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Background: Cervical cancer is a major cause of mortality and morbidity in women worldwide. This study aimed to estimate the association between common urogenital infections and cervical neoplasia., Methods: A multi-register national cohort study of 4,120,557 women aged ≥15 years (2002-2018) was conducted. The outcomes were cervical cancer and carcinoma in situ (Swedish Cancer Register). The main predictors were urogenital infections-(urinary) cystitis, (bacterial) vaginosis, (candida) vulvovaginitis. Incidence rates per 10,000 person-years were calculated (using the European Standard Population). Cox regression was used to estimate hazard ratios (HR) while adjusting for possible confounders-other genital infections (e.g., cervicitis, salpingitis, urogenital herpes), parity, and sociodemographic factors., Findings: In 39·0 million person-years of follow-up, the incidence rate for cervical cancer was 1·2 (95% CI 1·1-1·2) per 10,000 person-years and the figure for cervical carcinoma in situ was more than tenfold higher. The fully adjusted HRs for cervical cancer were 1·31 (95% CI 1·15 and 1·48) and 1·22 (95% CI 1·16 and 1·29) for vaginosis and cystitis, respectively. Vaginosis showed a gradient association to carcinoma in situ. Vulvovaginitis was inversely associated with cervical cancer, but not significantly related with carcinoma in situ in the fully adjusted model. A temporal association with cervical cancer was observed for vaginosis and vulvovaginitis (inversely) but not for cystitis., Interpretation: In this large nationwide cohort of women, medically attended common urogenital infections were independently associated with cervical neoplasia, but cystitis was not temporally associated with cervical neoplasia. These findings could be used to increase focus on preventive measures, HPV-vaccination programmes, HPV-analyses- and cervical cancer screening, especially in women suffering from vaginosis. Future studies on the causal mechanism are warranted before generalized public health recommendations can be made., Funding: Region Skåne, Tore Nilsons Stiftelse, and Swedish Society of Medicine., Competing Interests: The authors have nothing to disclose., (© 2022 The Author(s).)

Introduction: The screening program for cervical cancer in Sweden recommends the use of primary human papillomavirus (HPV) screening for women aged ≥30 to 65 years. Co-testing with both HPV analysis and cytology is recommended at the first screening after the age of 40 years. To fulfil co-testing, all screened women aged 40-42 years within the region of Skåne were co-tested. The aim of the audit was to investigate the proportion of severe dysplasia as diagnosed by cytology and histological follow-up among women with Aptima HPV-negative tests. We also calculated the cost of adding the cytology to the HPV primary screening program., Material and Methods: The local cytology registry was used to identify women aged 40-42 years who attended screening and were co-tested during the 4 years from January 2017 to December 2020. The Aptima HPV messenger RNA assay detects 14 HPV types. For Aptima HPV-negative women with high-grade cytology or histological high-grade squamous intraepithelial lesions (HSILs), we performed extended HPV typing for 40 HPV types with polymerase chain reaction using modified GP5+/6+ primers followed by a Luminex assay. To estimate the added cost of using cytology to identify each histologically confirmed cervical HSIL case among Aptima HPV-negative women, we used the current cost of €21.2 per cytology evaluation at our laboratory., Results: Of 19 599 women, 5.8% (1137/19 599) had abnormal cytology. Among Aptima HPV-negative women, 0.11‰ (2/18 132) had histologically confirmed HSIL. One of the women was infected with HPV18 and the other with HPV73 at the diagnosis of HSIL. The calculated cost to find one HSIL, by adding cytology to HPV-negative cases, was approximately €200 000., Conclusions: The clinical benefit of a single cytology co-test added to an HPV-based screening program in women aged 40-42 years appears doubtful and economically unreasonable., (© 2022 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Background/aim: Inflammation is a hallmark of cancer, and the role of neutrophils and neutrophil extracellular traps (NETs) in cancer and cancer-associated thrombosis has attracted a lot of interest. The NET-specific marker H3Cit has been found to be elevated in the plasma of patients with malignancies, suggesting NETs markers as novel cancer biomarkers. This study aimed to determine the levels of NETs markers (H3Cit and dsDNA) in the plasma of women with adnexal masses., Patients and Methods: Peripheral blood samples were obtained from 199 patients admitted for primary surgery of adnexal masses. Patients were grouped according to tumor type and stage. Plasma levels of H3Cit-DNA, dsDNA, and CA125 were quantified., Results: Plasma levels of H3Cit-DNA and dsDNA were not elevated in women with borderline or malignant ovarian tumors compared with those of the benign group. Increased levels of CA125 were found in the borderline and ovarian cancer group (p trend <0.001). In Cox regression analysis, CA125 levels dichotomized at 326 IU/ml (median) were associated with worse overall survival (HR=1.9; 95%CI=1.03-3.36; p=0.038). No differences were found in the survival analyses of malignant ovarian tumors by analyzing the dsDNA and H3Cit-DNA levels., Conclusion: There is no association between NETs markers and ovarian tumors., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Poor survival rates in different cancer types are sometimes blamed on diagnostic and treatment delays, and it has been suggested that such delays might be related to sociodemographic factors such as education and ethnicity. We examined associations of the wait time from diagnosis to surgery and survival in endometrial cancer (EC) and explored patient and tumour factors influencing the wait time., Material and Methods: In this historical population-based cohort study, The Swedish Quality Registry for Gynaecologic Cancer (SQRGC) was used to identify EC patients who underwent primary surgery between 2010 and 2018. Factors associated with a wait time > 32 d were analysed with logistic regression. The 32-d time point was defined in accordance with the Swedish Standardisation Cancer Care programme. Adjusted Poisson regression analyses were used to analyse excess mortality rate ratio (EMRR)., Results: Out of 7366 women, 5535 waited > 32 d for surgery and 1098 > 70 d. The overall median wait time was 44 d. The factors most strongly associated with a wait time > 32 d were surgery at a university hospital (adjusted odds ratio [OR] 1.34, 95% confidence interval [CI] 1.08-1.66) followed by country of birth (OR 1.31, 95% CI 1.10-1.55) and year of diagnosis. There were no associations between wait time and histology or age. A wait time < 15 d was associated with higher mortality (adjusted EMRR 2.29,95% CI 1.36-3.84) whereas no negative survival impact was seen with a wait time of 70 d. Age, tumour stage, histology and risk group were highly associated with survival, whereas education, country of origin and hospital level did not have any impact on survival., Conclusions: Surgery within the first two weeks after EC diagnosis was associated with worsened survival. A prolonged wait time did not seem to have any significant adverse effect on prognosis.HighlightsSurgery within the first two weeks after diagnosis of endometrial cancer (EC) was associated with poorer survival.A prolonged wait time to surgery did not worsen prognosis.Delay in time to surgery was associated with sociodemographic factors.

