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Objectives: Sexual dysfunction was reported to compromise the quality of life in childhood cancer survivors. The aim of our study was to evaluate the reproductive health in long-term pediatric cancer survivors by conducting a crosscut survey. Material and methods: Childhood cancer survivors over 18 years of age, who were in remission for more than 5 years, were invited to complete a gender-specific questionnaire surveying on their reproductive health. Demographic and treatment data were retrieved from their medical records. Treatment modalities were reviewed for its potential gonadotoxicity. Results: 34 (17 males and 17 females, respectively) from 346 addressed survivors (9.8%) completed the questionnaire. Median age and follow-up after diagnosis was 27 (18–35) and 14 (3–25) years, respectively. Some respondents reported sexual concerns: 11.8% males experienced problems with penetration, two males (11.8%) who underwent semen analysis were found to be azoospermic. Similarly, 11.8% females reported delayed puberty, the average age of menarche was 14 (12–17) years, 29.4% females reported irregular menstrual cycles. Cyclophosphamide equivalent dose (CED) differed significantly between the patients treated for leukemia, lymphoma and solid tumors (3000 vs 4352 vs 6660 mg/m2, respectively, p = 0.014). Conclusions: Low prevalence of sexual dysfunction, fertility related disorders or delayed puberty in childhood cancer survivors was found. However, the results should be interpreted with caution taking into account a low response rate.

// Gabrielis Kundrotas 1,2 , Evelina Gasperskaja 1 , Grazina Slapsyte 1 , Zivile Gudleviciene 2 , Jan Krasko 3 , Ausra Stumbryte 2 and Regina Liudkeviciene 2 1 Department of Botany and Genetics, Faculty of Natural Sciences, Vilnius University, Vilnius, Lithuania 2 Biobank, National Cancer Institute, Vilnius, Lithuania 3 Laboratory of Immunology, National Cancer Institute, Vilnius, Lithuania Correspondence to: Gabrielis Kundrotas, email: // Keywords : human mesenchymal stem cells, genomic stability, long-term expansion, PCR arrays, senescence markers, Gerotarget Received : August 04, 2015 Accepted : February 05, 2016 Published : February 17, 2016 Abstract Human bone marrow mesenchymal stem cells (hBM-MSCs) hold promise for treating incurable diseases and repairing of damaged tissues. However, hBM-MSCs face the disadvantages of painful invasive isolation and limited cell numbers. In this study we assessed characteristics of MSCs isolated from residual human bone marrow transplantation material and expanded to clinically relevant numbers at passages 3-4 and 6-7. Results indicated that early passage hBM-MSCs are genomically stable and retain identity and high proliferation capacity. Despite the chromosomal stability, the cells became senescent at late passages, paralleling the slower proliferation, altered morphology and immunophenotype. By qRT-PCR array profiling, we revealed 13 genes and 33 miRNAs significantly differentially expressed in late passage cells, among which 8 genes and 30 miRNAs emerged as potential novel biomarkers of hBM-MSC aging. Functional analysis of genes with altered expression showed strong association with biological processes causing cellular senescence. Altogether, this study revives hBM as convenient source for cellular therapy. Potential novel markers provide new details for better understanding the hBM-MSC senescence mechanisms, contributing to basic science, facilitating the development of cellular therapy quality control, and providing new clues for human disease processes since senescence phenotype of the hematological patient hBM-MSCs only very recently has been revealed.

Epigenetic alterations of human papillomavirus (HPV) genome play an important role in virus life cycle and carcinogenic progression. The aim of the current study was to investigate the correlation between the grade of cervical pathology and DNA methylation status within the L1 gene and the long control region (LCR) of HPV16, HPV18 and HPV51. HPV genomes were analyzed using bisulfite DNA modification procedure with the subsequent amplification of target DNA regions and sequencing. A collection of 202 cervical specimens was analyzed: 157 HPV16-positive specimens, 21 HPV18-positive specimens and 24 HPV51-positive specimens. This study revealed that methylation of CpG was significantly more prevalent in L1 gene as compared to LCR region of all three studied HPV types and the degree of DNA methylation level correlated with the severity of cervical neoplasia. An increased DNA methylation level of HPV16 promoter region in case of cervical cancer was determined.

