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Background Human papillomavirus (HPV) is the main cause of cervical cancer. HPV-vaccines have led to a significant decrease in HPV-infections and related cancer cases. The estimation of the current HPV-prevalence and distribution of different HPV-types among women with cervical dysplasia in the post-vaccination era is of great importance for the future vaccination strategy.Methods By using a multiplexed bead-based immunoassay, we revealed the prevalence of 27 HPV-types in 170 dysplasia women from Sweden, a country with high HPV-vaccination coverage.Results The prevalence of HPV in low-and high-grade squamous intraepithelial lesions (LSIL and HSIL, respectively) were 56.3% and 76.7%, respectively. The oncogenic HPV-types constituted 80.0%, and 97.1% among the HPV-positive LSIL and HSIL-groups, respectively, with HPV16 as the most prevalent type. We found a reduction in HPV-types covered by quadrivalent-Gardasil® vaccine in the vaccinated HSIL-group, suggesting the efficiency of the HPV-vaccine in preventing dysplasia caused by the covered HPV-types. Oncogenic HPV-types 39 and 59, not covered by any current vaccine have a high prevalence among patients with cervical dysplasiaConclusions Oncogenic-HPV-types are highly prevalent among women with HSIL. The current vaccine presents a high efficiency for reducing the covered HPV-types among dysplasia patients. Lastly, we provide evidence for the oncogenic-HPV-types that should be covered in the next generation of HPV-vaccines.

Context: The transition from medical student to junior doctor is challenging. Junior doctors need to become part of the physician community of practice (CoP), while dealing with new responsibilities, tasks and expectations. At the same time, they need to learn how to navigate the frontiers and intersections with the other communities of practice that form the Landscape of Practice (LoP). This study aims to understand how junior doctors experience interprofessional collaboration (IPC) and what elements shape these experiences considering their transition to clinical practice.Methods: In this multicentre qualitative study, 13 junior doctors individually drew two rich pictures of IPC experiences, one positive and one negative. A rich picture is a visual representation, a drawing of a particular situation intended to capture the complex and non-verbal elements of an experience. We used semi-structured interviews to deepen the understanding of junior doctors' depicted IPC experiences. We analysed both visual materials and interview transcripts iteratively, for which we adopted an inductive constructivist thematic analysis.Results: While transitioning into a doctor, junior doctors become foremost members of the physician CoP and shape their professional identity based on perceived values in their physician community. Interprofessional learning occurs implicitly, without input from the interprofessional team. As a result, junior doctors struggle to bridge the gap between themselves and the interprofessional team, preventing IPC learning from developing into an integrative process. This professional isolation leaves junior doctors wandering the landscape of practice without understanding roles, attitudes and expectations of others.Conclusions: Learning IPC needs to become a collective endeavour and an explicit learning goal, based on multisource feedback to take advantage of the expertise already present in the LoP. Furthermore, junior doctors need a safe environment to embrace and reflect on the emotions aroused by interprofessional interactions, under the guidance of experienced facilitators.

Purpose The primary aim of this study was to assess patient-centeredness of endometriosis care in a national sample of Swedish women with endometriosis. The secondary aims were to assess the importance of different dimensions of endometriosis care and to analyze demographic and clinical determinants associated with the experience of patient-centeredness. Methods This cross-sectional study included 476 women with confirmed endometriosis. An invitation to participate was sent to 1000 randomly selected women aged ≥ 18 years having any endometriosis diagnosis and who had visited a gynecological clinic due to endometriosis problems any time during the past five years. Participants were recruited from ten different-sized gynecology clinics all over Sweden. The invitation letter had a link to the digital survey, which consisted of demographic and clinical questions, and the ENDOCARE questionnaire (ECQ). ECQ measures experiences, importance and patient-centeredness of ten dimensions of endometriosis care. Univariate and multiple regression analyses were used to analyze which patient-specific demographic and clinical determinants were associated with the experience of patient-centeredness. Results The response rate was 48%. The results indicate that Swedish women with endometriosis experience low patient-centeredness and rate relational aspects with healthcare professionals as the most important aspects of care. Having a gynecologist with patient responsibility was an independent predictor for high patient-centeredness. Conclusion Women with endometriosis in Sweden experience low patient-centeredness, reflecting the urgent need for improvement. More effort should be given to develop the relational aspects of care. Women with endometriosis should have a responsible gynecologist to care for treatment and follow-up.

