HrHPV testing vs liquid-based cytology in cervical cancer screening among women aged 50 and older: a prospective study.

INTRODUCTION: Evidence supports high-risk human papilloma virus (HPV) testing as the primary cervical cancer screening tool. However, benefits and harms should be carefully considered before replacing liquid-based cytology. In women age 50 and older, we evaluated how a commercially available DNA amplification HPV test compares with routine liquid-based cytology. METHODS: This prospective study included 4043 patients who had a cervical sample analyzed from September 2011 to September 2012. Patients were followed between 64 and 76 months (median: 70 months). Samples were analyzed using both liquid-based cytology and the Cobas 4800 HPV DNA test. We calculated the diagnostic efficacy of liquid-based cytology and HPV, with or without the opposite test as triage, using cervical intraepithelial neoplasia (CIN2+/CIN3+) as reference. RESULTS: The patients had a median age of 58 years, (range; 50-90). At baseline, HPV prevalence was 8.0%: a total of 3.7% of patients had atypical squamous cells of undetermined significance or worse (ASCUS+). Positive test results were 1.9% for liquid-based cytology with HPV triage and 3.0% for HPV with liquid-based cytology triage. The cumulative incidence of CIN3+ was 1.0% (40/4043). Sensitivities for CIN3+ were: liquid-based cytology 47.5% (31.5%-63.9%); liquid-based cytology with HPV triage 45.0% (29.3%-61.5%); HPV 90.0% (76.3%-97.2%); and HPV with liquid-based cytology triage 67.5% (50.9%-81.4%). Corresponding specificities were: liquid-based cytology 96.6% (96.0%-97.2%); liquid-based cytology with HPV triage 98.5% (98.0%-98.8%); HPV 92.8% (92.0%-93.6%); and HPV with liquid-based cytology triage 97.7% (97.2%-98.1%). At baseline, HPV testing overlooked five cases of gynecological cancer other than cervical cancer. Five cervical cancers were detected, two had been overlooked at baseline by liquid-based cytology and two by HPV testing CONCLUSION: HPV screening using DNA amplification is a promising alternative to liquid-based cytology in women age 50 and older, but evaluation of alternative triage methods is warranted. The risk of overlooking cancers needs consideration when replacing liquid-based cytology with HPV testing as a method for primary screening.

The influence of total hysterectomy in a cervical cancer screening population: a register-based cross-sectional study.

BACKGROUND: High coverage of a screening program is essential to program success. Many European screening programs cover only 10-80% of their target population. A possible explanation for the low coverage may be that some women in the screening population have had a total hysterectomy, thus they are not at risk of cervical cancer. The aim of this study was to identify the prevalence of hysterectomy in the target population of the Danish National Cervical Cancer Screening Program (NCCSP) and to recalculate coverage after excluding women with total hysterectomy. Furthermore, to analyze the association between hysterectomy and sociodemographic factors within the screening population. METHODS: A population-based cross-sectional study using register data on all women in the target population of the NCCSP on January 12, 2012 (women born January 12, 1947, to January 12, 1986). The total coverage included women with hysterectomy in the target population whereas the recalculated coverage was calculated excluding women with total hysterectomy. To test the differences between the total coverage and the recalculated coverage, a two-sample z-test between the proportion of covered hysterectomized women and the proportion of covered non-hysterectomised women were used. A logistic regression model adjusted for age and sociodemographic characteristics was used to analyze the association between sociodemographic factors and total hysterectomy. RESULTS: The coverage among women aged 26-49 years and 55-64 years were 77.4% and 72.7%, respectively. The recalculated coverage was 78.2% (26-49 years) and 79.4% (55-64 years). Recalculating the coverage did not result in coverage higher than 82.7% at any age. The effect of excluding women with total hysterectomy increased with age, reaching its maximum of 8 % points for the oldest women. Women with higher socioeconomic status (higher education and higher disposable income) had lower odds of being hysterectomized compared to other women. Also, immigrants and descendants had lower odds of being hysterectomized compared to ethnic Danes. CONCLUSIONS: Excluding women with total hysterectomy only partly explained the low coverage of the NCCSP. Thus, initiatives must be made to improve acceptability of and accessibility to the NCCSP, especially in the youngest and the oldest women.