Study Question The 16th European IVF-monitoring (EIM) report presents the data of the treatments involving assisted reproductive technology (ART) and intrauterine insemination (IUI) initiated in Europe during 2012: are there any changes compared with previous years? Summary Answer Despite some fluctuations in the number of countries reporting data, the overall number of ART cycles has continued to increase year by year, the pregnancy rates (PRs) in 2012 remained stable compared with those reported in 2011, and the number of transfers with multiple embryos (3+) and the multiple delivery rates were lower than ever before. What is Known Already Since 1997, ART data in Europe have been collected and re-ported in 15 manuscripts, published in Human Reproduction. Study Design, Size, Duration Retrospective data collection of European ART data by the EIM Consortium for the European Society of Human Reproduction and Embryology (ESHRE). Data for cycles between 1 January and 31 December 2012 were collected from National Registers, when existing, or on a voluntary basis by personal information. Participants/Materials, Setting, Methods From 34 countries (+1 compared with 2011), 1111 clinics reported 640 144 treatment cycles including 139 978 of IVF, 312 600 of ICSI, 139 558 of frozen embryo replacement (FER), 33 605 of egg donation (ED), 421 of in vitro maturation, 8433 of preimplantation genetic diagnosis/preimplantation genetic screening and 5549 of frozen oocyte replacements (FOR). European data on intrauterine insemination using husband/partner's semen (IUI-H) and donor semen (IUI-D) were reported from 1126 IUI labs in 24 countries. A total of 175 028 IUI-H and 43 497 IUI-D cycles were included. Main Results and the Role of Chance In 18 countries where all clinics reported to their ART register, a total of 369 081 ART cycles were performed in a population of around 295 million inhabitants, corresponding to 1252 cycles per million inhabitants (range 325-2732 cycles per million inhabitants). For all IVF cycles, the clinical PRs per aspiration and per transfer were stable with 29.4 (29.1% in 2011) and 33.8% (33.2% in 2011), respectively. For ICSI, the corresponding rates also were stable with 27.8 (27.9% in 2011) and 32.3% (31.8% in 2011). In FER cycles, the PR per thawing/warming increased to 23.1% (21.3% in 2011). In ED cycles, the PR per fresh transfer increased to 48.4% (45.8% in 2011) and to 35.9% (33.6% in 2011) per thawed transfer, while it was 45.1% for transfers after FOR. The delivery rate after IUI remained stable, at 8.5% (8.3% in 2011) after IUI-H and 12.0% (12.2% in 2011) after IUI-D. In IVF and ICSI cycles, 1, 2, 3 and 4+ embryos were transferred in 30.2, 55.4, 13.3 and 1.1% of the cycles, respectively. The proportions of singleton, twin and triplet deliveries after IVF and ICSI (added together) were 82.1, 17.3 and 0.6%, respectively, resulting in a total multiple delivery rate of 17.9% compared with 19.2% in 2011 and 20.6% in 2010. In FER cycles, the multiple delivery rate was 12.5% (12.2% twins and 0.3% triplets). Twin and triplet delivery rates associated with IUI cycles were 9.0%/0.4% and 7.2%/0.5%, following treatment with husband and donor semen, respectively. LIMITATIONS, REASONS FOR CAUTION The method of reporting varies among countries, and registers from a number of countries have been unable to provide some of the relevant data such as initiated cycles and deliveries. As long as data are incomplete and generated through different methods of collection, results should be interpreted with caution. Wider Implications of the Findings The 16th ESHRE report on ART shows a continuing expansion of the number of treatment cycles in Europe, with more than 640 000 cycles reported in 2012 with an increasing contribution to birthrate in many countries. However, the need to improve and standardize the national registries, and to establish validation methodologies remains manifest. STUDY FUNDING/COMPETING INTERESTS The study has no external funding; all costs are covered by ESHRE. There are no competing interests.

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).

Objective: Head and neck squamous cell carcinoma (HNSCC) is a disease attributed to exposure to tobacco and alcohol. However, many epidemiological and molecular data suggest that human papillomavirus (HPV) infection may promote head and neck carcinogenesis. The objective of our study was to evaluate the prevalence of HPV and its various types in fresh HNSCC tumor samples using the polymerase chain reaction (PCR). Methods: 48 patients with primary diagnosed HNSCC carcinoma were investigated. HPV DNA was detected using PCR. HPV-positive samples were additionally tested for HPV16 and 18. Results: Of the 48 patients, 13 (27.1%) had detectable HPV. After HPV typing, HPV16 was found in only 4 cases (30.1%). Conclusions: Our study demonstrated a HPV detection rate of 27.1% in Lithuanian HNSCC patients; 30.1% of them harbored HPV16. There were no differences regarding the other risk factors (smoking, alcohol consumption and occupational history) between HPV-positive and HPV-negative patients with head and neck cancer in our study.

