Clinical course of cervical intraepithelial neoplasia grade 2: a population-based cohort study.

BACKGROUND: Cervical intraepithelial neoplasia grade 2 has historically been the threshold for surgical excision, but because of high regression rates, many countries are transitioning to active surveillance. However, estimates for regression rates are based on small studies with heterogeneous definitions of regression and progression. OBJECTIVE: This study aimed to describe regression and progression rates of cervical intraepithelial neoplasia grade 2 using nationwide healthcare registry data. STUDY DESIGN: This was a nationwide population-based cohort study on women aged 18 to 40 years who had undergone active surveillance for cervical intraepithelial neoplasia grade 2 in Denmark from 1998 to 2020. This study excluded women with a previous record of cervical intraepithelial neoplasia grade 2 or worse or surgical excision. Cumulative incidence functions were used to estimate the rates of regression and progression at 6, 12, 18, and 24 months after diagnosis. In addition, a modified Poisson regression was used to estimate the crude and adjusted relative risks of progression within 24 months stratified by index cytology and age. RESULTS: During the study period, 11,056 women underwent active surveillance, 6767 of whom regressed and 3580 of whom progressed within 24 months. This corresponded to regression rates of 62.9% (95% confidence interval, 61.9-63.8) and progression rates of 33.3% (95% confidence interval, 32.4-34.2) at 24 months of follow-up. Most women regressed (90%) or progressed (90%) within the first 12 months. Women with high-grade index cytology had a higher risk of progression than women with normal index cytology (adjusted relative, 1.58; 95% confidence interval, 1.43-1.76), whereas there was no difference in the risk of progression between women aged 30 and 40 years and women aged 23 to 29 years (adjusted relative risk, 0.98; 95% confidence interval, 0.88-1.10). CONCLUSION: The observed high regression rates of cervical intraepithelial neoplasia grade 2 supported the transition in clinical management from surgical excision to active surveillance, particularly among women with low-grade or normal index cytology.

Prayer and meditation practices in the early COVID-19 pandemic: A nationwide survey among Danish pregnant women. The COVIDPregDK study.

BACKGROUND: The emergence of the COVID-19 pandemic and the derived changes in maternity care have created stress and anxiety among pregnant women in different parts of the world. In times of stress and crisis, spirituality, including spiritual and religious practices, may increase. OBJECTIVE: To describe if the COVID-19 pandemic influenced pregnant women's considerations and practises of existential meaning-making and to investigate such considerations and practices during the early pandemic in a large nationwide sample. METHODS: We used survey data from a nationwide cross-sectional study sent to all registered pregnant women in Denmark during April and May 2020. We used questions from four core items on prayer and meditation practices. RESULTS: A total of 30,995 women were invited, of whom 16,380 participated (53%). Among respondents, we found that 44% considered themselves believers, 29% confirmed a specific form of prayer, and 18% confirmed a specific form of meditation. In addition, most respondents (88%) reported that the COVID-19 pandemic had not influenced their responses. CONCLUSION: In a nationwide Danish cohort of pregnant women, existential meaning-making considerations and practices were not changed due to the COVID-19 pandemic. Nearly one in two study participants described themselves as believers, and many practised prayer and/or meditation.

Risk factors for and pregnancy outcomes after SARS-CoV-2 in pregnancy according to disease severity: A nationwide cohort study with validation of the SARS-CoV-2 diagnosis.

