Antidepressant use and ovarian cancer risk: Evidence from nationwide studies with >14,000 cases from Denmark and Sweden.

OBJECTIVE: Given that the evidence regarding the link between antidepressant use and ovarian cancer risk is equivocal, we investigated this research question by conducting two nationwide nested case-control studies among the Danish and Swedish populations. METHODS: Altogether, 14,121 women with epithelial ovarian cancer (30-84 years old) (Denmark: 8976 diagnosed 2000-2019, Sweden: 5145 diagnosed 2010-2018) were randomly age-matched with 564,840 female controls (359,040 from Denmark, and 205,800 from Sweden) using risk set sampling. We used conditional logistic regression to estimate odds ratios (OR) with 95 % confidence intervals (CI) and combined the estimates based on the fixed-effect assumption. We also investigated potential effect modification by well-established risk factors for ovarian cancer. RESULTS: Antidepressant use was associated with an overall reduced risk of ovarian cancer (OR = 0.92, 95%CI: 0.88-0.96), and that reduction was more pronounced in postmenopausal women and long-term users. The effect was most pronounced for serous ovarian tumors (OR = 0.90, 95%CI: 0.86-0.95) but was also observed in other subtypes, although not statistically significant. Among different types of antidepressants, selective serotonin reuptake inhibitors in general and citalopram in particular exhibited a noteworthy reduction in ovarian cancer risk (OR = 0.89, 95%CI: 0.82-0.96). Additionally, use of oral contraceptives and hormone replacement therapy individually modified the association between antidepressant use and ovarian cancer risk. CONCLUSIONS: Use of an antidepressant was associated with a slight, but statistically significant, decrease in ovarian cancer risk. Given the morbidity and mortality associated with ovarian cancer, and increasing use of antidepressants, these findings may be of significance to cancer prevention and should be studied in more detail mechanistically.

Low-dose aspirin use and risk of ovarian cancer: a combined analysis from two nationwide studies in Denmark and Sweden.

BACKGROUND: Studies on association between low-dose aspirin use and ovarian cancer risk were mostly based on self-reported medication use and few had large enough sample size to investigate the potential modification effect by ovarian cancer risk factors. METHODS: In these two nationwide nested case-control studies among the Danish and Swedish female population, 11,874 women with ovarian cancer (30-84 years old) (Denmark: 7328 diagnosed in 2000-2019, Sweden: 4546 diagnosed in 2010-2018) were randomly age- matched with 473,960 female controls (293,120 from Denmark, and 181,840 from Sweden). We used conditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) and combined the estimates based the fixed-effect assumption. Effect modification by inflammation-related risk factors and by indication (cardiovascular disease, CVD) were also investigated. RESULTS: Ever use of low-dose aspirin was not strongly associated with the overall risk of ovarian cancer (OR = 0.97; 95%CI: 0.92-1.03). However, the association differed according to parity (nulliparous: OR = 0.80, 95%CI: 0.70-0.92; parous: OR = 1.00, 95%CI: 0.94-1.07; p-interaction = 0.0024), and according to history of CVD (no CVD: OR = 0.91, 95%CI: 0.82-1.00; ever CVD: OR = 1.05, 95%CI: 0.97-1.13; p-interaction =0.0204). CONCLUSIONS: Low-dose aspirin use was associated with a decreased ovarian cancer risk especially in nulliparous women and in women without CVD diagnosis.

Paracetamol use and risk of epithelial ovarian cancer: A nationwide nested case-control study.

