Comparison of different strategies for the triage to colposcopy of women tested high-risk HPV positive on self-collected cervicovaginal samples.

OBJECTIVE: To identify the optimal strategy for the triage of women who test high-risk (hr) HPV positive on self-collected cervicovaginal samples. METHODS: This is a diagnostic accuracy sub-analysis of the GRECOSELF study, which reported on HPV-DNA testing with self-sampling in Greece. More than 13,000 women, 25-60 years old, who resided in rural areas of Greece, provided a self-collected cervicovaginal sample. Samples were tested for HPV-DNA and HPV16/18 genotyping with the cobas® HPV test (Roche® Molecular Systems, Pleasanton, CA, USA). HrHPV positive women were referred for colposcopy. Prior to colposcopy a physician-collected sample was obtained for cytology. After colposcopy/biopsy, women were classified as having cervical disease or not, and treated accordingly. RESULTS: Out of 1070 hrHPV positive women, 773 were subjected to colposcopy. Seventeen triage strategies, combining HPV16/18 genotyping and cytology, were investigated. The strategy referring to colposcopy women positive for HPV16 regardless of the cytology report, and women positive for other hrHPVs, in case of a subsequent atypical squamous cells of undetermined significance or worse (ASCUS+) cytology report, presented optimal trade-off; sensitivity 96.36% [(95%CI: (91.41-100.0)], positive predictive value (PPV) 27.46% [95%CI: (21.16-33.76)], and number of colposcopies required to detect one case of Cervical Intraepithelial Neoplasia grade-2 or worse (CIN2+) 3.64. CONCLUSIONS: The optimal strategy for the triage to colposcopy of hrHPV positive women, detected with the cobas® HPV test on self-collected cervicovaginal samples, is referring all HPV16 positive women directly to colposcopy, and women positive for HPV18 or other hrHPVs only after an ASCUS or worse cytology report.

CIN2+ detection of the HPV DNA Array genotyping assay in comparison with the Cobas 4800 HPV test and cytology.

BACKGROUND: HPV DNA Array is an E1-targeting PCR genotyping test, with capability of distinguishing 18 high-risk (16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 73, 82) and 11 low-risk HPV types (6, 11, 40, 42, 44, 54, 67, 69, 70, 85, 97). HPV DNA Array uses multiplex PCR for E1-gene sequence amplification. The amplicons are detected and genotyped by reverse hybridization to immobilized DNA probes spotted as triplets in single 96 well-plate wells and read by AID ELISPOT reader. METHODS: Aim of the study was to evaluate the clinical performance of the assay against internationally accepted and FDA approved Cobas 4800 HPV test (Roche Diagnostics). Study population comprised of 500 cervical samples. RESULTS: HPV DNA Array demonstrated a very high sensitivity of 100% for CIN2+ and 100% for CIN3+ detection, same as Cobas 4800. HPV DNA Array showed greater sensitivity for CIN2+ detection than cytology (100% vs. 13.6%). The agreement to Cobas 4800 for HPV detection, irrespective of type, was 81.4% with κ = 0.613. The agreement for HPV 16 was 92.8% (κ = 0.929), and for HPV 18 54.2% (κ = 0.681). CONCLUSION: HPV DNA Array demonstrated good clinical performance for detection of high-grade lesions, and may be considered for usage in a screening setting.

Cigarette Smoking Promotes Infection of Cervical Cells by High-Risk Human Papillomaviruses, but not Subsequent E7 Oncoprotein Expression.

Persistent cervical infection with high-risk human papillomaviruses (hrHPVs) is a necessary, but not sufficient, condition for the development of cervical cancer. Therefore, there are other co-factors facilitating the hrHPV carcinogenic process, one of which is smoking. To assess the effect of smoking on high-risk (hr) HPV DNA positivity and on the expression of HPV E7 oncoprotein, as a surrogate of persistent hrHPV infection, we used data from women recruited for the PIPAVIR project, which examined the role of E7 protein detection in cervical cancer screening. Women were tested for hrHPV DNA, using Multiplex Genotyping (MPG), and E7 protein, using a novel sandwich ELISA method, and gave information on their smoking habits. Among 1473 women, hrHPV prevalence was 19.1%. The odds ratio (OR) for hrHPV positivity of smokers compared to non-smokers was 1.785 (95% confidence intervals (CI): 1.365-2.332, p < 0.001). The ORs for E7 positivity, concerning hrHPV positive women, ranged from 0.720 to 1.360 depending on the E7 detection assay used, but this was not statistically significant. Smoking increases the probability of hrHPV infection, and smoking intensity is positively associated to this increase. Smoking is not related to an increased probability of E7 protein positivity for hrHPV positive women.

