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.

Time to extend the indication for sentinel node biopsy in vulvar cancer? Results from a prospective nationwide Swedish study.

OBJECTIVE: To assess detection rates and negative predictive values of sentinel node biopsy in vulvar squamous cell carcinoma with tumors ≥4 cm, multifocal tumors, and in locally recurrent disease. METHODS: Between December 2019 and December 2022, patients with vulvar squamous cell carcinoma with tumors ≥4 cm (group 1), multifocal tumors (group 2), or a first local recurrence without or with previous groin treatment (groups 3 and 4, respectively) were included in a prospective, nationwide multicenter interventional pilot study. The participants underwent a sentinel node biopsy followed by inguinofemoral lymph node dissection. Detection rates, negative predictive values, the proportion of micrometastases, and isolated tumor cells were determined separately for each group. RESULTS: In all, 64 women were included, 36 women in group 1 (56%), and 17 women in group 2 (27%). Due to the small number and heterogeneity of the 11 women in groups 3 and 4, they were excluded from further analyses. In groups 1 and 2, 25 women (47%) were diagnosed with node-positive disease, and in 16 women (64%) only in the sentinel nodes. The detection rates varied between 94.1-100% per patient and 84.1-85.3% per groin. No false-negative sentinel nodes were identified, giving a negative predictive value of 100% for group 1 (95% CI 91.2% to 100%) and for group 2 (95% CI 83.9% to 100%). Of the node-positive patients, 32% had micrometastasis or isolated tumor cells only. One third of the metastases were detected by ultrastaging. In 27% of the non-mapping groins, metastases were found in the lymphadenectomy specimen, and in 75% the metastases showed extranodal growth. CONCLUSION: In this small cohort of patients, we provide further data that may widen the indication of the sentinel node technique to women with tumors ≥4 cm and multifocal tumors. TRIAL REGISTRATION NUMBER: NCT04147780.

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.

Early menopause and weight loss are significant factors associated with risk of future fracture in middle-aged women.

BACKGROUND: To identify factors related to reproductive history and weight change associated with first incident fracture in middle-aged women. METHODS: In total, 18,326 women from the Malmö Diet and Cancer study were included in this prospective population-based cohort study. Participants were included 1991-1996 and followed to 2016. Using data from the National Patient Registry, linked with every participants' unique personal identification number, any first fracture affecting spine, thoracic cage, upper and lower extremities was identified. The association of baseline factors with incident fracture risk was analyzed using Cox regression models. RESULTS: For participating women, median age 56.0 years, the multivariable Cox regression analysis observed that early menopause (40-44 years) (hazard ratio (HR) 1.14, 95% confidence interval (CI) 1.03-1.27) but not premature menopause < 40 years (HR 1.06, 95% CI 0.91-1.24) was associated with future fracture risk. Self-reported weight loss since age 20 was also associated with future fracture risk (HR 1.39, 95% CI 1.17-1.65) whereas a daily alcohol consumption in the third quartile (5.36-11.42 g/day) compared to the lowest quartile (0-0.80 g/day) was associated with decreased future fracture risk (HR 0.88, 95% CI 0.81-0.96). The multivariable Cox regression analysis also observed that increasing age and weight at baseline, current smoking, a positive history of previous fracture and family history of fractures were associated with increased fracture risk whereas an increasing BMI was associated with a decreased fracture risk. No association to parity or period of lactation was observed nor ever-use of oral contraceptives and menopausal hormone therapy. CONCLUSION: This study shows that early menopause between 40 to 45 years and self-reported weight loss since age of 20 are relevant factors associated with increased fracture risk in middle-aged women. These factors were independent of traditional predictors of fracture risk among women and may be considered in preventive initiatives. TRIAL REGISTRATION: Clinicaltrials.gov with identifier: NCT04151732, since Nov 5th 2018.

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.

Areas to Improve Quality of Life After Ovarian Tumor Surgery and Adjuvant Treatment.

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.

Can we extend the indication for sentinel node biopsy in vulvar cancer? A nationwide feasibility study from Sweden.

BACKGROUND: In squamous cell vulvar cancer, sentinel node biopsy is accepted as standard treatment in well-defined patient groups and has reduced surgical morbidity considerably. Currently, due to the lack of evidence, it cannot be offered to patients with tumors of 4 cm diameter or greater or with multifocal tumors, or in local recurrences. PRIMARY OBJECTIVE: This study is primarily a pilot and feasibility trial, aiming to evaluate if the prerequisites concerning detection rate and negative predictive value are satisfactory before the implementation of a multinational trial. STUDY HYPOTHESIS: Sentinel node biopsy has an acceptable negative predictive value and detection rate in the study cohort. TRIAL DESIGN: This study is planned as a prospective, national, multicenter interventional trial. Participating patients will undergo a sentinel node biopsy in addition to an inguinofemoral lymphadenectomy. INCLUSION AND EXCLUSION CRITERIA: Inclusion criteria: for women in group 1, a primary tumor ≥4 cm in diameter; in group 2, a multifocal primary tumor; in group 3, a local recurrence without previous inguinofemoral lymphadenectomy or radiation to the groins; in group 4, a local recurrence, with previous inguinofemoral lymphadenectomy and/or radiation to the groins. PRIMARY ENDPOINT: The primary endpoints are the detection rate and the negative predictive value of the sentinel node procedure. SAMPLE SIZE: In each of the four study arms, recruitment of 20-30 patients is planned. ESTIMATED DATES FOR COMPLETING RECRUITMENT AND PRESENTING RESULTS: Recruitment will take place between November 2019 and October 2021. Results will be available in December 2021. TRIAL REGISTRATION: The trial is registered at "ClinicalTrials.gov" (ID: NCT04147780).

Primary screening for increased fracture risk by the FRAX® questionnaire-uptake rates in relation to invitation method.

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.

Use of proton pump inhibitors (PPI) and history of earlier fracture are independent risk factors for fracture in postmenopausal women. The WHILA study.

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.

Low androstenedione/sex hormone binding globulin ratio increases fracture risk in postmenopausal women. The Women's Health in the Lund Area study.

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.