Matthias Jentschke

Evaluation of a multiplex real time PCR assay for the detection of human papillomavirus infections on self-collected cervicovaginal lavage samples.

Self-collection of cervical samples for human papillomavirus (HPV) testing can help to raise the participation rate in cervical cancer screening among non-responders. This study was conducted to compare the analytical and clinical performance of the Abbott RealTime High-Risk HPV Test (RealTime) with the Hybrid Capture 2 assay (HC2) on self-collected cervicovaginal lavage samples. One hundred samples from women referred for colposcopy (reference smears and biopsies in case of abnormalities) were included. Fifty-seven women had a normal cytology, 27 had low grade and 16 had high grade squamous intraepithelial lesions. Fourteen of 49 biopsies (28.6%) were benign, 14 (28.6%) cervical intraepithelial neoplasia 1, 11 (22.4%) cervical intraepithelial neoplasia 2, 8 (16.3%) cervical intraepithelial neoplasia 3 and 2 (4.1%) invasive cancer. The agreement between RealTime and HC2 in the self-collected and in the reference samples was 85% (κ=0.665) and 83% (κ=0.620), respectively. The agreement between self-sampling and the reference smears was higher with RealTime (93%; κ=0.849) than with HC2 (89%; κ=0.741). In the self-collected samples, the sensitivity and specificity for cervical intraepithelial neoplasia 2 or worse of RealTime/HC2 were 81.0%/66.7% (p=0.25) and 53.6%/57.1%, respectively. The sensitivity for cervical intraepithelial neoplasia 3 or worse of RealTime and HC2 were 80.0% and 70.0% (p=1.0). The specificity for cervical intraepithelial neoplasia 3 or worse was 43.6% (RealTime) and 51.3% (HC2). This study shows that RealTime can be used for HR-HPV testing of self-collected lavage samples in a referral population with at least equal quality and performance as HC2.

Direct comparison of two vaginal self-sampling devices for the detection of human papillomavirus infections

BACKGROUND AND OBJECTIVES Two devices for vaginal self-sampling of dry cell material (Evalyn Brush, Rovers Medical Devices; Qvintip, Aprovix) were compared using the Abbott RealTime High Risk HPV test. STUDY DESIGN Both self-sampling devices (change of order with every patient) including instructions for use and a questionnaire were handed to 146 patients in a colposcopy clinic prior to scheduled colposcopies with collection of cervical reference specimens by gynaecologists using a broom-like device. Matched self-collected and physician collected specimens were transferred to ThinPrep medium and tested for the presence of hr-HPV. Biopsies were taken if indicated by colposcopy. RESULTS Evaluation of 136 patients with complete data (136/146; 93.2%) showed high agreement of overall hr-HPV detection rates between self-collected and clinician-collected specimens (Evalyn: 91.2% [kappa 0.822]; Qvintip: 89.0% [kappa 0.779]). Colposcopy and histological evaluation revealed 55 women without cervical intraepithelial neoplasia (CIN), 32 CIN1, 34 CIN2, 14 CIN3 and one adenocarcinoma in situ. Hr-HPV testing detected all CIN3+ cases on the clinician-taken or Evalyn self-samples (14/14) and 93% of them on the Qvintip samples (13/14). There was no significant difference regarding the sensitivity for CIN2+ or CIN3+ and specificity of hr-HPV testing on self- vs. clinician samples and on Evalyn vs. Qvintip. Based on signal intensities of β-globin, the observed DNA concentration with Evalyn samples (mean CN: 22.0; 95%-CI: 21.5-22.6) was found to be significantly higher compared to that of Qvintip samples (mean CN: 23.8; 95%-CI 23.2-24.4), regardless of the order of self-sampling (p<0.0001). Most women considered self-sampling easy and comfortable. Qvintip was considered easier than the Evalyn Brush to understand (p<0.001) and to use (p=0.002). DISCUSSION This study confirms that hr-HPV testing with a clinically validated PCR-based HPV assay is as accurate on self-samples as on clinician-samples without significant difference between both self-sampling devices.

Enzyme‐linked immunosorbent assay for p16INK4a– a new triage test for the detection of cervical intraepithelial neoplasia?