Purpose: The Groningen International Study on Sentinel nodes in Vulvar cancer (GROINSS-V)-II investigated whether inguinofemoral radiotherapy is a safe alternative to inguinofemoral lymphadenectomy (IFL) in vulvar cancer patients with a metastatic sentinel node (SN)., Methods: GROINSS-V-II was a prospective multicenter phase-II single-arm treatment trial, including patients with early-stage vulvar cancer (diameter < 4 cm) without signs of lymph node involvement at imaging, who had primary surgical treatment (local excision with SN biopsy). Where the SN was involved (metastasis of any size), inguinofemoral radiotherapy was given (50 Gy). The primary end point was isolated groin recurrence rate at 24 months. Stopping rules were defined for the occurrence of groin recurrences., Results: From December 2005 until October 2016, 1,535 eligible patients were registered. The SN showed metastasis in 322 (21.0%) patients. In June 2010, with 91 SN-positive patients included, the stopping rule was activated because the isolated groin recurrence rate in this group went above our predefined threshold. Among 10 patients with an isolated groin recurrence, nine had SN metastases > 2 mm and/or extracapsular spread. The protocol was amended so that those with SN macrometastases (> 2 mm) underwent standard of care (IFL), whereas patients with SN micrometastases (≤ 2 mm) continued to receive inguinofemoral radiotherapy. Among 160 patients with SN micrometastases, 126 received inguinofemoral radiotherapy, with an ipsilateral isolated groin recurrence rate at 2 years of 1.6%. Among 162 patients with SN macrometastases, the isolated groin recurrence rate at 2 years was 22% in those who underwent radiotherapy, and 6.9% in those who underwent IFL ( P = .011). Treatment-related morbidity after radiotherapy was less frequent compared with IFL., Conclusion: Inguinofemoral radiotherapy is a safe alternative for IFL in patients with SN micrometastases, with minimal morbidity. For patients with SN macrometastasis, radiotherapy with a total dose of 50 Gy resulted in more isolated groin recurrences compared with IFL., Competing Interests: Brian SlomovitzConsulting or Advisory Role: Clovis Oncology, AstraZeneca, Genentech, Incyte, Agenus, GlaxoSmithKline, GOG Foundation, Myriad Genetics, Merck, Eisai Ignace VergoteConsulting or Advisory Role: Amgen, AstraZeneca, Clovis Oncology, Carrick Therapeutics, Deciphera, Elevar Therapeutics, Genmab, GlaxoSmithKline, Immunogen, Jazz Pharmaceuticals, Mersana, MSD, Novocure, OCTIMET Oncology NV, Oncoinvent, Sotio, Verastem, Zentalis, Roche, MillenniumResearch Funding: Roche, Genmab, Amgen, OncoinventTravel, Accommodations, Expenses: Roche, AstraZeneca, Tesaro, Amgen, MSD/Merck Mats BrännströmStock and Other Ownership Interests: EUGIN Sweden Martin WidschwendterStock and Other Ownership Interests: Sola Diagnostics, BreOva HealthPatents, Royalties, Other Intellectual Property: Patents relevant for risk prediction or diagnosis of women's cancers Paul A. DiSilvestroConsulting or Advisory Role: AstraZeneca, AgenusResearch Funding: Janssen Oncology, Tesaro, AstraZeneca, Genentech, AbbVie Robert MannelConsulting or Advisory Role: Tesaro Dorry BollResearch Funding: AstraZeneca David CibulaConsulting or Advisory Role: AstraZeneca, Sotio, Roche, GlaxoSmithKline Diane ProvencherConsulting or Advisory Role: AstraZeneca, GlaxoSmithKlineResearch Funding: AstraZeneca, AbbVie Ingo B. RunnebaumConsulting or Advisory Role: AbbVie (I), Amgen, AstraZeneca, Clovis Oncology, GlaxoSmithKline, Oncgnostics, Tesaro Preben KjølhedeResearch Funding: Leo Pharma AB Katharina E. KieserHonoraria: AstraZenecaConsulting or Advisory Role: MerckResearch Funding: AstraZeneca Nicola M. SpirtosResearch Funding: AbbVie, AstraZeneca, Genentech/Roche, Clovis Oncology, Seattle GeneticsPatents, Royalties, Other Intellectual Property: Application No. PCT/US 2019/19465 Cannabis Based Therapeutic and Method of Use Application No, US Patent 0024098766 Compounds Cannabidiol and Flavanones 63/047550 (July 1, 2020) 63/055458 (July 23, 2020) David M. O'MalleyConsulting or Advisory Role: Janssen Oncology, AstraZeneca, Clovis Oncology, Tesaro, Novocure, AbbVie, Genentech/Roche, OncoQuest, Immunogen, GOG Foundation, Translational Genomics Research Institute, Agenus, Marker Therapeutics, Eisai, Genelux, Iovance Biotherapeutics, Ambry Genetics, Tarveda Therapeutics, Leap Therapeutics, Myriad Genetics, GlaxoSmithKline, Regeneron, Sorrento Therapeutics, Rubius Therapeutics, Elevar Therapeutics, Novartis, Seagen, BBI Healthcare, Arquer Diagnostics, Toray Medical, Takeda, InxMed, Celsion, Roche Diagnostics MSAResearch Funding: Amgen, AstraZeneca, Genentech/Roche, Regeneron, Immunogen, Janssen Research & Development, Clovis Oncology, EMD Serono, Ergomed, Ajinomoto, Cerulean Pharma, PharmaMar, Array BioPharma, Bristol Myers Squibb, Agenus, Tesaro, TRACON Pharma, Genmab, Seattle Genetics, Iovance Biotherapeutics, Leap Therapeutics, Merck, AbbVie/Stemcentrx, AbbVie, Mersana, Eisai, BBI Healthcare, Sumitomo Dainippon Pharma Oncology Mario M. LeitaoHonoraria: Intuitive SurgicalConsulting or Advisory Role: Intuitive Surgical, Ethicon/Johnson & Johnson, Medtronic, TakedaResearch Funding: KCITravel, Accommodations, Expenses: Intuitive Surgical Melissa A. GellerResearch Funding: Tesaro, Genentech, FATE Therapeutics, Morphotek, Bayer Karl TamussinoOther Relationship: Medtronic Daniel H. TobiasConsulting or Advisory Role: Ethicon Jayanthi S. LeaConsulting or Advisory Role: Roche Brynhildur EyjolfsdottirOther Relationship: Intuitive Surgical Krishnansu S. TewariHonoraria: Tesaro, Clovis OncologyConsulting or Advisory Role: Roche/Genentech, Tesaro, Clovis Oncology, AstraZenecaSpeakers' Bureau: Roche/Genentech, AstraZeneca, Merck, Tesaro, Clovis OncologyResearch Funding: AbbVie, Genentech/Roche, Morphotek, Merck, RegeneronTravel, Accommodations, Expenses: Roche/Genentech Ranjit ManchandaHonoraria: AstraZeneca Linda Van LeConsulting or Advisory Role: EyePoint Pharmaceuticals, Novartis, Advarum, Neurotech, Iveric, Gemini Therapeutics, NaegisResearch Funding: GOG Partners Trial Bradley J. MonkLeadership: US OncologyHonoraria: AbbVie, Advaxis, Agenus, Akeso Biopharma, Amgen, Aravive, AstraZeneca, Asymmetric Therapeutics, Boston Biomedical, ChemoID, Clovis Oncology, Deciphera Pharmaceuticals, Eisai, Geistlich Pharma, Genmab/Seattle Genetics, ImmunoGen, Immunomedics, Incyte, Iovance Biotherapeutics, Laekna Health Care, Merck, Mersana, Myriad Pharmaceuticals, Nucana, Oncomed, Oncoquest, Oncosec, Perthera, Pfizer, Puma Biotechnology, Regeneron, Roche/Genentech, Senti Biosciences, Takeda, Tarveda Therapeutics, Tesaro/GSK, Vavotar Life Sciences, Vascular Biogenics, Vigeo Therapeutics, GOG Foundation, Starton Therapeutics, Elevar Therapeutics, Novocure, Gradalis, Karyopharm TherapeuticsConsulting or Advisory Role: AbbVie, Advaxis, Agenus, Akeso Biopharma, Amgen, Aravive, AstraZeneca, Asymmetric Therapeutics, Boston Biomedical, ChemoCare, ChemoID, Clovis Oncology, Deciphera Pharmaceuticals, Eisai, Geistlich Pharma, Genmab/Seattle Genetics, GOG Foundation, ImmunoGen, Immunomedics, Incyte, Iovance Biotherapeutics, Laekna Health Care, Merck, Mersana, Myriad Pharmaceuticals, Nucana, Oncomed, Oncoquest, Oncosec, Perthera, Pfizer, Puma Biotechnology, Regeneron, Roche/Genentech, Senti Biosciences, Takeda, Tarveda Therapeutics, Tesaro/GSK, Vavotar Life Sciences, Vascular Biogenics, Vigeo Therapeutics, Gradalis, Karyopharm Therapeutics, Sorrento Therapeutics, NovocureSpeakers' Bureau: Roche/Genentech, AstraZeneca, Clovis Oncology, Eisai, Tesaro/GSK, MerckResearch Funding: Novartis, Amgen, Genentech, Lilly, Janssen, Array BioPharma, Tesaro, Morphotek, Pfizer, Advaxis, AstraZeneca, Immunogen, Regeneron, Nucana Carien L. CreutzbergConsulting or Advisory Role: MerckResearch Funding: Elekta, Varian Medical SystemsNo other potential conflicts of interest were reported.

Introduction: Deep myometrial invasion (≥50%) is a prognostic factor for lymph node metastases and decreased survival in endometrial cancer. There is no consensus regarding which pre/intraoperative diagnostic method should be preferred. Our aim was to explore the pattern of diagnostic methods for myometrial invasion assessment in Sweden and to evaluate differences among magnetic resonance imaging (MRI), transvaginal sonography, frozen section, and gross examination in clinical practice., Material and Methods: This is a nationwide historical cohort study; women with endometrial cancer with data on assessment of myometrial invasion and FIGO stage I-III registered in the Swedish Quality Registry for Gynecologic Cancer (SQRGC) between 2017 and 2019 were eligible. Data on age, histology, FIGO stage, method, and results of myometrial invasion assessment, pathology results, and hospital level were collected from the SQRGC. The final assessment by the pathologist was considered the reference standard., Results: In the study population of 1401 women, 32% (n = 448) had myometrial invasion of 50% of more. The methods reported for myometrial invasion assessment were transvaginal sonography in 59%, MRI in 28%, gross examination in 8% and frozen section in 5% of cases. Only minor differences were found for age and FIGO stage when comparing methods applied for myometrial invasion assessment. The sensitivity, specificity, and accuracy to find myometrial invasion of 50% or more with transvaginal sonography were 65.6%, 80.3%, and 75.8%, for MRI they were 76.9%, 71.9%, and 73.8%, for gross examination they were 71.9%, 93.6%, and 87.3%, and for frozen section they were 90.0%, 92.7%, and 92.0%, respectively., Conclusions: In Sweden, the assessment of deep myometrial invasion is most often performed with transvaginal sonography, but the sensitivity is lower than for the other diagnostic methods. In clinical practice, the accuracy is moderate for transvaginal sonography and MRI., (© 2021 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Background/aim: To evaluate quality of life (QoL) in women treated for ovarian tumors one year after laparotomy., Patients and Methods: The validated quality of life questionnaires (EORTC QLQ-C30 and QLQ-OV28) were sent to women who had undergone laparotomy due to ovarian tumors 12 months after surgery. The answers were analyzed and grouped according to the ovarian tumor histology (benign, borderline and cancer)., Results: A total of 621 patients (87.5% out of 710) agreed to participate in the study. Ovarian cancer patients experienced statistically worse QoL one year after laparotomy in several analyzed parameters, including financial difficulties, compared to patients treated for benign and borderline tumors., Conclusion: Women with ovarian cancer still need further cancer rehabilitation and support one year after diagnosis to improve their QoL. The novel finding was that ovarian cancer patients suffered from financial difficulties even in a free of charge health care system., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objectives: HPV self-sampling is an option for cervical screening. The aim of this randomised study was to investigate the compliance, prevalence of HPV, and prevalence of severe dysplasia in a vaginal self-sampling group in comparison to cervical samples collected by midwives (control arm). The hypothesis was that there would be no difference between vaginal self-sampling and cervical sampling to find high-grade cervical dysplasia or cancer., Methods: Vaginal HPV self-sampling kits were sent by regular mail to 14 765 randomly selected women aged 30-64 years old in the screening programme. HPV-positive women were invited for a follow-up examination by their midwife in which they provided a cervical sample for cytological and HPV co-testing. The control arm consisted of 14 839 women who met the same inclusion criteria and were invited to have cervical sampling by midwives for primary HPV screening. All HPV samples were analysed by the Aptima HPV assay (Hologic Inc.)., Main Results: The participation rate was 33.5% in the self-sampling arm and 47.5% in the cervical sampling arm, (P < 0.0001). HPV was detected in 17.1% (95% confidence interval (CI), 16.1-18.23%) in the self-sampling arm and 4.5% (95% CI, 4.0-5.0%) in the cervical sampling arm. Histological, severe dysplasia was observed among 0.48% (95% CI, 0.3-0.72%) and 0.47% (95% CI, 0.3-0.66%) of the self-sampling and the cervical sampling groups, respectively., Conclusion: The self-sampling approach detects a similar proportion of severe dysplasia as regular screening. Thus, our study indicates that self-sampling could replace primary HPV screening of cervical samples., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The aim of this study was to analyze overall survival in endometrial cancer patients' FIGO stages I-III in relation to surgical approach; minimally invasive (MIS) or open surgery (laparotomy)., Methods: A population-based retrospective study of 7275 endometrial cancer patients included in the Swedish Quality Registry for Gynecologic Cancer diagnosed from 2010 to 2018. Cox proportional hazard models were used in univariable and multivariable survival analyses., Results: In univariable analysis open surgery was associated with worse overall survival compared with MIS hazard ratio, HR, 1.39 (95% CI 1.18-1.63) while in the multivariable analysis, surgical approach (MIS vs open surgery) was not associated with overall survival after adjustment for known risk factors (HR 1.12, 95% CI 0.95-1.32). Higher FIGO stage, non-endometrioid histology, non-diploid tumors, lymphovascular space invasion and increasing age were independent risk factors for overall survival., Conclusion: The minimal invasive or open surgical approach did not show any impact on survival for patients with endometrial cancer stages I-III when known prognostic risk factors were included in the multivariable analyses.

