Evaluation of the Long-Term Anti-Human Papillomavirus 6 (HPV6), 11, 16, and 18 Immune Responses Generated by the Quadrivalent HPV Vaccine

This quadrivalent human papillomavirus (qHPV) (HPV6, -11, -16, and -18) vaccine long-term follow-up (LTFU) study is an ongoing extension of a pivotal clinical study (FUTURE II) taking place in the Nordic region. The LTFU study was designed to evaluate the effectiveness, immunogenicity, and safety of the qHPV vaccine (Gardasil) for at least 10 years following completion of the base study. The current report presents immunogenicity data from testing samples of the year 5 LTFU visit (approximately 9 years after vaccination). FUTURE II vaccination arm subjects, who consented to being followed in the LTFU, donated serum at regular intervals and in 2012. Anti-HPV6, -11, -16, and -18 antibodies were detected by the competitive Luminex immunoassay (cLIA), and in addition, serum samples from 2012 were analyzed by the total IgG Luminex immunoassay (LIA) (n = 1,598). cLIA geometric mean titers (GMTs) remained between 70% and 93% of their month 48 value depending on HPV type. For all HPV types, the lower bound of the 95% confidence interval (CI) for the year 9 GMTs remained above the serostatus cutoff value. The proportion of subjects who remained seropositive based on the IgG LIA was higher than the proportion based on cLIA, especially for anti-HPV18. As expected, the anti-HPV serum IgG and cLIA responses were strongly correlated for all HPV types. Anti-HPV GMTs and the proportion of vaccinated individuals who are seropositive remain high for up to 9 years of follow-up after vaccination.     

Development of a dietary screening questionnaire to predict excessive weight gain in pregnancy

Excessive gestational weight gain (GWG) is a risk factor for several adverse pregnancy outcomes, including macrosomia. Diet is one of the few modifiable risk factors identified. However, most dietary assessment methods are impractical for use in maternal care. This study evaluated whether a short dietary screening questionnaire could be used as a predictor of excessive GWG in a cohort of Icelandic women. The dietary data were collected in gestational weeks 11–14, using a 40‐item food frequency screening questionnaire. The dietary data were transformed into 13 predefined dietary risk factors for an inadequate diet. Stepwise backward elimination was used to identify a reduced set of factors that best predicted excessive GWG. This set of variables was then used to calculate a combined dietary risk score (range 0–5). Information regarding outcomes, GWG (n = 1,326) and birth weight (n = 1,651), was extracted from maternal hospital records. In total, 36% had excessive GWG (Icelandic criteria), and 5% of infants were macrosomic (≥4,500 g). A high dietary risk score (characterized by a nonvaried diet, nonadequate frequency of consumption of fruits/vegetables, dairy, and whole grain intake, and excessive intake of sugar/artificially sweetened beverages and dairy) was associated with a higher risk of excessive GWG. Women with a high (≥4) versus low (≤2) risk score had higher risk of excessive GWG (relative risk = 1.23, 95% confidence interval, CI [1.002, 1.50]) and higher odds of delivering a macrosomic offspring (odds ratio = 2.20, 95% CI [1.14, 4.25]). The results indicate that asking simple questions about women's dietary intake early in pregnancy could identify women who should be prioritized for further dietary counselling and support.     

Relationship between dietary intake of cod liver oil in early pregnancy and birthweight

OBJECTIVE: To investigate the possible association between birth outcome and marine food and cod liver oil intake of healthy women in early (prior to 15 weeks of gestation) pregnancy. DESIGN: An observational study. SETTING: Free-living conditions in a community with traditional fish and cod liver oil consumption. POPULATION: Four hundred and thirty-five healthy pregnant Icelandic women without antenatal and intrapartum complications. METHODS: Dietary intake of the women was estimated with a semi-quantitative food frequency questionnaire (FFQ) covering food intake together with lifestyle factors for the previous three months. Questionnaires were filled out at between 11 and 15 weeks and between 34 and 37 weeks of gestation. The estimated intake of marine food and cod liver oil was compared with birthweight by linear and logistic regression controlling for potential confounding. MAIN OUTCOME MEASURES: Birthweight, cod liver oil intake, lifestyle factors (alcohol, smoking). RESULTS: Fourteen percent of the study population used liquid cod liver oil in early pregnancy. Regression analysis shows that these women gave birth to heavier babies (P < 0.001), even after adjusting for the length of gestation and other confounding. CONCLUSIONS: Maternal intake of liquid cod liver oil early in pregnancy was associated with a higher birthweight. Higher birthweight has been associated with a lower risk of diseases later in life and maternal cod liver oil intake might be one of the means for achieving higher birthweight.     

