Has time to chemotherapy from primary debulking surgery in advanced ovarian cancer an impact on survival? - A population-based nationwide SweGCG study.

OBJECTIVE: The aim of the study was to investigate if time to start chemotherapy (TTC) after primary debulking surgery (PDS) impacted relative survival (RS) in advanced epithelial ovarian/fallopian tube/primary peritoneal cancer (EOC). METHODS: Nationwide population-based study of women with EOC FIGO stages IIIC-IV, registered 2008-2018 in the Swedish Quality Register for Gynecologic Cancer, treated with PDS and chemotherapy. TTC was categorized into; ≤21 days, 22-28 days, 29-35 days, 36-42 days and > 42 days. Relative survival (RS) was estimated using the Pohar-Perme estimate of net survival. Multivariable analyses of excess mortality rate ratios (EMRRs) were estimated by Poisson regression models. RESULTS: In total, 1694 women were included. The median age was 65.0 years. Older age and no residual disease were more common in TTC >42 days than 0-21 days. The RS at 5-years was 37.9% and did not differ between TTC groups. In the R0 (no residual disease) cohort (n = 806), 2-year RS was higher in TTC ≤21 days (91.6%) and 22-28 days (91.4%) than TTC >42 days (79.1%). TTC >42 days (EMRR 2.33, p = 0.026), FIGO stage IV (EMRR 1.83, p = 0.007) and non-serous histology (EMRR 4.20, p < 0.001) were associated with 2-year worse excess mortality compared to TTC 0-21 days, in the R0 cohort. TTC was associated with 2-year survival in the R0 cohort in FIGO stage IV but not in stage IIIC. TTC was not associated with RS in patients with residual disease. CONCLUSIONS: For the entire cohort, stage IV, non-serous morphology and residual disease, but not TTC, influenced 5-year relative survival. However, longer TTC was associated with a poorer 2-year survival for those without residual disease after PDS.

Cervical cancer in Region Skåne, Sweden 2017-2020 after the implementation of primary HPV screening: A quality assurance audit.

INTRODUCTION: Primary human papilloma virus (HPV) screening to detect cervical cancer and dysplastic lesions was implemented in Region Skåne 2017 for women aged 30-70. The aim of this study was to characterize the screening history of women diagnosed with cervical cancer to evaluate the performance of the screening program, as well as to assess the cancer treatments given and shortcomings in the follow-up of women with cervical dysplasia. MATERIAL AND METHODS: We performed a quality assurance audit. The data was collected from the National Cervical Cancer Prevention Registry, Region Skåne Labmedicin database and the Melior Journal system in 2017-2020. RESULTS: We identified 247 women diagnosed with invasive cervical cancer in Region Skåne in 2017-2020. Of these, 35 (14.2%) had a screening history over at least two screening rounds before diagnosis. There were 25 (10.1%) women diagnosed with cervical cancer in between screening intervals, i.e., interval cancer. The most common screening history in women with cervical cancer was irregular screening (143, 57.9%), followed by women being above screening age (44, 17.8%). HPV was detected in 96% of the cases, either in cervical cytology or in the tumor tissue. The screening program detected the disease in 96 (38.9%) of the patients, 149 (60.3%) were diagnosed through symptoms and two (0.80%) as a result of incidental findings. CONCLUSIONS: The most powerful tool in the prevention of cervical cancer is screening program attendance. Prolongation with HPV screening among elderly women will also reduce the incidence of cervical cancer. Today, such cancers are usually discovered when symptoms appear.

Cervix cytology samples revealed increased methylation of the human markers FAM19A4/miR124-2 up to 8 years before adenocarcinoma.