Background: Despite improved surgical and oncological treatment, ovarian cancer continues to be the most lethal of the gynecologic malignancies. We aimed to analyze survival trends in epithelial ovarian cancer with regard to age, tumor site, and morphology in Sweden 1960 to 2014., Methods: A nationwide population-based study was conducted using data from the Swedish Cancer Registry on 46,350 women aged 18 or older with a diagnosis of epithelial ovarian, fallopian tube, peritoneal, or undesignated abdominal/pelvic cancer 1960 to 2014. Analyses of age-standardized incidence and relative survival (RS) were performed and time trends modelled according to age, tumor site, and morphology., Results: Overall incidence of ovarian, tubal, peritoneal, and undesignated abdominal/pelvic cancers declined since 1980. Median age at diagnosis increased. Serous carcinoma increased in incidence. RS at 1, 2 and 5 years from diagnosis improved since 1960, although not for the youngest and the oldest patients. Ten-year RS did not improve. The best RS was found for fallopian tube cancer and the worst RS for undesignated abdominal/pelvic cancer. Among the morphologic subgroups, endometrioid carcinoma had the best RS., Conclusions: Survival in epithelial ovarian, tubal, peritoneal, and undesignated abdominal/pelvic cancers in Sweden has improved over the last six decades. Advances in epithelial ovarian cancer treatment have extended life for the first 5 years from diagnosis but 10-year survival remains poor.

HPV73 is classified as possibly oncogenic and is not recognized by most commercial primary HPV screening platforms. The aim was to determine the prevalence of HPV73 among invasive cervical cancers, formalin-fixed paraffin embedded (FFPE) samples (N = 69), from southern Sweden during 2009 to 2010. Another aim was to determine proportions of HPV73 among Aptima HPV assay negative cervical cancers (N = 9, out of 206 cancers) and of high-grade cytological cervical diagnosis (N = 75, out of 5807 high grade lesions) in liquid-based cytology (LBC) samples collected between 2016 and 2019. We also investigated the distribution of HPV73 variants A1, A2 and B among HPV73-positive cases. HPV73 was detected by multiplex MGP-PCR and Luminex, and HPV73 variants were identified by sequencing PCR amplicons. HPV73 was detected in 2.9% (2/69, 95% CI: 0.18-9.9) of the FFPE cervical cancer series. Among the Aptima HPV-negative LBC samples, HPV73 was present in 55.5% (5/9) of the cancers and 29.3% (22/75) of the different grades of cervical diagnosis. The A1, A2 and B variants were present in 6.9% (2/29), 82.7% (24/29) and 10.3% (3/29) of the HPV73-positive women, respectively. Among the seven HPV73 cancer cases (two FFPE samples and five LBC samples), six A2 and one A1 isolate were detected. In summary, the A2 variant of HPV73 was most common in our region. In addition, the observed prevalence of HPV73 (2.9%) in cervical cancers and its relative high occurrence (55.5%) among Aptima HPV-negative cancers urge that detection of HPV73 should be included in future primary HPV screening programs., (© 2021 Union for International Cancer Control.)

Aim: The first Swedish National Guidelines for Ovarian Cancer (NGOC) were published in 2012. We aimed to evaluate surgical outcomes and survival in patients with stage IIIC-IV disease, before and after the NGOC implementation., Method: Women with primary epithelial ovarian cancer, FIGO stage IIIC-IV, registered in the Swedish Quality Registry for Gynecologic Cancer 2008-2011 and 2013-2016 were included. Surgical outcomes were analyzed, including frequency of complete cytoreduction (R0). Relative survival (RS) and excess mortality rate ratios (EMRRs) were computed as measures of survival. Univariable and multivariable regression (Poisson) were calculated., Results: In total, 3728 women were identified, 1746 before and 1982 after NGOC. After adjusting for age and stage, survival was improved 2013-2016 vs. 2008-2011 (EMRR 0.89; 95%CI:0.82-0.96, p < 0.05). For women undergoing primary debulking surgery (PDS), R0 frequency (28.9% vs. 53.3%; p < 0.001) and 5-year RS (29.6% (95%CI:26.8-32.8) vs. 37.4% (95%CI:33.6-41.7)) were increased, but fewer patients (58% vs. 44%, p < 0.001) underwent PDS after NGOC implementation. Median survival for the PDS cohort increased from 35 months (95%CI,32.8-39.2) to 43 months (95%CI,40.9-46.4). In the neoadjuvant chemotherapy (NACT) + interval debulking surgery (IDS) cohort, R0 increased (36.8% to 50.1%, p < 0.001), but not 5-year RS (17.5% vs. 20.7%, ns). Compared to PDS, the EMRR was 1.32 (95%CI,1.19-1.47, p < 0.001) for NACT+IDS and 3.00 (95%CI,2.66-3.38, p < 0.001) for chemotherapy alone. In multivariable analyses, PDS, R0, age ≤ 70 years, and stage IIIC were found to be independent factors for improved RS., Conclusion: Implementation of the first National Guidelines for Ovarian Cancer improved relative survival in advanced ovarian cancer., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2021. Published by Elsevier Inc.)

Cervical cancer is preventable through gynecological screening. To promote participation among non-attending women, self-collected vaginal samples for detection of high-risk human papillomavirus (hr-HPV) is an option. The aims of this study were to investigate the response of self-collected vaginal samples for hr-HPV testing among long-term non-attendees, to explore the attendance at follow-up among HPV-positive women, and to analyze the prevalence of hr-HPV and severe cervical dysplasia or cancer among the responders. A vaginal self-sampling kit was sent to 19,766 women aged 30-70 years who had not provided a cervical screening sample for ≥ 7 years in Skåne, Sweden. The self-sample was analyzed by the Aptima HPV mRNA assay (Hologic). Women testing positive for HPV were invited for follow-up. The response was 18.5% (3,646/19,757). The prevalence of HPV mRNA was 11.3% (412/3,636). Among HPV-positive women, 85.7% (353/412) attended follow-up, and of these, 44.8% (158/353) had HPV in the cervical sample. The HPV mRNA test of self-samples showed a positive predictive value of 9.3% ([33/353], 95% CI = 6.5-12.9) for detection of cytologically severe dysplasia. Histologically severe dysplasia or cancer was detected in 0.88% ([32/3,636], 95% CI = 0.6-1.2) among responders, including two cervical- and one vaginal cancer. In conclusion, almost one fifth of the long-term non-attendees participated in self-collected vaginal hr-HPV sampling. The prevalence of histologically confirmed high grade squamous intraepithelial lesion or cervical cancer was not increased significantly compared to regularly screened women in Sweden. The relatively high HPV prevalence among the self-samples indicates the importance of diagnostic follow-up with cervical HPV testing and reflex-cytology of HPV-positive cases., Competing Interests: CONFLICTS OF INTEREST Ola Forslund has received a speech honorarium from Hologic and his laboratory department (Laboratory Medicine, Region Skåne, Lund) has ongoing contracts with Hologic. Christer Borgfeldt has received a grant from Hologic Inc 2018 to perform HPV studies. None of the other authors have any conflicts of interest to declare. Hologic Inc. did not have any influence on the study design, statistical analyses, or manuscript writing., (Copyright © 2021 Korean Society of Cancer Prevention.)

