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Self-sampling for human papillomavirus (HPV) testing is an alternative to physician sampling particularly for cervical cancer screening nonattenders. The GRECOSELF study is a nationwide observational cross-sectional study aiming to suggest a way to implement HPV-DNA testing in conjunction with self-sampling for cervical cancer screening in Greece, utilizing a midwifery network. Women residing in remote areas of Greece were approached by midwives, of a nationwide network, and were provided with a self-collection kit (dry swab) for cervicovaginal sampling and asked to answer a questionnaire about their cervical cancer screening history. Each sample was tested for high-risk (hr) HPV with the Cobas HPV test. HrHPV-Positive women were referred to undergo colposcopy and, if needed, treatment according to colposcopy/biopsy results. Between May 2016 and November 2018, 13,111 women were recruited. Of these, 12,787 women gave valid answers in the study questionnaire and had valid HPV-DNA results; hrHPV prevalence was 8.3%; high-grade cervical/vaginal disease or cancer prevalence was 0.6%. HrHPV positivity rate decreased with age from 20.7% for women aged 25–29 years to 5.1% for women aged 50–60 years. Positive predictive value for hrHPV testing and for HPV16/18 genotyping ranged from 5.0% to 11.6% and from 11.8% to 27.0%, respectively, in different age groups. Compliance to colposcopy referral rate ranged from 68.6% (for women 25–29) to 76.3% (for women 40–49). For women residing in remote areas of Greece, the detection of hrHPV DNA with the Cobas HPV test, on self-collected cervicovaginal samples using dry cotton swabs, which are provided by visiting midwives, is a promising method for cervical cancer secondary prevention.

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Background: Human papillomavirus (HPV)-DNA testing combined with self-sampling could increase cervical cancer screening effectiveness, utilizing a sensitive screening modality and an easy sampling method with minimal pain or discomfort. Self-sampling acceptability, though, is pivotal. Materials and Methods: This study is a nested cross-sectional survey within GRECOSELF, a cross-sectional study on HPV-based screening with self-sampling, aiming at investigating self-sampling acceptability among Greek women residing in rural areas, and the factors affecting it. Women between 25 and 60 years old were recruited by midwives participating in a nationwide midwifery network. Participants, after self-sampling, filled out a questionnaire with three sections, one regarding demographic characteristics, a second with questions pertaining to the participants' cervical cancer screening history, and a third with questions regarding the self-sampling process per se. Results: The sample included 13,111 women. Most participants (67.9%), including those screened or not in the past, would prefer self-sampling if assured that the results are not inferior to standard testing. Discomfort or pain during self-sampling was absent or minimal in 97.1% and 96.5% of the cases, respectively, and 74.4% of the women felt adequately confident that they followed the instructions correctly. Women mostly preferred self-sampling at home compared with health care facilities. Pain and discomfort during the procedure, although rare, were significant factors against acceptance. Most of the women reporting a negative impression had a negative experience with conventional sampling in the past. Conclusion: Self-sampling is highly acceptable. Acceptance can be further improved with proper communication of the process and its noninferiority compared with conventional screening.

Self-sampling for human papillomavirus (HPV) testing is an alternative to physician sampling particularly for cervical cancer screening nonattenders. The GRECOSELF study is a nationwide observational cross-sectional study aiming to suggest a way to implement HPV-DNA testing in conjunction with self-sampling for cervical cancer screening in Greece, utilizing a midwifery network. Women residing in remote areas of Greece were approached by midwives, of a nationwide network, and were provided with a self-collection kit (dry swab) for cervicovaginal sampling and asked to answer a questionnaire about their cervical cancer screening history. Each sample was tested for high-risk (hr) HPV with the Cobas HPV test. HrHPV-Positive women were referred to undergo colposcopy and, if needed, treatment according to colposcopy/biopsy results. Between May 2016 and November 2018, 13,111 women were recruited. Of these, 12,787 women gave valid answers in the study questionnaire and had valid HPV-DNA results; hrHPV prevalence was 8.3%; high-grade cervical/vaginal disease or cancer prevalence was 0.6%. HrHPV positivity rate decreased with age from 20.7% for women aged 25–29 years to 5.1% for women aged 50–60 years. Positive predictive value for hrHPV testing and for HPV16/18 genotyping ranged from 5.0% to 11.6% and from 11.8% to 27.0%, respectively, in different age groups. Compliance to colposcopy referral rate ranged from 68.6% (for women 25–29) to 76.3% (for women 40–49). For women residing in remote areas of Greece, the detection of hrHPV DNA with the Cobas HPV test, on self-collected cervicovaginal samples using dry cotton swabs, which are provided by visiting midwives, is a promising method for cervical cancer secondary prevention.