INTRODUCTION: We identified risk factors and outcomes associated with SARS-CoV-2 infection in pregnancy in a universally tested population according to disease severity and validated information on SARS-CoV-2 during pregnancy in national health registers in Denmark. MATERIAL AND METHODS: Cohort study using data from national registers and medical records including all pregnancies between March 1, 2020 and February 28, 2021. We compared women with a validated positive SARS-CoV-2 test during pregnancy with non-infected pregnant women. Risk factors and pregnancy outcomes were assessed by Poisson and Cox regression models and stratified according to disease severity defined by hospital admission status and admission reason (COVID-19 symptoms or other). Using medical record data on actual period of pregnancy, we calculated predictive values of the SARS-CoV-2 diagnosis in pregnancy in the registers. RESULTS: SARS-CoV-2 infection was detected in 1819 (1.6%) of 111 185 pregnancies. Asthma was associated with infection (relative risk [RR] 1.63, 95% confidence interval [CI] 1.28-2.07). Risk factors for severe COVID-19 disease requiring hospital admission were high body mass index (median ratio 1.06, 95% CI 1.04-1.09), asthma (RR 7.47, 95% CI 3.51-15.90) and gestational age at the time of infection (gestational age 28-36 vs < 22: RR 3.53, 95% CI 1.75-7.10). SARS-CoV-2-infected women more frequently had hypertensive disorders in pregnancy (adjusted hazard ratio [aHR] 1.31, 95% CI 1.04-1.64), early pregnancy loss (aHR 1.37, 95% CI 1.00-1.88), preterm delivery before gestational age 28 (aHR 2.31, 95% CI 1.01-5.26), iatrogenically preterm delivery before gestational age 37 (aHR 1.49, 95% CI 1.01-2.19) and small-for-gestational age children (aHR 1.28, 95% CI 1.05-1.54). The associations were stronger among women admitted to hospital for any reason. The validity of the SARS-CoV-2 diagnosis in relation to pregnancy in the registers compared with medical records showed a negative predictive value of 99.9 (95% CI 99.9-100.0) and a positive predictive value of 82.1 (95% CI 80.4-83.7). CONCLUSIONS: Women infected with SARS-CoV-2 during pregnancy were at increased risk of hypertensive disorders in pregnancy, early pregnancy loss, preterm delivery and having children small for gestational age. The validity of Danish national registers was acceptable for identification of SARS-CoV-2 infection during pregnancy.

Abdominal tissue concentrations and penetration of carboplatin in a HIPEC procedure ‒ assessment in a novel porcine model.

Objectives: Peritoneal dissemination from intraabdominal cancers is associated with poor prognosis and rapid disease progression. Hyperthermic intraperitoneal chemotherapy (HIPEC) is an antineoplastic treatment, which has improved survival and recurrence-free survival, but little is known about the acquired chemotherapy concentrations in local tissues. The aim of this study was to assess concentrations of carboplatin during and after HIPEC treatment dynamically and simultaneously in various abdominal organ tissues by means of microdialysis in a novel porcine model. Methods: Eight pigs underwent imitation cytoreductive surgery followed by HIPEC (90 min) using a carboplatin dosage of 800 mg/m2. Microdialysis catheters were placed for sampling of drug concentrations in various solid tissues: peritoneum, liver, bladder wall, mesentery and in different depths of one mm and four mm in the hepatoduodenal ligament and rectum. During and after HIPEC, dialysates and blood samples were collected over 8 h. Results: No statistically significant differences in mean AUC0-last (range: 2,657-5,176 min·µg/mL), mean Cmax (range: 10.6-26.0 µg/mL) and mean Tmax (range: 105-206 min) were found between the compartments. In plasma there was a tendency towards lower measures. No difference between compartments was found for tissue penetration. At the last samples obtained (450 min) the mean carboplatin concentrations were 4.9-9.9 µg/mL across the investigated solid tissues. Conclusions: Equal carboplatin distribution in abdominal organ tissues, detectable concentrations for at least 6 h after HIPEC completion, and a carboplatin penetration depth of minimum four mm were found. The present study proposes a new HIPEC porcine model for future research.

Risk of atypical hyperplasia and endometrial carcinoma after initial diagnosis of non-atypical endometrial hyperplasia: A long-term follow-up study.

