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Objective: Few studies exist on trends in papillary thyroid cancer (PTC) survival and mortality according to stage and level of socioeconomic status. Design: Nationwide cohort study. Patients and Measurements: Patients diagnosed with PTC during 2000–2015 in Denmark were identified from the Danish Cancer Registry and followed until the end of 2020. We evaluated 5‐year all‐cause mortality and relative survival according to stage and 5‐year mortality rates with corresponding average annual percentage changes (AAPCs) according to stage and education. Finally, we assessed the association between several factors and mortality of PTC using Cox regression. Results: For the 2006 cases of PTC diagnosed during 2000–2015, relative survival tended to increase and mortality rates tended to decrease for all stages. For localized PTC, mortality rates tended to decrease among individuals with medium education (AAPC = −7.0, 95% confidence interval [CI]: −14.7 to 1.5), but showed an increasing pattern among individuals with long education (AAPC = 19.8, 95% CI: −4.2 to 50.0). For nonlocalized PTC, mortality rates showed a decreasing tendency among individuals with medium and long education (AAPC = −5.5, 95% CI: −13.2 to 2.9, and AAPC = −10.4, 95% CI: −20.8 to 1.4, respectively). Being diagnosed with PTC in a more recent calendar period and long education were associated with a lower mortality rate in the Cox regression analysis. Conclusions: A pattern of an increasing relative survival and decreasing mortality rates of PTC across all stages was seen in Denmark during 2000–2015. The decreasing pattern in mortality rates was most evident in individuals with localized stage and medium education, and in individuals with nonlocalized stage and medium or long education. [ABSTRACT FROM AUTHOR]

Purpose: Although some reproductive and metabolic characteristics of polycystic ovary syndrome (PCOS) are known risk factors for breast cancer, the evidence regarding a potential association between PCOS and breast cancer is scarce. In this population-based cohort study including all 1,719,452 women born in Denmark between 1940 and 1993, we investigated the association between PCOS and breast cancer. Methods: PCOS diagnoses, cancer diagnoses, covariates, migrations, and vital status were all obtained from national population and health registers. Hazard ratios (HR) and 95% confidence intervals (CI) for breast cancer overall and for histological subtypes separately were calculated based on adjusted cox proportional hazards models. Results: During a median follow-up of 26 years, 63,078 women were diagnosed with breast cancer. We found an increased risk of breast cancer overall among women with PCOS compared with women without PCOS (HR: 1.21, 95% CI 1.02–1.44). In analyses stratified for menopausal status, the increased risk was restricted to postmenopausal women (HR: 1.63, 95% CI 1.23–2.15). The results for ductal and lobular histological subtypes analyses separately resembled those observed for breast cancer overall. Conclusion: This is the first study to report an increased risk of breast cancer among women with a history of PCOS. The increased risk was seemingly confined to postmenopausal women. Our results therefore contribute to an increased knowledge of the etiology of breast cancer, but our findings should be further confirmed in other large cohort studies with an appropriately long follow-up period. [ABSTRACT FROM AUTHOR]

Vulvar 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. What's new? Vulvar lichen sclerosus (VLS) may progress to vulvar cancer risk, whereas the association with other cancer types is unknown. Here, the authors investigated the incidence of non‐vulvar cancers among women in Denmark who were diagnosed with biopsy‐verified VLS between 1978 and 2019. Relative to the general population, cancer risk was decreased among VLS patients. This was especially the case for cancers associated with human papillomavirus infection and for smoking‐related cancers. The findings suggest that VLS patients practice cancer‐avoiding behaviors or there may exist a yet unknown mechanism linking VLS with reduced risk of certain cancer types. [ABSTRACT FROM AUTHOR]

Background Women with a family history of breast and/or ovarian cancer have an increased ovarian cancer risk. Yet it remains uncertain if common ovarian cancer risk factors—especially those that are modifiable—affect this high-risk population similarly to the general population. Methods Using the Danish and Swedish nationwide registers, we established 2 nested case-control study populations in women with a family history of breast and/or ovarian cancer (2138 ovarian cancers, 85 240 controls) and women without (10 730 ovarian cancers, 429 200 controls). The overall and histology-specific associations were assessed with conditional logistic regression. The country-specific estimates were combined based on a fixed-effect assumption. Results Multiparity, hysterectomy, tubal ligation, salpingectomy, and oral contraceptive (OC) use were associated with a reduced risk of ovarian cancer in women with and without a family history, while endometriosis and menopausal hormone therapy were associated with increased risk. Multiparity and OC use presented protective effects across all histologic subtypes except mucinous ovarian cancer, which was not associated with OC use. Menopausal hormone treatment increased the risk of serous ovarian cancer but decreased the risk of the mucinous and clear cell cancers. Endometriosis was especially related to an increased risk of endometrioid and clear cell ovarian cancer. Conclusion Factors associated with a decreased ovarian cancer risk were similar between women with and without a family history of breast and/or ovarian cancer. Given the higher baseline risk for women with a family history, special attention should be paid to risk factors like endometriosis and nulliparity in this high-risk population. [ABSTRACT FROM AUTHOR]

Background In Denmark, a girls-only human papillomavirus (HPV) vaccination program was initiated in 2008–2009. The study aim was to assess the HPV prevalence and type distribution in younger men prior to HPV vaccination in men. Methods The study population was younger men who attended information days regarding military service. At random days (2019–2020), 280 men were included. We collected questionnaire data regarding risk factors for HPV infection and a penile swab for HPV testing. We compared results in this study with those from a previous study of young men (2006–2007). Results The majority of participants (94%) were 18–20 years old. The median number of lifetime sexual partners was 4. Altogether, 130 men (46.4%) were HPV positive. No infections with HPV types 6, 11, 16, 18, 31, and 45 were detected. The most frequent type was HPV-51 (detected in 11.1%). Comparison showed that the odds of high-risk HPV type infection were higher in 2019–2020 (prevalence odds ratio [POR], 1.7 [95% confidence interval {CI}, 1.1–2.7]) compared with 2006–2007. In contrast, the odds were lower (POR, 0.3 [95% CI,.1–.6]) for HPV types targeted by the 9-valent HPV vaccine. Conclusions The multicohort girls-only vaccination program has to a large degree protected young men against the HPV types included in the licensed vaccines. This does not speak against gender-neutral vaccination as the HPV prevalence is still high, although consisting largely of less carcinogenic HPV types. [ABSTRACT FROM AUTHOR]

Background: Tea and coffee are the most frequently consumed beverages in the world. Green tea in particular contains compounds with potential anti-cancer effects, but its association with survival after ovarian cancer is uncertain. Methods: We investigated the associations between tea and coffee consumption before diagnosis and survival using data from 10 studies in the Ovarian Cancer Association Consortium. Data on tea (green, black, herbal), coffee and caffeine intake were available for up to 5724 women. We used Cox proportional hazards regression to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI). Results: Compared with women who did not drink any green tea, consumption of one or more cups/day was associated with better overall survival (aHR = 0.84, 95% CI 0.71–1.00, p-trend = 0.04). A similar association was seen for ovarian cancer-specific survival in five studies with this information (aHR = 0.81, 0.66–0.99, p-trend = 0.045). There was no consistent variation between subgroups defined by clinical or lifestyle characteristics and adjustment for other aspects of lifestyle did not appreciably alter the estimates. We found no evidence of an association between coffee, black or herbal tea, or caffeine intake and survival. Conclusion: The observed association with green tea consumption before diagnosis raises the possibility that consumption after diagnosis might improve patient outcomes. [ABSTRACT FROM AUTHOR]

Introduction: In Denmark, where human papillomavirus (HPV) ‐based cervical cancer screening is being implemented, the aim of this pilot implementation study was to test a specific screening algorithm, assess follow‐up examination attendance, and measure the proportion of precancer lesions found in relation to the number of women referred for colposcopy. Material and Methods: From May 2017 to December 2020, 36 417 women in the uptake area of the Department of Pathology, Vejle Hospital, Region of Southern Denmark, were included in the HPV group. Women positive for HPV16/18 irrespective of cytology and women positive for other high‐risk HPV (hrHPV) types having concomitant abnormal cytology were referred directly to colposcopy. Women positive for other hrHPV types and normal cytology were referred to repeat screening after 12 months, and hrHPV negative to routine screening after three years. We obtained information on screening results and subsequent histological diagnosis from the Danish Pathology Databank through September 2022. Results: 3.6% of the women were referred to colposcopy after primary screening, 5% to repeat screening after 12 months, and 91.4% back to routine screening. High follow‐up rates were observed: 96% attended colposcopy after primary screening, with 91% attending colposcopy after repeat screening. CIN3+ was detected at colposcopy following the primary screening in 28.1% of HPV16/18‐positive women and 18.2% of those positive for other hrHPV types with concomitant abnormal cytology. Of the women with other hrHPV and simultaneous ASCUS/LSIL, 8% had CIN3+. At the repeat screening, 43% had become hrHPV negative, 55% were persistently positive for other hrHPV, and 2% had turned positive for HPV16/18. At the colposcopy following repeat screening, 10.1% of the women positive for other hrHPV were diagnosed with CIN3+, in comparison with 11.1% of the HPV16/18‐positive women. Conclusions: In this pilot implementation study, an algorithm for HPV‐based screening was evaluated in a Danish setting. The results demonstrated high attendance at follow‐up examinations and provided insights into the number of colposcopy referrals and the detection of CIN2 and CIN3+ cases. The results suggest that women testing positive for other hrHPV in combination with ASCUS/LSIL at primary screening could potentially be referred to repeat screening instead of an immediate colposcopy. [ABSTRACT FROM AUTHOR]