Objective: Vulvar cancer affects mainly elderly women and with an ageing population the incidence has increased. We explored the primary treatment patterns and relative survival of patients with vulvar squamous cell carcinoma (VSCC) by stage and age-group., Methods: A population-based nationwide study on women diagnosed with VSCC between 2012 and 2016 and registered in the Swedish Quality Registry for Gynecologic Cancer (SQRGC). Main outcome was 5-year relative survival (RS) estimated by the Pohar Perme method. The relative risk of excess mortality (EMRR) between different groups was analyzed by Poisson regression. The age-standardized relative survival (AS-RS) was estimated for the total cohort., Results: Median follow-up time was 41 months. The study population included 657 women; 33% were ≥ 80 years old. FIGO stage I was most common (55%). Primary surgery was performed in 96% stage I, 65% stage II, 80% stage III and 28% stage IV. In women ≥80 years, exploration of the groins and chemoradiotherapy was less often performed. They also received lower mean doses of radiation than younger women. The 5-year AS-RS was 74%. 5-year RS was 84% for stage I, 60% for stage II, 54% for stage III and 35% for stage IV. The EMRR for women ≥80 years compared with women <60 years was 4.3 (p < 0.001); 4.9 (p < 0.001) for stages I-II and 3.5(p = 0.007) for stage III., Conclusions: In general, primary treatment of patients with vulvar squamous cell carcinoma in Sweden adhered to guidelines. Areas of improvement include treatment for stage II and for the very old., Competing Interests: Declaration of Competing Interest Dr. Avall-Lundqvist: Honoraria: Roche; Advisory board: Astra Zeneca, Clovis Oncology, Tesaro and Genmab. The other authors have no conflicts of interest to declare., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background/aim: Vulva cancer surgery is associated with a high level of morbidity mostly due to wound healing disorders in the inguinal region following lymphadenectomy. Our aim is to evaluate the feasibility of negative pressure wound therapy (NPWT) using the PICO™ device in groin wounds after lymphadenectomy., Patients and Methods: The groins of twenty patients who underwent bilateral lymph node dissection were dressed with the PICO™ device. All patients were followed prospectively with clinical controls up to three months postoperatively using a standardized study protocol., Results: A total of 11 patients (55%) developed a surgical site complication (SSC). One patient suffered from a wound rupture two days after surgery, six a lymphocele and four a surgical site infection. Operation time, blood loss, number of lymph nodes removed, length of hospital-stay and duration of PICO™ treatment did not differ between women with and without SSCs., Conclusion: NPWT using the PICO™ device seems to be a feasible method to reduce the severity of healing disorders in the groin after lymphadenectomy in vulva cancer patients., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: During 2013 and 2016 the region of Skåne, Sweden started to analyse human papillomavirus (HPV) and cytology in postmenopausal women 60-65 years of age. Our aim was to evaluate high-risk (HR) HPV mRNA testing for the triage of HPV DNA-positive postmenopausal women with normal cytology., Methods: A total of 271 women, 60-65 years of age, underwent liquid-based cytology (LBC) and HPV testing by using the HR-HPV DNA MGP-PCR-Luminex assay. HR-HPV DNA-positive women with normal cytology underwent complimentary HPV mRNA testing (Aptima, Hologic Inc.). Over a period of 49 months (SD 11.0) the women received regular follow-ups at intervals of 12-18 months. Women with abnormal cytology and/or a positive HR-HPV DNA and/or mRNA result at two subsequent visits were scheduled for colposcopy and clinical examination., Results: Over the surveillance period, 3.6% (10/271) of the HR-HPV DNA-positive women developed histologically confirmed high-grade squamous intraepithelial lesions (HSILs) or worse. The cumulative incidence rates (CIR) were 29.7% (CI 24.8-30.1) for HSIL or worse among HPV mRNA-positive women at enrolment (39.5% 107/271) and 0% among HPV mRNA-negative women (60.5%, 164/271), (p = 0.002)., Conclusions: Postmenopausal women with normal cytology testing positive for HR-HPV mRNA are at increased risk for the development of high-grade cervical intraepithelial neoplasia (CIN), in contrast to women with a negative HR-HPV mRNA outcome. The HR-HPV mRNA APTIMA assay detecting 14 HR-HPV types may be a useful triage method among HPV DNA-positive postmenopausal women with normal cytology.

Objective: Survival in epithelial ovarian cancer (EOC) remains poor. Most patients are diagnosed in late stages. Early diagnosis increases the chance of survival. We used the proximity extension assay from Olink Proteomics to search for new protein biomarkers with the potential to improve the diagnostic performance of CA125 and HE4 in patients with ovarian tumors., Material and Methods: Plasma samples were obtained from 180 women with ovarian tumors; 30 cases of benign tumor, 28 cases with borderline tumors, 25 early EOC cases (FIGO stage I) and 97 advanced EOC cases (FIGO stages II-IV). Proteins were measured using the Olink® Oncology II and Inflammation panels. For statistical analyses, patients were categorized into benign tumors versus cancer and benign tumors versus borderline + cancer, respectively., Results: We analyzed 177 biomarkers. Thirty-four proteins had ROC AUC > 0.7 for discrimination between benign tumors and cancer. Fifteen proteins had ROC AUC > 0.7 for discrimination between benign tumors and borderline tumors + cancer. HE4 ranked highest for both comparisons. A reference model with HE4, CA125 and age (AUC 0.838 for benign tumors vs. cancer and AUC 0.770 for benign tumors vs. borderline tumors + cancer) was compared to the reference model with the addition of each of the remaining proteins with AUC > 0.7. ITGAV was the only individual biomarker found to improve diagnostic performance of the reference model, to AUC 0.874 for benign tumors vs. cancer and AUC 0.818 for benign tumors vs. borderline tumors + cancer (p < 0.05). Cross-validation and LASSO regression was combined to select multiple biomarker combinations. The best performing model for discrimination between benign tumors and borderline tumors + cancer was a 6-biomarker combination (HE4, CA125, ITGAV, CXCL1, CEACAM1, IL-10RB) and age (AUC 0.868, sensitivity 0.86 and specificity 0.82, p = 0.016 for comparison with the reference model)., Conclusion: HE4 was the best performing individual biomarker for discrimination between benign ovarian tumors and EOC including borderline tumors. The addition of other carcinogenesis-related biomarkers in a multiplex biomarker panel can improve the diagnostic performance of the established biomarkers HE4 and CA125., Competing Interests: The authors have declared that no competing interests exist.

Background/aim: Cervical cancer is the most common cancer among women in Ethiopia. The objective was to evaluate the participation rate of a free of charge vaginal self-sample (Aptima multitest swab, Hologic) for the detection of human papillomavirus (HPV) in an Ethiopian cohort., Patients and Methods: Specimens were collected from women employed by Ethiopian Airlines in Addis Abeba (N=5950). Samples were analysed for the presence of high-risk (HR) HPV mRNA by the Aptima HPV assay (Hologic) and HPV positive women were referred for cytology. Identification of HPV types among HPV positive samples was performed by Modified general primer-PCR and Luminex assay., Results: Participation rate was 3.1% and the prevalence of HPV mRNA was 20.6% (37/180)., Conclusion: Primary HPV mRNA screening with vaginal self-sampling may be an acceptable approach in Ethiopia. One out of five women harbor HPV in their vaginal self-sample in agreement with other similar studies from the region., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The efficacy of cervical cancer screening programs is dependent on the participation rate. To increase participation among women not attending cervical cancer screening, self-collected samples for detection of high-risk human papillomavirus (hr-HPV) may be an option.The aims of this study were: to investigate the response rate to sending a self-collected vaginal sample for hr-HPV mRNA detection to long-term non-attendees; the compliance with follow-up among women positive for HPV in the self-sample; the prevalence of cervical dysplasia (high grade squamous intraepithelial lesion (HSIL), atypical squamous cells that cannot exclude HSIL (ASC-H) or adenocarcinoma in situ (AIS)) or cancer among the responders; as well as to explore reasons for not returning a self-sample., Methods: A vaginal self-sampling kit was sent to 6023 women aged 30-70 years who had not provided a cervical screening sample for ≥7 years in the Region of Skåne, Sweden in November and December 2017. The self-sample was analyzed by Aptima HPV mRNA assay (Hologic). All vaginal self-samples returned no later than May 31, 2018 were included in the study. Follow-up of the results was registered until January 31, 2019 with a follow-up time varying between eight to 14 months. Women positive for hr-HPV mRNA were invited for a follow-up examination. This examination consisted of a cervical sample for cytological analysis and renewed Aptima HPV mRNA testing. Two hundred thirty-five women who had not returned the self-sample were randomly selected for telephone interviews, in order to explore their reasons., Results: The response rate for the self-collected vaginal hr-HPV sample was 13.2% [(797/6023), 95% CI 12.4-14.1%] and 9.9% [(79/796), 95% CI 7.9-12.2%] were positive for hr-HPV mRNA. The prevalence of severe dysplasia or cancer in the whole group of responders was 1.3% [(10/796), 95% CI 0.6-2.3%], with a cervical cancer prevalence of 0.4% [(3/796), 95% CI 0.1-1.1%]. Only 27 women participated in the telephone interviews, no particular reason for not returning self-samples was observed., Conclusions: Self-collected vaginal hr-HPV samples increased participation in the cervical cancer screening among long-term non-attendees. The prevalence of cervical cancer was almost seven times higher for long-term non-attendees than in the organized screening population., Competing Interests: Competing interestsHologic Inc. provided the sample kits and did not charge for the HPV analyses performed at the Laboratory in Lund, Sweden. Hologic Inc. did not have any influence on the study design, statistical analyses or manuscript writing. OF: Has received a speech honorarium from Hologic and his laboratory department (Laboratory Medicine, Region Skåne, Lund) has ongoing contracts with Hologic. None of the other authors have any conflicts of interest to declare., (© The Author(s) 2020.)

Objective: Survival in cervical cancer has improved little over the last decades. We aimed to elucidate primary treatment patterns and survival., Methods: Population-based study of patients included in the Swedish Quality Registry for Gynecologic Cancer diagnosed 2011-2015. Main outcome was 5-year relative survival (RS). Age-standardised RS (AS-RS) was estimated for the total cohort and for the pooled study population of squamous, adenosquamous-, adenocarcinoma., Results: Median follow-up time was 4.6 years. The study population consisted of 2141 patients; 97% of the 2212 patients in the total cohort and the 5-year AS-RS was 71% and 70%, respectively. RS stage IB1: surgery alone 95% vs. 72% for definitive chemoradiotherapy (CT-RT) (p < 0.001). In stage IIA1 74% had CT-RT, and 47% of operated patients received adjuvant (CT)-RT. RS stage IB2: surgically treated 81% (69% received adjuvant (CT)-RT) vs. 76% for (CT)-RT (p = 0.73). RS stage IIB: 77% for CT-RT + brachytherapy (BT), 37% for RT + BT (p = 0.045) and 27% for RT-BT (p < 0.001). Stages III-IVA; <40% received CT-RT + BT, RS 45% vs. 18% for RT-BT (RR 4.1, p < 0.001). RS stage IVB 7%., Conclusion: Primary treatment of cervical cancer in Sweden adhered to evidence-based standard of care. Areas of improvement include optimising treatment for stages III-IVA, and avoiding combining surgery and radiotherapy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The aim of this study is to evaluate the impact of lymphovascular space invasion (LVSI) on the risk of lymph node metastases and survival in endometrioid endometrial adenocarcinoma. Material and methods: As regard the study design, this is a cohort study based on prospectively recorded data. Patients with endometrioid endometrial adenocarcinoma registered in the Swedish Quality Registry for Gynecologic Cancer 2010-2017 with FIGO stages I-III and verified nodal status were identified ( n  = 1587). LVSI together with established risk factors, namely DNA ploidy, FIGO grade, myometrial invasion and age, were included in multivariable regression analyses with lymph node metastases as the dependent variable. Associations between the risk factors and overall and relative survival were included in multivariable models. Estimates of risk ratios (RR), hazard ratios (HR), excess mortality rate ratios (EMR), and 95% confidence intervals (95% CI) were calculated. Results: The presence of LVSI presented the strongest association with lymph node metastases ( RR  = 5.46, CI 3.69-8.07, p  < .001) followed by deep myometrial invasion ( RR  = 1.64, CI 1.13-2.37). In the multivariable survival analyses, LVSI (EMR = 7.69, CI 2.03-29.10,) and non-diploidy (EMR = 3.23, CI 1.25-8.41) were associated with decreased relative survival. In sub-analyses including only patients with complete para-aortic and pelvic lymphadenectomy and negative lymph nodes ( n  = 404), only LVSI ( HR  = 2.50, CI 1.05-5.98) was associated with a worsened overall survival. Conclusion: This large nationwide study identified LVSI as the strongest independent risk factor for lymph node metastases and decreased survival in patients with endometrioid adenocarcinomas. Moreover, decreased overall survival was also seen in patients with LVSI-positive tumors and negative lymph nodes, indicating that hematogenous dissemination might also be important.