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.

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.

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.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.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.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.

Objective Several studies have implicated PAX1 epigenetic regulation in cervical neoplasia. The aim of this meta-analysis was to assess PAX1 gene methylation as a potential biomarker in cervical cancer screening. Methods A systematical search of all major databases was performed, in order to include all relevant publications in English until December 31 st 2014. Studies with insufficient data, conducted in experimental models or associated with other comorbidities were excluded from the meta-analysis. Summary receiver operating characteristics (SROC) for Cervical Intraepithelial Neoplasia grade 2 or worse (CIN2 + ) versus normal, and CIN grade 3 or worse (CIN3 + ) versus normal, were estimated using the bivariate model. Results Out of the 20 initially included studies, finally 7 (comprising of 1385 subjects with various stages of CIN and normal cervical pathology) met the inclusion criteria. The sensitivity of CIN2 + versus normal was estimated to be 0.66 (CI 95%, 0.46-0.81) and the specificity 0.92 (CI 95%, 0.88-0.95). On the other hand, the sensitivity of CIN3 + versus normal was 0.77 (CI 95%, 0.58-0.89) and the specificity 0.92 (CI 95%, 0.88-0.94). Moreover, the area under the curve (AUC) in the former case was 0.923, and in the latter 0.931. Conclusion The results of this meta-analysis support the utility of PAX1 methylation as an auxiliary biomarker in cervical cancer screening. PAX1 could be used effectively to increase the specificity of HPV DNA by detecting women with more advanced cervical abnormalities.

A systematic review of the literature has been conducted (last update March 2014) for clinical studies reporting the prevalence of human papillomavirus (HPV) in the offspring of HPV-infected women in association to their mode of delivery. A meta-analysis was carried out according to the identification of concordant neonatal to maternal HPV types. Overall eight studies were included in the meta-analysis. Our pooled results, showed that caesarean section is associated with significantly lower rates of HPV transmission than vaginal birth (14.9% vs. 28.2%, risk ratio or RR: 0.515, 95% confidence interval or CI: 0.34-0.78). The number of caesarean sections needed to prevent one case of perinatal infection (number needed to treat or NNT) would be 7.5. As a conclusion it should be noted that caesarean section decreases the risk for perinatal HPV transmission by approximately 46%. Perinatal transmission still occurs in approximately 15% of the children born by caesarean section.

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.

Objective To investigate the association of preeclampsia with angiogenic imbalance, and the correlation of levels of angiogenic and anti-angiogenic factors to complications in mother and fetus. Study design Serum samples were obtained from 40 women with established preeclampsia (study group) and from 40 normotensive women (control group). Epidemiological characteristics of the two groups were analyzed. The levels of the angiogenic (VEGF and PlGF) and anti-angiogenic (sFlt-1) factors of the two study groups were determined in serum using ELISA. Neonatal adverse outcomes (late preterm, early term, low birth weight (LBW), very LBW (VLBW), intrauterine growth restriction (IUGR), and neonatal intensive care unit (NICU) admission) between the groups of the study were analyzed, as well as the association between the biomarkers of the study and neonatal adverse outcomes of the preeclamptic group of patients. Results sFlt-1 levels were significantly higher in the preeclamptic women compared to normotensive women (median (range): 21 297 (690–32 637) pg/ml vs. 846.45 (363–2867) pg/ml, respectively), whereas there was a significant decrease in the levels of VEGF (90 (90–211) pg/ml vs. 90.55 (90–521) pg/ml, respectively), as well as in the levels of PlGF (13.62 (8–532) pg/ml vs. 239.86 (61–685) pg/ml, respectively). The increased serum values of the anti-angiogenic sFlt-1 were associated with increased rates of late preterm and early term births and VLBW. Conclusion An imbalance between angiogenic and anti-angiogenic factors exists in preeclampsia and is associated with adverse maternal and neonatal outcomes.

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.

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. 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. 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). 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.