Introduction Obesity-associated adverse obstetric outcomes are well-known but still relatively rare and difficult to predict. Not all obese individuals are unhealthy; some have metabolically healthy obesity (MHO) and others have metabolic unhealthy obesity (MUO). Our aim was to investigate whether the MHO and MUO classification could be used for prediction of obesity-associated complications in pregnancy. Material and methods We included 547 pregnant women with obesity, 2302 pregnant women with overweight and 5852 normal weight pregnant women. The women with obesity were classified as MUO (n = 181, 33.1%) or MHO (n = 366, 66.9%) based on first trimester blood pressure, lipoprotein levels and nonfasting glucose levels. The risk of obstetric outcomes was evaluated by multivariable logistic regression. We compared cardiovascular risk markers in blood between obese pregnant women with MUO and MHO. Results Overall, 45.9% of women with MUO developed at least one adverse obesity-associated obstetric outcome, whereas corresponding proportions in women with MHO, overweight and normal weight were 35.0%, 27.6% and 21.2%, respectively. Following adjustment, the overall risk of at least one obesity-associated obstetric or perinatal complication in women with MUO, vs women with MHO, was increased (adjusted odds ratio 1.49, 95% confidence interval 1.03-2.15), but the predictive value of the model was low. Women with MUO had altered levels of cardiovascular risk markers such as cathepsin S, adiponectin, and cystatin C in comparison with women with MHO. Conclusions Women with MUO had an overall increased risk of adverse obstetric outcomes in comparison to women with MHO, but the classification had little relevance for risk prediction beyond that of body mass index.

Background Self-sampling for HPV testing, as an alternative to the conventional speculum based sampling, is highly acceptable to women of screening ages. The aim of this study was to describe older women’s (60 to 75 years) experiences of self-sampling. Methods In Sweden a descriptive study with quantitative and qualitative methods was designed to collect data from a survey of women who participated in self-sampling for HPV testing. Individual interviews were done with women who tested positive in the first self-sampling, and were either negative in their second HPV test or were positive in their second HPV test, but without precancerous lesions or cancer. Results Of 893 eligible women, 868 (97.2%) answered the survey. Among the surveyed women, 49.2% reported it was very easy to perform self-sampling, 46.8% answered it was easy and 2.0% answered it was not easy. A majority (58.9%) answered that they prefer self-sampling, 16.5% that they prefer sample collection by a healthcare provider, 23.7% did not have any preference and 0.9% did not answer the question. In the interviews, 13 of 16 invited women participated. Most of them reported that they prefer self-sampling because it was easy to perform, less embarrassing and less time consuming than a visit to a clinic. The majority of women reported that they were not worried when informed about having an HPV positive test. Overall, participating women with better knowledge about the significance of an HPV infection were more worried about having a positive HPV test. Conclusion Cervical cancer remains a highly preventable disease through screening and early treatment. Our results indicated that vaginal self-sampling for HPV testing was a well-accepted method for cervical cancer prevention in this group of older women. Trial registration https://www.researchweb.org/is/en/fouckfuu/project/272587. Registered 24 June 2019-retrospectively registered. www.researchweb.org

Knowledge on the effects of perfluorohexane sulfonate (PFHxS) on ovarian function is limited. In the current study, we investigated the sensitivity of oocytes to PFHxS during in vitro maturation (IVM), including conse-quences on embryo development at the morphological, transcriptomic, and epigenomic levels. Bovine cumulus-oocyte complexes (COCs) were exposed to PFHxS during 22 h IVM. Following fertilisation, developmental competence was recorded until day 8 of culture. Two experiments were conducted: 1) exposure of COCs to 0.01 mu g mL(-1) -100 mu g mL(-1) PFHxS followed by confocal imaging to detect neutral lipids and nuclei, and 2) exposure of COCs to 0.1 mu g mL(-1) PFHxS followed by analysis of transcriptomic and DNA methylation changes in blastocysts. Decreased oocyte developmental competence was observed upon exposure to & nbsp;>= 40 mu g mL(-1) PFHxS and altered lipid distribution was observed in the blastocysts upon exposure to 1-10 mu g mL(-1) PFHxS (not observed at lower or higher concentrations). Transcriptomic data showed that genes affected by 0.1 mu g mL(-1) PFHxS were enriched for pathways related to increased synthesis and production of reactive oxygen species. Enrichment for peroxisome proliferator-activated receptor-gamma and oestrogen pathways was also observed. Genes linked to DNA methylation changes were enriched for similar pathways. In conclusion, exposure of the bovine oocyte to PFHxS during the narrow window of IVM affected subsequent embryonic development, as reflected by morphological and mo- lecular changes. This suggests that PFHxS interferes with the final nuclear and cytoplasmic maturation of the oocyte leading to decreased developmental competence to blastocyst stage.