Background: We recently reported a sensitivity of 85.5% to detect high-grade squamous intraepithelial lesions (HSIL)/adenocarcinoma in situ (AIS)/cancer by the use of self-collected vaginal samples analysed by the Aptima mRNA HPV assay (AHPV)., Objectives: To increase detection of HPV among self-samples., Study Design: We used a pre-heating step at 90 °C for 1 h on our previously AHPV-negative self-samples (N = 20) among women with AHPV-positive cervical samples. We also analysed AHPV results before and after the heating among a series of self-samples from women who had not attended cervical screening for > 7 years (N = 173)., Results: After heating, 55% (11/20) of the self-samples became AHPV-positive. By updating our original series 93.1% (121/130, 95% CI: 87.3-96.8) of the self-samples were AHPV-positive among women with AHPV-positive cervical samples, and among women with histologically confirmed cervical intraepithelial neoplasia or worse (CIN2+) now 95.3% (61/64, 95% CI: 86.9-99.0) of the self-samples were AHPV-positive. Among the 11 AHPV-positive self-samples we detected high-risk HPV types in 10 of the samples (HPV16 3 cases, HPV18 1, HPV31 1, HPV33 1, HPV 45 1, HPV51 2, HPV 56 and 58 1, HPV42 and 90 1 [low risk]) by multiplex PCR and Luminex assay. Among the self-samples from the non-attenders 16% (27/170) and 5.3% (8/152) were AHPV-positive after and before the heating step, respectively (P = 0.0022). Concerning validity of AHPV-results, 99% (170/172) were valid after the heating step compared to 88% (152/172) before the heating step (P < 0.0001)., Conclusions: A pre-heating step on vaginal self-samples increased HPV detection by the AHPV assay., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Primary HPV screening for cervical cancer by HPV mRNA testing (Aptima) was implemented in January 2017, for women ≥30 through 70 years, in the Region of Skåne, Sweden. HPV positive samples underwent cytology assessment, and women with any degree of abnormal cytology were referred for colposcopy. The aim was to audit the primary HPV screening program, by comparing the cytology results to those of corresponding women (aged ≥30 through 65 years) screened with conventional cytology during 2016. Overall, HPV was detected among 7.0% (4433/63,055) of the women ≥30-70 years in the primary HPV screening program. Among a co-tested (cytology and HPV) subgroup aged 40-42 years (N = 5039), HPV was detected in 100% (28/28) of high-grade squamous intraepithelial lesions (HSIL) and atypical squamous cells of undetermined significance (ASCUS) where HSIL could not be excluded (ASCH) (9/9), and in 80% (4/5) of cases of atypical glandular cells (AGC). Among women ≥30-65 years, the proportion ASCUS or worse (ASCUS+) was similar with cytology (3.52% [2016]) and primary HPV screening (3.70% [2017]). Only the proportion of ASC-H changed by the use of primary HPV screening, from 0.13% (2016) to 0.23% (2017) (p < 0.001). The colposcopy referral rate increased by 54% (3.70 vs 2.41%), when primary HPV screening was introduced. In conclusion, the implemented primary HPV screening approach demonstrated similar prevalence of ASCUS+ cytology as conventional screening. In addition, primary HPV screening decreased cytology assessments by 86% in our screening population of women 30 through 70 years taken into account the co-tested women., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The aim of the study was to evaluate the feasibility and most efficient way of offering middle-aged Swedish women a primary fracture screening program via a questionnaire. Two out of five invited women returned the FRAX questionnaire and those contacted directly by mail were most prone to respond., Purpose: Osteoporosis and its associated fractures are increasing, and this study aims to explore ways to identify women at an increased risk of fracture using the FRAX® algorithm., Methods: Three thousand middle-aged women were invited and presented a questionnaire distributed by three different methods-by mail, at routine mammography, or internet-based., Results: In total, 1120 (37.3%) women responded to the questionnaire and agreed to participate. The response rates for the mail, mammography, and internet-based groups were 39.1%, 35.7%, and 25.2% respectively. Women in the mammography group weighed more, were slightly older than the other women, and also had a higher BMI than women from the mail and internet-based groups. No difference was observed between the groups regarding previous fracture, family history for fracture, current smoking, glucocorticoid use, and alcohol usage. The mammography group had a higher median (interquartile range) major osteoporotic FRAX® score (10.0% (7.8-17.0)) than the mail group (9.7% (7.1-15.0); p = 0.005) and the internet-based group (8.7% (6.7-14.0); p = 0.001)., Conclusions: Two out of five early postmenopausal women returned the questionnaire and women contacted directly by mail were more prone to respond. Out of the participants, 26.6% had a 10-year fracture risk score ≥ 15% according to the FRAX® algorithm.

Background/aim: Cervical cancer is associated with poorer diagnosis among the elderly and pap-smear screening has a lower sensitivity. Self-sampling for detection of high-risk human papillomavirus (hr-HPV) may be an alternative screening method. The aim of this study was to analyze the response rate to vaginal HPV self-sampling and the HPV mRNA prevalence among women 69-70 years., Materials and Methods: An HPV self-sampling kit was sent to 1,000 women 69-70 years whom had not taken a cervical smear in ≥5 years. The samples were analyzed by the Aptima HPV mRNA assay. HPV-positive women were recalled for a follow-up examination., Results: The self-sample response rate was 43.3%. The HPV mRNA prevalence was 6.2%. All HPV-positive women attended follow-up., Conclusion: HPV self-sampling was accepted among older women. Although the HPV mRNA prevalence was 6.2%, no high-grade cytological abnormalities were found. Larger studies are needed to elucidate hr-HPV self-sampling as a tool to identify older women at risk of cervical cancer., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objective: Danish ovarian cancer (OC) patients have previously been found to have worse prognosis than Swedish patients, and comorbidity has been suggested as a possible explanation for this survival difference. We aimed to investigate the prognostic impact of comorbidity in surgically treated OC patients in Denmark and Sweden., Methods: This comparative cohort study was based on data from 3118 surgically treated OC patients diagnosed in 2012-2015. The Swedish subcohort (n = 1472) was identified through the Swedish National Quality Register of Gynecological Surgery, whereas the Danish subcohort (n = 1646) originated from the Danish Gynecological Cancer Database. The clinical databases have high coverage and similar variables included. Comorbidity was classified according to the Ovarian Cancer Comorbidity Index and overall survival was the primary outcome. Data were analyzed using Kaplan Meier and Cox regression analyses. Multiple imputation was used to handle missing data., Results: We found comparable frequencies of the following comorbidities: Hypertension, diabetes and 'Any comorbidity'. Arteriosclerotic cardiac disease and chronic pulmonary disease were more common among Swedish patients. Univariable survival analysis revealed a significant better prognosis for Swedish than for Danish patients (HR 0.84 [95% CI 0.74-0.95], p < .01). In adjusted multivariable analysis, Swedish patients had nonsignificant better prognosis compared to Danish patients (HR 0.91 [95% CI 0.80-1.04], p = .16). Comorbidity was associated with survival (p = .02) but comorbidity did not explain the survival difference between the two countries., Conclusions: Danish OC patients have a poorer prognosis than patients in Sweden but the difference in survival seems to be explained by other factors than comorbidity.

[This corrects the article DOI: 10.1371/journal.pone.0179520.].