To compare the incidence of obstetric and neonatal outcomes between native and immigrant women. A retrospective cohort of singleton pregnancies was conducted concerning the period 2003-2009. Women were divided in group 1, including natives and group 2, including immigrants. Epidemiological characteristics, obstetric outcomes and neonatal morbidity parameters were studied. Out of 7033 singleton pregnancies delivered during this period, 6980 with complete information were finally included. Immigrants consisted 47.59 % of all gravidas (group 2, n = 3322), presenting significantly lower rates of emergency caesarean section, preeclampsia, preterm delivery, placenta praevia and fetal distress. Furthermore, all parameters of neonatal morbidity, including Mean Apgar score in the 1st and 5th minute as well as rates of NICU admission and emergency intubation were significantly improved in the group of immigrants. According to our results, pregnancies of immigrant women are less likely to be complicated by severe obstetric and neonatal outcomes.

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. (c) 2012 Wiley Periodicals, Inc. J Clin Ultrasound, 2012. J Clin Ultrasound

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. 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. 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. 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.

Summary 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.

The aim of the present study was to investigate whether normal pregnancy represents a complex state of oxidative stress, inflammation and insulin resistance.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.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 (p0.01) in the study group, but not in the controls, and no other significant correlation with any of the other parameters, in either of groups.Pregnancy is a state of insulin resistance, oxidative stress and pro-atherogenic hyperlipidemia. Adiponectin may, though, have cardioprotective role in pregnant women.

ObjectivePregnancy represents a state of insulin resistance (IR). Vaspin (SERPINA12) is a novel insulin-sensitizing adipokine that might be implicated in endogenous glucose regulation. However, its role in pregnancy and its circulating levels have not been adequately studied. We aimed to evaluate serum vaspin levels in pregnancy and their correlation with known markers of IR.DesignA group of 106 women (age 27.9±0.4 years) at the 24–30th week of gestation (pregnancy group) and another 106 age-matched healthy non-pregnant controls (control group) were included in the study.MethodsSerum glucose, insulin, vaspin, adiponectin, and lipid parameters were measured. The quantitative insulin sensitivity check index (QUICKI) was used as an insulin sensitivity index.ResultsPregnant women had significantly higher body mass index (BMI), lipids, and serum insulin and lower serum glucose and vaspin levels than controls. Vaspin was positively correlated to adiponectin in both groups (PPConclusionsVaspin cannot serve as a marker of IR in either pregnant or non-pregnant women, although it is significantly correlated with adiponectin. On the other hand, vaspin might be useful as a surrogate marker of lipid metabolism in pregnancy if confirmed by subsequent studies.

Endometrial cancer is uncommon in young women. However, almost 5% of patients are younger than 40 years old. Progestins such as medroxyprogesterone acetate (MPA) and megestrol acetate (MA), have been used as a fertility-sparing approach in this group of patients, with different dose regimens of cyclic (14 days every month) or continuous therapy successfully used. According to the present data, the overall response rate was 73% in a median time of 4 months (range 1-15 months). Endometrial biopsy every 3 months was the common approach to evaluate the patient's response during the treatment. The relapse rate was 36% in a median follow-up time of 22 months (range 6-73 months). Overall, 40% of patients who responded to the treatment successfully, conceived. Half of the patients used assisted reproductive technology to achieve an immediate pregnancy. Although, there are no definite recommendations concerning the conservative management of young patients with early stage endometrial cancer, progestin agents may be used in a selected group of patients for fertility-sparing reasons. After childbearing is completed, hysterectomy remains the standard treatment.

The most compelling question in evaluating the possible replacement of the conventional Papanicolaou smear from a high-risk HPV testing method is the balance between specificity and sensitivity for detection of cervical intraepithelial neoplasia grade ≥CIN 2 (CIN 2+). Multiple studies have shown that HPV testing has higher sensitivity than cytology for the detection of high-grade CIN. Positivity increases the test cut-off for HPV and may reduce false positive results without significantly compromising the sensitivity, potentially alleviating the concern of low specificity. Overall, available evidence convincingly shows that HPV testing is superior to traditional screening for the detection of high-grade cervical lesions, and efforts are focused on improving its sensitivity, either by increasing its cut-off for positivity or by selecting those subgroups where HPV testing is expected to have higher positive predictive value for cervical disease, or by seeking to optimize triage tests after a positive HPV result.

Despite the advent of the Papanicolaou smear test almost 50 years ago, cervical cancer remains the second most common malignant disease in women and the leading cause of cancer death in developing countries. Thus the two prophylactic human papillomavirus (HPV) vaccines currently available have been greeted with enthusiasm internationally, as an emerging primary prevention strategy against cervical cancer. Prior to licensure the vaccines were trialed in over 60,000 women and assessed as safe, within the statistical constraints of the trials to detect very rare events. Post-licensure surveillance is underway as vaccination programs are undertaken. We reviewed published post-licensure surveillance data, as at January 2009, and concur with international advisory bodies that both HPV vaccines are safe, effective and of great importance for women's health. Ongoing monitoring is required to maintain confidence in the safety of the vaccines.