Younger women with endometriosis report lower quality of life and seek more care. Patient-centeredness is a central part of quality of care. The aim of this study was to investigate if women younger than 35 years experience endometriosis care as less patient-centred than women 35 years and older. The ENDOCARE Questionnaire was sent to 1000 randomly selected women with verified endometriosis from 10 clinics in Sweden. Answers from 469 women were analysed using Mann-Whitneys U-test and Spearmans correlation. Our findings show that younger women experience care as less patient-centred regarding Physical comfort, Continuity, Access to care, Technical skills, and overall patient-centeredness score in comparison with older women. On the contrary, younger women experience more patient-centeredness in Emotional support. Positive correlations were found for age and Access to care and Technical skills, while a negative correlation was found for age and Emotional support. Impact Statement What is already known on this subject? There is a need for improvement of quality of endometriosis care. Patient-centeredness is an important part of care improvement work. Many factors have an impact on experienced patient-centeredness in endometriosis care, whereof age is one possible determinant. Given the impact of age on QoL and care seeking behaviour, age may also have influence on the experience patient-centeredness. What do the results of this study add? Our findings show that younger women experience their endometriosis care as less patient-centred than older women. What are the implications of these findings for clinical practice and/or further research? Our results highlight the need of improvement of endometriosis care, especially for younger women. The results contribute to the understanding of the experience of patient-centeredness, which may be used as a guidance to how healthcare recourses should be allocated. Further research is needed to identify other factors contributing to the experience of patient-centeredness. Future studies could also evaluate how different interventions can improve patient-centeredness. Funding Agencies|Medical Research Council of Southeast Sweden [FORSS-964282]; Stiftelsen Tornspiran

Purpose Cervical cancer prevention for older women can be challenging since there are no specific guidelines for this group. This study aimed to determine the incidence of oncogenic HPV and HPV-related dysplasia in elderly women 5 years after being HPV negative. Methods Invited women participated five years earlier in a study where self-sampling for HPV testing was applied, at this time, they were all HPV negative. The women were now, five years later invited to perform self-sampling for HPV testing. Women with a positive result performed a repeat HPV test. Those with a positive repeat HPV test were examined by colposcopy, biopsy and cytology. Results Of the 804 invited women, 634 (76.9%) agreed to participate in the study and a self-sampling kit was sent to them. Of these, 99.6% (632/634) sent a sample to the HPV laboratory. The participation rate in each age group was 93.3% at age 65, 74.0% at age 70, 80.7% at age 75 and 64.6% at age 80. Overall 18 women (2.8%, 95% CI 3.2 to 6.0) were HPV positive in the first test and 8 (1.3%, 95% CI 0.6 to 2.6) in the second test. Sampling for the second test was done on average 5.4 months after the first test. Fifty per cent (4/8) of the women with a positive repeat test had dysplasia in histology. Conclusion The incidence of HPV in previously HPV-negative elderly women was low. Among women who were HPV positive in a repeat test, there was a high prevalence of low grade dysplasia.

The gold standard for diagnosing endometriosis is by laparoscopic visual demonstration of ectopic endometrial lesions outside the uterus, preferably verified by biopsy and microscopical examination. Molecular markers to facilitate the microscopical diagnosis of endometriosis and for distinguishing endometriosis from other benign and malignant lesions are lacking. Our aim was to test and validate an immunohistochemical antibody panel for improved diagnostic accuracy of endometriosis. Both CD10 and HOXA11 have been implicated in regulation of endometrial homeostasis. Here we have analyzed the expression pattern of these two proteins using immunohistochemistry on human tissues in a tissue microarray format. CD10 and HOXA11 expression in endometriosis lesions were compared to expression patterns in a range of normal tissues and in primary- and metastatic lesions of endometrial-, cervical- and ovarian cancer. HOXA11 and CD10 were expressed in 98% and 91% of endometriosis lesions and the combined double-positive expression profile of both HOXA11 and CD10 was highly sensitive for ectopic endometrial tissue (90%). The specificity and sensitivity for this double-positive signature in endometriosis was significantly different from all investigated tissues, cancers and metastases except normal, eutopic endometrial- and cervical mucosa. The combination of HOXA11 and CD10 expression profiles provides a useful tool to identify ectopic endometrial tissue and for distinguishing endometriosis from various types of gynecological malignancies and metastases. De 2 första författarna delar förstaförfattarskapet