Aim: To compare the clinical performance of human papillomavirus (HPV) mRNA and DNA assays in postmenopausal women., Materials and Methods: A total of 5,925 postmenopausal women were tested with cytology and the Luminex HPV DNA assay. High risk-HPV-positive women with benign cytology underwent a complimentary HPV mRNA assay (APTIMA). Both assays and the cytological testing were repeated after 12 months., Results: A total of 334 women were found to be high-risk HPV-positive; 272 out of these women met the inclusion criteria. At follow-up, 25 (9.2%) out of the 272 included women had cytological abnormalities. HPV mRNA assay at follow-up had a sensitivity of 84% (95% confidence interval=63.9-95.4%) and a specificity of 60.2% (95% confidence interval=53.7-66.3%; p=0.0003) to detect these lesions. Corresponding values for the HPV DNA assay were 88% (95% confidence interval=68.8-97.4%) and 43.5% (95% confidence interval=37.2-49.4%)., Conclusion: The HPV mRNA assay offers a comparable sensitivity but a higher specificity than the HPV DNA assay in detecting precancerous cervical lesions., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: In order to increase coverage in the organized cervical screening program, self-sampling with HPV analyses has been suggested., Objectives: The aim was to compare human papillomavirus (HPV) mRNA detection in vaginal and urine self-collected samples with clinician-taken cervical samples and the corresponding clinician-taken histological specimens., Study Design: Self-collected vaginal, urine and clinician-taken cervical samples were analyzed from 209 women with the Aptima mRNA assay (Hologic Inc, MA, USA). Cervical cytology, colposcopy, biopsy and/or the loop electrosurgical excision procedure (LEEP) were performed in every examination., Results: The sensitivity of the HPV mRNA test in detecting high-grade squamous intraepithelial lesions (HSIL)/adenocarcinoma in situ (AIS)/cancer cases was as follows: for the vaginal self-samples 85.5% (95% CI; 75.0-92.8), the urinary samples 44.8% (95% CI; 32.6-57.4), and for routine cytology 81.7% (95% CI; 70.7-89.9). For the clinician-taken cervical HPV samples the sensitivity of the HPV mRNA test in detecting HSIL/AIS/cancer was 100.0% (95% CI; 94.9-100.0). The specificity of the HPV mRNA was similar for the clinician-taken cervical HPV samples and the self-samples: 49.0% vs. 48.1%. The urinary HPV samples had a specificity of 61.9% and cytology had a specificity of 93.3%., Conclusion: The sensitivity of the Aptima HPV mRNA test in detecting HSIL/AIS/cancer from vaginal self-samples was similar to that of routine cytology. The Aptima HPV mRNA vaginal self-sampling analysis may serve as a complement in screening programs., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: The International Federation of Gynecology and Obstetrics (FIGO) ovarian cancer staging system includes no sub-stage for lymph nodes (LN) as only distant disease manifestation. We explore the prognostic implication of LN as only stage IV classifier in serous ovarian cancer., Method: This is a nation-wide, population-based study on 551 women with serous stage IV cancers diagnosed between 2009-2014. We compare overall survival (OS) in women with LN as only distant metastatic site to those with pleural metastases only and to patients with other/multiple stage IV manifestations. Cox regression models were used for uni- and multivariable estimations., Results: Of 551stage IV cases, distant metastatic site was registered in 433. Median OS for women with LN (n = 51) was 41.4 months, compared to 25.2 and 26.8 months for patients with pleural (n = 195) or other/multiple (n = 187) distant metastases (p = .0007). The corresponding five-year survival rates were 32, 11 and 22%, respectively. Multivariable analyzes confirmed shorter survival for women with pleural (HR 2.99, p = .001) or other/multiple distant sites (HR 2.67, p = .007), as compared to LN cases. LN only patients lived 9.1 months longer after primary than after interval surgery, but this difference was not significant (p = .245)., Conclusion: Women with stage IV serous ovarian cancer having lymph nodes as only distant metastatic site live longer than other stage IV patients.

Aim: The aim of this study is to evaluate the quality of data on endometrial (EC) and ovarian, fallopian tube, peritoneal, abdominal or pelvic cancers (OC) registered in the Swedish Quality Register of Gynecologic Cancer (SQRGC)., Method: A random sample of 500 patients was identified in the SQRGC and their medical charts were reviewed for re-abstraction of 31 selected core variables by an independent validator. The data in the SQRGC and the re-abstracted data were compared. The data were collected from 25 hospitals evenly distributed throughout Sweden. The main outcomes were comparability, timeliness, completeness and validity. Coverage was compared with the National Cancer Register (NCR). Timeliness was defined as the speed of registration i.e. when patients were registered in the SQRGC relative to date of diagnosis. Internationally accepted coding systems for stage, grading and histologic type were used ensuring a high degree of comparability. Correlations were estimated using Pearson's correlation coefficient and Cohen´s kappa coefficient., Results: The completeness was 95%. The timeliness was 88-91% within 12 months of diagnosis. The median degree of agreement between re-abstracted data and data in the SQRGC was 82.1%, with a median kappa value of 0.73 for ordinate variables and a median Pearson's correlation coefficient of 0.96. The agreements for the type of surgery were 76% (95% CI 70-81%; kappa 0.49) and type of primary treatment 90% (95% CI 87-94%; kappa 0.85) in OC and in EC 88% (95% CI 84-93%; kappa 0.84). The agreements for the FIGO stage were in OC and EC 74% (95% CI 68-80%; kappa 0.69) and 87% (95% CI 82-91%; kappa 0.79), respectively., Conclusions: The data in the Swedish Quality Register for Gynecologic Cancer are of adequate quality in order to be used as a basis for research and to evaluate possible differences in treatment, lead times and treatment results.

Objective: The aim was to evaluate surgical routes for benign hysterectomy in a Swedish population, including abdominal and minimally invasive surgery., Study Design: Prospectively collected data from the Swedish National GynOp Registry 2009-2015: 13 806 hysterectomy cases were included: abdominal (AH, n = 7485), vaginal (VH, n = 3767), conventional laparoscopic (LH, n = 1539) and robotically-assisted (RAH, n = 1015)., Results: The VH group had the shortest operation time at 75 min, AH 97 min and RAH 104 min. LH was longest at 127 min (p < 0.005). The mean estimated blood loss was higher in the AH group (250 ml) compared to all minimally invasive surgery (MIS, 65-172 ml); p < 0.005). Conversion rates were 10% for LH, 4.8% for VH and 1.6% for RAH (p < 0.005). Hospitalization and patient-reported time to normal activities of daily living (ADL) were longer for AH compared to MIS (p < 0.005). Time to return to work was eight days longer in the AH group (35 days) compared with the MIS groups (p < 0.005). Complications were fewest in the VH group at 5.4% compared with AH 7.6% and RAH 8.7% (both p < 0.001), but did not significantly differ from the LH group at 6.6%. Overall patient satisfaction was reported to be 86-94% one year after surgery., Conclusion: Women operated on for benign hysterectomy with minimally invasive methods in Sweden 2009-2015 had reduced length of hospitalization, as well as time to resuming normal ADL and return to work, compared to AH. Postoperative outcome measures were improved by minimally invasive methods and MIS should preferably be used., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Recent research indicates a favourable influence of postmenopausal hormone therapy (HT) if initiated early, but not late, on subclinical atherosclerosis. However, the clinical relevance of timing of HT initiation for hard end points such as stroke remains to be determined. Further, no previous research has considered the timing of initiation of HT in relation to haemorrhagic stroke risk. The importance of the route of administration, type, active ingredient, and duration of HT for stroke risk is also unclear. We aimed to assess the association between HT and risk of stroke, considering the timing of initiation, route of administration, type, active ingredient, and duration of HT., Methods and Findings: Data on HT use reported by the participants in 5 population-based Swedish cohort studies, with baseline investigations performed during the period 1987-2002, were combined in this observational study. In total, 88,914 postmenopausal women who reported data on HT use and had no previous cardiovascular disease diagnosis were included. Incident events of stroke (ischaemic, haemorrhagic, or unspecified) and haemorrhagic stroke were identified from national population registers. Laplace regression was employed to assess crude and multivariable-adjusted associations between HT and stroke risk by estimating percentile differences (PDs) with 95% confidence intervals (CIs). The fifth and first PDs were calculated for stroke and haemorrhagic stroke, respectively. Crude models were adjusted for age at baseline only. The final adjusted models included age at baseline, level of education, smoking status, body mass index, level of physical activity, and age at menopause onset. Additional variables evaluated for potential confounding were type of menopause, parity, use of oral contraceptives, alcohol consumption, hypertension, dyslipidaemia, diabetes, family history of cardiovascular disease, and cohort. During a median follow-up of 14.3 years, 6,371 first-time stroke events were recorded; of these, 1,080 were haemorrhagic. Following multivariable adjustment, early initiation (<5 years since menopause onset) of HT was associated with a longer stroke-free period than never use (fifth PD, 1.00 years; 95% CI 0.42 to 1.57), but there was no significant extension to the time period free of haemorrhagic stroke (first PD, 1.52 years; 95% CI -0.32 to 3.37). When considering timing as a continuous variable, the stroke-free and the haemorrhagic stroke-free periods were maximal if HT was initiated approximately 0-5 years from the onset of menopause. If single conjugated equine oestrogen HT was used, late initiation of HT was associated with a shorter stroke-free (fifth PD, -4.41 years; 95% CI -7.14 to -1.68) and haemorrhagic stroke-free (first PD, -9.51 years; 95% CI -12.77 to -6.24) period than never use. Combined HT when initiated late was significantly associated with a shorter haemorrhagic stroke-free period (first PD, -1.97 years; 95% CI -3.81 to -0.13), but not with a shorter stroke-free period (fifth PD, -1.21 years; 95% CI -3.11 to 0.68) than never use. Given the observational nature of this study, the possibility of uncontrolled confounding cannot be excluded. Further, immortal time bias, also related to the observational design, cannot be ruled out., Conclusions: When initiated early in relation to menopause onset, HT was not associated with increased risk of incident stroke, regardless of the route of administration, type of HT, active ingredient, and duration. Generally, these findings held also for haemorrhagic stroke. Our results suggest that the initiation of HT 0-5 years after menopause onset, as compared to never use, is associated with a decreased risk of stroke and haemorrhagic stroke. Late initiation was associated with elevated risks of stroke and haemorrhagic stroke when conjugated equine oestrogen was used as single therapy. Late initiation of combined HT was associated with haemorrhagic stroke risk.