As knowledge of regional human papillomavirus (HPV) type distribution is essential for the optimization of prevention strategies, this study was carried out to explore the prevalence and type distribution of high-risk HPV in a screening population across Greece. Cervical samples were collected by local physicians and nurses in hospitals and health centers across the country from 4139 women attending for cervical cancer screening. High-risk HPV-DNA was detected by using Hybrid Capture-2 (HC2) and positive samples with adequate cellular content were further typed by restriction fragment length polymorphism-polymerase chain reaction. Almost six percent (5.9%) of women tested positive in HC2. The most common type was HPV16 (1.4% in the whole sample and 32.4% of the typed samples), followed by HPV53 (0.6 and 14.0%, respectively), HPV31 (0.6 and 12.9%, respectively), HPV35 (0.5 and 12.3%, respectively), HPV51 (0.4 and 7.8%, respectively), HPV18 (0.3 and 7.3%, respectively) and 22 more types. Almost 15% of the typed samples showed a coinfection with two HPV types and 2.1% with three types. There was a bimodal distribution by age, with the highest peak in women 20-29 years old and a lower peak in women 50-59 years old. Apart from the types originally included in HC2 cocktail, PCR analysis identified 15 more types (HPV6, HPV11, HPV34, HPV37, HPV38, HPV42, HPV53, HPV54, HPV55, HPV61, HPV62, HPV66, HPV73, HPV82, HPV83). Eleven percent of HC2-positive results arose from single-type infections with HPV53 (10%) and HPV66 (1%), which are potentially high-risk types. In conclusion, HPV16 is the most common type in the largest Greek screening sample used to date and, together with its related types, accounts for more than half of high-risk HPV infections. Approximately 10% of positive HC2 results arise from HPV53, which is not normally detected by the test, but may be clinically significant.

Background Cervical cancer is caused primarily by human papillomaviruses (HPV). The polymorphism rs1042522 at codon 72 of the TP53 tumour-suppressor gene has been investigated as a genetic cofactor. More than 80 studies were done between 1998 and 2006, after it was initially reported that women who are homozygous for the arginine allele had a risk for cervical cancer seven times higher than women who were heterozygous for the allele. However, results have been inconsistent. Here we analyse pooled data from 49 studies to determine whether there is an association between TP53 codon 72 polymorphism and cervical cancer.Methods Individual data on 7946 cases and 7888 controls from 49 different studies worldwide were reanalysed. Odds ratios (OR) were estimated using logistic regression, stratifying by study and ethnic origin. Subgroup analyses were done for infection with HPV, ethnic origin, Hardy-Weinberg equilibrium, study quality, and the material used to determine TP53 genotype.Findings The pooled estimates (OR) for invasive cervical cancer were 1.22 (95% CI 1.08-1-39) for arginine homozygotes compared with heterozygotes, and 1.13 (0.94-1.35) for arginine homozygotes versus proline homozygotes. Subgroup analyses showed significant excess risks only in studies where controls were not in Hardy-Weinberg equilibrium (1.71 [1.21-2.42] for arginine homozygotes compared with heterozygotes), in non-epidemiological studies (1.35 [1.15-1.58] for arginine homozygotes compared with heterozygotes), and in studies where TP53 genotype was determined from tumour tissue (1.39 [1.13-1.73] for arginine homozygotes compared with heterozygotes). Null results were noted in studies with sound epidemiological design and conduct (1.06 [0.87-1.29] for arginine homozygotes compared with heterozygotes), and studies in which TP53 genotype was determined from white blood cells (1.06 [0.87-1.29] for arginine homozygotes compared with heterozygotes).Interpretation Subgroup analyses indicated that excess risks were most likely not due to clinical or biological factors, but to errors in study methods. No association was found between cervical cancer and TP53 codon 72 polymorphism when the analysis was restricted to methodologically sound studies.Funding German Research Foundation (DFG).

Ajuts: the present study was developed on a self-funding base, using a personal budget of Evangelia Pavlidou for the reagents used in the laboratory analysis. 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.

