Thyroid cancer incidence has increased worldwide during the previous decades. In this nationwide study, we aimed to identify the overall incidence of thyroid cancer in Denmark during 66 years ...(1943–2008) and incidences of the four main histological types of thyroid cancer from 1978 to 2008. Data were obtained from the nationwide Danish Cancer Registry, and we focused especially on the period after implementation of compulsory iodine supplementation, which was established on a national level in 2000. We calculated age‐standardized incidence rates per 100,000 person‐years, and age‐period‐cohort models were fitted to describe trends in incidence. To quantify trends in incidence over time, log‐linear Poisson models were used to estimate annual percentage change. From 1943 to 2008, 1,947 men (29%) and 4,682 women (71%) were diagnosed with thyroid cancer. The age‐standardized incidence increased in both sexes; in men from 0.41 to 1.57 per 100,000 and from 0.90 to 4.11 per 100,000 in women, corresponding to a significant average annual percentage change of 1.7 and 1.8%, respectively. The incidence increased with younger birth cohorts. The rise was almost exclusively caused by papillary carcinomas, and it was particularly present during the last decades of the study period. It cannot be ruled out that iodine supplementation may play a role for the risk of thyroid cancer, but as the strongest increase in incidence began in the years before the implementation, it is likely that improvement in diagnostic modalities increased diagnostic activity, and/or new unknown risk factors are also important contributors to the increase.
Background Infection with high-risk human papillomavirus (HPV) is the main cause of high-grade cervical intraepithelial neoplasia (CIN) and cancer. It has been suggested that information about ...high-risk HPV type–specific infection might make cervical cancer screening more effective. Persistent HPV infection could also be a useful screening marker. We estimated the long-term risk of high-grade CIN after one-time detection of high-risk HPV DNA and after persistent infection with individual high-risk HPV types. Methods A cohort of 8656 women from the general population of Denmark was examined twice, 2 years apart (first study examination: May 15, 1991, to January 31, 1993; second study examination: October 1, 1993, to January 31, 1995). The women underwent a gynecological examination and cervical cytology and had swabs taken for HPV DNA analysis by the Hybrid Capture 2 and line probe assays. The women were followed up through the nationwide Danish Pathology Data Bank for cervical neoplasia for up to 13.4 years. The absolute risk of developing cervical lesions before a given time was estimated as a function of time. Results For women with normal cytological findings who were concurrently HPV16 DNA positive at the second examination, the estimated probability of developing CIN grade 3 (CIN3) or worse within 12 years of follow-up was 26.7% (95% confidence interval CI = 21.1% to 31.8%). The corresponding risks among those infected with HPV18 was 19.1% (95% CI = 10.4% to 27.3%), with HPV31 was 14.3% (95% CI = 9.1% to 19.4%), and with HPV33 was 14.9% (95% CI = 7.9% to 21.1%). The absolute risk of CIN3 or worse after infection with high-risk HPV types other than HPV16, HPV18, HPV31, or HPV33 was 6.0% (95% CI = 3.8% to 8.3%). The estimated absolute risk for CIN3 or cancer within 12 years of the second examination among women who were HPV16 DNA positive at both examinations was 47.4% (95% CI = 34.9% to 57.5%); by contrast, the risk of CIN3 or worse following a negative Hybrid Capture 2 test was 3.0% (95% CI = 2.5% to 3.5%). Conclusion HPV16, HPV18, HPV31, and HPV33 infection and especially HPV16 persistence were associated with high absolute risks for progression to high-grade cervical lesions. The results indicate the potential value of genotyping in cervical cancer screening. Given that HPV DNA–negative women retained their low risk of CIN3 or worse for many years, frequent screening of these women may be unnecessary.
In clinical trials, vaccines against human papillomavirus (HPV) have been highly effective against HPV16- or HPV18-associated cervical lesions. The quadrivalent HPV vaccine was licensed in 2006 and ...subsequently implemented in the Danish vaccination program. The study aim was to use individual information on HPV vaccination status to assess subsequent risk of cervical lesions.