Population‐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. [ABSTRACT FROM AUTHOR]

Aims: Teenage pregnancy may have negative consequences for the mother and the infant. The aim of the study was to examine whether selected individual factors occurring early in life were associated with teenage pregnancy. Methods: In a population-based, cross-sectional questionnaire study among 34,455 women from Denmark, Norway, and Sweden aged 20–45 years, who had first sexual intercourse (FSI) at age 13–19 years, we assessed the association between early smoking and drinking initiation (i.e., before the age of 13), contraceptive use at FSI, and teenage pregnancy. Log-linear binary regression models were fitted to estimate the relative risk (RR) with 95% confidence intervals (CIs) of teenage pregnancy according to the three exposure variables, overall and by age at FSI. Furthermore, the outcomes of the teenage pregnancies were examined according to age at FSI. Results: Teenage pregnancy occurred in 11% of the population. Both early smoking initiation (RR: 1.6; 95% CI: 1.4–1.8), early drinking initiation (RR: 1.2; 95% CI: 1.0–1.4), and non-use of contraceptives at FSI (RR: 1.9; 95% CI: 1.8–2.0) were associated with teenage pregnancy. The associations for early smoking initiation and non-use of contraceptives remained when analyses were stratified by age at FSI. Almost 60% of all teenage pregnant women had an induced abortion and less than 30% gave birth. Conclusions: Individual factors, including early smoking and drinking initiation, and non-use of contraceptives at FSI, were associated with teenage pregnancy regardless of age at FSI. This emphasizes the necessity of focusing on early risk-taking behavior as a potential modifier to prevent teenage pregnancy. [ABSTRACT FROM AUTHOR]

Use 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. [ABSTRACT FROM AUTHOR]

High‐risk human papillomavirus (hrHPV) is the cause of virtually all cervical cancers, most vaginal and anal cancers, and some vulvar cancer cases. With HPV testing becoming the primary screening method for cervical cancer, understanding the link between cervical hrHPV infection and the risk of other anogenital cancers is crucial. We assessed the risk of vulvar, vaginal and anal cancer and precancer (VIN2+, VaIN2+ and AIN2+) in a prospective cohort study including 455,349 women who underwent cervical hrHPV testing in Denmark from 2005 to 2020. We employed Cox proportional hazard models, adjusting for age, calendar year and HPV vaccination status, and estimated hazard ratios (HRs) and 95% confidence intervals (CI). We used the Aalen Johansen estimator to calculate the absolute risks of VIN2+, VaIN2+ and AIN2+. In total, 15% of the women were hrHPV positive at baseline. A positive cervical hrHPV test was associated with increased incidence of vulvar, vaginal and anal squamous cell carcinoma (SCC). Five‐year risk estimates of VIN2+, VaIN2+ and AIN2+ among hrHPV‐positive women (0.45%, 0.14% and 0.12%) were higher than among hrHPV‐negative women (0.14%, 0.01% and 0.05%). Particularly high risk was observed among the hrHPV‐positive women of the oldest age, with a history of anogenital precancer and those not HPV vaccinated. In conclusion, our study confirms the association between cervical hrHPV infection and non‐cervical anogenital precancers and cancers. Currently, no established risk threshold or guidelines for follow‐up. As HPV testing becomes the primary method for cervical cancer screening, future data will help define high‐risk groups and acceptable risk thresholds. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to investigate high-risk human papillomavirus (hrHPV) prevalence according to socioeconomic and demographic characteristics in a Danish screening population. Methods: We used data from HPV SCREEN DENMARK, which was an implementation study embedded into the routine cervical cancer screening programme. During 2017–2020, women aged 30–59 years screened in the Region of Southern Denmark were offered HPV testing or cytology. In the HPV group, liquid-based cytology samples were tested for 14 hrHPV types. We obtained registry information on socioeconomic and demographic characteristics and used log-binomial regression to estimate the prevalence ratio (PR) of hrHPV in three age groups (30–39, 40–49, 50–59 years), adjusting for age and marital status. Results: We included 31,124 HPV unvaccinated women. In all age groups, the age-adjusted hrHPV prevalence was higher in women with basic versus higher education (e.g. age 30–39: 11.9% vs. 9.5%; PRage-adjusted=1.24; 95% confidence interval (CI): 1.02–1.50); women who were unemployed vs. employed (e.g. age 30–39: 11.6% vs. 10.4%; PRage-adjusted=1.11; 95% CI: 0.95–1.28); and in women with highest vs. lowest income (e.g. age 30–39: 11.6% vs. 9.5%, PRage-adjusted=1.18, 95% CI: 0.98–1.44). In models adjusted for marital status, these associations largely disappeared. Conclusions: We found slightly higher hrHPV prevalences in women with basic education, low income and unemployment. The differences largely disappeared when taking into account marital status as a potential proxy for sexual behaviour. Our findings support a need for targeted information on safe sexual practices and promoting socioeconomic equality in HPV vaccination and cervical cancer screening participation. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Programmed cell death ligand‐1 (PD‐L1) expression in cancer may predict clinical response to immunotherapeutic treatment with PD‐1/PD‐L1 inhibitors. Within the vulvar cancer field, PD‐L1 expression has only been assessed by a few studies. We conducted a meta‐analysis to examine the prevalence of PD‐L1 positivity in vulvar cancer. PubMed, Embase, and Cochrane were searched for articles reporting on PD‐L1 expression in vulvar cancer. Study selection and data extraction were performed independently by two authors. We extracted data on PD‐L1 prevalence in vulvar cancer according to combined positive score (CPS) and tumour proportion score (TPS). Cutoff values for positivity were ≥1 or ≥10 for CPS and ≥1% and ≥5% for TPS. Random‐effects models were used to estimate pooled PD‐L1 prevalence, with 95% confidence intervals (CIs). Tests of between‐study heterogeneity were evaluated by the I2 statistics. Sources of heterogeneity were explored by subgroup analyses and meta‐regression. In total, 19 studies were included. Pooled PD‐L1 prevalence in vulvar cancer was 83.4% (95% CI: 70.8–91.3; I2 = 80.0) and 53.9% (95% CI: 37.4–69.6; I2 = 93.0) according to CPS and TPS, respectively. Based on TPS, human papillomavirus (HPV)‐associated vulvar squamous cell carcinomas (SCC) showed a lower PD‐L1 prevalence (39.9%; 95% CI: 13.3–74.2) compared with HPV‐independent SCC (62.6%; 95% CI: 33.7–84.6), but meta‐regression showed no significant variation in PD‐L1 prevalence by HPV status. PD‐L1 prevalence was similar in advanced (44.9%; 95% CI: 29.8–61.1) and localized vulvar cancer (56.7%; 95% CI: 18.9–76.7). In conclusion, PD‐L1 expression in vulvar cancer is frequent but between‐study heterogeneity was high. Based on a subgroup of heterogenous studies, we found no strong variation in PD‐L1 prevalence according to HPV status and stage. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The Danish SEQUEL cohort is a study that aims to investigate the inequalities and late effects experienced by cancer survivors in Denmark. The cohort includes adult survivors of breast, prostate, lung, colon and rectum cancer, melanoma, and lymphoma. It provides comprehensive data on tumor characteristics, cancer treatment, educational level, income, cohabitation, comorbidity, and more. The study has found that cancer survivors, especially those with lower education levels, have a greater need for healthcare services and experience impaired functioning and severe symptoms. The data from the cohort is not publicly available, but researchers can contact the principal investigator for collaborative research projects. The study has been approved by the National Board of Health Data and has received funding from various organizations. [Extracted from the article]

