Human papillomavirus E7 protein detection as a method of triage to colposcopy of HPV positive women, in comparison to genotyping and cytology. Final results of the PIPAVIR study.

The objective of the presented cross-sectional-evaluation-screening study is the clinical evaluation of high-risk(hr)HPVE7-protein detection as a triage method to colposcopy for hrHPV-positive women, using a newly developed sandwich-ELISA-assay. Between 2013-2015, 2424 women, 30-60 years old, were recruited at the Hippokratio Hospital, Thessaloniki/Greece and the Im Mare Klinikum, Kiel/Germany, and provided a cervical sample used for Liquid Based Cytology, HPV DNA genotyping, and E7 detection using five different E7-assays: "recomWell HPV16/18/45KJhigh", "recomWell HPV16/18/45KJlow", "recomWell HPV39/51/56/59", "recomWell HPV16/31/33/35/52/58" and "recomWell HPVHRscreen" (for 16,18,31,33,35,39,45,51,52,56,58,59 E7), corresponding to different combinations of hrHPVE7-proteins. Among 1473 women with eligible samples, those positive for cytology (ASCUS+ 7.2%), and/or hrHPV DNA (19.1%) were referred for colposcopy. Cervical Intraepithelial Neoplasia grade 2 or worse (CIN2+) was detected in 27 women (1.8%). For HPV16/18-positive women with no triage, sensitivity, positive predictive value (PPV) and the number of colposcopies needed to detect one case of CIN2+ were 100.0%, 11.11% and 9.0 respectively. The respective values for E7-testing as a triage method to colposcopy ranged from 75.0-100.0%, 16.86-26.08% and 3.83-5.93. Sensitivity and PPV for cytology as triage for hrHPV(non16/18)-positive women were 45.45% and 27.77%; for E7 test the respective values ranged from 72.72-100.0% and 16.32-25.0%. Triage of HPV 16/18-positive women to colposcopy with the E7 test presents better performance than no triage, decreasing the number of colposcopies needed to detect one CIN2+. In addition, triage of hrHPV(non16/18)-positive women with E7 test presents better sensitivity and slightly worse PPV than cytology, a fact that advocates for a full molecular screening approach.

Diagnostic accuracy of high-risk HPV DNA genotyping for primary cervical cancer screening and triage of HPV-positive women, compared to cytology: preliminary results of the PIPAVIR study.

PURPOSE: The purpose of the presented PIPAVIR (persistent infections with human papillomaviruses; http://www.pipavir.com ) subanalysis is to assess the performance of high-risk (hr) HPV-DNA genotyping as a method of primary cervical cancer screening and triage of HPV positive women to colposcopy compared to liquid-based cytology (LBC) in an urban female population. METHODS: Women, aged 30-60, provided cervicovaginal samples at the Family-Planning Centre, Hippokratio Hospital of Thessaloniki, Greece, and the Department of Gynecology and Obstetrics in Mare Klinikum, Kiel, Germany. Cytology and HPV genotyping was performed using LBC and HPV Multiplex Genotyping (MPG), respectively. Women positive for cytology [atypical squamous cells of undetermined significance (ASC-US) or worse] or hrHPV were referred for colposcopy. RESULTS: Among 1723/1762 women included in the final analysis, hrHPV and HPV16/18 prevalence was 17.7 and 9.6%, respectively. Cytology was ASCUS or worse in 7.6%. Cervical Intraepithelial Neoplasia grade 2 or worse (CIN2+) was detected in 28 women (1.6%). Sensitivity of cytology (ASCUS or worse) and HPV DNA testing for the detection of CIN2+ was 50.0 and 100%, and specificity was 94.49 and 85.49%, respectively. The screening approach according to which only women positive for HPV16/18 and for hrHPV(non16/18) with ASCUS or worse were referred to colposcopy presented 78.57% sensitivity and 13.17% positive predictive value (PPV). CONCLUSIONS: HPV testing represents a more sensitive methodology for primary cervical cancer screening compared to cytology. For triage of HPV positive women to colposcopy, partial HPV genotyping offers better sensitivity than cytology, at the cost of higher number of colposcopies.

Primary primitive neuroectodermal tumor of the cervix confirmed with molecular analysis in a 23-year-old woman: A case report.

Primitive Neuroectodermal Tumor (PNET) of the genital tract is very rare, especially in the cervix. A case report of a young woman with a diagnosis of PNET originating from the uterine cervix is presented here. A 23-year-old woman presented with abnormal uterine bleeding and sharp lower abdominal pain of two months duration. CT and MRI of the abdomen and thorax revealed the presence of a large mass in the uterine cervix, enlarged pelvic lymph nodes and broncho-pulmonary infiltrations with regional nodes. Pathological examination of the tumor revealed a malignant neoplasm composed predominantly of small cells, immunohistochemically positive for CD99, vimentin and c-Kit. Molecular testing demonstrated the expression of EWS/FLI1 fusion transcripts corresponding to the t(11;22)(q24;q12) translocation, which confirmed the diagnosis of PNET of the uterine cervix. Despite surgical excision and administration of the first cycle of adjuvant chemotherapy, the patient died from multiple-organ failure and cardiac arrest. PNET arising from the genital tract, especially in the uterine cervix, is very rare and presents a diagnostic challenge. A timely confirmation with molecular analysis is essential for the diagnosis of such a tumor at an unusual site as in the present case.

Idiopathic spontaneous haemoperitoneum due to a ruptured middle colic artery aneurysm.

INTRODUCTION: Idiopathic spontaneous intra-abdominal haemorrhage is a rare, but challenging condition, associated with high mortality if not managed appropriately. The preoperative diagnosis is difficult, despite the recent advances in imaging. We present the clinical manifestations of this condition, as well as the available diagnostic and therapeutic modalities. PRESENTATION OF CASE: We report a case of a spontaneously ruptured dissecting aneurysm of the middle colic artery, which was managed with an emergency laparotomy and aneurysmatectomy. Interestingly, no evidence of vasculitis, infection or collagen disease was discovered during the histopathology examination of the specimen. DISCUSSION: The treatment of idiopathic spontaneous intra-abdominal haemorrhage revolves around patient resuscitation and management of the source of bleeding. In case of a ruptured aneurysm of the middle colic artery, the surgical management includes emergency laparotomy, arterial ligation and resection of the aneurysm. Transarterial embolisation has been suggested as a safe and less invasive alternative approach. CONCLUSION: A ruptured middle colic artery aneurysm should be included in the differential diagnosis of any unexplained intra-abdominal haemorrhage. Aneurysmatectomy is the treatment of choice, with radiologic interventional techniques gaining ground in the management of this entity.