Using a cohort study design, we identified all girls and women born in Denmark in the period from 1989 to 1999 and obtained information on individual HPV vaccination status in the period from 2006 to 2012 from nationwide registries. Incident cases of cervical lesions were identified by linkage to the nationwide Pathology Data Bank. We compared vaccinated and unvaccinated girls and women stratified by birth cohort in Cox proportional hazards models.
Risk of atypia or worse (atypia+) and of cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3) were statistically significantly reduced among vaccinated women in birth cohorts 1991 to 1994 (1991-1992atypia+: hazard ratio HR = 0.46, two-sided 95% confidence interval CI = 0.39 to 0.56; 1991-1992CIN2/3: HR = 0.56, 95% CI = 0.37 to 0.84; 1993-1994atypia+: HR = 0.40, 95% CI = 0.29 to 0.56; 1993-1994 CIN2/3: HR = 0.27, 95% CI = 0.10 to 0.67). The birth cohort 1989 to 1990 had a statistically significantly reduced risk of atypia+ (HR = 0.75; 95% CI = 0.65 to 0.86); the risk of CIN2/3 was also decreased but not statistically significant. No events occurred among girls in the birth cohort 1997 to 1999, whereas for the birth cohort 1995 to 1996 a hazard ratio could be calculated only for atypia+.
Six years after licensure of the quadrivalent HPV vaccine in Denmark, a reduced risk of cervical lesions is observed at the population level.
The quadrivalent human papillomavirus vaccine is effective in preventing infection and disease related to HPV types 6, 11, 16, and 18. This phase 3 trial involving 14,000 women reports the efficacy ...of a 9-valent vaccine that targets additional HPV types.
The human papillomavirus (HPV) causes premalignant and malignant lesions of the cervix,
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vagina,
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vulva,
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anus,
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penis,
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and oropharynx,
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as well as genital warts.
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The recent development of prophylactic vaccines directed against the most relevant disease-causing HPV types has helped to prevent diseases related to HPV.
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In clinical trials, the bivalent HPV viruslike particle vaccine against HPV types 16 and 18 was efficacious against related infection with these types and against cervical dysplasia,
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and the quadrivalent HPV viruslike particle vaccine against types 6, 11, 16, and 18 was efficacious against related infection and against cervical, vaginal, . . .
Several environmental factors have been associated with increased risks for cervical cancer. We examined whether reproductive history, contraceptive use, or sexual behaviour increase the risk for ...cervical intraepithelial neoplasia grade 3 or worse (CIN3+) among women with persistent human papillomavirus (HPV) infection.
A population-based cohort of women participated in a personal interview and underwent a gynaecological examination at which cervical specimens were obtained for HPV DNA testing. Follow-up information (~13 years) on cervical lesions was obtained from the Danish Pathology Data Bank. Women who had a high-risk HPV infection comprised the overall study population (n=1353). A subgroup of women with persistent high-risk HPV infection (n=312) was identified. Hazard ratios (HRs) for a diagnosis of CIN3+ and the corresponding 95% confidence intervals (CIs) were calculated.
Women with persistent HPV infection who had given birth had a significantly increased risk for CIN3+ (HR=1.78; 95% CI: 1.07-2.94). No association was found with pregnancy, use of intrauterine devices, or sexual behaviour. Based on small numbers, women with persistent HPV infection had a decreased risk for CIN3+ with any use of oral contraceptives (HR=0.54; 95% CI: 0.29-1.00).
Childbirth increases the risk for subsequent CIN3+ among women with persistent HPV infection.
Regular aspirin use is associated with reduced risk of several malignancies. Epidemiologic studies analyzing aspirin, nonaspirin nonsteroidal anti-inflammatory drug (NSAID), and acetaminophen use and ...ovarian cancer risk have been inconclusive.
We analyzed pooled data from 12 population-based case-control studies of ovarian cancer, including 7776 case patients and 11843 control subjects accrued between 1992 and 2007. Odds ratios (ORs) for associations of medication use with invasive epithelial ovarian cancer were estimated in individual studies using logistic regression and combined using random effects meta-analysis. Associations between frequency, dose, and duration of analgesic use and risk of ovarian cancer were also assessed. All statistical tests were two-sided.
