Use of antidepressants and endometrial-cancer risk: a nationwide nested case-control study.

BACKGROUND: Preclinical studies have suggested that antidepressant drugs may possess antineoplastic properties. In a nationwide case-control study, we examined the association between use of antidepressants and endometrial-cancer risk with a particular focus on selective serotonin reuptake inhibitors (SSRIs). METHODS: From the Danish Cancer Registry, we identified all women with a histologically verified diagnosis of endometrial cancer between 2000 and 2016, and, for each woman, 15 age-matched controls. We obtained information on use of SSRIs, tricyclic antidepressants (TCAs) and other antidepressants based on records of filled prescriptions from the National Prescription Register. Using conditional logistic regression, we calculated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for associations between use of antidepressants and endometrial-cancer risk compared with non-use. In active comparator analyses, SSRI use was compared with TCA use. RESULTS: The study population comprised 8164 cases and 122 432 controls. Compared with non-use, SSRI use was associated with an OR of 0.88 (95% CI 0.82-0.96) for endometrial cancer, whereas the association with TCA use was close to unity (OR 1.05, 95% CI 0.90-1.22). Use of other antidepressants yielded an OR of 0.86 (95% CI 0.71-1.03). We observed no apparent trends in associations according to cumulative amount. The inverse association with SSRI use persisted when compared with TCA use (OR 0.81, 95% CI 0.66-0.99). CONCLUSIONS: Use of SSRIs was associated with a decreased risk of endometrial cancer, whereas no inverse association appeared with use of TCAs. The antineoplastic potential of SSRIs should be investigated in future studies.

Incidence of penile intraepithelial neoplasia and incidence and survival of penile cancer in Denmark, 1997 to 2018.

PURPOSE: Squamous cell carcinoma (SCC) of the penis is rare. Some studies have suggested that the incidence is increasing but the available literature is equivocal. We examined the incidence of high-grade penile intraepithelial neoplasia (PeIN), the incidence and 5-year relative survival as well as mortality of penile SCC in Denmark over the latest 20 years. METHODS: New cases of high-grade PeIN and penile cancer were identified from high-quality nationwide registries. Age-standardized (World) incidence rates per 100,000 person-years and average annual percentage change (AAPC) were estimated. For penile SCC, 5-year relative survival was calculated, and Cox regression was used to examine the effect of selected characteristics on mortality. RESULTS: Altogether, 1,070 new cases of high-grade PeIN were diagnosed (1997-2018) and the incidence increased from 0.87 to 1.84 per 100,000 person-years from 1997-1998 to 2017-2018 (AAPC = 4.73; 95% CI: 3.54-5.94). We identified 1,216 penile cancer cases (1997-2018) (95.7% SCC). The incidence of penile SCC increased slightly from 0.85 per 100,000 person-years in 1997-1998 to 1.13 per 100,000 person-years in 2017-2018 (AAPC = 1.01; 95% CI: 0.24-1.79). The 5-year relative survival of penile SCC did not change substantially, whereas the mortality tended to decrease. CONCLUSION: Penile SCC is increasing slightly in Denmark, while a pronounced increase in the incidence of high-grade PeIN is seen. The 5-year relative survival from penile cancer was relatively stable over time. Increasing exposure to HPV infection at the population level may have contributed to the observed increase in PeIN and penile SCC. Awareness of HPV may also have contributed to the increased detection of PeIN.

Low-dose aspirin use and risk of head and neck cancer-A Danish nationwide case-control study.

Results concerning a potential preventive effect of aspirin on head and neck cancer (HNC) are conflicting. We examined the association between low-dose aspirin use and HNC risk overall and by degree of human papillomavirus association in a nested case-control study using nationwide registries. Cases (n = 12 389) were all Danish residents diagnosed with primary HNC (2000-2015). Age- and sex-matched population controls (n = 185 835) were selected by risk-set-sampling. Using conditional logistic regression, we estimated multivariable-adjusted odds ratios and 95% confidence intervals for HNC associated with low-dose aspirin use (≥2 prescriptions). No association was observed between low-dose aspirin ever-use and overall HNC (odds ratio: 1.03, 95% confidence interval: 0.97-1.10). Estimates remained neutral according to patterns of use. Low-dose aspirin use appeared to slightly decrease HNC risk among the eldest (71-84 y), independently of human papillomavirus association, while slightly increase HNC risk among younger age groups (30-60, 61-70 y), driven by an increased risk of oral cancer. However, no consistent patterns in risk estimates were found according to duration and consistency of low-dose aspirin use in the age-stratified analyses.

Borderline ovarian tumors in Denmark 1997-2018: Time trends in incidence by histology, age and educational level.