Personal and parental acceptance of human papillomavirus vaccination prior to and during the economic crisis among women in Greece.

PURPOSE: To assess personal and parental human papillomavirus (HPV) vaccination acceptance and how it is influenced by demographic factors prior to (2005-2010) and during (2011-2016) the economic crisis in Greece. METHODS: During 2005-2016, 6,401 women aged 18-65 years, living in different areas of Greece filled in a questionnaire covering demographic characteristics, knowledge of HPV infection's natural history and its consequences and assessing their intention to receive the HPV vaccine for themselves and their children. RESULTS: Women's intention to get vaccinated before the economic crisis was higher (86.2%) than during it (82.8%). In addition, the intention of women to vaccinate their children was higher for girls during 2005-2010 (78.3%), while there was no statistically significant difference concerning boys. HPV vaccination acceptance per year showed a statistically significant variation. The initially high acceptance decreased following vaccine's release, mainly due to fear of side effects, increased following objective public education, and declined again. Demographic characteristics affected HPV vaccination acceptance at the time period before the economic crisis in Greece, but not during it. CONCLUSION: Demographic factors affecting a woman's attitude towards vaccination prior to the economic crisis in Greece, stopped playing a significant role during the crisis, reflecting its devastating effect on most parts of the population.

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.

Gene promoter methylation and protein expression of BRMS1 in uterine cervix in relation to high-risk human papilloma virus infection and cancer.

Cervical cancer is strongly related to certain high-risk types of human papilloma virus infection. Breast cancer metastasis suppressor 1 (BRMS1) is a tumor suppressor gene, its expression being regulated by DNA promoter methylation in several types of cancers. This study aims to evaluate the methylation status of BRMS1 promoter in relation to high-risk types of human papilloma virus infection and the development of pre-cancerous lesions and describe the pattern of BRMS1 protein expression in normal, high-risk types of human papilloma virus-infected pre-cancerous and malignant cervical epithelium. We compared the methylation status of BRMS1 in cervical smears of 64 women with no infection by high-risk types of human papilloma virus to 70 women with proven high-risk types of human papilloma virus infection, using real-time methylation-specific polymerase chain reaction. The expression of BRMS1 protein was described by immunohistochemistry in biopsies from cervical cancer, pre-cancerous lesions, and normal cervices. Methylation of BRMS1 promoter was detected in 37.5% of women with no high-risk types of human papilloma virus infection and was less frequent in smears with high-risk types of human papilloma virus (11.4%) and in women with pathological histology (cervical intraepithelial neoplasia) (11.9%). Methylation was detected also in HeLa cervical cancer cells. Immunohistochemistry revealed nuclear BRMS1 protein staining in normal high-risk types of human papilloma virus-free cervix, in cervical intraepithelial neoplasias, and in malignant tissues, where staining was occasionally also cytoplasmic. In cancer, expression was stronger in the more differentiated cancer blasts. In conclusion, BRMS1 promoter methylation and aberrant protein expression seem to be related to high-risk types of human papilloma virus-induced carcinogenesis in uterine cervix and is worthy of further investigation.

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.

Self-collected cervicovaginal sampling for site-of-care primary HPV-based cervical cancer screening: a pilot study in a rural underserved Greek population.

In the present pilot study, the feasibility of a site-of-care cervicovaginal self-sampling methodology for HPV-based screening was tested in 346 women residing in underserved rural areas of Northern Greece. These women provided self-collected cervicovaginal sample along with a study questionnaire. Following molecular testing, using the cobas® HPV Test, Roche®, HPV positive women, were referred to colposcopy and upon abnormal findings, to biopsy and treatment. Participation rate was 100%. Regular pap-test examination was reported for 17.1%. Among hrHPV testing, 11.9% were positive and colposcopy/biopsy revealed 2 CIN3 cases. Non-compliance was the most prevalent reason for no previous attendance. Most women reported non-difficulty and non-discomfort in self-sampling (77.6% and 82.4%, respectively). They would choose self-sampling over clinician-sampling (86.2%), and should self-sampling being available, they would test themselves more regularly (92.3%). In conclusion, self-sampling is feasible and well-accepted for HPV-based screening, and could increase population coverage in underserved areas, helping towards successful prevention.