OBJECTIVES: The strong association between atypical endometrial hyperplasia and endometrial carcinoma is well established, but data on the risk of atypical hyperplasia and carcinoma in Danish women with non-atypical endometrial hyperplasia are almost non-existent. This study aimed to investigate the prevalence of atypical hyperplasia and endometrial carcinoma diagnosed within 3 months of initial diagnosis (defined as concurrent disease) and the risk of atypical hyperplasia and carcinoma more than 3 months after initial diagnosis (classified as progressive disease) in Danish women initially diagnosed with non-atypical endometrial hyperplasia. DESIGN: This cohort study recruited 102 women diagnosed with non-atypical endometrial hyperplasia at Randers Regional Hospital in Randers, Denmark, between 2000 and 2015. METHODS: The endometrium was evaluated by transvaginal ultrasound examination and office mini-hysteroscopy with biopsies in all non-hysterectomized women. Data regarding subsequent hysterectomy or endometrial sampling were obtained from medical records and the Danish Pathology Registry (Patobank). RESULTS: A total of 15 women were diagnosed with atypical hyperplasia or carcinoma during follow-up. Concurrent atypical hyperplasia or carcinoma was seen in 2.9% (3/102), and among women who remained at risk for more than 3 months after initial diagnosis of non-atypical endometrial hyperplasia (n = 94), progression to atypical hyperplasia or carcinoma was seen in 13% (median follow-up 5.2 years, range 3.6 months to 15.1 years). Sixty-six percent of the women with progressive disease were diagnosed with atypical hyperplasia or carcinoma more than 1 year after initial diagnosis, but only two were diagnosed later than 5 years (5.2 and 9 years). CONCLUSIONS: The risk of being diagnosed with atypical endometrial hyperplasia or endometrial carcinoma more than 5 years after an initial diagnosis of non-atypical endometrial hyperplasia seems to be low in Danish women. Specialized follow-up more than 5 years after diagnosis of non-atypical endometrial hyperplasia may not be warranted.

Known Benefits and Unknown Risks of Active Surveillance of Cervical Intraepithelial Neoplasia Grade 2.

Cervical intraepithelial neoplasia grade 2 (CIN 2) is an equivocal diagnosis with high interobserver variation. Owing to high regression rates of 50%, many countries recommend active surveillance of CIN 2, especially in women younger than age 25-30 years, where regression rates are even higher (ie, 60%). Additionally, excisional treatment is associated with increased risk of reproductive harm, particularly preterm birth. Active surveillance typically consists of semi-annual follow-up visits for up to 2 years, including colposcopy and either cytology, testing for human papillomavirus, or both. Excisional treatment is recommended for progression or persistent disease after 2 years. Because active surveillance in younger women is relatively new, knowledge on subsequent risk of cervical cancer is limited. Considering human papillomavirus latency, women undergoing active surveillance might be at higher risk of cervical cancer than women undergoing excisional treatment. Furthermore, there are limited data describing preferences of women for the management of CIN 2, and it is also unclear how active surveillance may affect planning for future pregnancy. In this context, biomarkers for risk stratification of CIN 2 into either high or low probability of progression would allow for targeted treatment. Currently, immunohistochemical staining for p16 is used to clarify the histologic diagnosis, but whether it or other biomarkers can be used for risk-stratification in clinical management of women with CIN 2 remains unknown. In conclusion, active surveillance of CIN 2 needs further investigation, including understanding the long-term cervical cancer risk and evaluation of markers that may enable risk stratification of CIN 2.

The COVIDPregDK Study: A national survey on pregnancy during the early COVID-19 pandemic in Denmark.

AIM: We aimed to describe the aim, data collection and content from a survey completed among pregnant women during the first peak of the COVID-19 pandemic in Denmark. METHODS: The declaration of the COVID-19 pandemic in early 2020 challenged pregnant women's mental well-being due to a concern for their unborn child and their need for healthcare services through pregnancy and birth. To explore how the COVID-19 pandemic and the intensified measures such as the lockdown of Denmark impacted pregnant women's well-being and mental health, we conducted a questionnaire survey in the spring of 2020 when the COVID-19 pandemic was at its first peak, and the consequences for pregnant women and the unborn child were very uncertain. All women residing in Denmark and registered with an ongoing pregnancy on 24 April 2020 were invited to participate. The questionnaire included background information, variables on COVID-19 symptoms and validated batteries of questions on loneliness, anxiety, stress, quality of life, meditation and prayers. Additional questions were included to examine concerns related to pregnancy and childbirth during the pandemic. COHORT CHARACTERISTICS: Almost 18,000 women answered the questionnaire, which represents 60% of all invited women who experienced a national lockdown for the first time. Their median age was 30 years, and they were more likely to be multiparous. CONCLUSIONS: Data from the COVIDPregDK Study will enable us to gain valuable knowledge on how the pandemic, the intensified measures from the health authorities and the national lockdown affected pregnant women's mental health and their concerns during the COVID-19 pandemic.

