Purpose To elucidate the temporal relationship between detection of glaucomatous optic disc progression, as assessed by fundus photography, and visual field progression. Design Prospective, randomized, longitudinal trial. Participants Three hundred six study eyes with manifest glaucoma with field loss and 192 fellow eyes without any field defect at the start of the trial, from a total of 249 subjects included in the Early Manifest Glaucoma Trial (EMGT), were assessed. Methods Evaluation of visual field progression and optic disc progression during an 8-year follow-up period. Three graders independently assessed optic disc progression in optic disc photographs. Visual field progression was assessed using glaucoma change probability maps and the EMGT progression criterion. Main Outcome Measures Time to detection of visual field progression and optic disc progression. Results Among study eyes with manifest glaucoma, progression was detected in the visual field first in 163 eyes (52%) and in the optic disc first in 39 eyes (12%); in 1 eye (0%), it was found simultaneously with both methods. Among fellow eyes with normal fields, progression was detected in the visual field first in 28 eyes (15%) and in the optic disc first in 34 eyes (18%); in 1 eye (1%), it occurred simultaneously. Conclusions In eyes with manifest glaucoma, progression in the visual field was detected first more than 4 times as often as progression in the optic disc. Among fellow eyes without visual field loss at baseline, progression was detected first as frequently in the optic disc as in the visual field.

Background The pattern of cancer in long-term survivors from childhood cancer has not been investigated comprehensively. Methods We obtained a cohort of 47 697 children and adolescents aged 0–19 years with cancer as defined by the country-wide cancer registries of Denmark, Finland, Iceland, Norway, and Sweden during 1943–2005. Cohort members were followed through age 79 years for subsequent primary cancers notified to the registries, and the age-specific risk pattern of the survivors was compared with that of the national populations using country and sex standardized incidence ratios (SIRs). We used a multiplicative Poisson regression model to estimate relative risk of cancer for attained age, with adjustment for calendar period and age at diagnosis of primary cancer. We also calculated excess absolute risk (EAR) attributable to status as childhood cancer survivor and determined the cumulative incidence of second primary cancer as a function of attained age for three subcohorts defined by period of treatment for childhood cancer. Results A total of 1180 asynchronous second primary cancers were observed in 1088 persons, yielding an overall SIR of 3.3 (95% confidence interval = 3.1 to 3.5). The relative risk was statistically significantly increased in all age groups, even for cohort members approaching 70 years of age. The EAR for second primary cancer among survivors increased gradually from one additional case per 1000 person-years of observation in early life to six additional cases per 1000 person-years in the age group 60–69 years. For children treated in the prechemotherapy era (1943–1959), the cumulative risk for a second primary cancer reached 18%, 34%, and 48% at ages 60, 70, and 80 years, respectively. The age-specific incidence rates were highest for cohort members treated in the era of intensive, multiple-agent chemotherapy (1975–2005). Conclusion Survivors of childhood cancer have a persistent excess risk for a second primary cancer throughout their lives, accompanied by continuous changes in the risk of cancers at specific sites.

Summary Background The pattern of endocrine disorders in long-term survivors of childhood cancer has not been investigated comprehensively. Here, we aimed to assess the lifetime risk of these disorders in Nordic survivors of childhood cancer. Methods From the national cancer registries of Denmark, Finland, Iceland, Norway, and Sweden, we identified 31 723 1-year survivors of childhood cancer, notified since the start of registration in the 1940s and 1950s. From the national population registries, we randomly selected a comparison cohort of people matched by age, sex, and country. Study participants were linked to the national hospital registries, and observed numbers of first-time hospital contacts for endocrine disorders in survivors of childhood cancer were compared with the expected numbers derived from the population comparison cohort. We calculated the absolute excess risks attributable to status as a childhood cancer survivor and standardised hospitalisation rate ratios (SHRRs). Findings Of the childhood cancer survivors, 3292 had contact with a hospital for an endocrine disorder, yielding a SHRR of 4·8 (95% CI 4·6–5·0); the highest risks were in survivors of leukaemia (SHRR 7·3 [95% CI 6·7–7·9]), CNS tumours (6·6 [6·2–7·0]), and Hodgkin's lymphoma (6·2 [5·6–7·0]). The absolute excess risk for endocrine disorders was roughly 1000 per 100 000 person-years before 20 years of age, and 400 per 100 000 person-years during the remaining lifetime. For children with cancer diagnosed at 5–9 years of age, the cumulative risk for endocrine disorders was highest, and reached 43% at the age of 60 years. Diagnoses of pituitary hypofunction (SHRR 88·0), hypothyroidism (9·9), and testicular and ovarian dysfunction (42·5 and 4·7, respectively) together constituted 61% (655 of 1078) of all excess disease-induced and treatment-induced endocrine disorders in survivors of childhood cancer. Interpretation A cumulative risk for endocrine disorders at 60 years of age of above 40% in survivors of childhood cancer emphasises the importance of minimisation of damaging treatment, intensification of secondary prevention, and targeting of survivor follow-up throughout life. Since most long-term childhood cancer survivors are not followed in a specialised late-effect clinic, they are a growing challenge for the primary care physician and medical specialists working outside the late-effect area. Funding The Danish Council for Strategic Research.