Persistent organic pollutants (POPs) are industrial chemicals resistant to degradation and have been shown to have adverse effects on reproductive health in wildlife and humans. Although regulations have reduced their levels, they are still ubiquitously present and pose a global concern. Here, we studied a cohort of 185 women aged 21-43 years with a median of 2 years of infertility who were seeking assisted reproductive technology (ART) treatment at the Carl von Linne Clinic in Uppsala, Sweden. We analyzed the levels of 9 organochlorine pesticides (OCPs), 10 polychlorinated biphenyls (PCBs), 3 polybrominated diphenyl ethers (PBDEs), and 8 perfluoroalkyl substances (PFASs) in the blood and follicular fluid (FF) samples collected during ovum pick-up. Impact of age on chemical transfer from blood to FF was analyzed. Associations of chemicals, both individually and as a mixture, to 10 ART endpoints were investigated using linear, logistic, and weighted quantile sum regression, adjusted for age, body mass index, parity, fatty fish intake and cause of infertility. Out of the 30 chemicals, 20 were detected in more than half of the blood samples and 15 in FF. Chemical transfer from blood to FF increased with age. Chemical groups in blood crossed the blood-follicle barrier at different rates: OCPs > PCBs > PFASs. Hexachlorobenzene, an OCP, was associated with lower anti-Miillerian hormone, clinical pregnancy, and live birth. PCBs and PFASs were associated with higher antral follicle count and ovarian response as measured by ovarian sensitivity index, but also with lower embryo quality. As a mixture, similar findings were seen for the sum of PCBs and PFASs. Our results suggest that age plays a role in the chemical transfer from blood to FF and that exposure to POPs significantly associates with ART outcomes. We strongly encourage further studies to elucidate the underlying mechanisms of reproductive effects of POPs in humans.

Introduction/Background* Self-sampling for Human Papillomavirus (HPV) testing, as an alternative to the conventional speculum based sampling, is highly acceptable to women of screening ages. The aim of this study was to describe older women’s (60 to 75 years) experiences of self-sampling. Methodology In Sweden a descriptive study with quantitative and qualitative methods was designed to collect data from a survey of women who participated in self-sampling for HPV testing at home. Individual interviews were done with women who tested positive in the first self-sampling, and were either negative in their second HPV test or were positive in their second HPV test, but without precancerous lesions or cancer. Result(s)* Of eligible women, 97.2% answered the survey. Among the surveyed women, 49.2% reported it was very easy to perform self-sampling, 46.8% answered it was easy and 2.0% answered it was not easy. A majority (58.9%) answered that they prefer self-sampling, 16.5% that they prefer sample collection by a healthcare provider, 23.7% did not have any preference and 0.9% did not answer the question. In the interviews, 13 of 16 invited women participated. Most of them reported that they prefer self-sampling because it was easy to perform, less embarrassing and less time consuming than a visit to a clinic. The majority of women reported that they were not worried when informed about having an HPV positive test. Participating women with better knowledge about the significance of an HPV infection were more worried about having a positive HPV test. Conclusion* Cervical cancer remains a highly preventable disease through screening and early treatment. Our results indicated that vaginal self-sampling for HPV testing was a well-accepted method for cervical cancer prevention in this group of older women.

Human papillomavirus (HPV) is recommended as the primary test in cervical cancer screening, with co-testing by cytology for HPV-positive women to identify cervical lesions. Cytology has low sensitivity and there is a need to identify biomarkers that could identify dysplasia that are likely to progress to cancer. We searched for plasma proteins that could identify women with cervical cancer using the multiplex proximity extension assay (PEA). The abundance of 100 proteins were measured in plasma collected at the time of diagnosis of patients with invasive cervical cancer and in population controls using the Olink Multiplex panels CVD II, INF I, and ONC II. Eighty proteins showed increased levels in cases compared with controls. We identified a signature of 11 proteins (PTX3, ITGB1BP2, AXIN1, STAMPB, SRC, SIRT2, 4E-BP1, PAPPA, HB-EGF, NEMO and IL27) that distinguished cases and controls with a sensitivity of 0.96 at a specificity of 1.0. This signature was evaluated in a prospective replication cohort with samples collected before, at or after diagnosis and achieved a sensitivity of 0.78 and a specificity 0.56 separating samples collected at the time of diagnosis of invasive cancer from samples collected prior to diagnosis. No difference in abundance was seen between samples collected prior to diagnosis or after treatment as compared with population controls, indicating that this protein signature is mainly informative close to time of diagnosis. Further studies are needed to determine the optimal window in time prior to diagnosis for these biomarker candidates.

