Investigator
Danish Arctic Institute
Role of pre-diagnostic reproductive factors on long-term (10 years or greater) survival of epithelial ovarian cancer: The Extreme study
Several reproductive factors are associated with ovarian cancer risk but the association with survival is less clear. The main aim was to examine the impact of pre-diagnostic reproductive factors on long-term ovarian cancer survival (≥10 years). We included all women with epithelial ovarian cancer in Denmark, 1990-2014. Information on reproductive factors and covariates were obtained from nationwide registers. Using pseudo-values, we estimated the absolute and relative 10-year survival probabilities and 95% CIs for each reproductive factor and ovarian cancer overall, restricted to serous tumors and stratified into localized and non-localized tumors. A relative survival probability >1 indicates better survival. Adjusted models considered age, diagnosis year, histology, stage, comorbidity, and income. In a sub-population sensitivity analysis, we also adjusted for residual disease. The cohort comprised 11,870 women. In the adjusted models, pre-diagnostic parity (relative survival probability 1.08, 95% CI 1.01 to 1.16) and endometriosis (relative survival probability 1.17, 95% CI 1.02 to 1.34) increased the likelihood of surviving ≥10 years in women with localized cancer. Previous infertility also improved the 10-year survival in women with localized ovarian cancer (relative survival probability 1.18, 95% CI 1.07 to 1.29) and in women with a non-localized tumor (relative survival probability 1.45, 95% CI 1.15 to 1.84). Pre-diagnostic pelvic inflammatory disease enhanced 10-year survival in women with localized serous (relative survival probability 1.24, 95% CI 1.03 to 1.49) and non-localized cancer (relative survival probability 1.35, 95% CI 1.04 to 1.76). Previous tubal ligation or hysterectomy were not significantly associated with 10-year survival. Adjustment for residual disease did not substantially change estimates, except for parity and pelvic inflammatory disease, where the associations disappeared. Pre-diagnostic reproductive factors, such as endometriosis or infertility, were associated with improved long-term survival. However, causality cannot be established in this observational study, and more research to confirm our findings and into potential mechanisms is warranted.
Prediagnostic use of menopausal hormone therapy and long‐term survival of localized epithelial ovarian cancer: The Extreme study
AbstractUse of menopausal hormone therapy (MHT) prior to an epithelial ovarian cancer (EOC) diagnosis has been suggested to be associated with improved survival. In a recent nationwide cohort study, we found that prediagnostic long‐term MHT use, especially estrogen therapy (ET), was associated with improved long‐term survival in women with nonlocalized EOC. Our aim was to investigate the influence of prediagnostic MHT use on long‐term survival among women with localized EOC in the same nationwide study. Our study cohort comprised all women aged 50 years or older with an EOC diagnosis in Denmark 2000–2014 (n = 2097) identified from the Extreme study. We collected information on usage of systemic ET and estrogen plus progestin therapy (EPT) from the Danish National Prescription Registry. By using pseudo‐values, 5‐ and 10‐year absolute and relative survival probabilities were estimated with 95% confidence intervals (CIs) while adjusting for histology, comorbidity, and income. Relative survival probabilities >1 indicate better survival. The 5‐year absolute survival probabilities were 61% and 56%, respectively, among women who were nonusers and users of prediagnostic MHT, whereas these numbers were 46% and 41%, respectively, regarding 10‐year survival. Use of MHT was not significantly associated with an improved 5‐ or 10‐year survival in women with localized EOC (5‐year relative survival probability = 0.95, 95% CI: 0.89–1.02; 10‐year relative survival probability = 0.92, 95% CI: 0.84–1.02). Similar findings were seen for systemic ET or EPT use. Our findings do not suggest a positive benefit from prediagnostic MHT use on long‐term survival of localized EOC.
Risk of nonovarian cancer in a nationwide‐based study of nearly 5000 women with borderline ovarian tumors in Denmark
AbstractEvidence regarding cancer risk after borderline ovarian tumors (BOTs) is limited. We conducted a nationwide cohort study examining the incidence of nonovarian cancers in women with serous or mucinous BOTs compared with the general female population with up to 41 years of follow‐up. Through the nationwide Pathology Registry, we identified nearly 5000 women with BOTs (2506 serous and 2493 mucinous) in Denmark, 1978 to 2018. We computed standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) as relative risk estimates of specific nonovarian cancers. Compared with general female population rates, women with serous BOTs had increased rates of particularly malignant melanoma (SIR = 1.9; 95% CI: 1.3‐2.6), thyroid cancer (SIR = 3.0; 95% CI: 1.4‐5.4) and myeloid leukemia (SIR = 3.2; 95% CI: 1.5‐5.8), and women with mucinous BOTs had elevated rates of lung cancer (SIR = 1.7; 95% CI: 1.3‐2.1), pancreatic cancer (SIR = 1.9; 95% CI: 1.2‐2.9) and myeloid leukemia (SIR = 2.3; 95% CI: 0.9‐4.7). We found no convincing association with neither breast nor colorectal cancer in women with BOTs. This is the first large nationwide study showing that women with specific types of BOTs have increased risks of several nonovarian cancers, likely due to some shared risk factors or genetic characteristics.