Purpose Cancers of the digestive system constitute a major risk for childhood cancer survivors treated with radiotherapy once they reach adulthood. The aim of this study was to determine therapy-related risk factors for the development of a second malignancy in the digestive organs (SMDO) after a childhood cancer. Methods and Materials Among 4,568 2-year survivors of a childhood solid cancer diagnosed before 17 years of age at eight French and British centers, and among 25,120 patients diagnosed as having a malignant neoplasm before the age of 20 years, whose data were extracted from the Nordic Cancer Registries, we matched 58 case patients (41 men and 17 women) of SMDO and 167 controls, in their respective cohort, for sex, age at first cancer, calendar year of occurrence of the first cancer, and duration of follow-up. The radiation dose received at the site of each second malignancy and at the corresponding site of its matched control was estimated. Results The risk of developing a SMDO was 9.7-fold higher in relation to the general populations in France and the United Kingdom. In the case-control study, a strong dose–response relationship was estimated, compared with that in survivors who had not received radiotherapy; the odds ratio was 5.2 (95% CI, 1.7–16.0) for local radiation doses between 10 and 29 Gy and 9.6 (95% CI, 2.6–35.2) for doses equal to or greater than 30 Gy. Chemotherapy was also found to increase the risk of developing SMDO. Conclusions This study confirms that childhood cancer treatments strongly increase the risk of SMDO, which occur only after a very long latency period.

Summary Background Liver cirrhosis is characterized by a silent phase until decompensation, which is defined by ascites, bleeding from esophageal varices or hepatic encephalopathy. Aim To compare the clinical course, patterns of survival and causes of death by etiology during long‐term follow‐up in a large population‐based cohort of patients with incident cirrhosis. Methods We used population‐based medical registries for a cohort study of patients with liver cirrhosis diagnosed January 2001 to December 2010, in the Scania region of Sweden. Medical records were reviewed. Patients were classified according to etiology and clinical parameters were registered. Patients were followed until December 2017. Results The cohort comprised 1317 patients, 631 were decompensated at diagnosis and 387 decompensated during follow‐up. The cumulative 10‐year incidence of decompensation, with death and transplantation as competing risks, was 89% in alcoholic cirrhosis, 58% in hepatitis C and 75% in cryptogenic cirrhosis. The lowest 10‐year transplantation‐free survival rates were found in cryptogenic cirrhosis (11%), alcohol‐related cirrhosis (18%) and alcohol combined with hepatitis C (12%). Autoimmune hepatitis cirrhosis showed the best 10‐year survival (53%) and hepatitis C, non‐alcoholic steatohepatitis, primary biliary cholangitis, and primary sclerosing cholangitis and other causes averaged 30%. Decompensation at diagnosis was an important predictor for death in all etiologies apart from alcoholic cirrhosis. 991 patients died and 91 were transplanted. Conclusion Our results show that the clinical course and survival in cirrhosis differ considerably by both etiology and state at diagnosis.