Genetic polymorphisms of FAS and EVER genes in a Greek population and their susceptibility to cervical cancer: a case control study.

BACKGROUND: The aim of the study was to evaluate the association of two SNPs of EVER1/2 genes' region (rs2290907, rs16970849) and the FAS-670 polymorphism with the susceptibility to precancerous lesions and cervical cancer in a Greek population. METHODS: Among the 515 women who were included in the statistical analysis, 113 belong to the case group and present with precancerous lesions or cervical cancer (27 with persistent CIN1, 66 with CIN2/3 and 20 with cervical cancer) and 402 belong to the control group. The chi-squared test was used to compare the case and the control groups with an allelic and a genotype-based analysis. RESULTS: The results of the statistical analysis comparing the case and the control groups for all the SNPs tested were not statistically significant. Borderline significant difference (p value = 0.079) was only found by the allelic model between the control group and the CIN1/CIN2 patients' subgroup for the polymorphism rs16970849. The comparison of the other case subgroups with the control group did not show any statistically significant difference. CONCLUSIONS: None of the SNPs included in the study can be associated with statistical significance with the development of precancerous lesions or cervical cancer.

Comparison of cytology, HPV DNA testing and HPV 16/18 genotyping alone or combined targeting to the more balanced methodology for cervical cancer screening.

OBJECTIVES: The objective of the present study was to identify the most effective cervical cancer screening algorithm incorporating different combinations of cytology, HPV testing and genotyping. METHODS: Women 25-55years old recruited for the "HERMES" (HEllenic Real life Multicentric cErvical Screening) study were screened in terms of cytology and high-risk (hr) HPV testing with HPV 16/18 genotyping. Women positive for cytology or/and hrHPV were referred for colposcopy, biopsy and treatment. Ten screening algorithms based on different combinations of cytology, HPV testing and HPV 16/18 genotyping were investigated in terms of diagnostic accuracy. RESULTS: Three clusters of algorithms were formed according to the balance between effectiveness and harm caused by screening. The cluster showing the best balance included two algorithms based on co-testing and two based on HPV primary screening with HPV 16/18 genotyping. Among these, hrHPV testing with HPV 16/18 genotyping and reflex cytology (atypical squamous cells of undetermined significance - ASCUS threshold) presented the optimal combination of sensitivity (82.9%) and specificity relative to cytology alone (0.99) with 1.26 false positive rate relative to cytology alone. CONCLUSION: HPV testing with HPV 16/18 genotyping, referring HPV 16/18 positive women directly to colposcopy, and hrHPV (non 16/18) positive women to reflex cytology (ASCUS threshold), as a triage method to colposcopy, reflects the best equilibrium between screening effectiveness and harm. Algorithms, based on cytology as initial screening method, on co-testing or HPV primary without genotyping, and on HPV primary with genotyping but without cytology triage, are not supported according to the present analysis.

Distinct demographic factors influence the acceptance of vaccination against HPV.

PURPOSE: To investigate the possible effect of demographic factors on HPV vaccination acceptance in Greece. METHODS: Analysis was performed on data from the "LYSISTRATA" project, a prospective, cross-sectional study, focusing on questions regarding the acceptance of HPV vaccination among Greek women for themselves, and their 13-year-old daughter or son. In total, 5,379 women participated in the study, between 2005 and 2011. RESULTS: Women born and raised in Greece were more likely to accept HPV vaccination for themselves (aOR = 4.1, 95 % CI 2.9-5.8), their daughter (aOR = 3.3, 95 % CI 2.3-4.7) and son (aOR = 3.3, 95 % CI 2.3-4.8), compared with immigrants. Similarly, women who had a Papanicolaou's test were more likely to accept vaccination for themselves (aOR = 1.8, 95 % CI 1.4-2.3), their daughter (aOR = 1.5, 95 % CI 1.2-1.9) and son (aOR = 1.4, 95 % CI 1.1-1.7) than those never tested. Smokers were less likely to accept HPV vaccination for themselves (aOR = 0.8, 95 % CI 0.6-0.9); however, such an association was not documented concerning their children. Educational level had a rather inconsistent impact on HPV vaccination acceptance. The effect of womens' age, monthly income, residence, profession and marital status on HPV vaccination acceptance for themselves was different than that for their daughters, and even more for their sons. CONCLUSIONS: There are distinct demographic factors that influence HPV vaccination acceptance. Women's perception that male vaccination is not as necessary may lead to lower acceptance of HPV vaccination for young boys and men.