Background Perfluorinated substances (PFAS) are chemicals with endocrine disruptive properties that may interfere with the female reproductive system. However, few studies have explored the association between benign gynecological diseases and high PFAS exposure. Objectives The aim of this study was to investigate the possible associations between PFAS exposure and subsequent diagnosis of polycystic ovarian syndrome (PCOS), uterine leiomyoma (fibroids), and endometriosis in a cohort exposed to PFAS through drinking water. Material and methods In 2013, high levels (with sum of PFAS above 10,000 ng/L), dominated by perfluorooctanesulfonic acid (PFOS) and perfluorohexane sulfonic acid (PFHxS), were found in the drinking water from one of the two waterworks in Ronneby, Sweden. The contamination came from firefighting foams used at a nearby airfield. Females of all ages (n = 29,106) who had ever resided in the municipality between 1985 and 2013 formed a cohort. Individual exposure was assessed based on municipality waterworks distribution data linked to annual residential address data; 27% of the females had ever lived at an address with PFAS-contaminated water. Gynecological health outcomes were retrieved from the Swedish National Patient Register. The Cox proportional hazards model was used to estimate the association between exposure and each diagnosis. Results There were in all 161 cases of PCOS, 1,122 cases of uterine leiomyoma, and 373 cases of endometriosis. In women aged 20–50 years (n = 18,503), those with the highest estimated PFAS exposure had increased hazard ratios (HR) for PCOS (HR = 2.18; 95% confidence interval (CI) 1.43, 3.34) and uterine leiomyoma (HR = 1.28; 95% CI 0.95, 1.74). No increased HR for endometriosis was found (HR = 0.74; 95% CI 0.42, 1.29). Conclusions Exposure to high levels of PFAS in drinking water was associated with increased risk of PCOS and possibly uterine leiomyoma, but not endometriosis. The findings for PCOS are consistent with prior studies reporting positive associations between PCOS and PFAS exposure at background levels.

Primary screening with human papillomavirus (HPV) test is more effective in reducing cervical cancer incidence than cytology and it also offers the opportunity to self-sample. We conducted a randomized study to compare vaginal self-sampling with cervical sampling by medical professionals for HPV testing concerning prevalence of HPV and detection of cervical intraepithelial neoplasia (CIN) of grade 2 or worse (CIN2+) or grade 3 or worse (CIN3+) in primary screening. In total, 11 951 women aged 30-60 years were randomized into two groups, 5961 for self-sampling (SS arm) and 5990 for sampling by medical professionals (SMP arm). Sampling was performed with a RoversViba-brush in the SS arm and a cytobrush in the SMP arm. All samples were applied to an indicating FTA elute card and analyzed for HPV using a clinically validated real-time PCR test (hpVIR). All HPV-positive women performed repeated sampling about 6 months later using the same procedure as used initially. All HPV-positive women in the second sampling were referred to colposcopy. The prevalence of HPV in the first test did not differ between the SS arm (6.8%, 167/2466) and the SMP arm (7.8%, 118/1519) (P = .255). The prevalence of CIN2+ per 1000 screened women was 17 (43/2466 × 1000) (95%CI 13-24) in the SS arm and 21 (32/1519 × 1000) (95%CI 15-30) in the SMP arm. For CIN3+, the prevalence per 1000 screened women was 14 (35/2466 × 1000) (95%CI 10-20) in the SS arm and 15 (23/1519 × 1000) (95%CI 10-23) in the SMP arm. In conclusion, self-sampling and sampling by medical professionals showed the same prevalence of HPV and detection rate of CIN2+ and CIN3+ in histology.

Objectives: The need for quality improvement within endometriosis healthcare is widely acknowledged. The ENDOCARE questionnaire (ECQ) measures patient centeredness of endometriosis care. The aims of this study were (1) to translate and culturally adapt ECQ into Swedish, (2) to evaluate validity (construct validity), and (3) to measure reliability (internal consistency and test-retest reliability). Design: This is a cross-sectional randomized study. Participants, Setting, and Methods: ECQ was first translated according to a well-established guideline and was thereafter sent to 500 randomly selected women with endometriosis, who had visited participating clinics during the past 3 years. The first 150 women who returned their questionnaires were immediately sent the same questionnaire again. The ECQ consists of 3 parts. The first part contains demographic and clinical questions, while part II has 38 items that are answered according to 2 aspects: percentage of negative experience of care and mean personal importance. A patient-centeredness score (PCS) is calculated based on these 2 aspects. The items are also divided into 10 dimensions of care. Part III is a grading of overall experience and an open-ended question on any missing aspect in the questionnaire. Results: A total of 187 native Swedish-speaking women participated. Data completeness was high (>90%). The overall PCS median was 3.5. The highest median PCS was found in the dimension regarding endometriosis clinic staff and the lowest in emotional support and alleviation of fear and anxiety and the involvement of significant others. Factor analysis could roughly confirm 2 of the 10 dimensions. The Cronbach’s α coefficient for PCS ranged from 0.35 to 0.73. The test-rest analysis showed acceptable reliability. Limitations: The most important limitation was the relatively low participation rate and the risk of recall bias. It is likely that women gave their answers based on their most recent experiences. Conclusions: Overall, our results indicate that the Swedish version of the ECQ is a usable instrument to measure patient centeredness in endometriosis care, but due to the unstable factor analysis, conclusions based on the dimensions should be made with caution.