In the 1990s, two randomised clinical trials started in Scandinavia addressing whether hormone replacement therapy (HRT) is safe for women with previous breast cancer. We report the findings of the safety analysis in HABITS (hormonal replacement therapy after breast cancer—is it safe?), an open randomised clinical trial with allocation to either HRT or best treatment without hormones. The main endpoint was any new breast cancer event. All analyses were done according to intention-to-treat. Until September, 2003, 434 women were randomised; 345 had at least one follow-up report. After a median follow-up of 2·1 years, 26 women in the HRT group and seven in the non-HRT group had a new breast-cancer event. All women with an event in the HRT group and two of those in the non-HRT group were exposed to HRT and most women had their event when on treatment. We decided that these findings indicated an unacceptable risk for women exposed to HRT in the HABITS trial, and the trial was terminated on Dec 17, 2003. Published online Feb 3, 2004. http://image.thelancet.com/extras/03let12260web.pdf

Hypofractionated radiotherapy for prostate cancer has gained increased attention due to its proposed high radiation-fraction sensitivity. Recent reports from studies comparing moderately hypofractionated and conventionally fractionated radiotherapy support the clinical use of moderate hypofractionation. To date, there are no published randomised studies on ultra-hypofractionated radiotherapy. Here, we report the outcomes of the Scandinavian HYPO-RT-PC phase 3 trial with the aim to show non-inferiority of ultra-hypofractionation compared with conventional fractionation. In this open-label, randomised, phase 3 non-inferiority trial done in 12 centres in Sweden and Denmark, we recruited men up to 75 years of age with intermediate-to-high-risk prostate cancer and a WHO performance status between 0 and 2. Patients were randomly assigned to ultra-hypofractionation (42·7 Gy in seven fractions, 3 days per week for 2·5 weeks) or conventional fractionated radiotherapy (78·0 Gy in 39 fractions, 5 days per week for 8 weeks). No androgen deprivation therapy was allowed. The primary endpoint was time to biochemical or clinical failure, analysed in the per-protocol population. The prespecified non-inferiority margin was 4% at 5 years, corresponding to a critical hazard ratio (HR) limit of 1·338. Physician-recorded toxicity was measured according to the Radiation Therapy Oncology Group (RTOG) morbidity scale and patient-reported outcome measurements with the Prostate Cancer Symptom Scale (PCSS) questionnaire. This trial is registered with the ISRCTN registry, number ISRCTN45905321. Between July 1, 2005, and Nov 4, 2015, 1200 patients were randomly assigned to conventional fractionation (n=602) or ultra-hypofractionation (n=598), of whom 1180 (591 conventional fractionation and 589 ultra-hypofractionation) constituted the per-protocol population. 1054 (89%) participants were intermediate risk and 126 (11%) were high risk. Median follow-up time was 5·0 years (IQR 3·1–7·0). The estimated failure-free survival at 5 years was 84% (95% CI 80–87) in both treatment groups, with an adjusted HR of 1·002 (95% CI 0·758–1·325; log-rank p=0·99). There was weak evidence of an increased frequency of acute physician-reported RTOG grade 2 or worse urinary toxicity in the ultra-hypofractionation group at end of radiotherapy (158 [28%] of 569 patients vs 132 [23%] of 578 patients; p=0·057). There were no significant differences in grade 2 or worse urinary or bowel late toxicity between the t

Purpose: The choice of treatment for squamous cell carcinoma of the head and neck (SCCHN) is still primarily based on the tumor-node-metastasis classification. However, it is reasonable to believe that biological profiles of SCCHN may be independently associated with response to therapy. The aim of the present study was to examine genetic changes and gene expression profiles that might correlate with sensitivity to cisplatin [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay] in 10 SCCHN cell lines. Experimental Design: Five cisplatin-sensitive and five cisplatin-resistant cell lines [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay] were studied by comparative genomic hybridization, spectral karyotyping, and cDNA microarray analysis (21,632 sequence-validated human cDNA; confirmation by reverse transcriptase-PCR for selected genes). For the MET proto-oncogene, which showed low expression in the chemosensitive cell lines, we did immunohistochemical staining on SCCHN of 29 patients who received induction chemotherapy. Results: The five cisplatin-resistant cell lines showed significantly more genetic imbalances (regions of loss and amplification) and chromosomal abnormalities by comparative genomic hybridization and spectral karyotyping, respectively, than did the five cisplatin-sensitive cell lines. Microarray studies identified similar to60 genes that clearly distinguish between the two groups of cell lines. Some of these genes are known to be involved in tumor progression, metastasis, and drug resistance. We identified low expression of c-met (immunohistochemistry) as a predictive factor for complete response in nondiploid tumors (P = 0.026). Conclusions: We conclude that cisplatin sensitivity and resistance are related to distinctive differences in the genetic and expression profiles in individual SCCHN tumor cell lines and in SCCHN patients. The genes we have identified may serve as potential targets for novel treatment strategies.