Biopsy‐verified vulvar lichen sclerosus and the risk of non‐vulvar cancer: A nationwide cohort study
AbstractVulvar lichen sclerosus (VLS) is a chronic inflammatory mucocutaneous disease known to be associated with human papillomavirus‐independent vulvar squamous cell carcinoma. Evidence on the association with other types of cancer, however, is sparce. We conducted a large nationwide cohort study examining the incidence of non‐vulvar cancers among women with biopsy‐verified VLS compared with the general female population. By using the nationwide Pathology Registry, we identified all women in Denmark with a biopsy‐verified VLS diagnosis during 1978–2019 (n = 16,921). The cohort was followed up in the Danish Cancer Registry until 2022 for a subsequent non‐vulvar cancer diagnosis. Standardized incidence ratios (SIRs) were computed with 95% confidence intervals (CIs) as relative risk estimates of all specific non‐vulvar cancer sites. Compared with general female population rates, women with biopsy‐verified VLS had decreased rates of several non‐vulvar cancers, including HPV‐related cancers (combined estimate: SIR = 0.5; 95% CI: 0.3–0.7), and lung (SIR = 0.6; 95% CI: 0.5–0.7), liver (SIR = 0.5; 95% CI: 0.2–0.9), and thyroid cancer (SIR = 0.5; 95% CI: 0.3–0.9). The decreased SIRs tended to sustain throughout the follow‐up period following the VLS diagnosis. This large nationwide cohort study shows that women with biopsy‐verified VLS may have a long‐term reduced risk of developing HPV‐related (cervical, vaginal, oropharyngeal, and anal) and smoking‐associated cancers (lung, liver, and cervical) as well as thyroid cancer. Future studies focusing on the mechanisms behind the decreased cancer risk are needed.
Biopsy‐verified vulvar lichen sclerosus: Incidence trends 1997–2022 and increased risk of vulvar squamous precancer and squamous cell carcinoma
AbstractPopulation‐based data on the epidemiology of vulvar lichen sclerosus (LS) are sparse and only few prospective studies have investigated the malignant potential of the disease. We used the nationwide Danish Pathology Registry to first assess the incidence of biopsy‐verified vulvar LS in the period 1997–2022 and second to examine the incidence of vulvar high‐grade squamous precancer and squamous cell carcinoma (SCC) in women with biopsy‐verified vulvar LS (1978–2019) compared with that expected in the general female population. For the latter aim, we computed standardized incidence ratios (SIRs) with 95% confidence intervals (CIs). During our study period, the age‐standardized incidence rate of vulvar LS increased from 5.0 (1997–1998) to 35.7 (2021–2022) per 100,000 person‐years. Compared with the general female population, women with biopsy‐verified vulvar LS had significantly increased rates of vulvar high‐grade squamous precancer (SIR = 8.5; 95% CI: 7.2–10.0) and SCC (SIR = 16.2; 95% CI: 14.2–18.4). The SIRs of vulvar high‐grade squamous precancer and SCC did not vary substantially according to length of follow‐up. This nationwide and population‐based study shows a 7‐fold increase in the incidence of biopsy‐verified vulvar LS since 1997. Data also show that women with biopsy‐verified vulvar LS have 8.5 and 16 times higher than expected incidence of vulvar high‐grade squamous precancer and SCC, respectively. The substantially increased incidence of vulvar high‐grade squamous precancer and SCC following LS is important in relation to the clinical management and follow‐up of LS patients.
Use of statins and risk of ovarian cancer: evidence on effect modification by parity, menopause and endometriosis from nationwide nested case-control studies
Previous results on the association between statin use and risk of ovarian cancer (OC) are inconsistent, warranting further investigation. This study aims to examine the association between statin use and risk of OC in a large study population. Based on two nationwide nested case-control studies utilizing data from Danish and Swedish high-quality registries, we identified 11,874 OC cases who were individually matched on age to 474,960 controls using risk-set sampling. Conditional logistic regression was performed separately on the country-specific data to calculate odds ratios (ORs) and corresponding 95 % confidence intervals (CIs) for the association between statin use and risk of OC. Country-specific estimates were combined based on a fixed-effect assumption. Furthermore, we examined potential effect modifications by a priori selected OC risk factors on the association between statin use and OC risk. We found no overall association between statin use and risk of OC (OR = 0.96; 95 % CI: 0.91-1.01); neither with duration nor intensity of use. However, statin use was associated with a decreased risk of OC in subsets of women with endometriosis (OR = 0.70; 95 % CI: 0.53-0.91), and nulliparous women (OR = 0.86; 95 % CI: 0.79-0.93). We found an effect modification of some known ovarian cancer risk factors on the association between statin use and risk of OC. In women with endometriosis, and in nulliparous women, respectively, statin use was associated with a decreased risk of OC, suggesting statins may have potential as a preventive measure.