SARS-CoV-2 infection in pregnancy in Denmark-characteristics and outcomes after confirmed infection in pregnancy: A nationwide, prospective, population-based cohort study.

INTRODUCTION: Assessing the risk factors for and consequences of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during pregnancy is essential to guide clinical care. Previous studies on SARS-CoV-2 infection in pregnancy have been among hospitalized patients, which may have exaggerated risk estimates of severe outcomes because all cases of SARS-CoV-2 infection in the pregnant population were not included. The objectives of this study were to identify risk factors for and outcomes after SARS-CoV-2 infection in pregnancy independent of severity of infection in a universally tested population, and to identify risk factors for and outcomes after severe infection requiring hospital admission. MATERIAL AND METHODS: This was a prospective population-based cohort study in Denmark using data from the Danish National Patient Register and Danish Microbiology Database and prospectively registered data from medical records. We included all pregnancies between March 1 and October 31, 2020 and compared women with a positive SARS-CoV-2 test during pregnancy to non-infected pregnant women. Cases of SARS-CoV-2 infection in pregnancy were both identified prospectively and through register linkage to ensure that all cases were identified and that cases were pregnant during infection. Main outcome measures were pregnancy, delivery, maternal, and neonatal outcomes. Severe infection was defined as hospital admission due to coronavirus disease 2019 (COVID-19) symptoms. RESULTS: Among 82 682 pregnancies, 418 women had SARS-CoV-2 infection during pregnancy, corresponding to an incidence of 5.1 per 1000 pregnancies, 23 (5.5%) of which required hospital admission due to COVID-19. Risk factors for infection were asthma (odds ratio [OR] 2.19, 95% CI 1.41-3.41) and being foreign born (OR 2.12, 95% CI 1.70-2.64). Risk factors for hospital admission due to COVID-19 included obesity (OR 2.74, 95% CI 1.00-7.51), smoking (OR 4.69, 95% CI 1.58-13.90), infection after gestational age (GA) 22 weeks (GA 22-27 weeks: OR 3.77, 95% CI 1.16-12.29; GA 28-36 weeks: OR 4.76, 95% CI 1.60-14.12), and having asthma (OR 4.53, 95% CI 1.39-14.79). We found no difference in any obstetrical or neonatal outcomes. CONCLUSIONS: Only 1 in 20 women with SARS-CoV-2 infection during pregnancy required admission to hospital due to COVID-19. Risk factors for admission comprised obesity, smoking, asthma, and infection after GA 22 weeks. Severe adverse outcomes of SARS-CoV-2 infection in pregnancy were rare.

Ovarian cancer stage, variation in transvaginal ultrasound examination rates and the impact of an urgent referral pathway: A national ecological cohort study.

INTRODUCTION: The aim of this study was to determine whether variation in transvaginal ultrasound examination rates in Danish general practice populations is associated with ovarian cancer outcomes, and to explore the impact of the introduction of a cancer patient pathway for ovarian cancer. MATERIAL AND METHODS: We performed a national register-based cohort study of gynecological cancer-free women aged 40 years or above, living in Denmark and listed with a specific general practitioner in 2004-2014. Practice populations were divided into quartiles according to the general practitioners' transvaginal ultrasound propensity in the preceding year. Associations between transvaginal ultrasound rates and ovarian cancer outcomes were analyzed using Poisson and logistic regression. RESULTS: We included 2769 general practices with 1 739 422 listed women, of whom 5325 were diagnosed with ovarian cancer during the study period. Practices varied twofold in transvaginal ultrasound rates before and after the implementation of the cancer patient pathway. Before the cancer patient pathway was introduced, women listed with practices with the highest transvaginal ultrasound rates were diagnosed with earlier stages of ovarian cancer (odds ratio 1.38, 95% confidence interval 1.06 to 1.81) and had a higher proportion of borderline tumors (incidence rate ratio 1.38, 95% confidence interval 1.10 to 1.75) compared with women least exposed to transvaginal ultrasound. After the cancer patient pathway, no significant differences were identified between the groups. CONCLUSIONS: Before the cancer patient pathway, women exposed most to transvaginal ultrasound were significantly more likely to be diagnosed with early stage ovarian cancer compared with those least exposed to transvaginal ultrasound. After the cancer patient pathway was implemented, the difference disappeared. This suggests that increased awareness and access to transvaginal ultrasound is useful for diagnosing early-stage ovarian cancer.