OBJECTIVE: To investigate whether paracetamol use is associated with a reduced risk of epithelial ovarian cancer (EOC). DESIGN: A nationwide nested case-control study. SETTING: Danish female population. POPULATION: A total of 9589 EOC cases diagnosed from 2000 to 2019 were age-matched with 383 549 randomly selected female controls using risk set sampling. METHODS: Paracetamol use, reproductive history, history of medication and history of surgery were retrieved from Danish national registers. Paracetamol use was defined as at least two prescriptions for up to 1 year before the index date, and was further classified according to recency, duration, cumulative dose and intensity of dose. MAIN OUTCOME MEASURES: Conditional logistic regression was used to estimate odds ratios and 95% confidence intervals for the association between paracetamol and EOC risk, overall and by histological subtypes. RESULTS: 'Ever' use of paracetamol was associated with a reduced EOC risk after adjusting for potential confounding factors (OR 0.92, 95% CI 0.87-0.97). The association was only significant among recent users (OR 0.89, 95% CI 0.84-0.95). The risk declined further with the increasing level of cumulative dose and intensity; women from the group with a high cumulative dose and a high intensity had a 13% (OR 0.87, 95% CI 0.80-0.94) and 14% (OR 0.86, 95% CI 0.79-0.93) reduced risk, respectively. In the histological subtype analysis, reduced risk with 'ever' use was most pronounced for serous and clear cell tumours. CONCLUSIONS: Paracetamol use was associated with a decreased risk of EOC in a dose-response manner. Future studies are needed to validate the findings and investigate the mechanisms behind the association.

Risk of ovarian cancer after salpingectomy and tubal ligation: Prospects on histology and time since the procedure.

OBJECTIVE: Recent theories propose that most epithelial ovarian cancer (EOC), depending on histological type, originate from other gynecological tissues and involve the ovary secondarily. According to these theories, any protective effect of salpingectomy and tubal ligation may vary by histological type. The study aim was to examine the association between salpingectomy and tubal ligation, respectively, and risk of EOC, with a focus on associations specific for histological types. METHODS: We identified EOC cases and matching controls in national registries and gathered information on surgical procedures and potential confounders. Conditional logistic regression was used to estimate odds ratio (OR) with 95% confidence interval (CI) of EOC related to salpingectomy and tubal ligation, respectively, overall and stratified by histological type. Furthermore, we investigated the association according to timing of the procedures. RESULTS: Our study comprised 16,822 EOC cases. Each case was matched with 40 controls. There was an overall EOC risk reduction after unilateral (OR = 0.73; 95% CI: 0.60-0.87) and bilateral salpingectomy (OR = 0.46; 95% CI: 0.31-0.67). A slight risk reduction was seen among women with previous tubal ligation (OR = 0.91; 95% CI: 0.83-0.99). For salpingectomy, the risk reduction increased with increasing time since the surgical procedure and was only present among women younger than 50 years at salpingectomy. Unilateral and bilateral salpingectomy was associated with a risk reduction for most histological types. CONCLUSION: The association between previous salpingectomy and reduced risk of several histological subtypes of EOC supports the suggested theories about the site of origin of EOC and may be of clinical importance.

Factors associated with condom use during sexual intercourse with a new partner among Scandinavian women.

In this population-based, cross-sectional questionnaire study among 18-45-year-old women from Denmark, Sweden, and Norway conducted during 2011-2012 we examine factors associated with using condoms with a new partner. Condom use with a new partner was assessed among 6202 women having had a new partner in the recent six months. Odds ratios (OR) and 95% confidence intervals (CI) were estimated for the associations between sociodemographic and lifestyle factors, and sexual behavior, respectively, and condom use with a new partner using a logistic regression model. Always/almost always ("always") condom use served as the reference category in all analyses and was compared with sometimes/rarely ("sometimes") and never use in two separate analyses. Overall, respectively 36.3%, 26%, and 37.7% reported always, sometimes, or never condom use with a new partner. Married/cohabiting were more likely than single women to never (OR = 2.50, 95% CI: 2.07-3.02) or sometimes (OR = 1.30; 95% CI 1.04-1.62) use condoms with recent new partners. Increasing number of new partners in the recent six months was also associated with condom use with a new partner (never: OR for ≥3 partners = 0.56; 95% CI: 0.47-0.67; sometimes: OR for ≥3 partners = 1.64; 95% CI: 1.38-1.94). Furthermore, women reporting early age at first sexual intercourse, no contraception at first intercourse, or not being vaccinated against human papillomavirus used condoms with new partners less frequently. These findings may suggest that continued awareness about the risk of contracting sexually transmitted infections when practicing condomless sex is important.