Background Human papillomavirus (HPV) vaccination has shown high efficacy against anal HPV infection and lesions in clinical trials, and the HPV prevalence and type distribution in anal precancers and cancer predict a high preventable potential for HPV vaccination. However, the real-world effectiveness of HPV vaccination against anal high-grade lesions and cancer is yet to be shown. Methods We investigated HPV vaccine effectiveness against anal high-grade squamous intraepithelial lesion (HSIL) or worse in a nationwide cohort including all Danish women aged 17-32 years during October 2006 to December 2021 (n = 968 881). HPV vaccinations and first occurrence of anal HSIL or worse were retrieved from nationwide registries. Women were considered vaccinated after first dose and classified by age at vaccination. Using Cox regression, hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for anal HSIL or worse according to vaccination status. Results During follow-up, the number of incident histological anal HSIL or worse cases was 37 in unvaccinated women, and less than 5 and 26 in women vaccinated at ages younger than 17 years and 17-32 years, respectively. The overall number of cancers was less than 5. Compared with unvaccinated women, the risk of histological anal HSIL or worse was reduced for women vaccinated at age younger than 17 years (HR = 0.30, 95% CI = 0.10 to 0.87). For women vaccinated at age 17-32 years, the hazard rate of anal HSIL or worse was 1.21 (95% CI = 0.73 to 2.03). Conclusion This is the first study to demonstrate that HPV vaccination at a younger age is associated with substantially reduced risk of anal HSIL or worse in the general population. [ABSTRACT FROM AUTHOR]

Background: With a growing population of cancer survivors in Denmark, the evaluation of health‐related quality of life (HRQoL) has become increasingly important. We describe variations in HRQoL between educational groups in a national population of cancer survivors. Methods: We conducted a cross‐sectional questionnaire study among breast, prostate, lung, and colon cancer survivors diagnosed in 2010–2019 in Denmark. We used the EORTC QLQ‐C30 to assess HRQoL including physical, role, emotional, cognitive, social functioning, and symptoms (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Information on educational level and clinical data were extracted from national registers and clinical databases. Levels of impaired functioning and severe symptoms were identified using newly established thresholds for clinical importance. Multivariate logistic regression was used to examine associations between education and HRQoL. All statistical tests were 2‐sided. Results: In total, 27,857 (42%) participated in the study. Up to 72% and 75% of cancer survivors with short education (≤9 years) reported impaired functioning and severe symptoms, respectively. Cancer survivors with short compared to long education (>12 years) were more likely to report impaired functioning and severe symptoms, with for example significantly higher odds ratios (ORs) for impaired physical function (breast OR = 2.41, 99% CI = 2.01–2.89; prostate OR = 1.81, 99% CI = 1.48–2.21; lung OR = 2.97, 99% CI = 1.95–4.57; and colon cancer OR = 1.69, 99% CI = 1.28–2.24). Conclusions: Cancer survivors with short education are at greater risk of impaired HRQoL than survivors with long education 2–12 years after diagnosis. This underscores the need for systematic screening and symptom management in cancer aftercare, in order to reach all cancer survivors, also cancer survivors with short education. [ABSTRACT FROM AUTHOR]

An association between polycystic ovary syndrome (PCOS) and epithelial ovarian tumors is biologically plausible as conditions inherent to PCOS such as excessive androgenic hormones, reproductive factors and obesity are also risk factors for these hormone‐sensitive tumors. However, previous studies have showed conflicting results and have various methodological limitations. This population‐based cohort study investigates the association between PCOS and epithelial ovarian tumors and includes all women born in Denmark between January 1, 1940 and December 31, 1993 (n = 1 719 304). PCOS diagnoses, ovarian cancer and borderline ovarian tumor diagnoses, covariates, migration and vital status were obtained from the Danish national registers. Adjusted cox proportional hazard regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CI) for epithelial ovarian cancer and for borderline ovarian tumors overall as well as for histological subtypes separately. During median 26 years of follow‐up we identified 6490 women with ovarian cancer and 2990 women with borderline ovarian tumors. Overall, we observed no marked associations between a diagnosis of PCOS and overall epithelial ovarian cancer or overall epithelial borderline ovarian tumors, irrespective of time since diagnosis. However, we found an increased risk of ovarian cancer among postmenopausal women with PCOS (HR 2.28 95% CI 1.02‐5.09) and an increased risk of serous borderline ovarian tumors (HR 2.34 95% CI 1.21‐4.53) in women with PCOS compared with women without PCOS. Importantly, low statistical precision is a crucial limitation of our study and in previous studies and larger studies with longer follow‐up are therefore warranted. [ABSTRACT FROM AUTHOR]

Background: Many cancer survivors experience late effects after cancer. Comorbidity, health literacy, late effects, and help-seeking behavior may affect healthcare use and may differ among socioeconomic groups. We examined healthcare use among cancer survivors, compared with cancer-free individuals, and investigated educational differences in healthcare use among cancer survivors. Methods: A Danish cohort of 127,472 breast, prostate, lung, and colon cancer survivors from the national cancer databases, and 637,258 age- and sex-matched cancer-free individuals was established. Date of entry was 12 months after diagnosis/index date (for cancer-free individuals). Follow-up ended at death, emigration, new primary cancer, December 31st, 2018, or up to 10 years. Information about education and healthcare use, defined as the number of consultations with general practitioner (GP), private practicing specialists (PPS), hospital, and acute healthcare contacts 1–9 years after diagnosis/index date, was extracted from national registers. We used Poisson regression models to compare healthcare use between cancer survivors and cancer-free individuals, and to investigate the association between education and healthcare use among cancer survivors. Results: Cancer survivors had more GP, hospital, and acute healthcare contacts than cancer-free individuals, while the use of PPS were alike. One-to-four-year survivors with short compared to long education had more GP consultations (breast, rate ratios (RR) = 1.28, 95% CI = 1.25–1.30; prostate, RR = 1.14, 95% CI = 1.10–1.18; lung, RR = 1.18, 95% CI = 1.13–1.23; and colon cancer, RR = 1.17, 95% CI = 1.13–1.22) and acute contacts (breast, RR = 1.35, 95% CI = 1.26–1.45; prostate, RR = 1.26, 95% CI = 1.15–1.38; lung, RR = 1.24, 95% CI = 1.16–1.33; and colon cancer, RR = 1.35, 95% CI = 1.14–1.60), even after adjusting for comorbidity. One-to-four-year survivors with short compared to long education had less consultations with PPS, while no association was observed for hospital contacts. Conclusion: Cancer survivors used more healthcare than cancer-free individuals. Cancer survivors with short education had more GP and acute healthcare contacts than survivors with long education. To optimize healthcare use after cancer, we need to better understand survivors' healthcare-seeking behaviors and their specific needs, especially among survivors with short education. [ABSTRACT FROM AUTHOR]

Vulvar cancer is rare, but causes substantial morbidity in affected patients. A subset of vulvar cancers is caused by high‐risk human papillomavirus (hrHPV), which primarily exerts its oncogenic effect through upregulation of tumor suppressor protein p16. Tumors positive for both hrHPV and p16 (double positive) are assumed to be HPV‐driven, but only few large studies have investigated the combined prevalence of hrHPV and p16 positivity in vulvar cancer over time. In this Danish cross‐sectional study, we assessed the prevalence of p16 positivity and double positivity for hrHPV and p16 in a large sample of vulvar squamous cell carcinomas (VSCCs) diagnosed during 1990 to 2017. In a nationwide register, we identified VSCCs from 13 hospitals across Denmark, and collected archival tumor tissue for hrHPV testing with INNO‐LiPA and immunohistochemical p16 staining. We calculated the prevalence of hrHPV, p16 positivity and double positivity according to time, age and histological subtype and evaluated time trends through estimated annual percentage changes. We included 1278 VSCCs. Overall, 35.0% (95% confidence interval [CI]: 32.4‐37.6) were positive for p16 and 31.0% (95% CI: 28.4‐33.5) were positive for both hrHPV and p16. The prevalence of p16 positivity and double positivity increased over time, both in women aged ≤59 and ≥60 years. The double positive prevalence was higher in nonkeratinizing (60.7%) and warty/basaloid VSCCs (67.5%) than in keratinizing (16.1%) and verrucous VSCCs (5.0%). These results indicate that approximately one‐third of vulvar cancers were caused by hrHPV infection, supporting a substantial preventive potential of the HPV vaccine. [ABSTRACT FROM AUTHOR]