INTRODUCTION: Methylation analysis of the promoter region of tumor-suppressor genes has previously shown high sensitivity for detection of high-grade cervical intraepithelial neoplasia (CIN) and cancer. HPV-testing has a high sensitivity to identify women at risk to develop cancer, and has been implemented in cervical screening programs in several countries. But in most HPV-positive women the infection will clear and they will not develop cancer. Testing for methylation could help to identify women who have potentially progressive cervical disease and need closer follow-up. The goal of the present study was to investigate the potential use of methylation as a triage test of HPV-positive women in the screening program. MATERIAL AND METHODS: A collection of liquid-based cytology (LBC) samples from 106 women, collected between 4 months and 8 years before histologically confirmed cervical cancer or CIN3, was analyzed for hypermethylation of the human genes FAM19A4 and miR124-2. RESULTS: Methylation was detected in 45% (33/73) of normal LBC samples from women who later developed CIN3+, compared with 10% (3/31) of normal LBC samples from women without subsequent dysplasia (P = 0.0006). Overall, methylation was detected in 39% (14/36), 51% (19/37), 61% (14/23) and 70% (7/10) of LBC samples from women who later developed CIN3, adenocarcinoma in situ (AIS), squamous cell carcinoma (SCC) and adenocarcinoma (ADC), respectively. Positive methylation analysis was not significantly more frequent than abnormal cytology of atypical squamous cells of unclear significance or worse (ASCUS+) in LBC samples collected 4 months to 8 years before SCC or AIS; however, prior to the development of ADC, methylation was observed in 7/10 LBC samples, despite normal cytology. Overall, LBC samples collected before invasive cancer (ADC and SCC) were more frequently positive in the methylation analysis than in cytological analysis of ASCUS+ (P = 0.048). For LBC samples collected more than 2 years before the development of AIS, SCC or ADC, methylation analysis showed a higher positivity rate than cytology did. CONCLUSIONS: Testing for methylation of FAM19A4/miR124-2 as a triage for HPV-positive women would be useful to identify women at risk of cancer development, especially adenocarcinoma. Further studies are needed to estimate the cost-effectiveness before introducing methylation testing in the screening program.

Vulvar cancer incidence and net survival in Sweden 1960 to 2019: A population-based national study.

INTRODUCTION: Vulvar cancer is a rare gynecological cancer affecting mostly older women. The aim of this population-based study was to investigate the incidence and net survival of vulvar cancer in Swedish women from 1960 to 2019. MATERIAL AND METHODS: Data were retrieved from the mandatory Swedish Cancer Registry consisting of all women diagnosed with vulvar cancer between 1960 and 2019. Only women with a morphologically verified diagnosis of vulvar cancer were included. The individuals were then further matched with the Swedish Death Registry up until May 31, 2020. RESULTS: In total, 8499 women were included with the following morphologies: squamous cell carcinoma 7250 (85.8%), malignant melanoma 539 (6.4%), adenocarcinoma 401 (4.8%) and other: 259 (3.1%). More than 50% of vulvar cancer cases occurred in women aged between 65 and 84 years of age. The 5-year age-standardized net survival increased from 53.0% (95% confidence interval [CI] 48.9-57.5) in 1960 to 72.1% (95% CI 68.8-75.5) in 2019. The proportion of adenocarcinoma among all cases increased from 2.0% to 8.7% between the 1960s and 2010s and an increase in age-standardized 5-year net survival was found for adenocarcinoma. CONCLUSIONS: The age-standardized incidence of vulvar cancer cases in Sweden was stable between 1960 and 2019. During the study period, an increase in adenocarcinoma and a decrease in malignant melanoma cases was found. Five-year net survival increased by 20 percent units during the study period. For squamous cell carcinoma, an increased age-specific 5-year net survival was observed for all age groups, apart for women aged ≥85.

Post-conization surveillance in an organized cervical screening program with more than 23,000 years of follow-up.

