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Schmidt D.,Institute of Pathology | Bergeron C.,Laboratoire Cerba | Denton K.J.,North Bristol NHS Trust | Ridder R.,MTM Laboratories
Cancer Cytopathology | Year: 2011

BACKGROUND: The objective of this study was to analyze the diagnostic performance of a newly established immunocytochemical dual-stain protocol, which simultaneously detects p16INK4a and Ki-67 expression in cervical cytology samples, for identifying high-grade cervical intraepithelial neoplasia (CIN2+) in women with Papanicolaou (Pap) cytology results categorized as atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesions (LSIL). METHODS: Residual liquidbased cytology material from 776 retrospectively collected ASCUS/LSIL cases that were available from a recent study evaluating p16 cytology and HPV testing were subjected to p16/Ki-67 dual staining. The presence of 1 or more double-immunoreactive cell(s) was regarded as a positive test outcome, irrespective of morphology. Test results were correlated to histology follow-up. RESULTS: Sensitivity of p16/Ki-67 dualstain cytology for biopsy-confirmed CIN2+ was 92.2% (ASCUS) and 94.2% (LSIL), while specificity rates were 80.6% (ASCUS) and 68.0% (LSIL), respectively. Similar sensitivity/specificity profiles were found for both age groups of women aged <30 years versus women aged ≥30 years. Dual-stain cytology showed comparable sensitivity, but significantly higher specificity, when compared with human papillomavirus (HPV) testing. CONCLUSIONS: The results of this study show that p16/Ki-67 dual-stain cytology provided a high sensitivity for the detection of underlying CIN2+ in women with ASCUS or LSIL Pap cytology results, comparable to the rates previously reported for HPV testing and p16 single-stain cytology. However, the specificity of this morphology-independent interpretation of p16/Ki-67 dual-stain cytology testing was further improved compared with the earlier p16 single-stain cytology approach, which required morphology interpretation, and it is significantly higher when compared with HPV testing. Cancer (Cancer Cytopathol) 2011;119:158-66. © 2011 American Cancer Society. Source


Ikenberg H.,CytoMol | Bergeron C.,Laboratoire Cerba | Schmidt D.,Institute for Pathology | Griesser H.,Cytodiagnostics | And 13 more authors.
Journal of the National Cancer Institute | Year: 2013

Background: Pap cytology is known to be more specific but less sensitive than testing for human papillomavirus (HPV) for the detection of high-grade cervical intraepithelial neoplasia (CIN2+). We assessed whether p16/Ki-67 dual-stained cytology, a biomarker combination indicative of transforming HPV infections, can provide high sensitivity for CIN2+ in screening while maintaining high specificity. Results were compared with Pap cytology and HPV testing. Methods: A total of 27349 women 18 years or older attending routine cervical cancer screening were prospectively enrolled in five European countries. Pap cytology, p16/Ki-67 immunostaining, and HPV testing were performed on all women. Positive test results triggered colposcopy referral, except for women younger than 30 years with only positive HPV test results. Presence of CIN2+ on adjudicated histology was used as the reference standard. Two-sided bias-corrected McNemar P values were determined. Results: The p16/Ki-67 dual-stained cytology positivity rates were comparable with the prevalence of abnormal Pap cytology results and less than 50% of the positivity rates observed for HPV testing. In women of all ages, dual-stained cytology was more sensitive than Pap cytology (86.7% vs 68.5%; P <. 001) for detecting CIN2+, with comparable specificity (95.2% vs 95.4%; P =. 15). The relative performance of the tests was similar in both groups of women: younger than age 30 and 30 years or older. HPV testing in women 30 years or older was more sensitive than dual-stained cytology (93.3% vs 84.7%; P =. 03) but less specific (93.0% vs 96.2%; P <. 001). Conclusions: The p16/Ki-67 dual-stained cytology combines superior sensitivity and noninferior specificity over Pap cytology for detecting CIN2+. It suggests a potential role of dual-stained cytology in screening, especially in younger women where HPV testing has its limitations. © The Author 2013. Published by Oxford University Press. Source