Ovarian cancer suspicion, urgent referral and time to diagnosis in Danish general practice: a population-based study.

BACKGROUND: Ovarian cancer (OC) survival rates are lower in Denmark than in countries with similar health care. Prolonged time to diagnosis could be a contributing factor. The Danish cancer patient pathway (CPP) for OC was introduced in 2009. It provides GPs with fast access to diagnostic work-up. OBJECTIVE: To investigate cancer suspicion and pathway use among GPs and to explore the association between these factors and the diagnostic intervals (DIs). METHODS: We conducted a national population-based cohort study using questionnaires and national registers. RESULTS: Of the 313 women with participating GPs, 91% presented with symptoms within 1 year of diagnosis, 61% presented vague non-specific symptoms and 62% were diagnosed with late-stage disease. Cancer was suspected in 39%, and 36% were referred to a CPP. Comorbidity [prevalence ratio (PR): 0.53, 95% confidence interval (CI): 0.29-0.98] and no cancer suspicion (PR: 0.35, 95% CI: 0.20-0.60) were associated with no referral to a CPP. The median DI was 36 days. Long DIs were associated with no cancer suspicion (median DI: 59 versus 20 days) and no referral to a CPP (median DI: 42 versus 23 days). CONCLUSIONS: Nine in ten patients attended general practice with symptoms before diagnosis. Two-thirds initially presented with vague non-specific symptoms were less likely to be referred to a CPP and had longer DIs than women suspected of cancer. These findings underline the importance of supplementing the CPP with additional accelerated diagnostic routes.

Location of recurrences in high-risk stage Iendometrial cancer patients not given postoperative radiotherapy: A Danish gynecological cancer group study.

OBJECTIVES: To study recurrence rates in Danish high-risk stage I endometrial cancers not given radiotherapy in accordance with the decision of the Danish Gynecological Cancer Group. METHODS: This prospective national cohort study includes all 4707 endometrial carcinomas diagnosed from 2005 to 2012. Of these, 623 patients had grade 3 endometroid adenocarcinoma with >50% myometrial invasion or serous/clear/undifferentiated carcinoma (with any depth of invasion). In 305 patients with high-risk stage I on final pathology, 14.1% received adjuvant external beam radiotherapy and 9.6% adjuvant chemotherapy. No patients received brachytherapy. 5-year Kaplan-Meier survival estimates and actuarial recurrence rates were calculated, and adjusted Cox regression analysis used for comparison. Recurrence rates were compared with historical Danish population data (DEMCA 98-99). RESULTS: For non-irradiated patients, 5-year overall survival, cancer-specific survival, and progression-free survival rates in high-risk stage I patients were 65%, 78%, and 73%, respectively. For non-irradiated patients, isolated local recurrences were uncommon (vaginal 3.1%, pelvic 0.4%). Death was mainly due to a high occurrence of non-local recurrences, with 8.8% experiencing a first recurrence in the abdominal cavity (outside the field where radiation traditionally have been given) and 13.0% a distant metastasis outside the abdominal cavity. Grade 3 tumors with >50% myometrial invasion seem to be characterized by a different pattern of recurrences, with significantly more isolated vaginal recurrences (7.9% vs 2.2%) and fewer total number of abdominal recurrences (7.9% vs 15.3%) as compared with unfavorable tumor types. CONCLUSION: Isolated vaginal and pelvic recurrences were rare (3-5%) in patients with a final pathologic diagnosis of high-risk stage I endometrial cancer even after the Danish Gynecological Cancer Group decided to omit all types of postoperative radiotherapy and introduce lymph node staging.