HER-2/neu is an independent prognostic factor in type I endometrial adenocarcinoma.

PURPOSE: To define the prognostic significance of HER-2/neu and PTEN expression in patients with endometrioid (type I) endometrial cancer. METHODS: Seventy-seven patients with endometrioid endometrial carcinoma were included in the study, in a period between 1996 and 2009. Patients with coexisting malignancy and those having incomplete immunohistochemical data or clinical follow-up were excluded. Histological staging was defined according to the revised FIGO staging (2009). Clinico-pathologic and immunohistochemical characteristics were correlated in a multivariate Cox regression analysis with overall survival (OS), cancer-related survival (CRS) and disease-free survival (DFS). RESULTS: Mean age of the patients was 62.7 years. The median follow-up was 67 months (9-124 months). HER-2/neu expression was detected in 18.2 % (n = 14), and PTEN expression in 72.7 % (n = 56) of our patients. Multivariate Cox regression analysis showed that patient's age, FIGO staging and HER-2/neu expression were independent prognostic factors for OS, CRS and DFS. PTEN expression did not significantly affect survival outcomes of the present study. CONCLUSIONS: HER-2/neu but not PTEN expression is an independent prognostic factor for type I endometrial carcinoma.

High risk HPV-positive women cervicovaginal microbial profiles in a Greek cohort: a retrospective analysis of the GRECOSELF study.

Increasing evidence supports a role for the vaginal microbiome (VM) in the severity of HPV infection and its potential link to cervical intraepithelial neoplasia. However, a lot remains unclear regarding the precise role of certain bacteria in the context of HPV positivity and persistence of infection. Here, using next generation sequencing (NGS), we comprehensively profiled the VM in a series of 877 women who tested positive for at least one high risk HPV (hrHPV) type with the COBAS® 4,800 assay, after self-collection of a cervico-vaginal sample. Starting from gDNA, we PCR amplified the V3-V4 region of the bacterial 16S rRNA gene and applied a paired-end NGS protocol (Illumina). We report significant differences in the abundance of certain bacteria compared among different HPV-types, more particularly concerning species assigned to Lacticaseibacillus, Megasphaera and Sneathia genera. Especially for Lacticaseibacillus, we observed significant depletion in the case of HPV16, HPV18 versus hrHPVother. Overall, our results suggest that the presence or absence of specific cervicovaginal microbial genera may be linked to the observed severity in hrHPV infection, particularly in the case of HPV16, 18 types.

Increasing fear of adverse effects drops intention to vaccinate after the introduction of prophylactic HPV vaccine.

PURPOSE: The purpose of this study was (1) to explore for socio-demographic factors that could potentially affect the intention of women to vaccinate themselves, their 13-year-old daughter and their 13-year-old son against HPV, and (2) to investigate the main reasons for declining vaccination. METHODS: A structured questionnaire was used in participants of the project (N = 5,249). Logistic regression analysis was applied in order to examine the correlation between vaccine acceptability and a list of potential predictors. In women declining vaccination, the reported reasons for decline were analyzed. RESULTS: Residence in rural areas and low to medium tiers of family income were the most constant factors in favor of intention to vaccinate. Receiving information from a healthcare professional was found to positively affect vaccine acceptability for the woman herself, but it did not affect her intention to vaccinate her daughter or her son. The acceptance rates decreased significantly after the vaccine became available, both for the women themselves and for their daughters or sons. During the same year, a shift was noted in the reason for declining vaccination; the self-perception of insufficient knowledge significantly decreased and the fear of adverse effects significantly increased in all three cases. CONCLUSION: Apart from demographic factors which may favor or disfavor vaccine acceptability, the intention to vaccinate decreased significantly and the proportion of women rejecting vaccination for safety concerns increased significantly after the introduction of the vaccine, coinciding with isolated cases of negative publicity and highlighting the potential of misinformation by the media.

Emergency cervical cerclage after miscarriage of the first fetus in dichorionic twin pregnancies: obstetric and neonatal outcomes of delayed delivery interval.