A genome-wide study of allelic imbalance in human testicular germ cell tumors using microsatellite markers

Testicular germ cell tumors (TGCT) arise by multistep carcinogenesis pathways involving selective losses and gains of chromosome material. To locate cancer genes underlying this selection, we performed a genome-wide study of allelic imbalance (AI) in 32 tumors, using 710 microsatellite markers. The highest prevalence of AI was found at 12p, in line with previous studies finding consistent gain of the region in TGCTs. High frequency of AI was also observed at chromosome arms 4p, 9q, 10p, 11q, 11p, 13q, 16q, 18p, and 22q. Within 39 candidate regions identified by mapping of smallest regions of overlap (SROs), the highest frequency of AI was at 12p11.21 approximately p11.22 (62%), 12p12.1 approximately p13.1 (53%), 12p13.1 approximately p13.2 (53%), 11q14.1 approximately q14.2 (53%), 11p13 approximately p14.3 (47%), 9q21.13 approximately q21.32 (47%), and 4p15.1 approximately p15.2 (44%). Two genes known to be involved in cancer reside in these regions, ETV6 at 12p13.2 (TEL oncogene) and WT1 at 11p13. We also found a significant association (P = 0.02) between AI at 10q21.1 approximately q22.2 and higher clinical stage. This study contributes to the ongoing search for genes involved in transformation of germ cells and provides a useful reference point to previous studies using cytogenetic techniques to map chromosome changes in TGCTs.     

Liver diseases in Adult Life after Childhood Cancer in Scandinavia (ALiCCS): A population‐based cohort study of 32,839 one‐year survivors

Information on late onset liver complications after childhood cancer is scarce. To ensure an appropriate follow‐up of childhood cancer survivors and reducing late liver complications, the need for comprehensive and accurate information is presented. We evaluate the risk of liver diseases in a large childhood cancer survivor cohort. We included all 1‐year survivors of childhood cancer treated in the five Nordic countries. A Cox proportional hazards model was used to estimate hospitalisation rate (hazard) ratios (HRs) for each liver outcome according to type of cancer. We used the risk among survivors of central nervous system tumour as internal reference. With a median follow‐up time of 10 years, 659 (2%) survivors had been hospitalised at least once for a liver disease. The risk for hospitalisation for any liver disease was high after hepatic tumour (HR = 6.9) and leukaemia (HR = 1.7). The Danish sub‐cohort of leukaemia treated with haematopoietic stem cell transplantation had a substantially higher risk for hospitalisation for all liver diseases combined (HR = 3.8). Viral hepatitis accounted for 286 of 659 hospitalisations corresponding to 43% of all survivors hospitalised for liver disease. The 20‐year cumulative risk of viral hepatitis was 1.8% for survivors diagnosed with cancer before 1990 but only 0.3% for those diagnosed after 1990. The risk of liver disease was low but significantly increased among survivors of hepatic tumours and leukaemia. Further studies with focus on the different treatment modalities are needed to further strengthen the prevention of treatment‐induced late liver complications.     

Alcohol and labor supply: the case of Iceland

At a time when the government of Iceland is considering privatization of alcohol sales and a reduction of its governmental fees, it is timely to estimate the potential effects of this policy change. Given that the privatization of sales coupled with a tax reduction should lead to a decrease in the unit price of alcohol, one would expect the quantity consumed to increase. While it is of interest to project the impact of the proposed bill on the market for alcohol, another important consideration is the impact that increased alcohol consumption and, more specifically, probable alcohol misuse would have on other markets in Iceland. The only available study on this subject using Icelandic data yields surprising results. Tómasson et al. (Scand J Public Health 32:47–52, 2004) unexpectedly found no effect of probable alcohol abuse on sick leave. A logical next step would be to examine the effect of probable alcohol abuse on other important labor-market outcomes. Nationally representative survey data from 2002 allow for an analysis of probable misuse of alcohol and labor-supply choices. Labor-supply choices are considered with reference to possible effects of policies already in force, as well as proposed changes to current policies. Contrary to intuition, but in agreement with the previously mentioned Icelandic study, the adverse effects of probable misuse of alcohol on employment status or hours worked are not confirmed within this sample. The reasons for the results are unclear, although some suggestions are hypothesized. Currently, data to test those theories convincingly are not available.

Data quality at the Icelandic Cancer Registry: Comparability, validity, timeliness and completeness

Abstract Introduction. The nationwide Icelandic Cancer Registry (ICR) was established in 1954 and has been extensively used for research from the outset although formal quality assessment of the registry database has not previously been undertaken. In this paper we report the first formal evaluation of the comparability, validity, timeliness and completeness of the ICR. Material and methods. Data from the ICR for the period 1955-2009 (41 994 cancer diagnoses) were used, applying established quantitative and semi-quantitative methods. In order to evaluate the completeness of the ICR, record linkage was performed between the ICR and the population-based Hospital Discharge Registry to identify potential missing cases for tumour diagnoses in 2000 and 2001. Results. The registration is in accordance with internationally accepted standards. It has high validity, but random variation in rates is prominent in this small population. Record linkage with the Hospital Discharge Registry revealed that in addition to the 2459 cancers registered in 2000-2001, 21 cases were missing, indicating 99.15% completeness. Tumours of the central nervous system constituted 71%, and haematological malignancies 19% of these missing entries. Discussion. The ICR has high completeness, validity and timeliness and is comparable to the cancer registries of the other Nordic Countries. As cancer registries have many important roles, it is of great importance that their data are at all times as complete and valid as possible. Thus the ICR aims to constantly improve and update the data gathering process.     