When women require hysterectomy for a benign condition, the ovaries are sometimes removed at the same time, primarily to prevent future ovarian cancer. This article provides new information about how hysterectomy affects other possible outcomes, such as heart attack, stroke, other types of cancer, and life expectancy. Visual Abstract. Bilateral Salpingo-oophorectomy and Long-Term Health Consequences.: When women require hysterectomy for a benign condition, the ovaries are sometimes removed at the same time, primarily to prevent future ovarian cancer. This article provides new information about how hysterectomy affects other possible outcomes, such as heart attack, stroke, other types of cancer, and life expectancy. Background: More evidence is needed to substantiate current recommendations about removing ovaries during hysterectomy for benign conditions. Objective: To compare long-term outcomes in women with and without bilateral salpingo-oophorectomy (BSO) during hysterectomy for benign conditions. Design: Emulated target trial using data from a population-based cohort. Setting: Women in Denmark aged 20 years or older during 1977 to 2017. Participants: 142 985 women with hysterectomy for a benign condition, 22 974 with BSO and 120 011 without. Intervention: Benign hysterectomy with or without BSO. Measurements: The primary outcomes were overall hospitalization for cardiovascular disease (CVD), overall cancer incidence, and all-cause mortality through December 2018. Results: Compared with women without BSO, women with BSO who were younger than 45 years at surgery had a higher 10-year cumulative risk for hospitalization for CVD (risk difference [RD], 1.19 percentage points [95% CI, 0.09 to 2.43 percentage points]). Women with BSO had a higher 10-year cumulative risk for cancer for ages 45 to 54 years (RD, 0.73 percentage point [CI, 0.05 to 1.38 percentage points]), 55 to 64 years (RD, 1.92 percentage points [CI, 0.69 to 3.25 percentage points]), and 65 years or older (RD, 2.54 percentage points [CI, 0.91 to 4.25 percentage points]). Women with BSO had higher 10-year mortality in all age groups, although the differences were statistically significant only for ages 45 to 54 years (RD, 0.79 percentage point [CI, 0.27 to 1.30 percentage points]). The mortality at 20 years was inconsistent with that at 10 years in women aged 65 years or older. Limitation: Age was a proxy for menopausal status. Conclusion: The authors find that these results support current recommendations for conserving ovaries in premenopausal women without a high risk for ovarian cancer and suggest a cautious approach in postmenopausal women. Primary Funding Source: The Danish Cancer Society's Scientific Committee and the Mermaid Project. [ABSTRACT FROM AUTHOR]

Background: Kidney transplant recipients (KTRs) have increased risk of human papillomavirus (HPV)‐related cancers, including cervical and anal cancer. In this cross‐sectional clinical study, we investigated the prevalence of cervical high‐risk HPV (hrHPV) and low‐risk (lrHPV), risk factors for cervical hrHPV infection, and the prevalence of cervical and anal hrHPV co‐infection in KTRs and immunocompetent controls. Methods: During 2016–2017, we recruited 125 female KTRs and 125 female immunocompetent controls from one dermatology department (KTRs and controls) and five nephrology departments (KTRs) in Denmark. Liquid‐based cervical and anal cytology samples were tested for HPV DNA using the INNO‐LiPA test and participants answered a questionnaire on lifestyle. Odds ratios (ORs) were estimated using logistic regression, adjusting for age, lifetime sexual partners, smoking, and (in models concerning anal HPV) receptive anal sex. Results: KTRs had higher prevalence of cervical hrHPV than controls (35.5% vs. 18.2; ORadjusted = 2.9, 95% CI, 1.5–5.5). In contrast, the prevalence of lrHPV was similar in KTRs and controls (25.6% vs. 23.1; ORadjusted = 1.2, 95% CI, 0.7‒2.3). KTRs were more likely than controls to have cervical and anal hrHPV co‐infection (27.3% vs. 6.6%, ORadjusted = 6.3, 95% CI, 2.7–15.0). Conclusions: Female KTRs had high prevalence of cervical hrHPV, and co‐infection with anal and cervical hrHPV was common. Our results underline that KTRs are an important target group for preventive efforts against HPV‐related diseases. [ABSTRACT FROM AUTHOR]

In Denmark, vaccination against human papillomavirus (HPV) has been implemented in the children's vaccination program (January 2009) and in multiple catch‐up cohorts (October 2008 in girls 13‐15 years and in August 2012 in women up to 27 years). In the present study we estimate incidence of cervical intraepithelial neoplasia grade 3 (CIN3), adenocarcinoma in situ (AIS), squamous cell carcinoma (SCC) and adenocarcinoma (AC) during 2000‐2019. All cases of CIN3 and AIS were identified from the nationwide Pathology Data Bank, while SCC and AC were identified from the Danish Cancer Registry. We calculated age‐standardized incidence rates and estimated annual percentage change (EAPC) with corresponding 95% confidence interval (CI) for the periods before vaccination implementation (2000‐2005), early after implementation of childhood HPV vaccination and the first catch‐up vaccination program (2006‐2012), and after implementation of the second catch‐up program (2013‐2019). For CIN3 and AIS, age‐specific incidence rates and EAPCs were calculated. An increasing age‐standardized incidence was observed before introduction of HPV vaccination (2000‐2005) for CIN3 [EAPCCIN3: 3.0 (95% CI 1.7 to 4.3)] and AIS [EAPCAIS: 3.5 (95% CI 0.7 to 6.4)]. In the most recent period (2013‐2019), following implementation of the second catch‐up program, a decrease was observed for both CIN3 [EAPCCIN3: ‐6.5 (95% CI ‐8.3 to −4.8)], AIS [EAPCAIS: ‐8.7 (95% CI ‐12.3 to −5.1)] and for SCC [EAPCSCC: ‐3.9 (95% CI ‐7.5 to −0.2)]. In this study we document a decrease in the incidence of CIN3, AIS and SCC in the period after implementation of multi‐cohort HPV vaccination in Denmark. [ABSTRACT FROM AUTHOR]

Objective: To determine whether prior human papillomavirus (HPV) vaccination contributes to preterm birth risk. Design: Population‐based retrospective cohort study. Setting: Denmark. Population: A cohort of 243 136 primiparous females born in the period 1961–2004 who had a singleton delivery at >22 weeks of gestation occurring from October 2006 to December 2018. Methods: High‐quality nationwide registries were linked to provide information on demographics, birth outcomes, HPV vaccination status, smoking, body mass index (BMI), and cervical lesions and treatment history. Main outcome measures: We assessed the association between HPV vaccination status and spontaneous preterm birth using logistic regression. To address age at vaccination, we performed a stratified analysis by vaccination before and after 17 years of age. Results: In age‐adjusted and fully adjusted models, there was a nonsignificant difference in the odds of spontaneous preterm birth between vaccinated and unvaccinated women (OR 1.05 (95% CI 0.99–1.12) and OR 1.04 (95% CI 0.98–1.10), respectively). There was no difference in the odds of spontaneous preterm birth in relation to time between vaccination and pregnancy. In contrast, compared with unvaccinated women, the odds of preterm birth were lower among women vaccinated before the age of 17 years (fully adjusted OR 0.87, 95% CI 0.75–1.00). This association was not present for women vaccinated at ≥17 years of age. Conclusions: In this large, population‐based cohort, we found reduced odds of spontaneous preterm birth among women vaccinated against HPV at an early age compared with women who were unvaccinated. It seems conceivable that HPV vaccination may not only reduce the incidence of cervical cancer and severe precursors, but also reduce the risk of preterm birth related to HPV infection. [ABSTRACT FROM AUTHOR]

Background: High body mass index (BMI) has previously been associated with increased risk of differentiated thyroid cancer (DTC); however, only few studies have investigated the association with BMI in a large cohort assessed at a young age and with sufficient data on confounding factors. We assessed the association between excess body weight and the risk of DTC and papillary thyroid cancer (PTC) in a large cohort of young Danish women with substantial confounder control. Methods: We included all parous Danish women registered with a prepregnancy BMI ≥18.5 kg/m2 during 2004–2016 in the Danish Medical Birth Registry in the study population. Cox proportional hazards regression models were used to estimate the hazard ratios (HRs) with confidence intervals (CIs) of DTC according to BMI. In subanalyses, we investigated PTC as a separate group. Analyses were adjusted for calendar time, education, smoking status, benign thyroid disease (BTD), type II diabetes, parity, and oral contraceptive use. In addition, we examined the association with increasing BMI stratified for previous BTD. Results: A total of 443,403 women were included in the study population, and the median age at baseline was 30.0 years. Altogether, 463 women were diagnosed with DTC during follow-up. Excess body weight was associated with a higher rate of DTC (overweight, BMI 25–29.9 kg/m2: HR = 1.54; CI 1.25–1.90. Obese, BMI ≥30 kg/m2: HR = 1.32; CI 1.00–1.75) compared with normal weight. Results were similar in PTC. In addition, we found an increased rate of DTC with increasing BMI, when investigating BMI as a continuous variable per 5 kg/m2 increase (HR = 1.17; CI 1.07–1.27). The results were similar in women without previous BTD. Conclusions: Our study confirms that excess body weight is associated with an increased incidence of DTC and PTC in women. [ABSTRACT FROM AUTHOR]