BACKGROUND: Cervical cancer is preventable through screening and vaccination against high-risk human papillomavirus (hr-HPV). For a screening program to be successful it is vital that the clinical management and follow-up regime of patients with abnormal screening results is well developed and that the attendance rate for follow-up is high. The aim of the study was to analyze how effective conization with recommended follow-up was in preventing subsequent cervical cancer, and to evaluate how clinical follow-up recommendations are obeyed in the region of Skåne, Sweden. METHODS: All women (n = 8835) who had undergone conization in the region of Skåne, Sweden, between the years of 2015 and 2021 were identified. Individuals with confirmed cervical cancer in the conization material were referred for additional treatment (n = 114), leaving 8721 included in the follow-up. Adherence to follow-up and cytological, histopathological and HPV status at follow-up were collected at eight, 12 and 24 months post-conization. The total follow-up time was from January 1, 2015, to January 30, 2023. RESULTS: Within 12 months post-conization, 90% of the patients conducted a cytological cervical sample. The rates of a negative test of cure (HPV negative and normal cytology) were 69.7%, 76.3% and 84.4% at eight, 12 and 24 months post-conization respectively. The clearance of HPV was 79.6%, 80.8% and 87.8% at eight, 12 and 24 months post-conization respectively. Out of 5613 patients with a negative test of cure within one year after conization, no cervical cancer was found during follow-up and 11 (0.2%) women developed high-grade intraepithelial lesions/adenocarcinoma in situ (HSIL/AIS) with an average time from conization to new diagnosis of 42 months. The mean follow-up time was 32.1 months. CONCLUSIONS: The clearance rate of hr-HPV post cervical conization due to dysplasia appears to be high within eight months. With a negative test of cure post cervical conization, the risk of cervical cancer within the following three years seems to be extremely low and the risk of developing HSIL/AIS was lower than the incidence of HSIL/AIS in the general screening population.

Preoperative ctDNA Levels Are Associated With Poor Overall Survival in Patients With Ovarian Cancer.

BACKGROUND/AIM: Circulating tumor DNA (ctDNA), which is shed from cancer cells into the bloodstream, offers a potential minimally invasive approach for cancer diagnosis and monitoring. This research aimed to assess the preoperative ctDNA levels in ovarian tumors patients' plasma and establish correlations with clinicopathological parameters and patient prognosis. PATIENTS AND METHODS: Tumor DNA was extracted from ovarian tumor tissue from 41 patients. Targeted sequencing using a panel of 127 genes recurrently mutated in cancer was performed to identify candidate somatic mutations in the tumor DNA. SAGAsafe digital PCR (dPCR) assays targeting the candidate mutations were used to measure ctDNA levels in patient plasma samples, obtained prior to surgery, to evaluate ctDNA levels in terms of mutant copy number/ml and variant allele frequency. RESULTS: Somatic mutations were found in 24 tumor samples, 17 of which were from ovarian cancer patients. The most frequently mutated gene was TP53. Preoperative plasma ctDNA levels were detected in 14 of the 24 patients. With higher stage, plasma ctDNA mutant concentration increased (p for trend <0.001). The overall survival of cancer patients with more than 10 ctDNA mutant copies/ml in plasma was significantly worse (p=0.008). CONCLUSION: Pre-operative ctDNA measurement in ovarian cancer patients' plasma holds promise as a predictive biomarker for tumor staging and prognosis.

Risks of non-ovarian cancers in women with borderline ovarian tumor: a national cohort study in Sweden.