The effect of introducing pelvic lymphadenectomy on survival and recurrence rates in Danish endometrial cancer patients at high risk: a Danish Gynecological Cancer Group study.

OBJECTIVES: To evaluate the rate of survival and recurrence related to the introduction of pelvic lymphadenectomy in Danish high-risk endometrial cancer patients. STUDY DESIGN: Data on 713 high-risk patients defined as grade 3 with >50% myometrial invasion or serous/clear/undifferentiated carcinomas stage I-IV endometrial cancer patients diagnosed from 2005 to 2012 were retrieved from the Danish Gynecological Cancer Database. Of these, 305 were high-risk stage I. Five year Kaplan-Meier survival estimates and actuarial recurrence rates were calculated, and adjusted Cox used for comparison. Findings were compared with earlier Danish results. RESULTS: Lymphadenectomy in 390 radically operated high-risk patients resulted in upstaging of 31 patients from stage I to IIIC and 19 patients from stage II to IIIC corresponding to 12.8%. Upstaging from stage I to IIIC had a cancer-specific survival of 77%, almost comparable to lymph node-negative high-risk stage I patients (81%). Lymphadenectomy patients had a significant higher overall survival as compared with non-lymph node resected for all patients, but not for stage I patients. Lymphadenectomy, however, did not significantly affect cancer-specific survival, progression-free survival, recurrence rate or risk of local, distant, or lymph node recurrence. When the survival of high-risk stage I patients was compared with earlier Danish results, a small improvement in overall survival (7%) and cancer-specificsurvival (8%) was demonstrated. CONCLUSION: Only a small number of high-risk patients were upstaged from stage I to III due to lymphadenectomy. These patients showed a surprisingly good survival possibly due to correct stage identification and subsequent relevant adjuvant therapy. However, even though introduction of lymphadenectomy in the Danish high-risk population seems to increase overall survival, no significant change in cancer-specific survival, progression-free survival or recurrence patterns was demonstrated.

Impact of baseline covariates on the immunogenicity of the 9-valent HPV vaccine - A combined analysis of five phase III clinical trials.

BACKGROUND: The immunogenicity profile of the 9-valent HPV (9vHPV) vaccine was evaluated across five phase III clinical studies conducted in girls and boys 9-15 years of age and young women 16-26 years of age. The effect of baseline characteristics of subjects on vaccine-induced HPV antibody responses was assessed. METHODS: Immunogenicity data from 11,304 subjects who received ≥1 dose of 9vHPV vaccine in five Phase III studies were analyzed. Vaccine was administered as a 3-dose regimen. HPV antibody titers were assessed 1 month after dose 3 using a competitive Luminex immunoassay and summarized as geometric mean titers (GMTs). Covariates examined were age, gender, race, region of residence, and HPV serostatus and PCR status at day 1. RESULTS: GMTs to all 9 vaccine HPV types decreased with age at vaccination initiation, and were otherwise generally similar among the demographic subgroups defined by gender, race and region of residence. For all subgroups defined by race or region of residence, GMTs were higher in girls and boys than in young women. Vaccination of subjects who were seropositive at day 1 to a vaccine HPV type resulted in higher GMTs to that type, compared with those in subjects who were seronegative for that type at day 1. CONCLUSIONS: 9vHPV vaccine immunogenicity was robust among subjects with differing baseline characteristics. It was generally comparable across subjects of different races and from different regions. Greater immunogenicity in girls and boys versus young women (the population used to establish 9vHPV vaccine efficacy in clinical studies) indicates that the anti-HPV responses generated by the vaccine in adolescents from all races or regions were sufficient to induce high-level protective efficacy. This immunogenicity profile supports a widespread 9vHPV vaccination program and early vaccination.

Role of human papillomavirus testing and cytology in follow-up after conization.