Human papillomavirus (HPV) infection is one of the most common sexually transmitted diseases. To define the HPV-associated microbial community among a high vaccination coverage population, we carried out a cross-sectional study with 345 young Swedish women. The microbial composition and its association with HPV infection, including 27 HPV types, were analyzed. Microbial alpha-diversity was found significantly higher in the HPV-infected group (especially with oncogenic HPV types and multiple HPV types), compared with the HPV negative group. The vaginal microbiota among HPV-infected women was characterized by a larger number of bacterial vaginosis-associated bacteria (BVAB), Sneathia, Prevotella, and Megasphaera. In addition, the correlation analysis demonstrated that twice as many women with non-Lactobacillus-dominant vaginal microbiota were infected with oncogenic HPV types, compared with L. crispatus-dominated vaginal microbiota. The data suggest that HPV infection, especially oncogenic HPV types, is strongly associated with a non-Lactobacillus-dominant vaginal microbiota, regardless of age and vaccination status.

Background The vaginal microbiota has been reported to be associated with HPV infection and cervical cancer. This study was performed to compare the vaginal microbiota at two timepoints in women performing self-sampling and had a persistent or transient HPV16 infection. The women were tested for 12 high-risk HPV (hrHPV) types but only women with single type (HPV16) were included to reduce confounding variables. Methods In total 96 women were included in this study. Of these, 26 were single positive for HPV16 in the baseline test and HPV negative in the follow-up test and 38 were single positive for HPV16 in both tests and diagnosed with CIN2+ in histology. In addition, 32 women that were negative for all 12 HPV tested were included. The samples of vaginal fluid were analyzed with the Ion 16S™ Metagenomics Kit and Ion 16S™ metagenomics module within the Ion Reporter™ software. Results K-means clustering resulted in two Lactobacillus-dominated groups, one with Lactobacillus sp. and the other specifically with Lactobacillus iners. The two remaining clusters were dominated by a mixed non-Lactobacillus microbiota. HPV negative women had lower prevalence (28%) of the non-Lactobacill dominant cluster in the baseline test, as compared to women with HPV16 infection (42%) (p value = 0.0173). Transition between clusters were more frequent in women with persistent HPV16 infection (34%) as compared in women who cleared the HPV16 infection (19%) (p value = 0.036). Conclusions The vaginal microbiota showed a higher rate of transitioning between bacterial profiles in women with persistent HPV16 infection as compared to women with transient infection. This indicate an instability in the microenvironment in women with persistent HPV infection and development of CIN2+.

BackgroundThe 30-Item Endometriosis Health Profile (EHP-30) is a specific instrument measuring quality of life among women with endometriosis. Although the Swedish version of EHP-30 is widely used in research and clinical settings, it has not yet been evaluated psychometrically. Ensuring validity and reliability is of most importance when using translated instruments. Therefore, the aim of the study was to evaluate the psychometric properties of the Swedish version of the EHP-30.MethodsThis study was conducted at a Swedish referral university hospital specializing in endometriosis. Data collection was performed in January 2013. The EHP-30 was sent to 369 randomly selected women with a laparoscopy-verified endometriosis diagnosis. The psychometric evaluation included evaluation of data completeness, score distributions, floor and ceiling effects, internal consistency, factor analysis and test-retest reliability.ResultsOut of the 211 women with endometriosis who answered the questionnaire, 128 were native Swedish speakers who had experienced symptoms of endometriosis during the past 4 weeks, and were included in the psychometric evaluation. Data completeness was 99.5%. The highest median score was found in the Control and Powerlessness subscale, and lowest in Pain. Distributions towards ill health were found in all subscales except for the pain subscale, but there were no noteworthy floor or ceiling effects. Internal consistency was good (Cronbach’s α 0.83–0.96). Factor analysis could roughly confirm three of the five subscales. The test-rest analysis showed good reliability. Scores were systematically lower during the second measurement.ConclusionsWe conclude that the Swedish version of EHP-30 is a valid and reliable instrument to measure health-related quality of life in women with endometriosis. It is understandable, acceptable and usable and can be recommended for use in clinical daily routines and for research purposes.