Human papillomavirus (HPV) is the main cause of cervical cancer. Therefore, the detection of oncogenic HPV types is important in predicting the risk of cervical cancer. The aim of the current study was to estimate the prevalence of 16 carcinogenic and potentially carcinogenic HPV types in the study group of Lithuanian women with various grades of cervical pathology in comparison to healthy women. A total of 824 cervical specimens were investigated for HPV DNA: 547 specimens of women with abnormal cytology and 277 specimens of healthy women. Cytological diagnosis was confirmed by histology. For the detection of HPV infection, HPV DNA was amplified by PCR using three different primer systems. HPV DNA was detected in 67.6% of specimens collected from women with abnormal cytology and 24.2% of specimens collected from healthy women. The frequency of HPV-positive specimens correlated with the severity of cervical pathology: it ranged from 50.0% in the subgroup of atypical squamous cells to 80.6% in cervical cancer. In cases confirmed by histology the frequency of HPV-positive specimens ranged from 68.6% in the subgroup of cervical intraepithelial neoplasia grade 1 to 89.2% in cervical intraepithelial neoplasia grade 3 or carcinoma in situ. HPV DNA-positive samples were further investigated for the presence of 16 HPV types by multiplex PCR. The most common HPV type was HPV 16 (detected in 42.3% of HPV-positive specimens) followed by HPV 31 (10.1%), HPV 33 (8.2%), and HPV 56 (5.7%). In contrast, the frequency of HPV 18 was lower as compared to other countries.

Overall, head and neck sqamous cell carcinoma accounts for more than 550,000 cases annually worldwide. It is well known that human papillomavirus (HPV) is the main risk factor for cervical cancer development. As the incidence and the mortality of cervical cancer are closely related to the HPV prevalence, we hypothesized that there is the same association between HPV prevalence and head and neck squamous cell carcinoma. Therefore we performed the study aiming to compare the level of HPV infection and HPV type distribution between two groups of Lithuanian and Belarusian patients with head and neck sqamous cell carcinoma. One hundred ninety head and neck sqamous cell carcinoma patients were included in the study, 75 from Lithuania and 115 from Belarus. PCR was used for HPV detection and typing. The distribution of HPV infection among head and neck sqamous cell carcinoma patients was similar in the Lithuanian (20.0%) and Belarusian (18.3%) patient groups, however differences were found in the distribution of HPV types.

Cervical cancer is one of the most common cancers in Lithuania. It is the fourth cancer in women according to the morbidity. The incidence rate of cervical cancer has been increasing in Lithuania since 1992. One of the important risk factor for cervical cancer is human papillomavirus (HPV) infection. The aim of this study is to compare the prevalence of human papillomavirus among cervical cancer patients and women with cervical intraepithelial lesions and healthy women, to determine its types and HPV 16 variants. Polymerase chain reaction and DNA sequencing were used for analysis of specimens taken from cervix uteri. Human papillomavirus was detected in 92.7% of cervical cancer patients and in 26.7% of control women (p0.0001). It is important to notice that prevalence of HPV in women with high-grade squamous intraepithelial lesions was higher than in the control group. HPV 16 (55.8% in squamous cell carcinoma patients and 35.3% in cervical adenocarcinoma patients) and its European HPV 16 L83V variant were detected more frequently in cervical cancer patients. Studies on HPV, prevalence of its types and variants are very important for HPV based preventive strategies, especially for the vaccination.

Cervical cancer is the fourth most common cancer for women in Lithuania. One of the important cervical cancer risk factors is human papillomavirus (HPV) infection. Recent literature has considered p53 allelic polymorphism to be a putative predisposing factor for cervical carcinoma development.The aim of this study was to elucidate the prevalence of HPV, especially HPV 16, in cervical cancer patients and in healthy women, to investigate the distribution of p53 gene 72 codon polymorphism and to correlate these to cervical cancer risk in Lithuanian women.588 women were included in the study: 212 women with primary diagnosed cervical cancer (case group) and 376 healthy volunteers (control group).A high prevalence of HPV DNA was detected in cervical cancer patients, 92.0%, and in control women, 23.6% (P0.0001). HPV 16 is the most frequent HPV type in cervical cancer patients. In the case of squamous cell carcinoma, this type was detected in 55.8%, in adenocarcinoma - 35.3%. In the control group, this type was detected in 19.0%. A statistically significant difference in the distribution of p53 alleles between the case and the control groups was found.Cervical cancer risk in Lithuanian patients is associated with HPV infection (OR = 75.39; 95% CI 33.61-192.98), especially HPV 16 type (OR = 100.3; 95% CI 46.05-238.59) and p53 homozygous Arg/Arg allele (OR = 2.10; 95% CI 1.10-4.19).