BACKGROUND: Associations between different cancer types are known. The affirmation of the risk for non-ovarian cancer after ovarian borderline tumors (BOT) is, however, sparse. AIM: To analyze the risk of subsequent or simultaneous cancers in women with BOTs compared with the general female Swedish population. METHODS: An open cohort study (1995-2018) was conducted where a diagnosis of BOTs as well as subsequent or simultaneous cancer diagnoses were obtained from the Swedish Cancer Register and matched to the Total Population Register. Each woman with BOT was followed until non-ovarian cancer, death or emigration and could only be included once for the outcome. Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) for specific non-ovarian cancers were analyzed. RESULTS: The 4998 women with serous and mucinous BOTs were diagnosed during 1995-2018 with a mean age of 55.7 years (SD 16.0) at diagnosis. Compared with the general female population, women with BOTs had increased risks for non-ovarian cancer in colon (SIR = 2.5; 95% CI 2.0-3.1), rectum (SIR = 1.7; 95% CI 1.1-2.5), small intestine (SIR = 5.0; 95% CI 2.3-9.5), cervix (SIR = 2.5; 95% CI 1.4-4.2), endometrium (SIR = 2.4; 95% CI 1.9-3.1), pancreas (SIR = 2.3; 95% CI 1.4-3.5), upper aerodigestive tract (SIR = 2.2; 95% CI 1.2-3.8), lung (SIR = 1.8; 95% CI 1.4-2.3), kidney (SIR = 2.3; 95% CI 1.4-3.7) and bladder (SIR = 1.8; 95% CI 1.1-2.8). Among women with serous BOTs, the risk of thyroid gland cancer (SIR = 3.1; 95% CI 1.2-6.4) was also increased. Lung and pancreas cancer showed increased risks more than 1 year after a diagnosis of BOT. CONCLUSIONS: This Swedish population-based study demonstrated an increased risk of multiple malignancies including lung and pancreatic cancers beyond the first year of diagnosis in patients with borderline ovarian tumors (BOTs), suggesting a potential shared etiology.

Antibiotic prophylaxis in posterior colporrhaphy does not reduce postoperative infection: a nationwide observational cohort study.

INTRODUCTION AND HYPOTHESIS: The aim of this study was to explore if antibiotic prophylaxis prevents postoperative infection after a posterior colporrhaphy. METHODS: In this register-based nationwide cohort study data were collected from the "The Swedish National Quality Register of Gynecological Surgery" (GynOp). Women 18 years or older who underwent a primary posterior colporrhaphy between 1 January 2015 and 31 December 2020 were included. Patients undergoing any concomitant prolapse procedure, mesh surgery, or incontinence procedure were excluded. The cohort was divided into two groups based on administration of antibiotic prophylaxis (n = 1,218) or not (n = 4,884). The primary outcome of this study was patient-reported infectious complication requiring antibiotic treatment. Secondary outcome measures included patient satisfaction and prolapse-related symptoms at 1 year postoperatively. RESULTS: A total of 7,799 patients who underwent posterior colporrhaphy and met the inclusion criteria and did not meet the exclusion criteria were identified in the register database. Of these patients 6,102 answered the primary outcome question (79%). In the antibiotic prophylaxis group a total of 138 reported a postoperative infection (11%) and in the no antibiotic prophylaxis group the corresponding data were 520 (11%). There were no significant differences regarding either the primary or the secondary outcomes between the study groups. CONCLUSION: In this nationwide Swedish register study antibiotic prophylaxis was not associated with a reduced risk of postoperative infection after a posterior colporrhaphy.

HPV self-sampling versus healthcare provider collection on the effect of cervical cancer screening uptake and costs in LMIC: a systematic review and meta-analysis.