PURPOSE: To study the effectiveness of emergency cervical cerclage in order to delay the delivery interval after miscarriage of the first fetus in dichorionic twin pregnancies. METHODS: Dichorionic twin pregnancies after miscarriage of the first fetus (<24 weeks) were exclusively included in the present analysis. Prolongation of delivery interval was managed with additional emergency cervical cerclage in the already initiated tocolytic therapy. Obstetric outcomes (cervical dilatation, gestational age at delivery of the first twin, interval between miscarriage and delivery of the second fetus) and neonatal outcomes [neonatal birth weight, Apgar score in the first and fifth minute, admission to Neonatal Intensive Care Unit (NICU)] of the second twin were analyzed. RESULTS: Five cases of dichorionic twin pregnancies were included in our study. Cervical dilatation (mean ± SD) at admission time was 3.7 ± 1.4 cm. The gestational week at delivery of the first twin was 20.6 ± 2.6. The median delivery interval was 72 days and the maximum 121 days. Mean gestational age at delivery of the second twin was 28.8 ± 7.2 weeks and mean birth weight 1,772.5 ± 742 g. The rate of live birth was 80 %, while NICU admission was demanded in 75 % of the live births. All neonates discharged from NICU remained alive after 1 month of life. CONCLUSION: The present study demonstrated beneficial effect concerning obstetric and neonatal outcomes of the second twin after performing emergency cervical cerclage to postpone the delivery interval in premature dichorionic twin pregnancies.

Thalamic volume measurement in normal fetuses using three-dimensional sonography.

PURPOSE: Brain thalami are important for a wide range of sensorimotor and neuropsychiatric functions. This study was carried out to calculate normative values for thalami volume during fetal life. METHODS: Fetal thalami volumes were measured using 3D ultrasound in 122 normal, singleton fetuses at 20(+0) -34(+6) weeks' gestation. Virtual Organ Computer-aided AnaLysis (VOCAL) was used to obtain a sequence of six sections of each thalamus, starting from the transthalamic view of the brain at an axial plane. Thalamic contour was drawn manually. Volume contrast imaging was used to enhance image quality when needed. The volume of the thalamus distal to the transducer was also measured by a second operator in 30 randomly selected cases, blind to the measurements of the first, to calculate interobserver agreement. RESULTS: Thalamic volume increased with gestational age, following a quadratic equation (R(2) = 0.83). There was no significant difference in volume between the right and left thalamus. The mean volume of each thalamus increased from 0.45 ml at 20(+0) weeks, to 1.39 ml at 28(+0) weeks, to 2.17 ml at 34(+0) weeks. The 95% limits of interobserver agreement for thalamic volume were -14.3% to +17.2%. CONCLUSIONS: The increase in thalamic volume with gestation can be described adequately by a quadratic equation. The moderate interobserver repeatability is attributed to the similar echogenicity between the thalamus and its surrounding structures.

Apelin levels in normal pregnancy.

OBJECTIVE: Apelin is an adipokine secreted from adipose and other tissues with increased expression in obesity, role in glucose metabolism and atherosclerosis, as well as in oxidative stress. Pregnancy is considered a state of hyperlipidemia, oxidative stress and decreased insulin sensitivity. The aim of the present study is to investigate the levels of apelin in human pregnancy and its relation to insulin sensitivity. PATIENTS AND MEASUREMENTS: One hundred and six pregnant women (24th-28th week of gestation), aged 27·9 ± 0·4 years, were compared to 106 age-matched healthy, nonpregnant women (controls). Measured parameters included serum levels of glucose, insulin, apelin, adiponectin, total cholesterol, high-density lipoprotein (HDL) and low-density lipoprotein (LDL), triglycerides and oxidized LDL (ox-LDL). The body mass index (BMI) and the quantitative insulin sensitivity check index (QUICKI) were calculated as well. RESULTS: BMI, serum lipids and insulin levels were significantly higher, whereas serum apelin and glucose levels were lower in the pregnancy group compared to the control group. There was a significant negative correlation between apelin and adiponectin, in both groups. Additionally, apelin was negatively correlated with ox-LDL and HDL-cholesterol in the pregnancy group. CONCLUSIONS: Although strongly correlated with adiponectin, apelin cannot be used as a marker of insulin sensitivity, but it could serve as a marker of oxidative stress in pregnancy.

Oxidized low-density lipoprotein and adiponectin levels in pregnancy.