Objective: To determine whether prior human papillomavirus (HPV) vaccination contributes to preterm birth risk. Design: Population‐based retrospective cohort study. Setting: Denmark. Population: A cohort of 243 136 primiparous females born in the period 1961–2004 who had a singleton delivery at >22 weeks of gestation occurring from October 2006 to December 2018. Methods: High‐quality nationwide registries were linked to provide information on demographics, birth outcomes, HPV vaccination status, smoking, body mass index (BMI), and cervical lesions and treatment history. Main outcome measures: We assessed the association between HPV vaccination status and spontaneous preterm birth using logistic regression. To address age at vaccination, we performed a stratified analysis by vaccination before and after 17 years of age. Results: In age‐adjusted and fully adjusted models, there was a nonsignificant difference in the odds of spontaneous preterm birth between vaccinated and unvaccinated women (OR 1.05 (95% CI 0.99–1.12) and OR 1.04 (95% CI 0.98–1.10), respectively). There was no difference in the odds of spontaneous preterm birth in relation to time between vaccination and pregnancy. In contrast, compared with unvaccinated women, the odds of preterm birth were lower among women vaccinated before the age of 17 years (fully adjusted OR 0.87, 95% CI 0.75–1.00). This association was not present for women vaccinated at ≥17 years of age. Conclusions: In this large, population‐based cohort, we found reduced odds of spontaneous preterm birth among women vaccinated against HPV at an early age compared with women who were unvaccinated. It seems conceivable that HPV vaccination may not only reduce the incidence of cervical cancer and severe precursors, but also reduce the risk of preterm birth related to HPV infection. [ABSTRACT FROM AUTHOR]

Cervical cancer is the most common female cancer in Eastern Africa, and the World Health Organization (WHO) recommends human papillomavirus (HPV)‐based screening as a key element to eliminate the disease. In this cross‐sectional study from Tanzania, we compared nine HPV‐based cervical cancer screening strategies, including HPV testing at standard cut‐off; HPV testing at increased viral load cut‐offs; HPV testing with partial/extended genotyping, and HPV testing with visual inspection with acetic acid (VIA). We pooled data collected during 2008 to 2009 and 2015 to 2017 from 6851 women aged 25 to 65. Cervical cytology samples were HPV tested with Hybrid Capture 2, and HPV positive samples were genotyped with INNO‐LiPA Extra II. Human immunodeficiency virus (HIV) testing and VIA were done according to local standards. We calculated sensitivity, specificity, positive and negative predictive value of screening strategies, with high‐grade cytological lesions as reference, separately for women with and without HIV. HPV testing at standard cut‐off (1.0 relative light units [RLU]) had highest sensitivity (HIV+: 97.8%; HIV−: 91.5%), but moderate specificity (HIV+: 68.1%; HIV−: 85.7%). Increasing the cut‐off for HPV positivity to higher viral loads (5.0/10.0 RLU) increased specificity (HIV+: 74.2%‐76.5%; HIV−: 89.5%‐91.2%), with modest sensitivity reductions (HIV+: 91.3%‐95.7%; HIV−: 83.5%‐87.8%). Limiting test positivity to HPV types 16/18/31/33/35/45/52/58 improved specificity while maintaining high sensitivity (HIV+: 90.2%; HIV−: 81.1%). Triage with VIA and/or partial genotyping for HPV16/18 or HPV16/18/45 had low sensitivities (≤65%). In conclusion, HPV testing alone, or HPV testing with extended genotyping or increased viral load cut‐offs, may improve cervical cancer screening in Sub‐Saharan Africa. [ABSTRACT FROM AUTHOR]

Background: Human papilloma virus (HPV) is a sexually transmitted infection causing more than 80% of cervical cancers. WHO recommends using of sensitive screening methods like HPV-testing to timely prevent future morbidity and mortality from cervical cancer. Pilot studies have shown that HPV-testing is feasible and can be scaled in developing country like Tanzania. However, there is limited information on women understanding, reactions and psychological challenges following diagnosis of high risk HPV (HR-HPV). This study explored the knowledge of women on HPV and their experience after HPV positive results in Kilimanjaro, Tanzania. Methods: The study was part of a larger study that assessed incidence and persistence of HR-HPV among women aged 18 years and above in Kilimanjaro. This was a cross sectional study conducted in Moshi municipal council among women who had HR-HPV positive results at enrollment. In-depth interviews were conducted with 13 randomly selected women who were attending for follow-up after enrollment. Interviews were conducted at the health facility and Atlas.ti.8 was used to analyze the data using thematic framework analysis. Results: Women had knowledge on HPV infection but they had different reactions following receiving positive HPV results. Reaction toward the positive HPV results had two extremes; some women had psychological effect (hopeless, death sentence, having cancer, being shocked, failure to disclose and psychosexual effects) while others women explained positive results is good as they are identified earlier, will be followed up and it has made them plan to continue with cervical cancer screening in future. Conclusion: Women had knowledge on HPV, but positive results lead to negative and positive experiences by women. Clinicians and programs need to develop interventions and good strategies to minimize the psychological and social burden of testing positive for HPV. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate whether previous ovarian removal concomitant with benign hysterectomy improves prognosis in a cohort of women with breast cancer. Methods: In this nationwide register-based cohort study, risk of recurrence and mortality were examined in 4563 women with invasive breast cancer and previous bilateral salpingo-oophorectomy (BSO) concomitant with benign hysterectomy, during 1977–2018. Comparing with benign hysterectomy alone, hazard ratios (HRs) and 95% confidence intervals (CIs) were evaluated by Cox-proportional hazards regression models. Analyses were stratified on age at hysterectomy as a proxy for menopausal status (< 45, 45–54 and ≥ 55 years); tumor characteristics, estrogen receptor (ER)-status, and use of hormone therapy (HT) were included in multivariable models. Results: Compared with hysterectomy alone, premenopausal (< 45 years) BSO at benign hysterectomy was associated with an age and calendar period adjusted HR of 1.48 (95% CI 0.83–2.65) for breast cancer recurrence within 10 years of follow-up, a HR of 1.07 (95% CI 0.66–1.72) for overall mortality after breast cancer, and a HR of 0.59 (95% CI 0.26–1.32) for breast cancer-specific mortality. The corresponding HRs for postmenopausal (≥ 55 years) BSO at benign hysterectomy were 1.51 (95% CI 0.73–3.12) for recurrences, 1.34 (95% CI 0.74–2.44) for overall mortality, and 1.78 (95% CI 0.74–4.30) for breast cancer mortality. Adjusting for tumor characteristics, ER-status and HT did not alter the results. Conclusion: Results from this cohort study did not indicate an improvement in breast cancer prognosis when removing the ovaries at benign hysterectomy prior to the cancer diagnosis. [ABSTRACT FROM AUTHOR]

Prediagnostic use of menopausal hormone therapy (MHT) has been suggested to be associated with improved survival of epithelial ovarian cancer (EOC). We investigated the potential long‐term survival benefit of prediagnostic MHT use in women ≥50 years with nonlocalized EOC using the Extreme study including all women in Denmark registered with nonlocalized EOC during 2000 to 2014 (N = 3776). We obtained individual‐level information on prediagnostic use of systemic estrogen therapy (ET) and estrogen plus progestin therapy (EPT) from the National Prescription Registry and estimated absolute and relative 5‐ and 10‐year survival probabilities with 95% confidence intervals (CIs) using pseudo‐values, taking into account histology, comorbidity, income and residual disease. Among women not having used prediagnostic MHT, 5‐ and 10‐year absolute survival probabilities were 19% and 11%, respectively. Compared to MHT nonusers, prediagnostic systemic ET use for 3 to 4 years and ≥ 5 years was associated with 1.43 (95% CI: 1.01‐2.02) and 1.22 (95% CI: 0.96‐1.55) times higher 5‐year survival probabilities, respectively. Ten‐year survival probabilities were also increased but not statistically significantly. Among prediagnostic EPT users, increased 5‐year (1.14, 95% CI: 0.85‐1.53) and 10‐year (1.38, 95% CI: 0.91‐2.08) survival probabilities were observed after use for 3 to 4 years compared to MHT nonuse, whereas EPT use for ≥5 years was not associated with long‐term survival of nonlocalized EOC. Our findings may suggest a better long‐term survival of nonlocalized EOC in women having used long‐term prediagnostic ET. However, the statistical precision of our results did not allow firm conclusions and more studies are needed. [ABSTRACT FROM AUTHOR]

