόχου και το επίπεδο συμμόρφωσης. Οι αναλύσεις διεξήχθησαν υπό την οπτική του συστήματος υγείας και βασίστηκαν ως επί το πλείστων στην κλινική μελέτη HERMES (HEllenic Real life Multicentric cErvical Screening), για τις κλινικές και επιδημιολογικές παραμέτρους των υποδειγμάτων και σε δεδομένα της κοινωνικής ασφάλισης για τις τιμές των παρεμβάσεων υγείας και των ιατρικών πράξεων. Δεδομένης της απουσίας δεδομένων σχετικά με το κόστος διαχείρισης της νόσου χρησιμοποιήθηκαν ευρωπαϊκά δεδομένα τα οποία μετατράπηκαν σε ελληνικές σχετικές τιμές με την χρήση των Δεικτών Τιμών Καταναλωτή (Consumer Price Index, CPI) ιατροτεχνολογικών υπηρεσιών και προϊόντων και των δεικτών Ισοτιμίας Αγοραστικής Δύναμης (Purchasing Power Parity, PPP). Τέλος, για τον έλεγχο της αξιοπιστίας των αποτελεσμάτων διεξήχθη μια σειρά από ντερμινιστικές (one way sensitivity analyses) και πιθανολογικές αναλύσεις ευαισθησίας (probabilistic sensitivity analyses). Η αποτελεσματικότητα των στρατηγικών προέκυψε ότι μεγιστοποιείται με τις 4 στρατηγικές (HPV test ταυτόχρονη γονοτύπηση, HPV test μετέπειτα γονοτύπηση, συνδυασμός κυτταρολογικής εξέτασης & HPV test μετέπειτα γονοτύπηση, συνδυασμός κυτταρολογικής εξέτασης & HPV test ταυτόχρονη γονοτύπηση,) οι οποίες προσφέρουν HPV test με γονοτύπηση ανά 3 έτη και απευθύνονται σε γυναίκες 25-69 με πλήρη συμμόρφωση στον έλεγχο (100%). Οι στρατηγικές αυτές δύνανται να μειώσουν την επίπτωση της νόσου σε γυναίκες 25-85 ετών κατά 24,5% σε σχέση με την τρέχουσα πρακτική (7,64 περιστατικά/100.000 γυναίκες, 95% CI 7,56 – 7,69 έναντι 10,12, 95% CI 9,99 – 10,26) και κατά 34,9% σε σχέση με της χαμηλότερης αποτελεσματικότητας στρατηγικής HPV test χωρίς γονοτύπηση ανά 5 έτη (11,47, 95% CI 11,30 – 11,61). Ο λόγος κόστους-χρησιμότητας της στρατηγικής με HPV test και ταυτόχρονη γονοτύπηση ανά 3 ή 5 έτη σε σχέση με την τρέχουσα πρακτική εκτιμήθηκε στα 3.918€/QALY και στα –162.843€/QALY, αντίστοιχα, αρκετά χαμηλότερα από το συμβατικό όριο των 52.437€/QALY. Η υιοθέτηση ενός προγράμματος προσυμπτωματικού ελέγχου με HPV test και ταυτόχρονη γονοτύπηση ανά 3 ή 5 έτη για γυναίκες 25-69 ετών αποτελεί μια οικονομικά αποδοτική επιλογή η οποία βελτιώνει τις εκβάσεις υγείας των γυναικών και βελτιστοποιεί την κατανομή των πόρων που επενδύονται στην πρόληψη του καρκίνου του τραχήλου της μήτρας στην Ελλάδα.

HER2 ‐amplified cervical gastric‐type mucinous carcinoma with a primitive enterocyte phenotype

2020 ◽  
Vol 77 (3) ◽  
pp. 511-513
Author(s):  
Masakazu Fujimoto ◽  
Sachiko Minamiguchi ◽  
Ayami Ishida ◽  
Shinji Sumiyoshi ◽  
Naoki Horikawa ◽  
...  
Keyword(s):  
Mucinous Carcinoma ◽  
Gastric Type

scholarly journals Validation of a Human Papillomavirus (HPV) DNA Cervical Screening Test That Provides Expanded HPV Typing

2018 ◽  
Vol 56 (5) ◽  
Author(s):  
Maria Demarco ◽  
Olivia Carter-Pokras ◽  
Noorie Hyun ◽  
Philip E. Castle ◽  
Xin He ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Excellent Agreement ◽  
Cervical Screening ◽  
Weighted Kappa ◽  
Clinical Value ◽  
Becton Dickinson ◽  
Major Question ◽  
Dna Test ◽  
Hpv Dna ◽  
Hpv Test