Risk of deep vein thrombosis and pulmonary embolism after gynecological day surgery.

OBJECTIVE: To investigate the risk of venous thromboembolism (VTE) in Danish women operated within a day surgery setting and to evaluate whether the current use of thromboprophylaxis without using graduated elastic compression stockings (GCS) is an appropriate treatment to prevent VTE. STUDY DESIGN: A retrospective cohort study including women who underwent laparoscopic hysterectomy or vaginal prolapse operation for benign disease from January 2014 to December 2017 at the Gynecology Day Surgery Unit, Regional Hospital of Randers, Denmark. The primary outcome was VTE diagnosed within three months postoperatively. Only one dose of pharmacological thromboprophylaxis (PTP) was given to women stratified at high risk of VTE. None of the women used GCS. RESULTS: A total of 671 women were included. Vaginal prolapse operations were performed on 626 women, and laparoscopic hysterectomy on 45 women. PTP was used for only 220 (32.8%) of these women. A total of 346 (51.5%) women were stratified as at high risk of VTE according to the national recommendations. Only 218 (63%) of these women received PTP, while 128 women (37%) did not receive PTP. The incidence of VTE within three months postoperatively was 0%. Only 13 (1.9%) of the women were readmitted within 14 days postoperatively due to hemorrhaging or hematoma; six out of these 13 women (46%) received PTP postoperatively. Re-operation was performed in seven (1%) women due to hemorrhaging, and three out of the seven (42.9%) had PTP postoperatively. CONCLUSION: The risk of VTE in Danish women operated within a day surgery setting is probably very low since we found no cases of VTE in our setup. The beneficial effect of routine use of GCS and one dose of PTP postoperatively given to all women who had undergone MIS in a day surgery setting are questioned. One dose of PTP postoperatively without GCS can be considered to only women stratified as high-risk of VTE until there is more evidence whether these women actually need thromboprophylaxis postoperatively at all. PRECIS: The incidence of VTE in women undergoing laparoscopic hysterectomy or vaginal prolapse operation in a day surgery setting without using graduated elastic compression stockings is very low.

Mutant epidermal growth factor receptor in benign, borderline, and malignant ovarian tumors.

PURPOSE: Dysfunction of the epidermal growth factor (EGF) complex is essential to the growth and development of many human tumors. Overexpression of the EGF receptor (EGFR) is a characteristic finding in a considerable number of solid tumors and often signalizes poor prognosis. There is a major disagreement among researchers about both the frequency and possible clinical importance of EGFR overexpression in ovarian cancer. The type III variant of EGFR (EGFRvIII) is a mutant with a deletion. Contrary to the wild-type, it is constitutively active. EGFRvIII has not been found in normal tissue, and consequently, it is an attractive tumor-specific candidate for molecular targeted treatment. The literature dealing with this mutation in ovarian cancer has been very sparse. EXPERIMENTAL DESIGN: Tissue from 225 patients who underwent surgery for a pelvic mass was collected consecutively. The samples included 99 ovarian/peritoneal/tuba cancers, 17 ovarian borderline tumors, 66 benign ovarian tumors, 15 other cancer types, 24 normal ovarian biopsies, and 4 miscellaneous. The presence of EGFRvIII was investigated both by PCR analyses for EGFRvIII gene expression and with protein analysis by Western blots. RESULTS: None of the tissue samples was positive for the EGFRvIII mutation neither at the mRNA level nor at the protein level. CONCLUSIONS: The EGFRvIII mutation seems to be very rare in ovarian tissue. Our data indicate that EGFRvIII is not a part of the malignant phenotype in ovarian cancer and should not be pursued as a therapeutic target for treatment of this disease.