Persistent infections by high-risk papilloma viruses (HPV) are the main etiological factor for cervical cancer, and E7 oncoproteins were suggested as new markers for tumor progression. The objective of this study was to generate a new Enzyme-Linked Immunosorbent Assay (ELISA)-based detection system to monitor expression of the E7 proteins of the high-risk HPV (hrHPV) types HPV-16, HPV-18, and HPV-45 in cervical smears. Using a combination of rabbit monoclonal antibodies raised against E7 proteins of HPV-16 and HPV-18/HPV-45, respectively, a trivalent E7-ELISA was developed and validated, using recombinant E7 proteins of various HPV types and lysates from E7- positive cervical carcinoma cells. The amount of 0.5 picogram of E7 protein per well was determined as detection limit. The E7-ELISA was used to determine E7 protein levels in cervical smears obtained from a total of 67 women. E7 protein concentration was below the detection limit in all HPV-negative smears, and E7 protein concentrations above background were found in some HPV-positive cervical samples. Together the work described herein provides a new tool for the simultaneous detection of E7 proteins of the three most prevalent in cervical neoplasia hrHPV types.

Aim: To investigate a possible relationship between tibolone therapy and recurrence or mortality in breast cancer survivors. Methods: In a retrospective study, data from files of 247 patients who had been treated for breast cancer were analyzed. Twenty women were treated with tibolone because of menopausal symptoms (Group 1: mean duration of tibolone use 37.1 months). One hundred and one women who did not take tibolone were selected as the control group (Group 2). All women were followed up in our Department on our standard protocol (mean follow up: 73.4 months in Group 1, 67.4 months in Group 2). Comparison of the survival curves was applied with the Wilcoxon (Gehan) statistic. Cox regression analysis was also applied in order to identify significant coefficients in the survival curve. Results: Recurrence of breast cancer was observed in two (10%) Group 1 women versus 21 (21%) Group 2 women (P = NS). Two Group 1 women died (one from breast cancer recurrence) versus 15 Group 2 women (14 from breast cancer recurrence). Conclusions: Despite of the inherent limitations of this small retrospective study, it seems that tibolone does not reveal an apparent negative impact on breast cancer outcome when given to breast cancer survivors.

Objective. To compare the performance of human papillomavirus (HPV) DNA detection against routine Papanicolaou smear for the detection of low- and high-grade cervical intraepithelial neoplasia in a low-risk population. Materials and methods. A cross-sectional study was performed involving 1296 women attending six outpatient clinics in Northern Greece (Thessaloniki, Thermi, Mihaniona, Corfu, Veria, and Serres). Women underwent a gynecological examination, including collection of exfoliated cervical cells for Papanicolaou cytology and HPV DNA detection. Cytology was processed according the conventional routine manner, and HPV DNA was determined using the polymerase chain reaction technique. In positive cases of either method, a complete colposcopic evaluation was performed with directed biopsies. Tests (HPV DNA, cytology, and colposcopy) performance characteristics were determined using the histopathologic diagnosis as the reference standard. Results. HPV DNA testing showed a significantly better sensitivity than the Papanicolaou smear in detecting cervical intraepithelial neoplasia (75% versus 50% for high-grade lesions and 81.2% versus 50% for lesions of any grade, respectively). Specificity, and positive and negative predictive values did not significantly differ. Even after dividing women in younger or older than 30 years, the sensitivity of the HPV DNA test was greater than cytology (100% and 70% versus 50% for cytology in both groups, respectively), with a 6.3% loss in specificity when performed in women younger than 30 years. Conclusion. HPV testing could be useful in screening women at low risk for cervical cancer, either as an adjunct tool to augment existing cytology programs or as a unique test of its own.

The polymorphism of codon 72 in the p53 tumour suppressor gene has been associated in the last decade with the risk of developing various neoplasias. An influence of this polymorphism on ovarian and endometrial cancer has also been suggested. We examined the genotype frequency of this polymorphism in archival samples from 56 patients with endometrial neoplasias and 51 patients with ovarian neoplasias. Cervical smears from 30 healthy, human papillomavirus (HPV)-negative women with normal cytology and colposcopy, served as control sample. Women with ovarian neoplasias, especially adenocarcinomas, had Arg/Arg more often than healthy controls [odds ratio (OR) 4.16 at P = 0.0058]. No statistically significant difference was found between women with endometrial cancer and controls. Differentiation of ovarian tumours did not appear to be associated in a statistically significant manner with the genotype, whereas a positive linear trend of Arg/Arg towards poor differentiation was noted in endometrial malignancies (mainly endometrioid adenocarcinomas). Our results suggest that homozygous arginine at codon 72 of p53 may represent a risk factor for developing ovarian malignancies and may affect the differentiation of endometrial cancer. Further studies need to be carried out in order to establish the clinical use of this polymorphism for risk assessment and possibly outcome prediction of ovarian and endometrial neoplasias.