Background Human papillomavirus (HPV) testing is recommended in primary cervical screening to improve cancer prevention. An advantage of HPV testing is that it can be performed on self-samples, which could increase population coverage and result in a more efficient strategy to identify women at risk of developing cervical cancer. Our objective was to assess whether repeated self-sampling for HPV testing is cost-effective in comparison with Pap smear cytology for detection of cervical intraepithelial neoplasia grade 2 or more (CIN2+) in increasing participation rate in primary cervical screening. Methods A cost-effectiveness analysis (CEA) was performed on data from a previously published randomized clinical study including 36,390 women aged 30–49 years. Participants were randomized either to perform repeated self-sampling of vaginal fluid for HPV testing (n = 17,997, HPV self-sampling arm) or to midwife-collected Pap smears for cytological analysis (n = 18,393, Pap smear arm). Results Self-sampling for HPV testing led to 1633 more screened women and 107 more histologically diagnosed CIN2+ at a lower cost vs. midwife-collected Pap smears (€ 229,446 vs. € 782,772). Conclusions This study resulted in that repeated self-sampling for HPV testing increased participation and detection of CIN2+ at a lower cost than midwife-collected Pap smears in primary cervical screening. Offering women a home-based self-sampling may therefore be a more cost-effective alternative than clinic-based screening. Trial registration Not registered since this trial is a secondary analysis of an earlier published study (Gustavsson et al., British journal of cancer. 118:896-904, 2018).

Endometriosis is a chronic, inflammatory and estrogen-dependent disease affecting about 10 % of the female population in fertile ages. There is no cure for endometriosis. The main symptoms include severe menstrual pain, ovulation pain, dyspareunia, dysuria and painful bowel movements. Endometriosis is associated with infertility. Endometriosis affects every day life with pain and fatigue and a negative impact on education, career, social life and quality of life. Endometriosis can emerge at the first menstruations and also continue to give symptoms after menopause. The symptoms can vary greatly between individuals and also during life. The pathofysiology is unknown but the most accepted theory is retrograde menstruation where endometrial cells implant into the peritoneum affecting different abdominal organs. The immune system fails to clear the endometrial cells which results in endometriotic lesions that might cause inflammation, pain and adhesions. The treatment includes hormone treatment, surgical treatment, pain medication, physiotherapy, counseling and sometimes multi-disciplinary pain rehabilitation. It is important to increase the knowledge of this common disease both among the public and health professionals since early treatment is of great importance to reduce the risk for chronic pain and severe effects on quality of life. We hope that the recently published clinical guidelines will result in better and more equal care for patients with endometriosis in Sweden.

The Endometriosis Health Profile-30 (EHP-30) is focusing on the effect of endometriosis symptoms upon health-related quality of life. The aim of this study was to pre-test and culturally adapt the Swedish version of EHP-30. Eighteen Swedish-speaking women with laparoscopically verified diagnosis of endometriosis answered the questionnaire and 17 were interviewed regarding their interpretations of the questionnaire. Demographics, distribution of answers, roof-ceiling effects and missing answers were analysed. The interviews were analysed using the qualitative approach proposed by Beaton et al. The Swedish version of EHP-30 was experienced as accessible with 100% data completeness and a roof effect (11%) in one dimension. Some women had difficulties with the instructions and one word should be replaced in order to culturally adapt the questionnaire. In conclusion, the Swedish version of EHP-30 is a useful and well-accepted questionnaire for women with endometriosis in Sweden, but a minor change of wording is recommended.Impact statement What is already known on this subject? Cross-cultural adaptation and psychometric testing are crucial when introducing translated questionnaires. Cross-cultural adaptation is a process that looks at both translational and cultural issues when a questionnaire is being prepared for use in another country than the original. EHP-30 has been translated into Swedish but has not yet been cross-culturally adapted. What do the results of this study add? The Swedish version of EHP-30 was experienced as a useful and well-accepted questionnaire for women with endometriosis, but a minor change of wording is recommended in one question to make the questionnaire convergent with the original version. Hanna Grundström and Anna Rauden share first authorship

We conducted a randomised study to compare vaginal self-sampling with assisted sampling by medical personnel on the cervix for HPV testing in primary screening. The first aim was to determine if th ...

To develop a high resolution mass spectrometry (HRMS) method to quantify levonorgestrel (LNG) in serum.Levonorgestrel was extracted using solid phase extraction and measured using liquid chromatography (LC) HRMS.Low limit of quantification (LLOQ) was 25 pg/mL and low limit of detection (LLOD) was 12.5 pg/mL. Precision and accuracy bias were10%. LNG in serum samples from Mirena® users ranged between 37 to 219 pg/mL (n=12). In eight out of 22 patients with suspected intrauterine device (IUD) expulsion LNG was detected (26-1272 pg/mL).A sensitive, fast and simple LC-HRMS method was developed to detect trace levels of LNG.