Background and aims: Liver cirrhosis is a risk factor for hepatocellular carcinoma (HCC). While the HCC risk is thought to be highest in hepatitis B and hepatitis C, the risk in other cirrhosis etiologies is not fully established. Therefore, we aimed to study the risk and outcome of HCC in alcoholic cirrhosis compared to cirrhosis of other etiologies, in Sweden. Material and methods: We used population-based medical registries to identify patients diagnosed with cirrhosis in the Scania region in southern Sweden between 2001 and 2010. Medical records were reviewed to identify all HCC cases and to register clinical parameters. All patients were followed until death, emigration or December 2017. Results: The cohort comprised 1317 patients with cirrhosis. A total of 200 patient developed HCC, including 75 with prevalent HCC. The annual incidence of HCC after six months was 1.5% in alcoholic cirrhosis and 4.7% in hepatitis C cirrhosis. In alcoholic cirrhosis, 40 patients were diagnosed with HCC during follow-up, of which 15 patients fulfilled the Milan criteria and 10 received treatment, curative or palliative. The overall median survival after HCC diagnosis was 7.7 months, with 4.5, 11 and 9.3 months, in cirrhosis due to alcohol, hepatitis C or remaining causes, respectively. Conclusion: We find an annual incidence of HCC in alcoholic cirrhosis of 1.5% indicating need for surveillance in these patients. Survival after HCC diagnosis was worst in alcoholic cirrhosis due to more advanced stage at diagnosis with few patients eligible for treatment.

Our purpose was to assess the risk of developing a second malignant neoplasm (SMN) after cancer in childhood and adolescence associated with different treatment modalities. Our investigation was performed as a nested case‐control study within a Nordic cohort of 25,120 patients younger than 20 years old at first malignant neoplasm (FMN) diagnosed in 1960 through 1987. SMNs were diagnosed in 1960 through 1991. For each case of SMN, 3 controls were sampled, matched by sex, age, calendar year of diagnosis and length of follow‐up. For the final analysis, there were 234 cases and 678 controls. Relative risks (RRs) of various exposures were estimated by means of conditional logistic regression, with non‐exposed as the reference. The RR of developing SMN in the radiated volume was 4.3 (95% confidence interval 3.0–6.2). The risk was highest in children diagnosed before the age of 5 years; it increased with the dose of radiation and with increasing follow‐up time after FMN. Chemotherapy alone was not associated with an increased RR, but it significantly potentiated the effect of radiotherapy. RRs were unchanged between the periods 1960–1973 and 1974–1987, and since the use of chemotherapy increased in the latter period, the number of SMNs may increase. Hereditary factors were important for the occurrence of SMN independently of therapy. We conclude that radiation was the most important treatment‐related risk factor for the development of SMN. Chemotherapy appeared to play only an accessory role during the study period, potentiating the carcinogenic effect of radiotherapy. Int. J. Cancer 88:672–678, 2000. © 2000 Wiley‐Liss, Inc.