OBJECTIVE: Adequate follow-up of women who have undergone conization for high-grade cervical lesions is crucial in cervical cancer screening programs. We evaluated the performance of testing for high-risk human papillomavirus (HPV) types, cytology alone, and combined testing in predicting cervical intraepithelial neoplasia grade 2 or worse (CIN2+) after conization. DESIGN: Prospective cohort study. SETTING: Denmark. POPULATION: 667 women attending for conization. METHODS: Cervical specimens were collected during 2002-2006 at first visit after conization for cytological examination and Hybrid Capture 2 detection of high-risk HPV. The women were passively followed until 2 years after first follow-up visit by linkage to the nationwide Pathology Data Bank. RESULTS: At first visit after conization (median time, 3.4 months), 20.4% were HPV-positive and 17.2% had atypical squamous intraepithelial lesions or more severe cytology (ASCUS+). The 2-year incidence of CIN2+ after conization was 3.6%. Sensitivity for detection of CIN2+ after conization was 81.0% [95% confidence interval (CI) 58.1-94.6] for positive cytology (ASCUS+ threshold) and 95.2% (95% CI 76.2-99.9) for HPV testing and for combined testing. Specificity of ASCUS+ cytology (85.2%; 95% CI 82.0-88.0) was higher than that of HPV testing (82.4%; 95% CI 79.0-85.4) and markedly higher than that of combined testing (73.2%; 95% CI 69.3-76.8). The margin status had no significant added value. CONCLUSIONS: Testing for high-risk HPV three to four months after conization is more sensitive than ASCUS+ cytology for identifying women at risk for relapse of CIN2+ within 2 years. Further studies are needed to evaluate whether HPV testing could be a stand-alone test in follow up after conization.

Preoperative staging of endometrial cancer using TVS, MRI, and hysteroscopy.

OBJECTIVES: To evaluate the accuracy of different preoperative modalities for staging of endometrial cancer to restrict extensive surgery to patients at high risk of metastatic disease. SETTING: Aarhus University Hospital. POPULATION: 156 women referred in 2006-2011 because of atypical endometrial hyperplasia (G0) or endometrial cancer. METHODS: Patients were offered preoperative transvaginal ultrasonography (TVS), magnetic resonance imaging (MRI), and hysteroscopic-directed biopsies from the uterine tumor and cervix. Final pathology of the removed uterus was the reference standard. Patients were divided into low risk (<50% myometrial invasion, and grades 0, 1, 2, and no cervical invasion) or high risk (all others). MAIN OUTCOME MEASURES: Accuracy, sensitivity, specificity, positive/negative predictive value. RESULTS: Patients were aged 32-88 years, with a mean body mass index of 29. At final pathology 81% had cancer and 19% G0 or no residual tumor; 54% were high risk. Hysteroscopy-directed biopsies had a higher accuracy (92%) than endometrial biopsy (58%) for differentiating G0 from cancer (p < 0.001); grade 3 tumor identification had similar accuracy (93 vs. 92%). Deep myometrial invasion was estimated with higher accuracy by MRI (82%) than TVS (74%) (p < 0.02). For cervical involvement, hysteroscopy-directed biopsies had higher accuracy (94%) than MRI (84%,) and TVS (80%) (p < 0.02). Accuracy for identifying high-risk women was highest (83%) using a combination of MRI and hysteroscopic-directed biopsies, compared with TVS and endometrial biopsy (72%) (p < 0.05). CONCLUSION: Preoperative staging with MRI and hysteroscopy-directed biopsy can identify eight of 10 women with high risk of lymph node metastases and spare eight of 10 low-risk women extended surgery.

Symptom interpretation and health care seeking in ovarian cancer.