Perfluorooctane sulfonate (PFOS) has been added to Stockholm Convention for global phase out, but will continue to contribute to the chemical burden in humans for a long time to come due to extreme persistence in the environment. In the body, PFOS is transferred into to the ovarian follicular fluid that surrounds the maturing oocyte. In the present study, bovine cumulus oocyte complexes were exposed to PFOS during 22 h in vitro maturation. Concentrations of 2 ng g(-1) (PFOS-02) representing average human exposure and 53 ng g(-1) (PFOS-53) relevant to highly exposed groups were used. After exposure, developmental competence was recorded until day 8 after fertilisation. Blastocysts were fixed and either stained to evaluate blastomere number and lipid distribution using confocal microscopy or frozen and pooled for microarray-based gene expression and DNA methylation analyses. PFOS-53 delayed the first cleavage to two-cell stage and beyond at 44 h after fertilisation (p < .01). No reduction of proportion blastocysts were seen at day 8 in either of the groups, but PFOS-53 exposure resulted in delayed development into more advanced stages of blastocysts seen as both reduced developmental stage (p = .001) and reduced number of blastomeres (p = .04). Blastocysts showed an altered lipid distribution that was more pronounced after exposure to PFOS-53 (increased total lipid volume, p=.0003, lipid volume/cell p < .0001) than PFOS-02, where only decreased average lipid droplet size (p=.02) was observed. Gene expression analyses revealed pathways differently regulated in the PFOS-treated groups compared to the controls, which were related to cell death and survival through e.g., P38 mitogen-activated protein kinases and signal transducer and activator of transcription 3, which in turn activates tumour protein 53 (TP53). Transcriptomic changes were also associated with metabolic stress response, differentiation and proliferation, which could help to explain the phenotypic changes seen in the blastocysts. The gene expression changes were more pronounced after exposure to PFOS-53 compared to PFOS-02. DNA-methylation changes were associated with similar biological functions as the transcriptomic data, with the most significantly associated pathway being TP53. Collectively, these results reveal that brief PFOS exposure during oocyte maturation alters the early embryo development at concentrations relevant to humans. This study adds to the evidence that PFOS has the potential to affect female fertility.

The objective was to evaluate the effect of lignocaine on cytokine expression and secretion in vitro in peritoneal fluid macrophages and endometriotic stromal cells.Experimental in vitro study on human cells.Peritoneal fluid (n = 10) and samples from endometriotic cysts (n = 7) were collected from 13 women (women with endometriosis n = 8, and healthy controls n = 5) during surgery for clinical reasons.Macrophages from the peritoneal fluid and cells from the inside of the endometriotic cysts capsules were isolated and cultivated for 24 to 48 hours in medium with and without the supplement of lignocaine 0.1 or 1.0 mg/mL. Relative gene expression of monocyte chemotactic protein 1 (MCP-1), interleukin 6 (IL-6), and IL-8 was evaluated with quantitative polymerase chain reaction and compared between treated and untreated cells with Wilcoxon matched pairs. The concentrations of MCP-1, IL-6, and IL-8 were measured using enzyme-linked immunosorbent assay and were compared between treated and untreated cells with Wilcoxon matched pairs.The gene expression and protein secretion of IL-8 in endometriotic stromal cells after incubation with lignocaine 0.1 mg/mL were significantly decreased after 24 hours compared to the controls ( P = .028 and P = .018). Macrophages from healthy controls had a significant lower gene expression of all tested cytokines ( P = .043) after treatment with lignocaine, but there were no significant differences in protein level. Macrophages from women with endometriosis showed diverging results since 3 of 5 samples showed increased gene expression of 1 (n = 2) or 2 cytokines (n = 1) after lignocaine treatment.Lignocaine can affect the gene expression and secretion of some proinflammatory cytokines in vitro.

Introduction: Endometriosis is known for its substantial effect on women’s wellbeing and quality of life. In order to evaluate disease burden, treatments and health services, assessments of healthcare consumption and cost estimates are necessary. Objectives: The aim of this study was to estimate healthcare consumption and annual cost per woman with endometriosis in Sweden and to examine healthcare consumption and costs in different age groups. Methods: A questionnaire was distributed to 400 members of the Endometriosis Association and to 400 randomly selected women with surgically confirmed endometriosis. Official statistics were obtained via correspondence, publications, and database searches. Results: Analysis of the 431 returned questionnaires showed that women under 30 years utilized more inpatient and outpatient care than older women. The mean annual cost among all women was EUR 8,768/woman. The direct healthcare cost of managing the disease was EUR 4,282, while the indirect cost was EUR 4,486. Absence from work was reported by 32% of the women, while 36% reported reduced time at work because of endometriosis. Conclusion: Our results confirm the substantial negative effect of endometriosis upon women’s lives and their relatively high healthcare consumption.