Little is known about risk factors for progression of high‐grade anal intraepithelial neoplasia (AIN) to anal squamous cell carcinoma (ASCC). In this large, population‐based study, we assess the role of factors related to immune status for the risk of ASCC among individuals from the general population with a diagnosis of AIN3. Individuals diagnosed with AIN3 during 1985‐2016 were identified in the Danish Pathology Registry and followed for subsequent development of ASCC. The study population was linked to the National Patient Registry, the Danish Prescription Registry and the Danish HIV Cohort Study for information on autoimmune disease, genital warts and HIV status. To study the progression rate, Cox regression models with hazard ratios (HR) and 95% confidence intervals (CI) were applied with time since AIN3 as the underlying time scale and with adjustment for age at AIN3 diagnosis, year of AIN3 diagnosis and sex. The study population comprised 1222 individuals with AIN3 contributing 12 824 person‐years of follow‐up. Ninety‐seven individuals (7.9%) developed ASCC. Individuals registered with an autoimmune disease or genital warts before and/or after the AIN3 diagnosis had an increased rate of progression to ASCC compared to individuals without these conditions. People living with HIV had a higher progression rate than HIV‐negative individuals (HR = 4.25; 95% CI: 1.87‐9.65) with the highest progression rate among those with CD4 count ≤200 cells/μL. These associations may be caused by an interplay between HPV infection and immunosuppression. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the association between fertility drugs and tumors of the central nervous system (CNS).Methods: This cohort study was based on The Danish Infertility Cohort and included 148,016 infertile women living in Denmark (1995-2017). The study cohort was linked to national registers to obtain information on use of specific fertility drugs, cancer diagnoses, covariates, emigration, and vital status. Cox proportional hazard regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for all CNS tumors and separately for gliomas, meningiomas and diverse benign tumors of the brain and other parts of the CNS.Results: During a median 11.3 years of follow-up, 328 women were diagnosed with CNS tumors. No marked associations were observed between use of the fertility drugs clomiphene citrate, gonadotropins, gonadotropin-releasing hormone receptor modulators and progesterone and CNS tumors. However, use of human chorionic gonadotropin was associated with a decreased rate of meningiomas (HR 0.49 95% CI 0.28-0.87). No clear associations with CNS tumors were observed according to time since first use or cumulative dose for any of the fertility drugs.Conclusion: No associations between use of most types of fertility drugs and CNS tumors were observed. However, our findings only apply to premenopausal women and additional studies with longer follow-up time are necessary. [ABSTRACT FROM AUTHOR]

Background: Thyroid cancer incidence has increased over the past decades. Differences in incidence trends have been observed depending on socioeconomic status. Here, we describe trends in the incidence of papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC) in Denmark by level of education and income. Methods: All PTC and FTC cases registered in the Danish Cancer Registry from 1995 to 2019 were identified. Individual-level information on education and income was obtained from nationwide registries. We calculated age-standardized incidence rates according to sex, tumor size, education and income, and estimated incidence trends by average annual percentage change (AAPC) and corresponding confidence intervals [CIs] for the periods 1995 to 2004 and 2005 to 2019 by using Poisson regression models. Results: We identified 3454 cases of PTC and 972 cases of FTC. From 2005 to 2019 among women, the incidence of PTC increased across all levels of education (AAPCshort education = 12.5% [CI 9.8 to 15.3]; AAPCmedium education = 8.1% [CI 6.4 to 9.9]; AAPClong education = 7.3% [CI 5.4 to 9.2]). The same pattern was seen for income. The incidence of FTC increased in all levels of education (AAPCshort education = 10.5% [CI 5.8 to 15.4]; AAPCmedium education = 4.0% [CI 0.9 to 7.3]; AAPClong education = 4.3% [CI 0.6 to 8.1]), with the same pattern for income. Similar trends were observed among men, in both small (≤2 cm) and large (>2 cm) PTCs and from 1995 to 2004 in both sexes. Conclusions: Enhanced detection of thyroid cancer among all levels of education and income cannot be ruled out, and in addition, our results may suggest a true increase in the incidence of differentiated thyroid cancer. [ABSTRACT FROM AUTHOR]

Introduction: Human papillomavirus (HPV) testing as the primary cervical cancer screening method is implemented in several countries. We report data from the first round of a large Danish pilot implementation of HPV-based screening. Our aim was to compare colposcopy referrals, detection of high-grade cervical intraepithelial neoplasia (CIN) and cervical cancer, and positive predictive value (PPV) of colposcopy referral in HPV vs cytology-based screening.Material and Methods: From May 2017 to October 2018, women aged 30-59 years attending cervical cancer screening in the uptake area of the Department of Pathology, Vejle Hospital, Region of Southern Denmark were screened by primary HPV testing (n = 16 067) or primary cytology (n = 23 981) depending on municipality of residence. In the HPV group, women with HPV16/18, or other high-risk HPV types and abnormal cytology, were referred to immediate colposcopy. Women with other high-risk HPV types and normal cytology were invited for repeat screening with HPV test and cytology after 12 months. From a nationwide pathology register, we obtained information on screening results and subsequent histological diagnoses during up to 2.9 years after the first screen. PPVs included diagnoses within 1 year after referral.Results: In the HPV group, 3.7% were referred to immediate colposcopy and 2.8% were referred at the 12-month repeat screening. The total referral to colposcopy was higher in the HPV (6.6%) than cytology group (2.1%) (age-adjusted relative referral = 3.05, 95% confidence interval [CI] 2.75-3.38). The detection of CIN3+ was higher in the HPV (1.5%) than the cytology group (0.8%) (age-adjusted relative detection = 1.88, 95% CI 1.56-2.28). The probability of CIN3+ among women referred to colposcopy (= PPV) was lower in the HPV (21.1%; 95% CI 18.7%-23.7%) than the cytology group (34.6%; 95% CI 30.7%-38.9%). In the HPV group, the PPV was lower among women referred at repeat screening (12.1%) than among women referred immediately (27.8%).Conclusions: Compared with cytology-based screening, HPV-based screening provided a 90% increased CIN3+ detection at the cost of a threefold increase in colposcopy referrals, when considering complete data from the prevalence round. Our findings support implementation of HPV-based screening in Denmark, but modifications of screening algorithms may be warranted to decrease unnecessary colposcopy referrals. [ABSTRACT FROM AUTHOR]