INTRODUCTION: The aim of the present study was to investigate whether normal pregnancy represents a complex state of oxidative stress, inflammation and insulin resistance. SUBJECTS AND METHODS: One hundred and six pregnant women, between 24th and 28th week of pregnancy (age 27.9 ± 0.4 years) (study group) and one hundred and six age-matched, healthy, non-pregnant women (control group) participated in the study. Serum levels of glucose, insulin, adiponectin, oxidized LDL (oxLDL) and lipid parameters, i.e. total cholesterol (TC), triglycerides (TG), HDL and LDL, were determined. Body mass index (BMI) and QUantitative Insulin sensitivity ChecK Index (QUICKI) were also calculated. RESULTS: Pregnant women presented higher BMI values, insulin and oxLDL serum levels and lower glucose serum levels than controls. Serum levels of lipids (TC, TG, LDL and HDL) were higher in pregnant women. There was a significant positive correlation of oxLDL to adiponectin (p < 0.01) in the study group, but not in the controls, and no other significant correlation with any of the other parameters, in either of groups. CONCLUSIONS: Pregnancy is a state of insulin resistance, oxidative stress and pro-atherogenic hyperlipidemia. Adiponectin may, though, have cardioprotective role in pregnant women.

Infant births during the internal night are at increased risk for operative delivery and NICU admission.

PURPOSE: The purpose of the present study was to compare neonatal morbidity between night and the rest of day and investigate potential differences of birth outcomes during the internal night. METHODS: We conducted a retrospective study based on maternal and neonatal data of period 2004-2007, enrolling exclusively spontaneous deliveries of term (≥ 37 weeks), singleton pregnancies with cephalic presentation that were in labor. Time of day was divided into the night-shift period, from 11.00 p.m. to 7.00 a.m. (period 1) and the rest-of-day period, from 7.00 a.m. to 11.00 p.m. (period 2). The night-shift period was further sub-divided into period 1a (11.00 p.m.-3.00 a.m.) and period 1b (3.00 a.m.-7.00 a.m.). Epidemiological and obstetric characteristics as well as neonatal outcomes were initially compared between periods 1 and 2 and thereafter between sub-periods 1a and 1b. RESULTS: There were 3,055 cases with complete data meeting our inclusion criteria, of which 871 (28.5%) were delivered during period 1 and 2,184 (71.5%) during period 2. Furthermore, 51.3% of night-born infants were delivered during period 1a and the remaining 48.7% during period 1b. All examined parameters were not significantly different between periods 1 and 2. Analyzing night internally, the rate of emergent CS was significantly higher for period 1a (13.2%), compared with period 1b (4%). Furthermore, incidence of NICU admission was significantly higher for the first half of the night-shift period (2.7%) compared to the relative of the second half (0.5%). CONCLUSIONS: Neonatal morbidity was comparable between night-shift and rest-of-day periods, but the rates of emergent CS and NICU admission were significantly increased in the first half of the night-shift period (11.00 p.m.-3.00 a.m.).

Effect of type-specific human papillomavirus incidence on screening performance and cost.

BACKGROUND: Implementation of human papillomavirus (HPV) vaccination is expected to change the epidemiology of HPV infection. METHODS: Using age-dependent (inhomogeneous) Markov chains, we tested the effect of type-specific (ie, HPV-16/HPV-18 and other high-risk HPV types) HPV incidence on 3 screening strategies in a cohort of 100,000 women, starting screening at the age of 25 years and continuing until the age of 34 years. All the strategies started with an HPV test; if the result was positive, the next step was triage with cytology (strategy 1), cytology and colposcopy together (strategy 2), or colposcopy only (strategy 3). Published background data were used for the models. RESULTS: Strategy 2 had the highest sensitivity; the absolute number of missed cervical intraepithelial neoplasia (CIN)3+ cases was associated with HPV incidence in all the strategies, but their relative sensitivity remained unaffected. Strategy 2 was cheaper per diagnosed CIN3+ for very low HPV incidence rates, but this changed for higher incidence rates. For any given pair of HPV-16/HPV-18 and other high-risk-type incidence, the cost of the triage and the total cost of screening was highest in screening 2 and lowest in screening 1. For each screening strategy, the cost per diagnosed CIN3+ was mainly determined by the incidence of HPV-16/HPV-18, and the cost of the triage and the total screening cost by the incidence of other high-risk types. CONCLUSIONS: Type-specific HPV incidence affects the absolute number of missed CIN3+ cases and the cost of screening in a mathematically describable way and can be used for prediction of changes in these outcomes with changing HPV epidemiology.