Temporal Trends in Papillary and Follicular Thyroid Cancer Incidence from 1995 to 2019 in Adults in Denmark According to Education and Income.

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.

Base of tongue/tonsillar and laryngeal cancer in Denmark 1994-2018: Temporal trends in incidence according to education and age.

OBJECTIVES: Base-of-tongue (BOT)/tonsillar cancer incidence is rising, primarily due to human papillomavirus; meanwhile, rates of the mainly smoking-associated laryngeal cancer is declining. Little is known about whether these trends are seen in all socioeconomic levels and age-groups. We describe incidence trends of BOT/tonsillar and laryngeal cancer in Denmark 1994-2018 by educational level and age. METHODS: BOT/tonsillar and laryngeal cancer cases diagnosed 1994-2018 were identified from the Danish Cancer Registry. We obtained individual-level educational information from nationwide registries. We estimated age-standardized incidence rates of BOT/tonsillar and laryngeal cancer according to sex, education and age. Temporal incidence trends were evaluated by the average annual percentage change (AAPC) with corresponding 95% confidence intervals (CIs) using linear and Poisson regression models for age-standardized incidence rates. RESULTS: We identified 4245 individuals with BOT/tonsillar cancer and 6123 with laryngeal cancer. BOT/tonsillar cancer incidence increased among men with short (AAPC:3.4, 95% CI 2.1;4.6) and long (AAPC:5.1, 95% CI 3.2;7.1) education, and all age-groups, while decreased from 2012 among men with medium education (AAPC:-4.3, 95 %CI -7.6;-1.0). Laryngeal cancer incidence decreased from 2007 in men with medium (AAPC:-4.7, 95% CI -6.7;-2.7) and long (AAPC:-2.4, 95% CI -3.4;-1.4) education, and all age-groups, whereas increased in men with short education (AAPC:1.0, 95% CI 0.2;1.8). Similar trends were seen among women. CONCLUSIONS: Over the last 25 years, BOT/tonsillar cancer incidence in Denmark has generally increased in all age-groups and educational levels. In contrast, social inequality was seen in laryngeal cancer trends as incidence decreased in individuals with medium and long education, while incidence increased in individuals with short education.

Non-aspirin NSAIDs and head and neck cancer mortality in a Danish nationwide cohort study.

BACKGROUND: Evidence suggests that non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) have antineoplastic properties of potential importance for survival of head and neck cancer. METHODS: We conducted a nationwide cohort study including all individuals with primary head and neck squamous cell carcinoma in Denmark during 2000-2016 at age 30-84 years, with no history of cancer (except non-melanoma skin cancer), and alive at 1 year after diagnosis. Nationwide registries provided information on drug use, causes of death and potential confounders, and additional clinical information was obtained for a subpopulation. We conducted Cox proportional hazards regression to estimate multivariable-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for the association between post-diagnosis non-aspirin NSAID use (defined as ≥1 filled prescription within first year after diagnosis) and cancer-specific mortality. RESULTS: Among 10,770 head and neck cancer 1-year survivors, the HR for cancer-specific mortality with non-aspirin NSAID use was 1.68 at 1 year after diagnosis, but declined and stabilized around 1.15 (95% CI 1.02-1.29) at 2 years after diagnosis. Among 2-year survivors, the HRs for cancer-specific mortality with non-aspirin NSAID use remained slightly increased in analyses stratified by age, sex, stage, and pre-diagnosis non-aspirin NSAID use. Similar results were seen in the subpopulation (n = 1029) with additional clinical information, and among 5-year survivors with additional non-aspirin NSAID exposure assessment. CONCLUSION: In this nationwide cohort of patients with head and neck cancer, use of non-aspirin NSAIDs was associated with a slightly increased mortality risk, warranting further evaluation.

Low-dose aspirin use and mortality risk in patients with head and neck cancer: A nationwide cohort study of 10 770 patients.

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.

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

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

Human papillomavirus prevalence in oral potentially malignant disorders: Systematic review and meta-analysis.

OBJECTIVES: We aimed to provide pooled estimates of human papillomavirus (HPV) prevalence in oral potentially malignant disorders (OPMD) and evaluate the impact of presence of epithelial dysplasia. METHODS: We searched PubMed, Embase, and Cochrane Library databases for studies that examined the prevalence of HPV DNA in OPMD tested by polymerase chain reaction (PCR). RESULTS: Across 52 eligible studies (2,677 cases), we found an overall pooled HPV prevalence of 22.5% (95% confidence interval [CI] 16.6-29.0). Between-study heterogeneity was 93%. When stratified by subgroup, the pooled HPV prevalence in leukoplakia (1,232 cases) was 20.2% (95% CI 11.2-31.1), lichen planus (767 cases) 23.0% (95% CI 15.0-32.2), oral submucous fibrosis (238 cases) 28.6% (95% CI 23.0-34.5), proliferative verrucous leukoplakia (60 cases) 24.7% (95% CI 1.8-62.0), and OPMD unspecified (377 cases) 25.4% (95% CI 16.2-35.8). Information on presence of epithelial dysplasia was available in 19 studies, and the results did not vary substantially between non-dysplastic and dysplastic samples. HPV16 was the predominant genotype among HPV-positive OPMD cases (48.2%, 95% CI 31.4-65.2). CONCLUSION: We found a pooled HPV DNA prevalence of 22.5% in OPMD cases with great between-study heterogeneity. The HPV prevalence appeared to be comparable across subgroups and independent of epithelial dysplasia.