Background: High-risk (HR) human papillomavirus (HPV) persistence is the most important risk factor for cervical cancer. We have assessed the type-specific HR HPV persistence among HIV positive and HIV negative Tanzanian women and factors associated with HR HPV persistence. Methods: In a cohort study including 4080 Tanzanian women, 3074 attended follow-up examination (up to 32 months after enrollment). Cervical samples were obtained for liquid-based cytology and HPV DNA testing using Hybrid Capture 2 and Inno-Lipa Extra II. Information on lifestyle factors was collected through a personal interview. The probability of HR HPV persistence at a given time point since enrollment was estimated non-parametrically using the EMICM algorithm. Results: Among the 462 women HR HPV positive at enrollment, 158 had at least one identical type detected at follow-up. The probability of persistence at 18 months after enrollment was 34.2 (95% CI 29.0–39.4). Stratifying by HIV status, the persistence probability was 42.9% (95% CI 33.5–51.9) among HIV positive, and 28.0% (95% CI 22.1–34.2) among HIV negative. Overall, HR HPV persistence was most common for HPV58, 35, 16, 31, and 52. Among HIV positive women it was HPV45, and HPV16, followed by HPV58 and HPV18, and among HIV negative women it was HPV31, HPV33 and HPV58. Risk factors associated with persistence of HR HPV were older age, longer interval between enrollment and follow-up, binge drinking, and HIV status. Conclusions: HR HPV persistence was common in Tanzania, and most common among HIV positive women. Overall, persistence was most frequent for HPV 58, 35, 16, 31 and 52. The nonavalent HPV vaccine should be considered. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Simple Summary: Low-grade serous cancer (LGSC) accounts for approximately 5% of all ovarian cancers. It is characterized by its high resistance to chemotherapy. Cytoreductive surgery, therefore, is the primary treatment modality for this disease and previous studies have shown that complete removal of all visible tumor tissue should be achieved. In this study, 176 women with LGSC were included and most of them had advanced disease stages, where the disease had already spread. CA-125 is a biomarker that has been previously studied in ovarian cancer. We have found that CA-125 level following treatment of LGSC is an important and independent prognostic factor for progression-free and overall survival. It may be a better surrogate for the true amount of residual disease following treatment compared to the gross estimation of visible residual disease during surgery. Objective: Studies on low-grade serous ovarian cancer (LGSC) are limited by a low number of cases. The aim of this study was to define the prognostic significance of age, stage, and CA-125 levels on survival in a multi-institutional cohort of women with pathologically confirmed LGSC. Methods: Women with LGSC were identified from the collaborative Ovarian Cancer Association Consortium (OCAC). Cases of newly diagnosed primary LGSC were included if peri-operative CA-125 levels were available. Age at diagnosis, FIGO stage, pre- and post-treatment CA-125 levels, residual disease, adjuvant chemotherapy, disease recurrence, and vital status were collected by the participating institutions. Progression-free (PFS) and overall survival (OS) were calculated. Multivariable (MVA) Cox proportional hazard models were used and hazard ratios (HR) calculated. Results: A total of 176 women with LGSC were included in this study; 82% had stage III/IV disease. The median PFS was 2.3 years and the median OS was 6.4 years. Age at diagnosis was not significantly associated with worse PFS (p = 0.23) or OS (p = 0.3) (HR per year: 0.99; 95%CI, 0.96–1.01 and 0.98; 95%CI 0.95–1.01). FIGO stage III/IV was independently associated with PFS (HR 4.26, 95%CI 1.43–12.73) and OS (HR 1.69, 95%CI 0.56–5.05). Elevated CA-125 (≥35 U/mL) at diagnosis was not significantly associated with worse PFS (p = 0.87) or OS (p = 0.78) in MVA. Elevated CA-125 (≥35 U/mL) after completion of primary treatment was independently associated with worse PFS (HR 2.81, 95%CI 1.36–5.81) and OS (HR 6.62, 95%CI 2.45–17.92). In the MVA, residual disease was independently associated with PFS (0.022), but not OS (0.85). Conclusion: Advanced LGSC was associated with poor long-term prognosis. FIGO stage and abnormal post-treatment CA-125 level are key prognostic factors inversely associated with PFS and OS. Highlights: 1. Through a multi-center collaborative effort, data from 176 women with low-grade serous ovarian cancer were analyzed. 2. Although low-grade serous ovarian cancer is often considered indolent, the progression-free and overall survival are poor. 3. Elevated post-treatment CA-125 levels are independently associated with poor survival. [ABSTRACT FROM AUTHOR]

Study Question: Do fertility drugs increase the risk of thyroid cancer among infertile women?Summary Answer: The use of most types of fertility drugs was not associated with an increased risk of thyroid cancer.What Is Known Already: The incidence of thyroid cancer is higher for women than men, especially during reproductive years, indicating that reproductive hormones may be involved in the development of thyroid cancer. Only a few previous studies have examined the association between the use of fertility drugs and incidence of thyroid cancer and the results are inconclusive.Study Design, Size, Duration: A retrospective, population-based cohort study including all 146 024 infertile women aged 20-45 years and living in Denmark in the period 1995-2017. The women were followed from the date of entry in the cohort (i.e. date of first infertility diagnosis) until the occurrence of thyroid cancer or any other cancer (except non-melanoma skin cancer), death, emigration, total thyroidectomy or the end of follow-up (31 December 2018), whichever occurred first. The median length of follow-up was 11.3 years.Participants/materials, Setting, Methods: In total, 167 women were diagnosed with thyroid cancer during the follow-up period. Information on the use of specific fertility drugs (clomiphene citrate, gonadotropins, hCGs, GnRH receptor modulators and progesterone), thyroid cancer, covariates and vital status was obtained from the Danish Infertility Cohort and various Danish national registers. Cox proportional hazard regression models were used to calculate hazard ratios (HRs) and 95% CIs for thyroid cancer overall and for papillary thyroid cancer.Main Results and the Role Of Chance: After adjustment for the calendar year of infertility diagnosis, the highest obtained level of education, parity status, obesity or thyroid disease and mutual adjustment for other registered fertility drugs, no marked associations were observed between the use of clomiphene citrate, hCG, gonadotropins or GnRH receptor modulators and risk of overall or papillary thyroid cancer. However, ever use of progesterone was associated with an increased rate of both overall (HR 1.63; 95% CI 1.07-2.48) and papillary (HR 1.66, 95% CI 1.04-2.65) thyroid cancer after mutual adjustment for other specific fertility drugs. For most specific fertility drugs, we observed a tendency toward higher associations with thyroid cancer within the first 5 years after the start of drug use than after 5 years from the start of use. No marked associations were detected according to the cumulative dose for any of the specific fertility drugs.Limitations, Reasons For Caution: Despite a large study population, the statistical precision in some subgroup analyses may be affected due to the low number of thyroid cancer cases. Although we were able to adjust for a number of potential confounders, residual and unmeasured confounding may potentially have affected the observed associations, as we could not adjust for some factors that may influence the association between fertility drugs and thyroid cancer, including age at menarche and BMI.Wider Implications Of the Findings: Although this study, which is the largest to date, provides reassuring evidence that there is no strong link between the use of fertility drugs and thyroid cancer incidence, we observed a modest increased thyroid cancer incidence after the use of progesterone. However, we cannot rule out that this is a chance finding and the potential association between the use of progesterone and thyroid cancer should therefore be investigated further in large epidemiological studies. The results of the present study provide valuable knowledge for clinicians and other health care personnel involved in the diagnosis and treatment of infertility.Study Funding/competing Interest(s): The study was supported by research grants from the Jascha Foundation and the Aase and Ejner Danielsens Foundation. B.N. received honoraria and/or non-financial support by Gedeon Richter Nordics AB, IBSA Nordic APS and Merck KGAA. The remaining authors have no competing interests.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Background: Childhood cancer is a devastating experience for the family. The objective of the current study was to assess the impact of having a child with cancer on parental separation, divorce, and future family planning among families residing in Denmark.Methods: The authors conducted a nationwide cohort study using Danish registry data. Parents of children diagnosed with cancer between 1982 and 2014 (7066 children and 12,418 case parents) were matched with 10 comparison parents of cancer-free children per case parent (69,993 children and 125,014 comparison parents). We used discrete-time Cox regression models to compare the risk of separation (end of cohabitation) and divorce between case and comparison parents, and to identify risk factors for separation and divorce among case parents only. Descriptive statistics were used to compare family planning between case and comparison parents.Results: Case parents were found to have a slightly lower risk of separation (hazard ratio, 0.96; 95% confidence interval, 0.93-0.99) and divorce (hazard ratio, 0.92; 95% confidence interval, 0.87-0.97) than comparison parents. The authors found that case parents who were aged <45 years, with short education (an International Standard Classification of Education code indicating early childhood education, primary education, and lower secondary education), and who were unemployed were at an increased risk of separation and divorce. Moreover, the parents of children diagnosed with cancer at a young age (aged <15 years) were more likely to separate or divorce. No differences with regard to the total number of children and time to a next child after the cancer diagnosis were observed between case and comparison parents.Conclusions: Having a child with cancer was not associated with an overall adverse impact on parents' risk of separation or divorce and future family planning. These encouraging findings should be communicated to parents to support them along their child's cancer trajectory. [ABSTRACT FROM AUTHOR]

Background: Studies have shown that fertility treatment in mothers is associated with neurological problems in children. However, knowledge about any association between maternal use of fertility treatment and febrile seizures in children is lacking.Objective: To determine whether maternal use of fertility treatment is associated with febrile seizures in children.Methods: All liveborn children in Denmark during 1996-2012 (n = 1 065 901) were linked with the Danish Infertility Cohort and the Danish national registers and were followed from one year of age until the first episode of a febrile seizure, death, emigration, loss to follow-up, or end of follow-up (December 2015). Cox proportional hazard regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) with adjustment for potential confounders.Results: Approximately 16% children (n = 172 140) were conceived by infertile women, and approximately 3% (n = 34 082) were diagnosed with febrile seizures during follow-up. Compared with children conceived by fertile women, children conceived following any fertility treatment (HR 1.11, 95% CI 1.06, 1.16), following specific fertility treatment, for example IVF (HR 1.15, 95% CI 1.05, 1.25), ICSI (HR 1.20, 95% CI 1.10, 1.32), and following fertility drugs (HR 1.06, 95% CI 1.00, 1.11) had slight increase in risk of febrile seizures, after adjusting for calendar year of birth, parental age, education, parity status, and maternal smoking during pregnancy. The associations were unchanged when children conceived naturally by infertile women were used as the reference group.Conclusions: Children conceived following fertility treatment had slightly increased relative risk for febrile seizures. [ABSTRACT FROM AUTHOR]