Aspirin use was associated with a reduced risk of ovarian cancer (OR = 0.91; 95% confidence interval CI = 0.84 to 0.99). Results were similar but not statistically significant for nonaspirin NSAIDs, and there was no association with acetaminophen. In seven studies with frequency data, the reduced risk was strongest among daily aspirin users (OR = 0.80; 95% CI = 0.67 to 0.96). In three studies with dose information, the reduced risk was strongest among users of low dose (<100 mg) aspirin (OR = 0.66; 95% CI = 0.53 to 0.83), whereas for nonaspirin NSAIDs, the reduced risk was strongest for high dose (≥500 mg) usage (OR = 0.76; 95% CI = 0.64 to 0.91).
Aspirin use was associated with a reduced risk of ovarian cancer, especially among daily users of low-dose aspirin. These findings suggest that the same aspirin regimen proven to protect against cardiovascular events and several cancers could reduce the risk of ovarian cancer 20% to 34% depending on frequency and dose of use.
To examine risk factors for Type I and Type II endometrial cancer (EC) and to directly compare the influence of risk factors for Type II with Type I tumors. Furthermore, to examine whether risk ...factors for high-grade Type I and Type II tumors differed from low-grade Type I tumors.
Women with EC diagnosed during 2000–2016 were identified in the Danish Cancer Registry. A case-control analysis was conducted with 1:15 random population controls matched on age and gender. Using conditional logistic regression, odds ratios and 95% confidence intervals on risk factors for Type I and II tumors were estimated. In case-case analyses, risk factors were evaluated in a direct comparison of cases grouped by tumor type and grade.
We identified 6958 women with Type I EC and 1206 women with Type II EC. In the case-control analysis, nulliparity and diabetes were associated with increased risk of both tumor types, whereas hormone replacement therapy only increased the risk of Type I EC. When directly comparing Type I and II tumors, the influence of BMI ≥ 30, current smoking, and parity ≥ 3 was strongest for Type I EC. The associations for the majority of risk factors were similar for Type II and high-grade Type I tumors compared with low-grade Type II tumors.
Risk factors for Type I and II tumors were overlapping suggesting that Type II tumors may be less estrogen-independent than previously anticipated. High-grade Type I tumors seemed to resemble Type II tumors more than low-grade Type I tumors.
•Risk factors for Type I and Type II endometrial tumors seem to be overlapping when compared with random population controls.•Associations with increasing parity, HRT use, smoking, and BMI ≥ 30 were strongest for Type I tumors.•High-grade Type I tumors may resemble Type II tumors more than low-grade Type I tumors.
In an attempt to decrease social disparities in cancer survival, it is important to consider the mechanisms by which socioeconomic position influences cancer prognosis. We aimed to investigate ...whether any associations between socioeconomic factors and survival after cervical cancer could be explained by socioeconomic differences in cancer stage, comorbidity, lifestyle factors or treatment.
We identified 1961 cases of cervical cancer diagnosed between 2005 and 2010 in the Danish Gynaecological Cancer database, with information on prognostic factors, treatment and lifestyle. Age, vital status, comorbidity and socioeconomic data were obtained from nationwide administrative registers. Associations between socioeconomic indicators (education, income and cohabitation status) and mortality by all causes were analysed in Cox regression models with inclusion of possible mediators. Median follow-up time was 3.0 years (0.01-7.0).
All cause mortality was higher in women with shorter rather than longer education (hazard ratio (HR), 1.46; 1.20-1.77), among those with lower rather than higher income (HR, 1.32; 1.07-1.63) and among women aged<60 years without a partner rather than those who cohabited (HR, 1.60; 1.29-1.98). Socioeconomic differences in survival were partly explained by cancer stage and less by comorbidity or smoking (stage- and comorbidity-adjusted HRs being 1.07; 0.96-1.19 for education and 1.15; 0.86-1.52 for income).