ABSTRACT As cervical cancer screening shifts from cytology to human papillomavirus (HPV) testing, a major question is the clinical value of identifying individual HPV types. We aimed to validate Onclarity (Becton Dickinson Diagnostics, Sparks, MD), a nine-channel HPV test recently approved by the FDA, by assessing (i) the association of Onclarity types/channels with precancer/cancer; (ii) HPV type/channel agreement between the results of Onclarity and cobas (Roche Molecular Systems, Pleasanton, CA), another FDA-approved test; and (iii) Onclarity typing for all types/channels compared to typing results from a research assay (linear array [LA]; Roche). We compared Onclarity to histopathology, cobas, and LA. We tested a stratified random sample ( n = 9,701) of discarded routine clinical specimens that had tested positive by Hybrid Capture 2 (HC2; Qiagen, Germantown, MD). A subset had already been tested by cobas and LA ( n = 1,965). Cervical histopathology was ascertained from electronic health records. Hierarchical Onclarity channels showed a significant linear association with histological severity. Onclarity and cobas had excellent agreement on partial typing of HPV16, HPV18, and the other 12 types as a pool (sample-weighted kappa value of 0.83); cobas was slightly more sensitive for HPV18 and slightly less sensitive for the pooled high-risk types. Typing by Onclarity showed excellent agreement with types and groups of types identified by LA (kappa values from 0.80 for HPV39/68/35 to 0.97 for HPV16). Onclarity typing results corresponded well to histopathology and to an already validated HPV DNA test and could provide additional clinical typing if such discrimination is determined to be clinically desirable.

Levels of anxiety and distress following receipt of positive screening tests in Australia’s HPV-based cervical screening programme: a cross-sectional survey

2020 ◽  
Vol 96 (3) ◽  
pp. 166-172 ◽  
Author(s):  
Rachael Helen Dodd ◽  
Olivia Mac ◽  
Julia M L Brotherton ◽  
Erin Cvejic ◽  
Kirsten J McCaffery
Keyword(s):  
Online Survey ◽  
Screening Program ◽  
Cervical Screening ◽  
Screening Tests ◽  
Cross Sectional Survey ◽  
Cross Sectional ◽  
General Distress ◽  
Hpv Test ◽  
Hpv Screening ◽  
Test Result

ObjectiveFrom December 2017, the Australian National Cervical Screening Program commenced 5 yearly primary human papillomavirus (HPV) screening; one of the first high-income countries to implement primary HPV screening. This study aimed to examine the psychosocial impact of self-reporting testing HPV positive in a sample of women screened since the renewal of the programme.MethodsWomen in Australia aged 25–74 years who reported participating in cervical screening since December 2017 were recruited through an online market research company to complete a cross-sectional survey. The primary outcomes were anxiety and general distress.Results1004 women completed the online survey; 80.9% reported testing HPV negative (HPV−), 6.5% reported testing HPV positive (HPV+) and 12.9% did not know/remember their test result. Women who reported testing HPV+ had significantly poorer psychological outcomes on a range of measures. Those who reported testing HPV+ had higher anxiety scores (53.03 vs 43.58 out of 80, p<0.001), showed more general distress (3.94 vs 2.52 out of 12, p=0.004), concern about their test result (5.02 vs 2.37, p<0.001), expressed greater distress about their test result (7.06 vs 4.74, p<0.001) and cancer worry (quite or very worried 35.4% vs 11.6%, p<0.001) than women who reported testing HPV−. Concern regarding test results was also significantly higher in women who did not know/remember their test result (3.20 vs 2.37, p<0.001) compared with women who reported testing HPV−. Women who reported testing HPV+ had greater knowledge of HPV (9.25 vs 6.62, p<0.001) and HPV testing (2.44 vs 1.30, p<0.001) than women who reported testing HPV−.ConclusionsReceipt of an HPV+ test result was associated with high levels of anxiety and distress, which reached clinical significance. Further work is needed to understand whether distress and concern could be reduced by ensuring all women receive high-quality standardised information with their results or by other interventions.

Extremely Long Survival under Combined Immunotherapy in a Metastatic Functional Neuroendocrine Neoplasia Patient

2017 ◽  
Vol 106 (4) ◽  
pp. 381-388 ◽  
Author(s):  
Daniel Schmidt ◽  
Bertram Wiedenmann
Keyword(s):  
Advanced Disease ◽  
Residual Disease ◽  
Ki 67 ◽  
Neuroendocrine Neoplasia ◽  
Gastric Type ◽  
Tumor Load ◽  
Stage Ivb ◽  
Multimodality Approach ◽  
Combined Immunotherapy