BACKGROUND: Cervical cancer is a major global health issue, with 89% of cases occurring in low- and middle-income countries (LMICs). Human papillomavirus (HPV) self-sampling tests have been suggested as an innovative way to improve cervical cancer screening uptake and reduce the burden of disease. The objective of this review was to examine the effect of HPV self-sampling on screening uptake compared to any healthcare provider sampling in LMICs. The secondary objective was to estimate the associated costs of the various screening methods. METHOD: Studies were retrieved from PubMed, Embase, CINAHL, CENTRAL (by Cochrane), Web of Science, and ClinicalTrials.gov up until April 14, 2022, and a total of six trials were included in the review. Meta-analyses were performed mainly using the inverse variance method, by pooling effect estimates of the proportion of women who accepted the screening method offered. Subgroup analyses were done comparing low- and middle-income countries, as well as low- and high-risk bias studies. Heterogeneity of the data was assessed using I2. Cost data was collected for analysis from articles and correspondence with authors. RESULTS: We found a small but significant difference in screening uptake in our primary analysis: RR 1.11 (95% CI: 1.10-1.11; I2 = 97%; 6 trials; 29,018 participants). Our sensitivity analysis, which excluded one trial that measured screening uptake differently than the other trials, resulted in a clearer effect in screening uptake: RR: 1.82 (95% CI: 1.67-1.99; I2 = 42%; 5 trials; 9590 participants). Two trials reported costs; thus, it was not possible to make a direct comparison of costs. One found self-sampling more cost-effective than the provider-required visual inspection with acetic acid method, despite the test and running costs being higher for HPV self-sampling. CONCLUSION: Our review indicates that self-sampling improves screening uptake, particularly in low-income countries; however, to this date, there remain few trials and associated cost data. We recommend further studies with proper cost data be conducted to guide the incorporation of HPV self-sampling into national cervical cancer screening guidelines in low- and middle-income countries. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020218504.

A Multiplex Biomarker Assay Improves the Prediction of Survival in Epithelial Ovarian Cancer.

BACKGROUND/AIM: Epithelial ovarian cancer (EOC) is usually diagnosed in advanced stages and has a high mortality rate. In this study, we used the proximity extension assay from Olink Proteomics to search for new plasma protein biomarkers to predict overall survival (OS) in patients with EOC. MATERIALS AND METHODS: Peripheral blood samples were obtained preoperatively from 116 EOC patients undergoing primary debulking surgery: 28 early EOC cases (FIGO stage I-II) and 88 advanced EOC cases (FIGO stage III-IV). Proteins were measured using the Olink Oncology II and Inflammation panels. In total, 177 unique protein biomarkers were analysed. Cross-validation and LASSO regression were combined to select prediction models for OS. RESULTS: The model including age and the three-biomarker combination of neurotrophin-3 (NT-3)+transmembrane glycoprotein NMB (GPNMB)+mesothelin (MSLN) predicted worse OS with AUC=0.79 (p=0.004). Adding cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) to the model further improved performance (AUC=0.83; p=0.003). In a postoperative model including age and stage (III+IV vs. I+II), the three-biomarker panel of chemokine (C-C motif) ligand 28 (CCL28)+T-cell leukaemia/lymphoma protein 1A (TCL1A)+GPNMB improved the prediction of OS (from AUC=0.83 to AUC=0.90; p=0.05). In the postoperative model including age and dichotomized stage (III vs. I+II), the biomarkers CCL28 and GPNMB1 improved the prediction of OS (AUC=0.86; p<0.001). The combination of high levels of both CA125 and HE4 predicted worse survival (p=0.05). CONCLUSION: In this explorative study evaluating the performance of plasma protein biomarkers in predicting OS, we found that adding biomarkers, especially NT-3, to the panel improved the prediction of OS.

[Pharmacological treatment of idiopathic diarrhea]. / Viktigt att stegvis öka insatser vid farmakologisk diarrébehandling.

The basic principle for treatment of idiopathic diarrhea is to delay transit through the gut in order to promote absorption of electrolytes and water. Under mild conditions bulking agents may suffice. With increasing severity, antidiarrheal pharmaceuticals may be added in a stepwise manner. Bile salt malabsorption is a clear indication for adsorptive resins, while in idiopathic diarrhea peripherally-acting opioid receptor agonists, such as loperamide, is the first-line treatment. Second-line treatment with approved indication for severe diarrhea when other treatment options fail includes opium drops. More advanced treatments are to be used by clinicians with specialist knowledge and experience in the field.

Increased incidence and improved survival in endometrial cancer in Sweden 1960-2014: a population-based registry survey.