Socioeconomic disparities in survival after cervical cancer were partly explained by socioeconomic differences in cancer stage. The results point to the importance of further investigations into reducing diagnosis delay among disadvantaged groups.
To examine trends in incidence and survival of non-epithelial ovarian cancer in Denmark over nearly 40 years, using nationwide, population-based cancer registry data.
From 1978 to 2016, we identified ...the non-epithelial ovarian cancer cases among all ovarian malignancies in the Danish Cancer Registry. Age-specific incidence rates, age-standardized incidence rates, and average annual percentage change (AAPC) were estimated with 95% confidence intervals (CIs). Overall and 5-year relative survival analyses were conducted and supplemented with Cox regression to explore the effect of different characteristics on overall mortality.
A total of 720 non-epithelial ovarian cancers were identified, corresponding to 3.4% of all ovarian malignancies. The majority of non-epithelial ovarian cancers were germ cell tumors (49.9%) and sex cord-stromal tumors (38.6%). The age-standardized incidence rate of germ cell tumors was stable over the study period, ranging between 0.33 and 0.39 per 100,000 woman-years. In contrast, the age-standardized incidence rate of sex cord-stromal tumors declined from 0.30 (1978–1987) to 0.09 (2008–2016) per 100,000 woman-years (AAPC = −5.15%; 95% CI: −7.29, −2.96). The 5-year relative survival of germ cell tumors and sex cord-stromal tumors was 94% and 79%, respectively, in the most recent period (2008–2011). Cox regression showed that overall mortality was associated with calendar year, age, and stage.
The incidence of germ cell tumors was stable over calendar time, whereas the incidence of sex cord-stromal tumors decreased significantly. Non-epithelial ovarian cancer overall mortality has decreased during the study period and this could not be explained by taking stage and age at diagnosis into account.
•Non-epithelial ovarian cancer comprises 3.4% of all ovarian malignancies in Denmark.•The incidence of germ cell tumors in Denmark 1978–2016 was stable.•The incidence of sex cord-stromal tumors in Denmark 1978–2016 decreased significantly by 5% per year.•The survival of non-epithelial ovarian cancer improved over calendar time.
To examine time trends in ovarian/tubal cancer relative survival, excess mortality, and all-cause mortality for different histological types and levels of socioeconomic position.
Women with ...ovarian/tubal cancer diagnosed 1996–2017 were identified in the Danish Cancer Registry (n = 11,755). Age-standardized 5-year relative survival over time was estimated by histology, socioeconomic status, and stage. Furthermore, 5-year excess mortality rate ratios (EMRR) according to calendar time for all categories of histology and socioeconomic status were calculated using a Poisson regression model. Finally, all-cause mortality by histology and socioeconomic status was estimated in multivariate Cox proportional hazards regression models.
Statistically significant improvements in 5-year relative survival occurred for all histological types over time except mucinous tumors (5-year EMRR, localized: 0.92 (95% CI: 0.71–1.16); advanced: 0.96 (95% CI: 0.85–1.08). Increase in relative survival over time and corresponding decrease in excess mortality was observed for all categories of socioeconomic status except for women with localized disease in the lowest income group (5-year EMRR = 0.91 (95% CI:0.76–1.10)). The impact of histology and socioeconomic status on all-cause mortality depended on time since diagnosis. Among the socioeconomic factors, especially low educational level and living alone were associated with increased all-cause mortality, particularly in the first year after diagnosis.
Ovarian/tubal cancer survival generally increased over time across histological types and socioeconomic factors. However, the lack of improvement for mucinous tumors needs further research. Additionally, the results for women with low income and education shows that continued focus on social equality in survival is necessary.
•5-year relative survival of ovarian/tubal cancer improved over time for all histological types except mucinous tumors.•5-year relative survival of ovarian/tubal cancer increased over time except for low income women with localized disease.•The influence of histology and socioeconomic factors on all-cause mortality depended on time since diagnosis.•One year after diagnosis, low educational level and living alone were associated with increased all-cause mortality.
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