Petry K.U.,Klinikum der Stadt Wolfsburg | Schmidt D.,Institute of Pathology | Scherbring S.,Klinikum der Stadt Wolfsburg | Luyten A.,Klinikum der Stadt Wolfsburg | And 7 more authors.
Gynecologic Oncology | Year: 2011

Objective: Testing for human papillomavirus (HPV) has been shown to increase the sensitivity and negative predictive value for detection of high-grade cervical intraepithelial neoplasia (CIN2+), either when used in conjunction with Pap cytology testing or alone. However, there is no satisfying clinical management algorithm for women testing Pap negative/HPV positive. We therefore evaluated the clinical utility of a novel dual biomarker-based approach (p16/Ki-67 Dual-stained cytology) for the identification of CIN2+ in women with Pap negative/HPV positive screening results, without the need to refer all women to immediate colposcopy. Methods: All women aged ≥ 30 enrolled during 2007/2008 into a regional prospective Pap/HPV co-testing screening pilot project and tested Pap negative, but positive for HPV (n = 425) were included in the analysis. p16/Ki-67 Dual-stained cytology was performed from residual cellular material available from the liquid-based cytology vial collected during the initial Pap/HPV co-testing screening visit. Results were correlated to the presence of CIN2+ confirmed during preliminary follow-up. Results: p16/Ki-67 Dual-stained cytology tested positive at baseline in 108 out of 425 (25.4%) Pap negative/HPV positive cases. Sensitivity of Dual-stain testing for the detection of biopsy-confirmed CIN2+ during preliminary follow-up within the group of Pap negative/HPV positive women was 91.9% for CIN2+ (34/37 cases), and 96.4% for CIN3+ (27/28 cases). Specificity was 82.1% for CIN2+ on biopsy, and 76.9% for CIN3+, respectively. Conclusions: Triaging Pap negative/HPV positive screening test results with p16/Ki-67 Dual-stained cytology may identify women with a high probability of underlying CIN2+ and may efficiently complement HPV-based screening programs to prevent cervical cancer. © 2011 Elsevier Inc. Source


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2011.2.4.1-3 | Award Amount: 4.19M | Year: 2011

Human papillomavirus (HPV) is responsible for approximately 25% of head and neck cancer (HNC) worldwide and appears to be associated with a better response to treatment and improved prognosis. Evidence suggests that HPV-induced HNC has steadily increased in the USA and some European countries in the last decades. However, whether this is a worldwide phenomenon and specific risk factors are associated with it remains to be proven. In addition, little is known on the natural history and risk factors of oral HPV infection. HPV-AHEAD network aims to address these and other unanswered questions on HNC etiology and epidemiology with a focus on the role of HPV. We will assemble and analyze a large collection of plasma/sera and HNC tissues from 42 centres in 16 European countries as well as HNC tissues from 7 Indian centres together with epidemiological and clinical data. HPV status in human specimens will be evaluated by different assays in central laboratories. Epidemiological studies will be conducted to establish the overall proportion and type distribution of HPV-positive HNC at different anatomical sites in European and Indian regions as well as the time trend of the proportion of HPV-positive HNC in recent decades. Using the follow-up information on HNC patients, we will further investigate whether HPV positivity confers a better prognosis and survival. We will also conduct a study in HPV-vaccinated and non-vaccinated women in order to determine risk factors and natural history of oral HPV infections. In addition, we will search for new surrogate markers for oral HPV infection to facilitate novel screening strategies. Finally, the HPV-AHEAD consortium aims to transfer technology to Indian centres as well as to develop several strategies for the training of European and Indian researchers in infections and cancers. This study will provide important insights for the screening, diagnosis, treatment and prophylaxis of HPV-associated HNC in Europe, India and elsewhere.


The present invention relates to a method for discrimination of p16

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