INTRODUCTION: After some decades with an increasing incidence of borderline ovarian tumors, more recent studies have observed that the incidence rate seems to be leveling off or declining. In this study, we describe the incidence of borderline ovarian tumors in Denmark 1997-2018 by histology, age at diagnosis and educational level. MATERIAL AND METHODS: All borderline ovarian tumors registered in the Danish Pathology Registry during 1997-2018 were identified and individual-level educational information was retrieved from nationwide registers. Age-standardized incidence rates were estimated according to histology, age at diagnosis and educational level. To investigate incidence trends over time, the average annual percentage change and corresponding 95% confidence intervals (CIs) were estimated using Poisson regression. RESULTS: We identified 3927 women with borderline ovarian tumors during the study period, of which 1997 (50.9%) were serous and 1743 (44.4%) were mucinous. The age-standardized incidence rate of serous borderline ovarian tumors did not change significantly over calendar time (average annual percentage change = -0.13, 95% confidence interval [CI] -1.13 to 0.88). For mucinous tumors, the age-standardized incidence rate was also relatively stable during the first half of the study period, followed by a decrease from 2.56 to 1.25 per 100 000 person-years between 2007-2011 and 2017-2018. Over the entire study period, the incidence rate of mucinous borderline tumors declined on average by 2.91% (95% CI -4.24 to -1.51) per year. The incidence of both types of borderline ovarian tumors seemed to be highest among women with a low educational level. Over calendar time, the incidence of mucinous tumors decreased in all educational groups, whereas the incidence of serous tumors decreased exclusively in women with a high educational level. Time trends did not differ markedly by age at diagnosis. CONCLUSIONS: In Denmark, the incidence of serous borderline ovarian tumors was stable during 1997-2018, whereas the incidence of mucinous borderline ovarian tumors decreased. The incidence rates of both types of borderline ovarian tumors tended to be highest among women with a low educational level throughout the study period.

Use of nonaspirin nonsteroidal anti-inflammatory drugs and risk of head and neck cancer: A nationwide case-control study.

Head and neck cancer (HNC) is the sixth most frequent malignancy with high mortality and substantial morbidity and hence there is a need for identification of preventive factors. Preclinical and observational studies have reported antineoplastic effects of nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs), but studies of nonaspirin NSAID use and risk of HNC are sparse and with inconsistent results. We therefore conducted a register-based case-control study nested in the entire Danish population. Cases (n = 12,389) comprised all Danish residents aged 30-84 years with a histologically verified primary HNC diagnosis during 2000-2015. Based on the literature, cases were categorized into four groups of anticipated association with human papillomavirus (HPV): strong, potential, no/weak and uncertain. Age- and sex-matched population controls (n = 185,835) were selected by risk-set-sampling. We obtained information on filled prescriptions of nonaspirin NSAIDs, other drug use, comorbid conditions and socioeconomic parameters from nationwide Danish registries. Ever-use (≥2 prescriptions) of nonaspirin NSAIDs was not associated with the overall risk of HNC after adjustment for potential confounders (odds ratio [OR]: 0.99, 95% confidence interval [CI]: 0.95-1.03). However, long-term consistent use (≥5 years) was associated with a 25% reduction in HNC risk (OR: 0.75, 95% CI: 0.62-0.90). Stratified analyses by anticipated HPV-association showed no material differences in estimates. In conclusion, ever-use of nonaspirin NSAIDs was not associated with the risk of HNC with no apparent influence on the estimates by the anticipated HPV-association. However, long-term consistent use may be associated with a reduced risk of HNC and merits further investigation.

Low-dose aspirin use and endometrial cancer mortality-a Danish nationwide cohort study.

BACKGROUND: Accumulating evidence suggests that aspirin use may improve survival in cancer patients, however, for endometrial cancer, epidemiological evidence is limited and results are equivocal. In a nationwide cohort study, we examined the association between post-diagnostic low-dose aspirin use and endometrial cancer mortality. METHODS: From the Danish Cancer Registry, we identified all women with a primary diagnosis of endometrial cancer. Women diagnosed between 2000 and 2012, aged 30-84 years, who had no history of cancer (except non-melanoma skin cancer) and were alive 1 year after the cancer diagnosis were eligible. We obtained information on pre- and post-diagnostic use (≥1 prescription) of low-dose aspirin, mortality and potential confounding factors from nationwide registries. Using Cox regression models, we estimated adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between post-diagnostic low-dose aspirin use and endometrial cancer mortality. The exposure was modelled as both time-varying as well as time-fixed within exposure windows of 1 and 5 years. RESULTS: We identified 6694 endometrial cancer patients with a maximum follow-up of 13 years. In the time-varying analysis, post-diagnostic low-dose aspirin use was associated with a HR of 1.10 (95% CI 0.90-1.33) for endometrial cancer mortality. We found no indication of a dose-response association according to increasing tablet strength, cumulative amount or duration of use, and the HRs were similar for pre-diagnostic and post-diagnostic low-dose aspirin use compared with non-use. CONCLUSIONS: We found no indication that post-diagnostic low-dose aspirin use was associated with reduced mortality for endometrial cancer; rather our findings suggested a concern for increased mortality.