Validation of epithelial ovarian cancer and fallopian tube cancer and ovarian borderline tumor data in the Danish Gynecological Cancer Database.

OBJECTIVE: To validate the data on epithelial ovarian cancer, fallopian tube cancer and borderline ovarian tumors registered in the nationwide Danish Gynecological Cancer Database (DGCD) in 2005 and 2006. The DGCD is a multidisciplinary database that contains data for research and quality improvement. DESIGN: Comparative registry-based study supplemented with data from medical records. SETTING: Six hospitals in Denmark. PARTICIPANTS: Women registered with epithelial ovarian cancer, fallopian tube cancer and borderline ovarian tumor. MAIN OUTCOME MEASURE: Data completeness and strength of agreement. RESULTS: The estimated completeness of reporting to the DGCD was 94.2% and the strength of agreement between the variables in the DGCD and the medical file varied from moderate to very good. The important quality indicator 'complication' had the lowest strength of agreement. CONCLUSION: The validity of ovarian cancer data in the DGCD is sufficient for quality monitoring in gynecological oncology.

Protein levels and gene expressions of the epidermal growth factor receptors, HER1, HER2, HER3 and HER4 in benign and malignant ovarian tumors.

The epidermal growth factor receptors, HER1, HER2, HER3 and HER4 play a key role in the growth of malignant tumors. The receptors of the EGF receptor family are not cancer-specific proteins since these receptors are expressed to some extent in both normal and benign tissue, but this is not elucidated in detail in ovarian tissue. High tumor-to-normal-tissue concentration ratios would be favorable for molecular targeted anti-cancer treatment. The primary aim of the study was to analyze the potential differential protein content and gene expression of the four receptors in benign and malignant ovarian tumors. Tissue from 207 patients (101 malignant, 19 borderline, 64 benign ovarian tumors and 23 normal ovaries) were analyzed by quantitative ELISA for HER1-HER4 protein concentrations and by real-time PCR for HER1-HER4 gene expression. HER2 was also analyzed by immunohistochemistry. The HER2-4 receptor protein content and the median gene expression level was significantly higher in ovarian cancer patients compared to patients with benign ovarian tumors and normal ovaries (p<0.0000001). The protein content of the HER1 receptor was significantly lower in ovarian cancer compared to borderline tumors (p=0.012), benign ovarian tumors (p=0.049) and to normal ovaries (p=0.000069). A sound correlation between the protein levels and gene expressions was documented. In conclusion, decreased concentration of HER1 protein and increased HER2, HER3 and HER4 protein concentration were observed, as also elevated HER2-HER4 gene expression levels in ovarian cancer patients with barely any overlap of the HER3 and HER4 expression in malignant ovarian tumors compared to benign ovarian tissues.

[Uterine rupture without preexisting caesarean section after perforation of the uterus during evacuation]. / Uterusruptur uden forudgående kejsersnit ti år efter perforation i forbindelse med udskrabning.

Uterine rupture is a serious complication, associated with perinatal and maternal morbidity and mortality. This case report describes uterine rupture in a patient who did not have any previous caesarean section. The patient had acute abdominal pain, hypertonic uterus, blood in the amniotic fluid and abnormal cardiotocographic values. An abruption of the placenta was suspected, and an acute caesarean section was performed during which a rupture in fundus uteri was found. It was later experienced that the patient ten years earlier had suffered a uterine perforation during evacuation after a late abortion.

[Limited evidence of the effect of prophylactic pelvic floor training on genital prolapse]. / Begrænset evidens for effekt af forebyggende bækkenbundstræning på udvikling af genital prolaps.

A growing number of women are bothered by genital prolapse. The treatment of genital prolapse includes pelvic floor exercise in variable extent, but only few data are published. Variations in interventions, follow-up time, outcome etc. complicates a comparison. Because of the very limited material it is difficult to conclude if pelvic floor exercises have any effect on genital prolapse. There is need for studies concerning the clinical relevance and a cost-benefit analysis.