Introduction: Sexual behavior at the population level impacts on public health. Recent representative sexual behavior data are lacking.Material and Methods: Cross-sectional surveys in 2005 and 2012 on women age 18-45 years randomly selected from the general population in Denmark (n = 40 804), Norway (n = 30 331) and Sweden (n = 32 114).Results: Median (interquartile range) age at first intercourse was 16 (15-18) years in Denmark, 17 (16-18) years in Norway, and 17 (15-18) years in Sweden. Women in the most recent birth cohort had sexual debut at the lowest age, and were most likely to have sexual debut before the legal age of consent. Proportions with debut age ≤14 years among women born 1989-1994 vs 1971-1976, odds ratio (95% confidence interval) were: 18.4% vs 10.9%, 1.95 (1.74-2.18) in Denmark, 12.9% vs 6.3%, 2.38 (2.01-2.82) in Norway, 17.8% vs 11.4%, 1.75 (1.55-1.98) in Sweden. Median (interquartile range) number of lifetime sexual partners was 6 (3-10) in Denmark, 5 (2-10) in Norway, and 6 (3-11) in Sweden. The proportion of women reporting >10 sexual partners was also highest in the most recent survey. The percentage with odds ratio (95% confidence interval) in 2012 vs 2005 surveys were: 24.9% vs 22.8%, 1.13 (1.07-1.18) for Denmark; 23.8% vs 19.8%, 1.27 (1.19-1.34) for Norway; and 28.3% vs 23.8%, 1.31 (1.24-1.38) for Sweden. Similarly, the proportion of women reporting ever having had a sexually transmitted infection among women age <30 years were: 29.4% vs 26.4%, 1.21 (1.13-1.31) in Denmark, 28.9% vs 25.0%, 1.20 (1.10-1.31) in Norway, and 29.4% vs 22.2%, 1.45 (1.33-1.58) in Sweden.Conclusions: Scandinavian women reported lower age at first intercourse in younger birth cohorts. Moreover, they reported more lifetime sexual partners and a higher prevalence of ever having a sexually transmitted infection in 2012 than in 2005. Our findings may inform the interpretation of trends in outcomes associated with sexual health, and public health policies. [ABSTRACT FROM AUTHOR]

Introduction: The optimal clinical management of women diagnosed with low-grade squamous intraepithelial lesions (LSIL) during cervical cancer screening remains unclear. In this prospective cohort study, we compared the clinical performance of two human papillomavirus (HPV) mRNA tests for triage of women with LSIL in Denmark.Material and Methods: In a nationwide pathology register, we identified women aged 23-65 years with LSIL during 2008-2012. We included women tested for HPV mRNA with the PreTect HPV Proofer test for five high-risk HPV types (n = 2176) or the Aptima assay for 14 high-risk HPV types (n = 426). Subsequent histological diagnoses of cervical intraepithelial neoplasia grades 2, 3 or cancer (CIN2+) were identified in the register. We calculated the sensitivity and specificity for CIN2+ at 18 and 36 months of follow up, and the cumulative incidence of CIN2+ among women testing positive and negative, overall and by age (23-29, 30-39, 40-65 years).Results: The proportion of women with a positive mRNA test at baseline was higher in women tested with Aptima (66.7%) than in women tested with Proofer (42.8%). After 18 months, Aptima had higher sensitivity for CIN2+ than Proofer (98% [95% CI 94% to 100%] vs 85% [95% CI 82% to 88%]), whereas Proofer showed higher specificity than Aptima (67% [95% CI 64% to 70%]) vs (40% [95% CI 33% to 46%]). Aptima had particularly low specificity in women aged <40 years (23-29: 19% [95% CI 5% to 36%]; 30-39: 10% [95% CI 0% to 33%]). The 36-month cumulative incidence of CIN2+ was higher in Proofer positive (54.3% [95% CI 50.9% to 57.8%]) than in Aptima positive women (37.6% [95% CI 31.2% to 44.8%]). In women with a negative mRNA test, the 36-month cumulative incidences of CIN2+ were 13.1% (95% CI 10.8% to 15.8%) and 5.9% (95% CI 1.7% to 19.0%) for Proofer and Aptima, respectively.Conclusions: In women with LSIL, Aptima had high sensitivity for CIN2+, but low specificity, especially in women aged <40 years. The Proofer test may be useful to limit immediate colposcopy referrals in younger women with LSIL, but given its low sensitivity and negative predictive value, Proofer negative women must be followed with repeat cytology. [ABSTRACT FROM AUTHOR]

Several recent observational studies have linked low‐dose aspirin use to improved survival in patients with head and neck cancer. However, studies of patterns of aspirin use and risk of cancer‐specific mortality are lacking. This nationwide cohort study included all patients in the Danish Cancer Registry with a primary diagnosis of head and neck squamous cell cancer (HNSCC) during 2000 to 2016, aged 30 to 84 years, without prior cancer (except nonmelanoma skin cancer) and alive 1 year after diagnosis. Nationwide registries provided information on filled prescriptions, mortality and potential confounding factors. For a subpopulation, a clinical database provided additional information, including human papillomavirus (HPV) tumor status. We used Cox proportional hazards regression models to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for the association between postdiagnostic low‐dose aspirin use (≥1 prescription within first year after diagnosis) and risk of cancer‐specific mortality. We identified 10 770 patients with HNSCC during a median follow‐up of 3.9 years. Of these, 1799 (16.7%) were low‐dose aspirin users. Postdiagnostic use of low‐dose aspirin was associated with a HR of 0.97 (95% CI 0.82‐1.15) for cancer‐specific mortality. Similar neutral associations were found according to patterns of aspirin use. No apparent trends emerged according to age, sex, topography or stage. A tendency towards a decreased cancer‐specific mortality risk with low‐dose aspirin use was observed among HPV‐positive patients; however, the statistical precision was low. In conclusion, we did not observe an association between postdiagnostic low‐dose aspirin use and cancer‐specific mortality in a nationwide cohort of patients with HNSCC. What's new? Long‐term use of low‐dose aspirin is associated with improved all‐cause survival in patients with head and neck squamous cell carcinoma (HNSCC). The relationship between low‐dose aspirin and cancer‐specific mortality, however, remains unclear. In this nationwide cohort study, associations between low‐dose aspirin use and cancer‐specific mortality were evaluated in patients with HNSCC. No associations were observed between post‐diagnostic low‐dose aspirin use and cancer‐specific mortality. Nor were modifying effects observed for patient age and sex, tumor topography and stage, or patterns of aspirin use. Additional studies are needed to elucidate possible associations with HPV‐positive OPSCC. [ABSTRACT FROM AUTHOR]

Importance: The incidence of central nervous system (CNS) tumors in children appears to be increasing, yet few risk factors are established. There is limited information regarding whether maternal hormonal contraception use increases this risk.Objective: To examine the association between maternal hormonal contraception use and CNS tumors in children (<20 years).Design, Setting, and Participants: In this nationwide cohort study based on population-based registry data, 1 185 063 children born in Denmark between January 1, 1996, and December 31, 2014, were followed up for a diagnosis of a CNS tumor (final follow-up on December 31, 2018).Exposures: Maternal hormonal contraception use was analyzed according to any use, regimen (combined/progestin only), and route of administration (oral/nonoral), categorized as recent use (≤3 months before start and during pregnancy), previous use (>3 months before start of pregnancy), and no use. For injections, implants, and intrauterine devices that are used for a different time period, the categorization was appropriately altered.Main Outcomes and Measures: Hazard ratio (HR) and incidence rate difference (IRD) of CNS tumors diagnosed at younger than 20 years.Results: After 15 335 990 person-years of follow-up (mean follow-up, 12.9 years), 725 children were diagnosed with a CNS tumor. The mean age at diagnosis was 7 years, and 342 (47.2%) of the diagnosed children were female. The adjusted incidence rate of CNS tumors per 100 000 person-years was 5.0 for children born to mothers with recent hormonal contraception use (n = 136 022), 4.5 for children born to mothers with previous use (n = 778 843), and 5.3 for children born to mothers with no use (n = 270 198). The corresponding HRs were 0.95 ([95% CI, 0.74-1.23]; 84 children with CNS tumors; IRD, -0.3 [95% CI, -1.6 to 1.0]) for recent use and 0.86 ([95% CI, 0.72-1.02]; 421 children with CNS tumors; IRD, -0.8 [95% CI, -1.7 to 0.0]) for previous use, compared with no use. No statistically significant associations were found for recent or previous use of oral combined, nonoral combined, oral progestin only, or nonoral products compared with no use of hormonal contraception.Conclusions and Relevance: Among Danish children, there was no statistically significant association between any maternal hormonal contraception use and CNS tumor risk. [ABSTRACT FROM AUTHOR]