Factors associated with a cervical high-grade lesion on cytology or a positive visual inspection with acetic acid among more than 3300 Tanzanian women.

OBJECTIVES: Cervical cancer screening by visual inspection with acetic acid (VIA) is a widely used alternative to cytology in developing countries. This study aimed to evaluate risk factors associated with a positive VIA test and with cervical high-grade lesions on cytology. METHODS: We conducted a large cross-sectional study among 3339 women from urban and rural Tanzania. Study participants were interviewed about socio-demographic, reproductive and lifestyle factors. Blood samples were tested for HIV, and a gynaecological examination was performed. Human papillomavirus (HPV) status was determined by Hybrid Capture 2, and HPV genotyping was done using the LiPA Extra test. We used multivariable logistic regression to estimate adjusted odds ratios (ORs) and confidence intervals (CIs). RESULTS: The strongest risk factors for VIA positivity were positivity to HIV (OR = 3.48; 95% CI: 2.34-5.17) or to high-risk HPV (HrHPV) (OR = 1.97; 95% CI: 1.37-2.85). HrHPV was by far the strongest predictor of high-grade cytology (OR = 110.1; 95% CI: 50.4-240.4), while there was no significant association with HIV in the multivariable analysis (OR = 1.27; 95% CI: 0.78-2.08). After adjustment for HrHPV, HIV and age, the risk of high-grade cytology also increased with increasing age, number of births and low body mass index (BMI), while high BMI decreased the risk of VIA positivity. CONCLUSIONS: Infection with HrHPV is a major risk factor for high-grade cytology, while VIA positivity is associated with HIV and to a lesser extent with HrHPV.

Adverse pregnancy outcomes and infant mortality after quadrivalent HPV vaccination during pregnancy.

BACKGROUND: Few studies have studied the association between unintended human papillomavirus (HPV) vaccination and adverse pregnancy outcomes. This study set out to determine the association between HPV vaccination during pregnancy and subsequent risk of spontaneous abortion, stillbirth, and one-year infant mortality. METHODS: Population-based study including all pregnancies in Denmark (October 2006-December 2014) among women born 1975-1992. From nationwide health registries using the personal identification numbers, we obtained information on HPV vaccination, pregnancy outcomes, and infant mortality. The exposure window went from four weeks before conception date until 22 weeks of gestation for the outcome spontaneous abortion, and until birth for stillbirth and infant mortality outcomes. In the analyses of spontaneous abortion, we used time to event models, for stillbirth logistic regression models, and for infant mortality Cox regression was applied. RESULTS: We included 522,705 pregnancies for the outcome spontaneous abortion (7487 exposed to at least one dose during pregnancy); 351,878 births (5262 exposed to at least one dose during pregnancy) for the stillbirth; and 350,739 live births (5245 exposed to at least one dose during pregnancy) for infant mortality. No significantly increased rate of spontaneous abortion among women vaccinated during pregnancy compared with unvaccinated women was found. In addition, we found no association between HPV vaccination during pregnancy and stillbirth (adjusted odds ratio = 0.96 [95% CI: 0.57-1.61]), or infant mortality (adjusted hazard ratio = 0.94 [95% CI: 0.53-1.67]). A secondary analysis showed no association between number of doses and timing of administration (i.e. vaccination before or during pregnancy) and an increased risk of spontaneous abortion. CONCLUSION: We found no increased risk of spontaneous abortion, stillbirth, or infant mortality following unintended HPV vaccination during pregnancy.

Time trends in the incidence of hysterectomy-corrected overall, type 1 and type 2 endometrial cancer in Denmark 1978-2014.