BACKGROUND: Ovarian cancer is the leading cause of death among women suffering from gynaecological malignancies in the Western world. Worldwide, approximately 200,000 women are diagnosed with the disease each year. This article deals with the health care seeking and symptom interpretation process among Danish women, who have a very high mortality rate. METHODS: The health seeking and symptom interpretation process was analysed via combining study methods. The material consisted of registry data dealing with the use of public health care and hospital services of Danish women, newly diagnosed with ovarian cancer. These results were combined with findings from semi-structured qualitative research interviews on women's bodily experiences with symptom development. RESULTS: A number of 663 Danish women with ovarian cancer attended 27 different kinds of primary health care providers in a total of 14,009 visits during 2007. The women also had 6,214 contacts with various hospitals, and obtained 562 different diagnoses.From the main theme "Women's experiences with the onset of symptoms" three sub-themes were identified: "Bodily sensations", "From bodily sensation to symptom", and "Health seeking and treatment start". In all cases the General Practitioner represented the first contact to public health care, acting as gate-keeper to specialist and hospital referral.The women were major users of public health care throughout the diagnostic process and subsequent treatment. All women held personal knowledge concerning the onset of their symptoms. The early symptoms of ovarian cancer might be uncharacteristic and non-disease-specific when interpreted as personal experiences, but they had similarities when analysed together. CONCLUSIONS: Diagnostic delay in ovarian cancer seems far from being exclusively a medical problem, as the delay proved to be influenced by organisational, cultural, and social factors, too. Initiatives facilitating the diagnostic process and research concerning the selection of individuals for further investigation are indicated. The way in which the women interpreted their symptoms was influenced by their personal experiences, their cultural, and their social background. This became crucial to the diagnostic process. These issues need to be explored through further research on women's experiences during the diagnostic process.

Evaluation of the risk of persistent trophoblastic disease after twin pregnancy with diploid hydatidiform mole and coexisting normal fetus.

OBJECTIVE: This study was undertaken to evaluate the risk of persistent trophoblastic disease and obstetric complications related to a multiple pregnancy comprising a diploid hydatidiform mole and normal cofetus(es). STUDY DESIGN: From a database of 270 consecutively collected hydatidiform moles, 8 multiple and 154 singleton molar pregnancies were identified. Molar and fetal ploidy was determined, and data on clinical features and chemotherapy were collected. Differences between groups were assessed with Fisher's exact or Mann-Whitney test. RESULTS: The molar component in all 8 multiple pregnancies was diploid. Five patients with diploid mole and coexisting fetus pregnancy chose to terminate their pregnancy, 2 aborted spontaneously, and 1 patient delivered a healthy child. Two diploid mole and coexisting fetus pregnancies (25%) and 17% of the singleton molar pregnancies were followed by persistent trophoblastic disease (P = .63). CONCLUSION: The risk of persistent trophoblastic disease after a diploid mole with coexisting fetus pregnancy is similar to that after a singleton molar pregnancy, and expectant management instead of therapeutic abortion can be pursued.

A nine-nucleotide deletion and splice variation in the coding region of the interferon induced ISG12 gene.

Interferons (IFNs) are a family of cytokines with growth inhibitory, and antiviral functions. IFNs exert their biological actions through the expression of more than 1000 IFN stimulated genes, ISGs. ISG12 is an IFN type I induced gene encoding a protein of M(r) 12,000. We have identified a novel, IFN inducible splice variant of ISG12 lacking exon 2 leading to a putative truncated protein isoform of M(r) 7400, ISG12-S. In cells from blood and cervical cytobrush material from healthy women, the level of ISG12-S expression was higher than ISG12 expression, whereas the expression pattern was more evenly distributed between ISG12 and ISG12-S in breast carcinoma cells, in cancer cell lines and in cervical cytobrush material with neoplastic lesions. In addition, we have found a nine-nucleotide deletion situated in exon 4 of the ISG12 gene. This deletion leads to a three-amino-acid deletion (AMA) in the putative ISG12 gene products, ISG12Delta and ISG12-SDelta. We have determined the prevalence of the deletion ISG12Delta in normal and neoplastic cells. Homozygosity ISG12(0/0) and ISG12(Delta/Delta), and heterozygosity ISG12(0/Delta) were found, although the ISG12(Delta/Delta) genotype was rare. In heterozygous cells from cytobrush material with neoplastic lesions, we found a preference for expression of the ISG12(0) allele.