Treatment and prognosis of neuroendocrine neoplasia depends on tumor size, stage, grade, resectability, and extent of distant metastasis. In most cases a multimodality approach including surgical, locally invasive procedures, peptide-guided radioreceptor therapy (PRRT), and medical therapies represent the mainstay of treatment in advanced disease. In the reported case, a 68-year-old man was diagnosed in 2010 with an initially functional (histamine) neuroendocrine tumor of gastric type III, G2, stage IVB, cT4cN1cM1 (hepatic, peritoneal, nodal, osseous), including a hepatic tumor load of 25%. Intensive multimodality approaches including combined immunotherapy (vaccination and PD-1/CTLA-4 blockade) led to a survival of 8 years until now with a high quality of life and minimal residual disease (only a single, small paragastric recurrence) despite the dedifferentiation of the tumor into a neuroendocrine carcinoma G3 (Ki-67 of 80%) including a nonfunctional stage.

scholarly journals Raman Spectroscopy of Liquid-Based Cervical Smear Samples as a Triage to Stratify Women Who Are HPV-Positive on Screening

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2008
Author(s):  
Damien Traynor ◽  
Cara M. Martin ◽  
Christine White ◽  
Stephen Reynolds ◽  
Tom D’Arcy ◽  
...  
Keyword(s):  
Raman Spectroscopy ◽  
Cervical Screening ◽  
Hpv Infection ◽  
Classification Model ◽  
Cell Nuclei ◽  
Hpv Dna ◽  
Hpv Dna Testing ◽  
Large Numbers ◽  
Hpv Test ◽  
Triage Test

The role of persistent high-risk human papillomavirus (HPV) infection in the development of cervical precancer and cancer is now well accepted, and HPV testing has recently been introduced for primary cervical screening. However, the low specificity of HPV DNA testing can result in large numbers of women with an HPV-positive result, and additional triage approaches are needed to avoid over-referral to colposcopy and overtreatment. The aim of this study was to assess Raman spectroscopy as a potential triage test to discriminate between transient and persistent HPV infection. HPV DNA status and mRNA status were confirmed in ThinPrep® cervical samples (n = 60) using the Cobas 4800 and APTIMA HPV test, respectively. Raman spectra were recorded from single-cell nuclei and subjected to partial least squares discriminant analysis (PLSDA). In addition, the PLSDA classification model was validated using a blinded independent test set (n = 14). Sensitivity of 85% and specificity of 92% were achieved for the classification of transient and persistent HPV infection, and this increased to 90% sensitivity and 100% specificity when mean sample spectra were used instead of individual cellular spectra. This study showed that Raman spectroscopy has potential as a triage test for HPV-positive women to identify persistent HPV infection.

scholarly journals Clinical and Histopathological Features of Early Gastric Cancer With Unclear Lateral Demarcation

2021 ◽  
Author(s):  
Kengo Nagai ◽  
Yoshito Hayashi ◽  
Ryotaro Uema ◽  
Takanori Inoue ◽  
Keiichi Kimura ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Early Gastric Cancer ◽  
Narrow Band Imaging ◽  
Ki 67 ◽  
Histopathological Features ◽  
Gastric Cancers ◽  
Antibody Staining ◽  
Gastric Phenotype ◽  
History Of ◽  
Superficial Epithelium

Abstract Background Magnifying-endoscopy with narrow band imaging (M-NBI) is useful to determine lateral demarcation of early gastric cancers, but determining the lateral demarcation is sometimes difficult. Features related to the unclear lateral demarcation remain unknown. We evaluated the clinical and histopathological features of early gastric cancers with unclear lateral demarcation by M-NBI. Methods This single-center retrospective cohort study analyzed early gastric cancer treated by endoscopic submucosal dissection (ESD) from January 2013 to August 2015. We evaluated clinicopathological and immunohistochemical features using anti-p53, -Ki-67, -MUC5AC, -MUC6, -MUC2, and -CD10 antibody staining. We compared the lateral demarcation between the demarcation clear (DC) and demarcation unclear (DU) lesions by using M-NBI. Results A total of 224 differentiated adenocarcinomas (DU group: 18 lesions; DC group: 206 lesions) were analyzed. The history of successful Helicobacter pylori eradication was significantly more frequent in the DU group (p = 0.001). We examined tissues of 72 lesions immunohistochemically, including 18 lesions in the DU group and 54 randomly selected lesions in the DC group. Non-neoplastic superficial epithelium is more frequently observed in the DU group (p = 0.0058). Additionally, the DU group showed a significantly higher expression of gastric phenotype marker (p = 0.023), lower p53 score (p = 0.0002), and lower Ki-67 labeling index (p = 0.0293). The non-neoplastic superficial epithelium and low p53 score were significant independent variables associated with unclear lateral demarcation by M-NBI in the multivariate analysis. Conclusions Non-neoplastic superficial epithelium and low p53 score were associated with the difficultly in determining lateral demarcation in early gastric cancers by M-NBI.

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