OBJECTIVE: To investigate time trends in the incidence of overall, type 1 and type 2 endometrial cancer in Denmark 1978-2014, correcting for hysterectomy. METHODS: Based on the Danish Cancer Registry and the Danish National Patient Registry we calculated hysterectomy-corrected incidence rates of overall, type 1 and type 2 endometrial cancer. Separate analyses for women <55years (defined as pre- and perimenopausal age) and women aged ≥55years (defined as postmenopausal age) and analyses allowing for different time trends before and after the study period midyear 1996 were performed. Log-linear Poisson models were used to estimate annual percentage change (APC) in incidence with 95% confidence intervals (CI). RESULTS: The overall incidence of endometrial cancer decreased slightly from 1978 to 1995, but in the last two decades of the study period the incidence has been stable (APC=0.16; 95% CI: -0.19; 0.50). In the study period (1978-2014) type 1 endometrial cancer incidence decreased slightly (APC=-0.67; 95% CI:-0.83; -0.52), whereas the incidence of type 2 endometrial cancer increased substantially (APC=4.85; 95% CI: 4.47; 5.23). The decrease in type 1 endometrial cancer was most pronounced before 1996 in women younger than 55 years (APC=-2.79; 95% CI: -3.65; -1.91), while the largest increase in type 2 endometrial cancer was observed after 1996 (APC=6.42; 95% CI: 5.72; 7.12). CONCLUSIONS: Over a period of more than 35 years, the incidence of type 1 endometrial cancer decreased, mainly in pre- and perimenopausal women, while type 2 endometrial cancer incidence increased.

Risk factors for HIV positivity among more than 3,400 Tanzanian women.

In a cross-sectional study of 3,424 women from urban (Dar es Salaam) and rural (Pwani, Mwanza, and Mtwara) Tanzania, conducted in 2008-2009, we investigated risk factors for human immunodeficiency virus (HIV) and the association between different measures of human papillomavirus (HPV) and HIV positivity. Study participants were interviewed about socio-demographic and reproductive factors and sexual behavior. Blood samples were tested for HIV, and the women underwent a gynecological examination. HPV status was determined by Hybrid Capture 2, and HPV genotyping was performed using the LiPA Extra test. Multivariable logistic regression models estimating odds ratios (OR) and 95% confidence intervals (CI) were used. The overall HIV prevalence was 10.2%. HIV-positive women were more likely to have high-risk (HR) HPV detected (OR = 4.11; 95% CI: 3.23-5.24) and clinically visible genital warts (OR = 4.37; 95% CI: 1.81-10.5). Other risk factors included age, place of residence, education, number of births, lifetime number of sexual partners, and time in present relationship. HIV risk factors among urban and rural women and among HPV-positive and HPV-negative women were similar. HPV vaccination may provide some protection against HIV infection in Tanzania, but focus must still be on preventing established risk factors for HIV.

Prevalence of Human Papillomavirus in endometrial cancer: a systematic review and meta-analysis.

OBJECTIVE: HPV is a common sexually transmitted infection and is considered to be a necessary cause of cervical cancer. The anatomical proximity to the cervix has led researchers to investigate whether Human Papillomavirus (HPV) has a role in the etiology of endometrial cancer. METHODS: We conducted a systematic review and meta-analysis to investigate the pooled prevalence of HPV DNA in endometrial cancer. Using meta-regression, we further analyzed whether factors such as geographical region, HPV DNA detection method, publication year and tissue type were associated with HPV prevalence. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for studies providing data on HPV prevalence in cases with endometrial cancer and in controls with normal or hyperplastic endometrial tissue. RESULTS: We identified 28 papers (29 studies) examining the prevalence of HPV DNA in tumor tissue from endometrial cancer comprising altogether 1026 cases of endometrial cancer. The HPV prevalence varied considerably from 0% to 61.1%. From the random effects meta-analysis, the pooled prevalence of HPV DNA in endometrial cancer was 10.0% (95% CI: 5.2-16.2) with large between-study heterogeneity (I(2)=88.2%, p<0.0001). The meta-regression showed that HPV DNA detection method was statistically significantly associated with HPV prevalence (p=0.0016): the pooled HPV prevalence was 6.0% (95% CI: 1.5-13.0) using general primers, 18.9% (95% CI: 8.6-32.1) using type-specific primers and 1.0% (95% CI: 0.0-3.6) using non-PCR based methods. None of the other a priori defined variables were statistically significantly associated with HPV prevalence. The pooled OR was 1.43 (95% CI: 0.68-3.00) indicating that the odds of HPV was not increased in cases versus controls. CONCLUSIONS: HPV appears to have a limited or no role in the etiology of endometrial cancer.