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.

The aim of the present cohort study was to assess the long-term (follow-up period up to 22 years) recurrence rate of preinvasive disease and the newly detected invasive disease rate in a cohort of women treated with excisional methods for high-grade cervical intraepithelial neoplasia (CIN). Women treated with large loop excision of the transformation zone (LLETZ) and cold knife conization (CKC) for histologically proven high-grade CIN were followed up for up to 22 years. Surgical specimens underwent histological examination and the status of endocervical as well as ectocervical margins was recorded. Follow-up protocol included conventional Pap test, colposcopy and pelvic examination at 3, 6, and 12 months after the initial treatment, and every 12 months thereafter, provided that the results were normal. In case of high-grade cytological findings and/or atypical colposcopic impression, multiple punch biopsies were taken in order to verify or exclude recurrent disease. In total, 804 women were followed for a mean time of 77.1 months (range: 6–266). LLETZ was used in 569 (70.7%) and CKC in 235 cases (29.2%). No woman developed invasive cervical cancer. Recurrent high-grade disease, developed in 9 women (1.1%, 95% confidence interval 0.5–2.2). Median treatment-to-recurrence time was 46.5 months (range: 6–235.3). One woman treated for squamous CIN2 on clear margins developed adenocarcinoma in situ 59.2 months post-treatment. Women having undergone excisional treatment for high-grade CIN indicate a very low risk for recurrent disease and potentially negligible risk for invasive cancer, provided that a strict and vigorous follow-up is offered after treatment.

Inherited thrombophilia has been associated with obstetric complications through mechanisms that are not yet fully elucidated. The aim of this study was to investigate the relationship between specific obstetric adverse outcomes and factor V Leiden and prothrombin G20210A mutations.Forty-five women with adverse pregnancy outcome defined as severe pre-eclampsia, abruptio placentae, intrauterine growth restriction and stillbirth, were tested for factor V Leiden and prothrombin G20210A mutations. The control group comprised 100 women with at least one normal pregnancy and no history of thrombosis.Overall, 13 women with one or more of the above-mentioned pregnancy complications (28%) had either thrombophilic mutation, as compared with six in the control group (6%) (p0.001, odds ratio (OR) 6.1; 95% confidence interval (CI) 1.9-20). The factor V Leiden mutation was detected in ten of the women with complicated pregnancies (22%) and in four of the controls (4%) (p0.001, OR 6.6; 95% CI 1.7-27.2). The prothrombin G20210A mutation was detected in three women in the group with complications (6%) and in two of the controls (2%) (p = 0.17, OR 3.4; 95% CI 0.4-30.5). Compared to controls, the prevalence of the factor V Leiden mutation was significantly higher in the subgroups of severe pre-eclampsia, abruptio placentae and fetal growth restriction. The prevalence of the prothrombin G20210A mutation does not appear to be significantly different from that in the controls in any of the groups studied.Our data suggest that inherited thrombophilia, and specifically the factor V Leiden mutation, may be associated with adverse pregnancy outcome. The role of the prothrombin G20210A mutation remains to be elucidated.

The objective of this study was to assess the overall prevalence of the human papilloma virus (HPV) infection and distribution of high-risk HPV (hrHPV) types in Greece and evaluate the participation of women in primary and secondary cervical cancer prevention. This was a prospective, cross-sectional study carried out between October 2005 and January 2011 in Greece; 5379 women filled out the study questionnaire anonymously. 5107 women underwent cervical HPV-DNA testing, either by Hybrid Capture 2, followed by restriction fragment length polymorphism-PCR, or by the Abbott Real-Time High-Risk HPV test. Overall, 5.8% (295/5107) of women were positive for hrHPV infection. The most common hrHPV type was HPV-16 (24.8% among infected women; 1.4% overall), followed by HPV types 31, 35, 53, 18, 51, 56, 58, 52, 39, 66, 45, 33, 59, and 68. In respect to primary prevention of cervical cancer, acceptance of anti-HPV vaccination appeared to decrease over time (from 85-89.9% annually during 2005-2008 to 64.4-60.5% during 2009-2010, P

To investigate the possible effect of demographic factors on HPV vaccination acceptance in Greece. 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. 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. 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.