Prevalence of human papillomavirus in oral epithelial dysplasia: Systematic review and meta-analysis.

The purpose of this systematic review and meta-analysis was to estimate the overall and type-specific prevalence of human papillomavirus (HPV) DNA in oral epithelial dysplasia and assess p16INK4a overexpression in relation to HPV-status. A systematic literature search identified 31 eligible studies (832 cases) evaluating the presence of HPV DNA in oral epithelial dysplasia cases by PCR. Of these, six studies evaluated p16INK4a overexpression in relation to HPV-status. The overall pooled prevalence of HPV DNA in oral epithelial dysplasia was 27.2% (95% CI: 17.6-38.1). We observed substantial interstudy heterogeneity, which could not be explained by differences in continent, tissue type, or severity of epithelial dysplasia. HPV16 was the predominant genotype detected. Moreover, 62.2% of HPV positive and 17.8% of HPV negative oral epithelial dysplasia samples stained intensively positive for p16INK4a . This meta-analysis found that 27% of oral epithelial dysplasia harbor HPV DNA. Whether this represents a transient infection or has a carcinogenic role is unknown.

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

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

Human papillomavirus types in cervical high-grade lesions or cancer among Nordic women-Potential for prevention.

It is valuable to establish a population-based prevaccination baseline distribution of human papillomavirus (HPV) types among women with high-grade cervical intraepithelial neoplasia (CIN) grade 2 or 3 and cervical cancer in order to assess the potential impact of HPV vaccination. In four countries (Denmark, Norway, Sweden, and Iceland), we collected consecutive series of cervical cancers (n = 639) and high-grade precancerous cervical lesions (n = 1240) during 2004-2006 before implementation of HPV vaccination and subjected the specimens to standardized HPV genotyping. The HPV prevalence was 82.7% (95% confidence interval [CI] 79.0-86.4) in CIN2, 91.6% (95% CI 89.7-93.5) in CIN3, and 86.4% (95% CI 83.7-89.1) in cervical cancer. The most common HPV types in CIN2/3 were HPV16 (CIN2: 35.9%, 95% CI 31.2-40.6; CIN3: 50.2%, 95% CI 46.8-53.6) and HPV31 (CIN2: 10.9%, 95% CI 7.8-13.9; CIN3: 12.1%, 95% CI 9.9-14.3), while HPV16 and HPV18 were the most frequent types in cervical cancer (48.8%, 95% CI 44.9-52.7 and 15.3%, 95% CI 12.5-18.1, respectively). The prevalence of HPV16/18 decreased with increasing age at diagnosis in both CIN2/3 and cervical cancer (P < 0.0001). Elimination of HPV16/18 by vaccination is predicted to prevent 42% (95% CI 37.0-46.7) of CIN2, 57% (95% CI 53.8-60.5) of CIN3 and 64% (95% CI 60.3-67.7) of cervical cancer. Prevention of the five additional HPV types HPV31/33/45/52/58 would increase the protection to 68% (95% CI 63.0-72.2) in CIN2, 85% (95% CI 82.4-87.2) in CIN3 and 80% (95% CI 77.0-83.2) in cervical cancer. This study provides large-scale and representative baselines for assessing and evaluating the population-based preventive impact of HPV vaccination.

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.

[Acute post-partum presentation of Bochdalek hernia in a grown-up woman].

Congenital diaphragmatic hernias are rare embryonic defects, mostly diagnosed in newborns with respiratory distress. The defect is often situated posterolaterally as a Bochdalek hernia. We report an unusual case of a 27-year old woman presenting with diffuse abdominal pain five days postpartum. An X-ray and a computed tomography displayed a herniation of the colon into the left chest cavity. Through converted open surgery, the 6 x 3 cm defect was repaired and the recovery was uneventful. Bochdalek hernias in adults may present as gastrointestinal emergencies and rapid diagnosis and operation are crucial.

Enhanced self-administration of alcohol in muscarinic acetylcholine M4 receptor knockout mice.

Modulation of cholinergic neurotransmission via nicotinic acetylcholine receptors is known to alter alcohol-drinking behavior. It is not known if muscarinic acetylcholine receptor subtypes have similar effects. The muscarinic M4 receptor is highly expressed in the brain reinforcement system and involved in regulation of cholinergic and dopaminergic transmission. Here we investigate, for the first time, the role of the M4 receptor in alcohol consumption using M4 knockout (M4(-/-)) and wild-type (M4(+/+)) mice. Experimentally naïve M4(-/-) and M4(+/+) mice were trained to orally self-administer 5%, 8% and 10% alcohol in 60min sessions, 6 days/week, after having undergone a standard sucrose fading training procedure on a fixed ratio schedule. The mice were further subjected to an extinction period followed by a 1 day reinstatement trial. M4(-/-) mice consumed more alcohol at 5% and 8% compared to their M4(+/+) littermates. The highest alcohol concentration used (10%) did not immediately result in divergent drinking patterns, but after 4 weeks of 10% alcohol self-administration, baseline levels as well as a pattern of M4(-/-) mice consuming more alcohol than their M4(+/+) controls were re-established. Moreover, the M4(-/-) mice displayed a reduced capacity to extinguish their alcohol-seeking behavior. Taken together, alcohol consumption is elevated in M4(-/-) mice, indicating that the M4 receptor is involved in mediating the reinforcing effects of alcohol. The M4 receptor should be further explored as a potential target for pharmacological (positive allosteric modulators or future agonists) treatment of alcohol use disorders.