CYP17 promoter polymorphism and breast cancer risk in males and females in relation to BRCA2 status

A T-C polymorphism in the promoter region of the CYP17 gene has been associated with male and female breast cancer risk as well as early-onset familial breast cancer. The potential role of this polymorphism was investigated in relation to breast cancer risk in Icelandic male and female carriers and noncarriers of a BRCA2 mutation. The study population consisted of 39 male and 523 female breast cancer cases and 309 male and 395 female controls. Of the cases, 15 males and 55 females carried a BRCA2 mutation. We did not find a significant association between male breast cancer risk and CYP17 genotypes. Among male breast cancer cases, the frequency of the CC genotype was higher among carriers of the 999del5 mutation (33.3%) than noncarriers (16.7%), although this difference also did not reach a statistical significance. No association was observed with breast cancer risk among females irrespective of menopausal status, stage of the disease or BRCA2 status. Our findings do not indicate a role for the CYP17 T-C polymorphism in female breast cancer, but a role in male carriers of a BRCA2 mutation could not be excluded because of the small sample size.     

Hospital admission for neurologic disorders among 5-year survivors of noncentral nervous system tumors in childhood: A cohort study within the Adult Life after Childhood Cancer in Scandinavia study

Large, comprehensive studies of the risk for neurologic disorders among long-term survivors of noncentral nervous system (CNS) childhood cancers are lacking. Thus, the aim of our study was to assess the lifetime risk of Nordic non-CNS childhood cancer survivors for neurologic disorders. We identified 15,967 5-year survivors of non-CNS childhood cancer diagnosed in Denmark, Iceland, Finland and Sweden in 1943–2008, and 151,118 matched population comparison subjects. In-patient discharge diagnoses of neurologic disorders were used to calculate relative risks (RRs) and absolute excess risks (AERs). A neurologic disorder was diagnosed in 755 of the survivors while 370 were expected, yielding a RR of 2.0 (95% confidence interval (CI) 1.9–2.2). The highest risks were found among survivors of neuroblastoma (4.1; 95% CI 3.2–5.3) and leukemia (2.8; 95% CI 2.4–3.2). The AER decreased from 331 (278–383) excess neurologic disorders per 100,000 person-years 5–9 years after diagnosis to 82 (46–118) ≥ 20 years after diagnosis. Epilepsy was the most common diagnosis (n = 229, 1.4% of all survivors), and significantly increased risks were seen among survivors of eight out of 12 types of childhood cancer. Survivors of neuroblastoma had remarkably high risks (RR ≥ 10) for hospitalization for paralytic syndromes and hydrocephalus, while survivors of leukemia had additional high risks for dementia and encephalopathy. In conclusion, survivors of non-CNS childhood cancer are at high risk for neurologic disorders, especially within the first decade after diagnosis. Therefore, intensive follow-up to identify those who require close management is needed.     

Colon and rectal cancer risk after bariatric surgery in a multicountry Nordic cohort study

Obesity is a risk factor for colorectal cancer. Yet, some research indicates that weight-reducing bariatric surgery also increases colorectal cancer risk. Our study was undertaken because current evidence examining bariatric surgery and risk of colorectal cancer is limited and inconsistent. This population-based cohort study included adults with a documented obesity diagnosis in Denmark, Finland, Iceland, Norway or Sweden in 1980–2015. The incidence of colorectal cancer in participants with obesity who had and had not undergone bariatric surgery was compared to the incidence in the corresponding background population by calculating standardized incidence ratios (SIR) with 95% confidence intervals (CI). Additionally, operated and nonoperated participants with obesity were compared using multivariable Cox regression, providing hazard ratios (HR) with 95% CIs adjusted for confounders. Among 502,772 cohort participants with an obesity diagnosis, 49,931(9.9%) underwent bariatric surgery. The overall SIR of colon cancer was increased after bariatric surgery (SIR 1.56; 95% CI 1.28–1.88), with higher SIRs ≥10 years postsurgery. The overall HR of colon cancer in operated compared to nonoperated participants was 1.13 (95% CI 0.92–1.39) and 1.55 (95% CI 1.04–2.31) 10–14 years after bariatric surgery. Bariatric surgery did not significantly increase the risk of rectal cancer (SIR 1.14, 95% CI 0.83–1.52; HR 1.08, 95% CI 0.79–1.49), but the risk estimates increased with longer follow-up periods. Our study suggests that bariatric surgery is associated with an increased risk of colon cancer, while the support for an increased risk of rectal cancer was weaker.