Objective. To evaluate enzyme‐linked immunosorbent assay (ELISA) for cyclin‐dependent kinase inhibitor 2A protein (p16INK4a) on self‐collected cervicovaginal lavage samples as an additional triage test to identify women with high‐grade cervical intraepithelial neoplasia (CIN). Design. Retrospective feasibility, sensitivity and specificity study. Setting. University Medical School, Germany. Sample. One hundred and fifty‐two patients from the colposcopy clinic were included. Methods. All women used a cervico‐vaginal lavage device (Delphi Screener) for self‐sampling and had gynecological examinations with Pap smears, cervical smears in ThinPrep PreservCyt solution and Cervatec medium for human papillomavirus (HPV) testing (Qiagen Hybrid Capture 2) and colposcopic examinations with biopsies if abnormalities were detected (72 women; 51%). All cytological samples were examined by p16INK4a ELISA. Main outcome measures. Sensitivity and specificity of p16INK4a ELISA for high‐grade CIN. Results. Complete data were available for 140 women. Among these, 62 women (46%) presented with an atypical Pap smear and 65 (46.4%) were high‐risk HPV positive in the reference smear sample. Seventeen women (12%) had CIN 3+. Twenty‐seven (19%) physician‐collected samples were p16INK4a ELISA positive. In contrast, p16INK4a ELISA turned out to be positive in only one (1%) vaginal lavage sample. Conclusions. Our study shows that self‐sampling with cervicovaginal lavage followed by p16INK4a ELISA is not suitable for the detection of high‐grade CIN.

WITHDRAWN: Comparative evaluation of two vaginal self-sampling devices for the detection of human papillomavirus infections

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Application of sentinel lymph node dissection in gynecological cancers: results of a survey among German hospitals

PurposeEvaluating the application of the sentinel lymph node dissection (SLND) in gynecological cancers among German hospitals.MethodsBetween March and June 2016 an online questionnaire on SLND in gynecologic cancers was sent by email to all German gynecologic cancer centers, all university hospitals and general hospitals for which an email address was available. The survey contained 61 questions regarding the SLND in vulvar, cervical, endometrial and ovarian cancer.ResultsIn total, 63 clinics, including 13 (20.6%) university hospitals, 28 (44.4%) hospitals offering maximum care and 22 (34.9%) general hospitals, responded to the questionnaire. Most clinics (46/63, 73%) performed SLND in vulvar cancer with a median amount of 7.8 (range 1–43) SLND per year. 56.5% of the clinics included patients according to the German national guidelines and performed ultrastaging of negative SLN. Furthermore, 18/63 (28.5%) of the responding clinics applied SLND in cervical cancer including 7 (77.8%) centers which conducted isolated SLND without radical pelvic lymph node dissection (LND). Preoperative imaging with planar lymphoscintigraphy (LSG) was applied in 12/18 (66.7%) of the clinics. SLND in endometrial cancer was reported by 4/63 (6.4%) hospitals. Three of them (75%) regularly performed a subsequent radical pelvic LND. One clinic (1.5%) reported SLND in ovarian cancer in combination with radical LND.ConclusionEspecially in vulvar and cervical cancer, isolated SLND appears to be partially implemented in the routine surgical treatment. However, this survey illustrates a wide heterogeneity regarding inclusion criteria and application of the SLND approach.

Excellent analytical and clinical performance of a dry self‐sampling device for human papillomavirus detection in an urban Chinese referral population

To evaluate the analytical and clinical effectiveness of cervicovaginal self‐sampling with a dry sampling device (Evalyn Brush) for high‐risk human papillomavirus (hr‐HPV) testing and detection of cervical disease.

Sentinel lymphonodectomy in early vaginal cancer using combined near infrared fluorescence from indocyanine green and technetium-99m nanocolloid – a first case report

Nowadays, sentinel diagnostic is been made with technetium-99m-(Tc-99m)-nanocolloide as a radioactive marker and sometimes patent blue. In the last years, indocyanin green has been evaluated for sentinel diagnostic in different tumor entities. Indocyane greene is a fluorescent molecule which emits a light signal in the near infrared band after excitation. Our study aims to evaluate indocyanin green compared to the gold standard Tc-99m-nanocolloid. We report over a patient with an unifocal vaginal cancer. Sentinel diagnostic was carried out using Tc-99m-nanocolloid, indocyanin green and patent blue. After SPECT/CT, we examined each groin for light signals from the near infrared band, for radioactivity and for blue staining. A sentinel lymph node was defined as a Tc99m-nanocolloide positive lymph node. All sentinel lymph nodes and all additional blue or fluorescent lymph nodes were excised and tested; then sent to histologic examination. The procedure could be accomplished without problems. We found four sentinel lymph nodes with indocyanin green fluorescence, which were positive for radioactivity from Tc-99m and therefore defined as sentinel lymph nodes. Two further lymph nodes, which showed positivity for indocyanin green signals, but not for Tc-99m were found in the left groin. The final tumor stage was pT1b, pN0 (0/6, 0/4 SLN). We saw no adverse events or complications in this patient. Our case report shows that near infrared fluorescence deriving from ICG is a promising approach for sentinel identification in vaginal cancer. If studies using sentinel lymphonodectomy will be planned, a combined approach using Tc-99m-nanocolloide and indocyanin green could be useful. Correspondence to: Philipp Soergel, MD, MHBA, Department of Obstetrics and Gynecology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany; Tel: 0049 511 532 6144; Fax: 0049 511 532 6145; E-mail: soergel.philipp@mh-hannover.de