BACKGROUND: An investigation of trends of incidence and net survival (NS) for endometrial cancer in Sweden. METHODS: Morphologically verified endometrial carcinoma diagnosed 1960 to 2014 were collected from the nation-wide Swedish Cancer Registry. Endometrial cancer patients were assessed with regards to time trends for incidence and 54,825 cases remained for survival analyses. Cases diagnosed 1995 to 2014 were categorized according to detailed morphology and from 2005 to 2014 FIGO stage was also categorized. RESULTS: There was a trend of increasing incidence of endometrial carcinoma for women above 55 years of age. NS was improved at 5- and 10-year follow-up. The 5-year net survival in 2010-2014 was 86%. The most prominent improvement in NS was found in the elderly women above 75 years of age. CONCLUSIONS: This study observed increased incidence of endometrial cancer in Sweden from 1960 to 2014. The progress in diagnostics and treatment, seem to have improved the net survival, especially in elderly women.

Cervical neoplasia in relation to socioeconomic and demographic factors - a nationwide cohort study (2002-2018).

INTRODUCTION: Cervical cancer is a major cause of mortality and morbidity. We aimed to estimate the association between sociodemographic factors and cervical neoplasia. MATERIAL AND METHODS: In this Swedish nationwide open cohort study, 4 120 557 women aged ≥15 years at baseline were included between January 1, 2002 and December 31, 2018. The two outcomes were cervical cancer and carcinoma in situ identified in the Swedish Cancer Register. Sociodemographic factors (age, education level, family income level, region of residency, country of origin) were the main predictors. Incidence rates per 10 000 person-years were calculated. Cox regression was used to estimate hazard ratios. Sensitivity analyses were conducted, including parity, urogenital infections, alcohol- and drug-use disorders, and chronic obstructive pulmonary disease (used as a proxy for tobacco abuse). RESULTS: In 38.9 million person-years of follow-up, 5781 (incidence rate: 1.5, 95% confidence interval [CI] 1.4-1.5) and 62 249 (incidence rate 16.9, 95% CI 15.9-16.1) women were diagnosed with cervical cancer and carcinoma in situ, respectively. Women from Eastern Europe had a hazard ratio of 1.18 (95% CI 1.05-1.33) for cervical cancer compared with Swedish-born women, while women from non-Western regions were inversely associated with cervical cancer and carcinoma in situ. Women with a low education level had a hazard ratio of 1.37 (95% CI 1.29-1.45) for cervical cancer compared with women with a high education level. CONCLUSIONS: Women from the Middle East and Africa living in Sweden seem to suffer less from cervical neoplasia, whereas women with low education and women from Eastern Europe seem to suffer more from cervical cancer.

Applicability of polygenic risk scores in endometriosis clinical presentation.

BACKGROUND: Risk prediction is an essential part of preventative medicine and in recent years genomic information has become an interesting factor in risk models. Polygenic risk scores (PRS) combine the effect of many genetic variations into a single score which has been shown to have predictive value for many diseases. This study aimed to investigate the association between PRS for endometriosis and the clinical presentation of the disease. METHODS: Women with endometriosis (N = 172) were identified at the Department of Gynecology. All participants answered questionnaires regarding sociodemographic factors, lifestyle habits and medical history, registered bowel symptoms on the Visual Analog Scale for Irritable Bowel Syndrome and passed blood samples. DNA was extracted and samples were genotyped, and a PRS was calculated based on previous genome-wide association studies of endometriosis. Inflammatory proteins and TSH receptor antibodies (TRAb) in serum were analyzed. RESULTS: Inverse associations were identified between PRS and spread of endometriosis, involvement of the gastrointestinal tract and hormone treatment. However, significance was lost when calculated as p for trend and the specificity and sensitivity were low. There were no correlations between PRS and TRAb or inflammatory proteins. CONCLUSION: The findings indicate that specific PRS should be developed to predict clinical presentations in patient with endometriosis.

Time Trends for Incidence and Net Survival of Cervical Cancer in Sweden 1960-2014-A Nationwide Population-Based Study.