Genital chlamydia, genital herpes, Trichomonas vaginalis and gonorrhea prevalence, and risk factors among nearly 70,000 randomly selected women in 4 Nordic countries.

BACKGROUND: The aim of this study was to assess the prevalence of women reporting ever having genital chlamydia, genital herpes, Trichomonas vaginalis, and gonorrhea, and to identify factors associated with each of these sexually transmitted infections (STIs). METHODS: The study was based on a large cross-sectional survey conducted in 2004-2005 among randomly sampled women (18-45 years) from the computerized population registries in Denmark, Iceland, Norway, and Sweden. A total of 69,567 women were included in the study. RESULTS: The overall prevalence in Denmark, Iceland, Norway, and Sweden was 1.5% for reporting ever having had Trichomonas vaginalis, 1.9% for gonorrhea, 4.8% for genital herpes, and 17.0% for genital chlamydia. The prevalence of each of these STIs varied with birth cohort and country. In addition, they were strongly associated with lifetime number of partners and having a previous diagnosis of another sexually transmitted infection. Moreover, a diagnosis of genital chlamydia or gonorrhea was associated with early age at first intercourse and smoking initiation. Finally, reporting genital chlamydia was associated with early age at drinking initiation, and ever use of hormonal contraceptives and condoms. CONCLUSION: Genital chlamydia occurs frequently among women in the Nordic countries. Risk-taking behavior, particularly sexual behavior, is strongly associated with STIs, which suggest that further information is needed about STIs and their consequences, targeting high-risk groups. There is also a need for continued monitoring of STIs in order to follow the prevalence and to gain further knowledge about risk factors.

[Smoking among more than 45,000 randomly sampled Danish women and men]. / Rygning blandt 45.000 tilfaeldigt udvalgte danskere.

INTRODUCTION: The aim of the study was to describe smoking and examine the association between socio-demographic factors (age, educational level and degree of urbanization) and smoking status, age at smoking initiation and heavy smoking. MATERIAL AND METHODS: The study is based on data from two cross-sectional surveys conducted in 2004 and 2006 among randomly sampled women and men (18-45 years). A total of 22,199 women (response rate: 81.4%) and 23,080 men (response rate: 71.0%) were included in the study. RESULTS: One third of the participating women and men reported being smokers. The majority smoked more than 15 cigarettes/day (59% women, 74% men). The proportion of never smokers was higher among the youngest. The proportion of daily smokers was lowest in the youngest age groups, especially among women. The prevalence of daily smokers was highest among participants with limited education, among women living in the southern suburbs of Copenhagen, and among men living in peripheral rural areas. In the multivariate analysis, smoking more than 15 cigarettes/day was strongly associated with age (less prevalent among the youngest) and educational level (more prevalent among participants with limited education). Age at smoking initiation seemed to decrease, as it was lowest among the youngest participants and among those with the lowest educational level. CONCLUSION: Fewer and particularly fewer young persons start smoking. However, we found an uneven distribution in the proportion of smokers especially in relation to educational level but also in relation to degree of urbanization.

[Personal health contact systems for cancer patients in Danish hospital wards]. / Kontaktpersonordninger til kraeftpatienter på danske hospitalsafdelinger.

INTRODUCTION: We examined personal health contact systems for cancer patients in Danish hospital wards and investigated whether there is a relation between patients' experience of having a personal health contact and the presence of a health contact system. MATERIAL AND METHODS: The personal health contact systems were examined by means of a questionnaire survey. Data from the questionnaire were combined with data from an earlier questionnaire study on cancer patients' needs to examine the relation between patients' experience of having a personal health contact and the presence of a health contact system. RESULTS: The majority of hospital wards included in the study had introduced a personal health contact system, but the time of implementation and specific organization of the systems vary. We found a statistically significant relation between the presence of personal health contact systems and patients' experience of having a personal health contact, but it was weak. CONCLUSION: Although most hospital wards have introduced personal health contact systems, their actual impact has been limited.