Background/aim: To compare human papillomavirus (HPV) DNA detection in self-collected vaginal and urine samples with clinician-taken cervical samples in relation to histology., Materials and Methods: Self-collected vaginal, urine and clinician-taken cervical samples were analyzed from 218 women with the Cobas 4800 HPV test (Roche Molecular Diagnostics)., Results: The sensitivity for detection of HPV in the vaginal self-sampling test was 96.4% and in urine was 83.9% relative to detection by clinician-taken cervical sample. The vaginal self-sampling and the clinician-taken HPV tests had the same sensitivity of 92.8% (95% confidence interval=86.3-96.8%) and specificity for detection of high-grade squamous intraepithelial lesion (HSIL) and adenocarcinoma in situ (AIS). Detection in urine samples had a sensitivity of 76.3% (95% confidence interval=67.9-84.2%) for HSIL/AIS., Conclusion: The Cobas 4800 HPV test detects high-grade pre-cancerous cervical lesions in self-collected vaginal samples with the same high sensitivity as in clinician-taken cervical samples., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: High-risk (HR) human papillomavirus (HPV) infection is an established cause of malignant disease. We used a societal perspective to estimate the cost of HR HPV-related cervical, vulvar, vaginal, anal, and penile precancer and cancer, and oropharyngeal cancer in Sweden in 2006, 1 year before HPV vaccination became available in the country., Materials and Methods: This prevalence-based cost-of-illness study used diagnosis-specific data from national registries to determine the number of HR HPV-related precancers and cancers. The HR HPV-attributable fractions of these diseases were derived from a literature review and applied to the total burden to estimate HR HPV-attributable costs. Direct costs were based on health care utilization and indirect costs on loss of productivity due to morbidity (i.e., sick leave and early retirement) and premature mortality., Results: The total annual cost of all HR HPV-attributable precancers and cancers was €94 million (€10.3/inhabitant). Direct costs accounted for €31.3 million (€3.4/inhabitant) of the total annual cost, and inpatient care amounted to €20.7 million of direct costs. Indirect costs made up €62.6 million (€6.9/inhabitant) of the total annual cost, and premature mortality amounted to €36 million of indirect costs. Cervical precancer and cancer was most costly (total annual cost €58.4 million). Among cancers affecting both genders, anal precancer and cancer, and oropharyngeal cancer were the most costly (€11.2 million and €11.9 million, respectively). For oropharyngeal cancer, males had the highest health care utilization and represented 71% of the total annual cost. Penile precancer and cancer was least costly (€2.6 million)., Conclusion: The economic burden of HR HPV-related precancers and cancers is substantial. The disease-related management and treatment costs we report are relevant as a point of reference for future economic evaluations investigating the overall benefits of HPV vaccination in females and males in Sweden.

Background/aim: To evaluate ovarian cancer surgery in tertiary centers (TC) and regional hospitals (RH)., Patients and Methods: Data from the GynOp registry on patients undergoing surgery for ovarian cancer or borderline tumor from 2013 to 2015 were analyzed., Results: Four TC and 21 RH reported 1,108 cases of surgery with curative intent, 770 cases (69.5%) in TC and 338 cases (30.5%) in RH. Out of 458 patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIIC-IV disease 396 (86.5%) had surgery in TC. We found differences in selection for primary debulking surgery (PDS) (45% to 93%, p<0.001) and PDS achieving no residual tumor (36% to 70%, p<0.001) between the four TC. Major complications, re-admissions and re-operation rates did not differ between TC and RH., Conclusion: Tertiary centers perform more extensive surgery compared to regional hospitals without increased frequency of major complications. Tertiary centers display significant differences among patient selection for PDS, as well as achieving no residual tumor., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objective: The aim of the study was to determine survival outcome in patients with serous cancer in the ovary, fallopian tube, peritoneum and of undesignated origin., Methods: Nation-wide population-based study of women≥18years with histologically verified non-uterine serous cancer, included in the Swedish Quality Registry for primary cancer of the ovary, fallopian tube and peritoneum diagnosed 2009-2013. Relative survival (RS) was estimated using the Ederer II method. Simple and multivariable analyses were estimated by Poisson regression models., Results: Of 5627 women identified, 1246 (22%) had borderline tumors and 4381 had malignant tumors. In total, 2359 women had serous cancer; 71% originated in the ovary (OC), 9% in the fallopian tube (FTC), 9% in the peritoneum (PPC) and 11% at an undesignated primary site (UPS). Estimated RS at 5-years was 37%; for FTC 54%, 40% for OC, 34% for PPC and 13% for UPS. In multivariable regression analyses restricted to women who had undergone primary or interval debulking surgery for OC, FTC and PPC, site of origin was not independently associated with survival. Significant associations with worse survival were found for advanced stages (RR 2.63, P<0.001), moderate (RR 1.90, P<0.047) and poor differentiation (RR 2.20, P<0.009), neoadjuvant chemotherapy (RR1.33, P<0.022), residual tumor (RR 2.65, P<0.001) and platinum single (2.34, P<0.001) compared to platinum combination chemotherapy., Conclusion: Survival was poorer for serous cancer at UPS than for ovarian, fallopian tube and peritoneal cancer. Serous cancer at UPS needs to be addressed when reporting and comparing survival rates of ovarian cancer., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: Human papillomavirus (HPV) infection is an objective marker with a high sensitivity for finding cervical dysplasia. The objective of the current study is to investigate whether HPV testing, combined with liquid-based cytology, is reliable as a test of cure after the loop electrical excision procedure (LEEP)., Material and Methods: The LEEP was performed in 330 women for excision of cervical dysplasia. Follow up consisted of HPV testing and liquid-based cytology at six, 12, and 36 months after treatment. Patients with negative co-testing after 6 months were re-examined after 3 years. Patients who tested positive for high-risk HPV and/or dysplasia were followed up 12 months postoperatively., Results: At 6 months, the co-testing was double negative in 169 of 260 tested cases (65%). A positive high-risk HPV test (n = 40) was associated with cytological abnormalities (p < 0.001). After 3 years, 227 of 275 examined cases (83%) co-tested negative, including 154 patients who had already tested negative at 6 months and 37 cases with viral clearance at 12 months. Of 26 patients with high-risk HPV at the 3-year follow up, six had LSIL findings on liquid-based cytology, but neither HSIL lesions nor glandular atypia or cervical cancer was found. A negative high-risk HPV test showed a negative predictive value for HSIL of 100% (95% CI 99.8-100%)., Conclusions: Negative co-testing 6 months after LEEP can be considered a reliable test of cure as 3-year follow-up results are consistent with neither HSIL or cancer., (© 2016 Nordic Federation of Societies of Obstetrics and Gynecology.)

Introduction: The aim was to evaluate surgical treatment of newly diagnosed uterine cancer in a Swedish population., Material and Methods: Data in the GynOp registry from 2008 to 2014 were analyzed., Results: In total, 3443 cases were included: 430 (12%) were robotic-assisted laparoscopic, 272 (8%) laparoscopic, and 2741 (80%) abdominal operations. There was an increasing trend in minimally invasive surgery from 2008 to 2014 (41%). Women with lymph nodes removed in the robotic-assisted laparoscopic group experienced less blood loss (mean 105 vs. 377 mL), shorter length of hospital stay (2.4 vs. 4.1 days), and fewer days to normal activities of daily living (6.5 vs. 12.7 days) (all p < 0.001) compared with the abdominal group, but operating time did not differ. Similar results were found in women with no lymph node removal and in women with body mass index ≥35. Major complications during hospital stay, reoperations, and time to work were less in both minimally invasive groups. More lymph nodes were retrieved in the abdominal (mean 34.4) than in the robotic-assisted laparoscopic (mean 26.0) group, but the number of women with lymph node metastases did not differ, totaling 211/960 (21.9%; 95% CI 19.4-24.7%). Isolated para-aortic lymph node metastases were found in 3.9% (95% CI 2.4-5.6%) of women., Conclusions: Minimally invasive surgery in uterine cancer patients reduces days to normal activities of daily living, number of days to return to work, length of hospital stay, and blood loss in patients without and with lymph node dissection and in obese patients., (© 2016 Nordic Federation of Societies of Obstetrics and Gynecology.)

Introduction: We conducted an evaluation of incidence and survival of women with borderline ovarian tumors in Sweden., Material and Methods: All women diagnosed with borderline ovarian tumor in the Swedish Cancer Register 1960-2007 (n = 6252) combined with follow up in the Swedish Death Registry to 1 July 2009 were included. Estimation of age-standardized relative survival rate according to time periods for diagnosis., Results: The incidence of borderline ovarian tumors increased during the study period, with a steep increase during the 1980s. The age standardized 5-year relative survival including all borderline tumors diagnosed 2000-07 was 97% (95% CI 92-99%). In women aged ≤64 years, the 10-year relative survival related to age at diagnosis of borderline tumors ranged from 95 to 98% and was 89% in women aged 65-74 years. In a multivariable analysis including age and decade of diagnosis relative survival for every decade increased. The 10-year relative survival in women with mucinous and serous borderline tumors did not differ significantly (p = 0.121)., Conclusions: Results of the present study are reassuring about long-term survival in women with borderline ovarian tumors. The age-standardized relative survival rate increased across time periods for diagnosis. There was no difference in long-term survival between mucinous and serous borderline ovarian tumors., (© 2016 Nordic Federation of Societies of Obstetrics and Gynecology.)

Background/aim: To assess preoperative blood levels of a biomarker panel in relation to the new classification system of epithelial ovarian cancer (EOC) type I and II., Patients and Methods: Preoperative plasma levels of B7-family protein homolog 4 (B7-H4), intact and cleaved soluble urokinase plasminogen activator receptor (suPAR), human epididymis protein 4 (HE4) and cancer antigen 125 (CA125) were analyzed in 350 patients with adnexal lesions., Results: The levels of suPAR(II-III), HE4, CA125 were all higher in EOC II than in EOC I, borderline and benign ovarian tumors. B7-H4 was increased in EOC II compared with benign ovarian tumors. The combination of suPAR(II-III), HE4, CA125 and age in premenopausal women discriminates EOC and borderline tumors from benign tumors to higher accuracy compared to the Risk of Ovarian Malignancy Algorithm (p=0.007)., Conclusion: The biomarker panel suPAR(II-III), HE4, CA125 and age in premenopausal women improved discrimination of malignant and benign ovarian tumors. The plasma levels of B7-H4 were increased in patients with EOC II compared to those with benign ovarian tumors., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Ovarian cancer is the most common cause of death from a gynecologic cancer. Every year around 700 women contracts ovarian cancer in Sweden. The overall survival is among the highest in Europe, but still long term relative survival is only 46%. It is a long-held myth that ovarian cancer is a disease without symptoms. Almost 90% of women have symptoms, even in the early stages. Symptoms that should arise suspicion of ovarian cancer and initiate diagnostic work-up are continuous abdominal extension, early feeling of satiety, pelvic or abdominal pain, urinary urge and postmenopausal bleeding. Women's awareness of symptoms and willingness to seek medical advice and the organization of the health care system are important factors determining cancer survival. Ovarian cancer is a heterogeneous group of diseases with different tumor traits and prognosis. Personalized medicine and preventive measures recognizing recent knowledge about tumor biology will positively affect survival.