BACKGROUND: The aim was to investigate time trends for incidence and long-term net survival in the morphologic subtypes and stages of cervical cancer in Sweden during the period 1960 to 2014. METHODS: Women with invasive cervical cancer were identified through the Swedish Cancer Registry. Incidence and net survival were calculated according to morphology, age at diagnosis, and FIGO stage at diagnosis. RESULTS: In total, 29,579 cases of invasive cervical cancer between 1960 and 2014 were included. The age-standardized incidence for squamous cell carcinoma (SCC) decreased until 2000; thereafter, the incidence rate stagnated, and a small increase was found in 2014. The incidence of adenocarcinoma continuously increased. The age-standardized 5-year net survival increased. However, decreasing net survival with increasing age was found. A higher stage at diagnosis showed a worse net survival. SCC and adenocarcinoma did not statistically differ as regards net survival in the last years of the study. CONCLUSIONS: Age-standardized 5-year net survival improved between 1960 and 2014. A positive trend for short- and long-term net survival was seen for women ages 18 to 64 years but long-term net survival for women ≥75 years decreased. In this study, age and FIGO stage at diagnosis were found to be important prognostic factors in determining net survival. The morphologies, SCC, and adenocarcinoma did not statistically differ as regards net survival in the last years of the study. IMPACT: This study demonstrates longitudinal data on cervical cancer in Sweden for over 50 years with sub analyses on morphology, age, and stage at diagnosis.

Long-term incidence of endometrial cancer after endometrial resection and ablation: A population based Swedish gynecologic cancer group (SweGCG) study.

INTRODUCTION: Minimally invasive methods to reduce menorrhagia were introduced in the 1980s and 1990s. Transcervical endometrial resection (TCRE) and endometrial ablation (EA) are two of the most frequently used methods. As none of them can guarantee a complete removal of the endometrium, there are concerns that the remaining endometrium may develop to endometrial cancer (EC) later in life. The primary aim was to analyze the long-term incidence of EC after TCRE and EA in a nationwide population. The secondary aim was to assess the two treatment modalities separately. MATERIAL AND METHODS: The Swedish National Patient Registry and National Quality Registry for Gynecological Surgery were used for identification of women who had TCRE or EA performed between 1997-2017. The cohort was followed from the first TCRE or EA until hysterectomy, diagnosis of EC, or death. Follow-up data were retrieved from the National Cancer Registry and the National Death Registry. Expected incidence for EC in Swedish women was calculated using Swedish data retrieved from the NORDCAN project after having taken into account differences of age and follow-up time. Cumulative incidence of EC after TCRE and EA, was calculated. A standardized incidence ratio was calculated based on the expected and observed incidence, stratified by age and year of diagnosis. RESULTS: In total, 17 296 women (mean age 45.1 years) underwent TCRE (n = 8626) or EA (n = 8670). Excluded were 3121 who had a hysterectomy for benign causes during follow up. During a median follow-up time of 7.1 years (interquartile range 3.1-13.3 years) the numbers of EC were 25 (0.3%) after TCRE and 2 (0.02%) after EA, respectively. The observed incidence was significantly lower than expected (population-based estimate) after EA but not after TCRE, giving a standardized incidence ratio of 0.13 (95% confidence interval [CI] 0.03-0.53) after EA and 1.27 (95% CI 0.86-1.88) after TCRE. Median times to EC were 3.0 and 8.3 years after TCRE and EA, respectively. CONCLUSIONS: There was a significant reduction of EC after EA, suggesting a protective effect, whereas endometrial resection showed an incidence within the expected rate.

The association between common urogenital infections and cervical neoplasia - A nationwide cohort study of over four million women (2002-2018).

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.

Co-testing in cervical screening among 40- to 42-year-old women is unreasonable.

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.

Circulating Markers of Neutrophil Extracellular Traps (NETs) in Patients With Ovarian Tumors.

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 (ptrend<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.

The wait time to primary surgery in endometrial cancer - impact on survival and predictive factors: a population-based SweGCG study.

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.