Aim: To develop and validate a biomarker-based index to optimize referral and diagnosis of patients with suspected ovarian cancer. Furthermore, to compare this new index with the Risk of Malignancy Index (RMI) and Risk of Ovarian Malignancy Algorithm (ROMA)., Patients and Methods: A training study, consisting of patients with benign ovarian disease (n=809) and ovarian cancer (n=246), was used to develop the Copenhagen Index (CPH-I) utilizing the variables serum HE4, serum CA125 and patient age. Eight international studies provided the validation population; comprising 1060 patients with benign ovarian masses and 550 patients with ovarian cancer., Results: Overall, 2665 patients were included. CPH-I was highly significant in discriminating benign from malignant ovarian disease. At the defined cut-off of 0.070 for CPH-I the sensitivity and specificity were 95.0% and 78.4% respectively in the training cohort and 82.0% and 88.4% in the validation cohort. Comparison of CPH-I, ROMA and RMI demonstrated area-under-curve (AUC) at 0.960, 0.954 and 0.959 respectively in the training study and 0.951, 0.953 and 0.935 respectively in the validation study. Using a sensitivity of 95.0%, the specificities for CPH-I, ROMA and RMI in the training cohort were 78.4%, 71.7% and 81.5% respectively, and in the validation cohort 67.3%, 70.7% and 69.5% respectively., Conclusion: All three indices perform well at the clinically relevant sensitivity of 95%, but CPH-I, unlike RMI and ROMA, is independent of ultrasound and menopausal status, and may provide a simple index to optimize referral of women with suspected ovarian cancer., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To evaluate current surgical cervical cancer treatment in Sweden 2008-12., Design and Setting: Analysis of data in the Swedish National Quality Register for Gynecological Surgery (GynOP)., Sample: A total of 249 cervical cancer patients undergoing surgery., Methods: Analysis of prospectively gathered preoperative and postoperative data including patient-reported information., Main Outcome Measures: Mean operating time, blood loss/transfusion, length of hospital stay, return to activities of daily living., Results: The patients undergoing laparoscopic robot-assisted surgery (n = 64) or laparotomy (n = 185) did not differ in age, body mass index, American Society of Anesthesiologists score, International Federation of Gynecology and Obstetrics (FIGO) stage or mean operating time. Blood loss was higher in the laparotomy group (p < 0.001). Thirteen patients in the laparotomy group (7%) received a blood transfusion, but none in the robot group. Intraoperative complications were more common in the laparotomy group (p = 0.03). Re-admission or operations did not differ between the groups. The number of pelvic lymph nodes removed was significantly higher in the laparotomy group (median 31 vs. 24, p < 0.001). There was no difference regarding the number of patients with lymph node metastases in the two groups. The postoperative length of hospital stay was longer in the laparotomy group compared with the robot group (6.1 days vs. 2.1 days, p = 0.01). The patient-reported time to resume normal activities of daily living was longer in the laparotomy than the robot group (13.4 days vs. 9.7 days, p = 0.04)., Conclusions: Laparoscopic robotic-assisted surgery is preferable to laparotomy for cervical cancer patients because it entails a significantly shorter hospital stay, less blood loss, fewer intraoperative complications and shorter time to normal daily activities., (© 2014 Nordic Federation of Societies of Obstetrics and Gynecology.)

Aim: To evaluate women with atypical glandular cells (AGC) or adenocarcinoma in situ (AIS) on cytology., Patients and Methods: Population-based data of cervical smears taken between 2008-2012 were analyzed., Results: Cancer was diagnosed in 107 out of 199 patients (54%) with AGC or AIS; 30 with cervical adenocarcinoma and 77 with endometrial cancer. All women with endometrial cancer were 50 years or older. In women younger than 50 years, cervical pre-cancerous lesions were found in 44 (47%) and cervical adenocarcinoma in 24 out of 92 cases (26%). High-risk HPV infection was found in 62 out of 103 women (60%). The detection rate of high-risk HPV at finding histopathological AGC, AIS, low-grade squamous intraepithelial lesions, high-grade squamous intraepithelial lesions or cervical cancer was 98% (95% confidence interval=0.903-1.000) (54/55)., Conclusion: AGC or AIS indicates endometrial neoplasia in women 50 years or older and pre-cancerous or invasive glandular cervical lesions in younger women. HPV testing seems to identify underlying cervical adenocarcinoma and high grade squamous intraepithelial lesions., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Aim: To analyze the cervical screening history in women with cervical cancer and their outcome., Design: All women diagnosed with cervical cancer between January 2009 and December 2010 in the South Sweden region were included in the audit., Materials and Methods: Cervical cancer was registered in 165 women in 2009 and 2010. Their screening history was analyzed, and was classified as normal or imperfect. The method of discovering the cancer was either by symptoms or by screening. The main outcome measured was overall survival in cervical cancer related to cervical screening history., Results: Women above 65 years of age were more frequently diagnosed with advanced-stage disease (The International Federation of Gynecology and Obstetrics II-IV) (n=36 out of 43; 84%) compared to women below 65 years of age (n=35 out of 122; 29%) (p<0.001). All patients diagnosed by the cervical screening program were still alive (30/30) at the median follow-up time (36 months), showing better overall survival compared to women below screening age in whom cancer was discovered due to symptoms (68/98; p<0.001). Cox proportional hazards model showed that women beyond screening age (>65 years old) with normal screening history had a worse prognosis, with a hazard ratio of 4.8 (95% confidence interval=1.9-12.1, p=0.001), and women (>65 years old) who had not followed the screening program had a hazard ratio of 5.9 (95% confidence interval I 2.4-14.6, p<0.001), compared to women under 65 years old who had followed the screening program., Conclusion: Cervical cancer in women above the age of 65 years is discovered at advanced stages of the disease and their prognosis is poor., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Postmenopausal women in the Western world are highly burdened by osteoporotic fractures. The aim of this study is to investigate risk factors at baseline for fracture in 6416 postmenopausal women during long-term follow-up. At baseline, all women completed a questionnaire regarding background factors, diseases, current use of medications and reproductive and contraceptive history, a physical examination and laboratory analyses. Fracture occurrence after inclusion in the study was recorded with the help of official registries. All significant variables in univariate logistic regression with a decreased or increased risk for fracture were analysed in a multivariate logistic regression. Increased fracture risk was observed in women currently using proton pump inhibitors (PPI), odds ratio (OR) 2.53 (95% confidence interval (CI)) 1.28-4.99, and women having had a fracture after the age of 40, but before inclusion in the study, OR 1.70 (95% CI 1.24-2.32). A protective effect against fractures was observed in women with a positive family history of diabetes OR 0.66 (95% CI 0.44-0.98). A significant interaction was observed between fracture risk, use of PPI and HT status (p=0.014) and women with HT had an increased fracture risk with use of PPI (OR 3.37 (95% CI 1.96-5.80)) compared to women without HT (OR 1.13 (95% CI 0.57-2.24)). In conclusion, usage of PPIs was associated with a doubled risk for fracture in postmenopausal women. Women with previous fractures using PPI should be considered for prophylactic treatment reducing fracture risk., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Many cervical cancers occur among women who have not attended cervical screening. Strategies to reach non-attending women may improve the effectiveness of cervical screening programmes., Objective: To compare the responses among long-term non-attending women to either (i) HPV-testing of a self-collected vaginal sample, or (ii) cytological screening with a flexible no-fee appointment for sampling at an outpatient clinic., Study Design: Among the 242,000 women aged 32-65 years in Southern Sweden, we identified 28,635 women who had not had any cervical smears taken for >9 years. We randomized 1000 women to invitation to HPV self-sampling, and 500 women to flexible outpatient clinic appointments. Responding women received a questionnaire about their reasons for previous non-attendance., Results: The response rate to HPV self-sampling was three times higher than the flexible outpatient clinic invitations (147/1000 women (14.7%) compared to 21/500 (4.2%) p<0.0001). High-risk (hr)-HPV was found in 10/147 self-sampled women (6.9%). 7/10 hr-HPV-positive women attended colposcopy, but no HSIL was found. Among the clinic-sampled women, 2/21 had hr-HPV and 1/21 had HSIL. Reasons for not attending were "uncomfortable with vaginal examination", "feel healthy", "lack of time" and "experience of unfriendly health workers"., Conclusions: Although the response rate was low for both interventions, the invitation to vaginal HPV self-sampling was more effective for increasing the coverage of the screening programme. The fact that "uncomfortable with vaginal examination" was the most common reason for non-attending suggests that self-sampling could be further explored as a strategy to increase the coverage of cervical screening programmes., (Copyright © 2013 Elsevier B.V. All rights reserved.)

The Women's Health in the Lund Area (WHILA) project (n=6917) is a cohort study that started in 1995 and includes a postal questionnaire, physical examination, bone density measurement and blood laboratory analyses. Fracture data have been added, and in this report fracture risk and its association with sex hormones was analysed in postmenopausal women without current hormone therapy (HT). A total of 409 women (median age 56.8 years) with 489 fractures were identified from the postmenopausal women without HT during a median follow-up time of 8.4 years. Lower serum levels of androstenedione (p<0.001), testosterone (p=0.008), androstenedione/sex hormone binding globulin (SHBG) ratio (p<0.001), testosterone/SHBG ratio (p=0.003) and higher levels of SHBG (p=0.005) were observed in women with fractures compared to no fracture. No difference in oestradiol levels was observed. Androstenedione and androstenedione/SHBG ratio were further divided into percentiles. Increased fracture risk was found in postmenopausal women with androstenedione in 5th percentile compared to 11-89th percentile HR 1.51 (95% CI 1.02-2.24). The androstenedione/SHBG ratio (11-89th percentile as reference) showed increased fracture risk in women with low ratio 5th percentile HR 1.75 (95% CI 1.20-2.54) and decreased fracture risk with high ratio 95th percentile HR 0.52 (95% CI 0.28-0.98). An increased fracture risk during follow-up was encountered in postmenopausal women with low serum androstenedione and androstenedione/SHBG ratio at baseline and a decreased fracture risk with high androstenedione/SHBG ratio. This study suggests that postmenopausal osteoporosis is influenced by lower levels of androgens., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)