Liver cirrhosis is characterized by a silent phase until decompensation, which is defined by onset of ascites, variceal bleeding, or encephalopathy. Although it is presumed that the survival of decompensated patients is the same regardless of when decompensation occurs, data to support this are scarce. We aimed to study the impact of time of decompensation on the clinical course and survival of patients with cirrhosis in a large population-based cohort. We used medical registries to define a 10-year cohort of 1317 patients with incident liver cirrhosis in the Scania region of Sweden. Medical records were reviewed. Patients were followed until December 2011, and for death or transplantation until December 2014. In the cohort, 629 patients were decompensated at diagnosis, of which 505 had ascites and 44 variceal bleeding only. During follow-up, 228 patients developed ascites and 39 variceal bleeding as first complication. Patients with ascites as first complication showed worse survival than patients who had ascites at diagnosis. (5-year survival 33% vs. 15%, HR 1.60 (95% CI 1.34-1.90)). This difference persisted after adjustment for confounders, including hepatocellular cancer (HR 1.38 (95% CI 1.15-1.67)). Worse survival was also seen when bleeding from varices occurred during follow-up rather than at diagnosis. Our results provide evidence for an association between transplantation-free survival after decompensation and the time of decompensation in liver cirrhosis, with worse survival when decompensation occurs during follow-up, thus challenging the generally held, view that the survival after decompensation is independent of when decompensation occurs.

Abstract Purpose To evaluate altered protein expression with tissue microarray methodology for 15 different markers with potential prognostic significance in invasive bladder cancer. Materials and Methods Invasive tumor was sampled with the tissue-arraying instrument in 133 consecutive patients who underwent radical cystectomy, and at least 3, 0.6-mm tissue cores were obtained. With immunohistochemistry, the expressions of TP53, RB1, CDKN1A (p21), MKI67 (Ki67), PTGS2 (Cox-2), CTNNA1 (α-catenin), CTNNB1 (β-catenin), AKT, PTEN, RHOA, RHOC, STAT1, VEGFC, EGFR, and ERBB2 (HER2) were quantified, and correlations were made with tumor grade, pathologic stage, lymph node status, and disease-specific survival. Results Decreased immunohistochemical expression of CTNNA1 and of PTEN correlated with higher pathologic tumor stages ( P = 0.01 and P = 0.01, respectively), whereas increased AKT1 and ERBB2 correlated with lower pathologic tumor stages ( P = 0.01 and P = 0.03, respectively). Increased RHOA expression was more common in grade 3 than in grade 2 tumors ( P = 0.016). There were no other correlations among the 15 factors studied and pathologic stage, lymph node status, or tumor grade. No association was found between bladder cancer death and altered marker status for any of the markers studied. Conclusions Currently, there are reasons to have a skeptical attitude toward the value of tissue microarray based immunohistochemistry as a method for evaluating prognostic markers in invasive bladder cancer. In this study, 15 antibodies were tested but were found to be of little clinical value. Whether this negative finding is related to the group of patients or factors studied, or the methodology is unclear.

The aim of the study was to assess the risk with radiation therapy and chemotherapy of the first cancer in childhood and adolescence for the development of a second malignant solid tumor (SMST). Also, the role of relapse of the primary tumor was studied. It is a nested case-control study within a Nordic cohort of patients less than 20 years of age at first diagnosis 1960 - 1987. SMSTs were diagnosed in 1960-1991. There were 196 cases and 567 controls. The risk was increased only for radiotherapy given more than five years before the development of the SMST. A significantly increased relative risk of 1.8 was found already at doses below 1 Gy. The risk increased rapidly up to a maximum of 18.3 for doses above 30 Gy. Chemotherapy alone did not increase the risk to develop an SMST. However, in combination with radiotherapy, chemotherapy showed a significant potentiating effect. Relapse was found to be an independent risk factor for development of an SMST, with a higher relative risk for females than for males.

Purpose To compare the earliest detection of progression in visual fields and monoscopic optic disc photographs at different stages of manifest glaucoma. Methods This study evaluated 306 eyes in 249 patients with manifest open‐angle glaucoma included in the Early Manifest Glaucoma Trial (EMGT). All patients in the trial were followed up regularly by standard automated perimetry and monoscopic optic disc photography, and the median follow‐up time was 8 years. Progression was assessed in series of optic disc photographs and in series of visual fields using glaucoma change probability maps and the predefined EMGT progression criterion. The proportion of progressions detected first in visual fields and the proportion detected first in optic disc photographs were compared at different stages of glaucoma severity defined by the perimetric mean deviation (MD) of the baseline visual field. Results Assessment of 210 eyes with early visual field loss, 83 eyes with moderate field loss, and 13 eyes with advanced field loss showed that, among the eyes exhibiting progression, the progression was detected first in the visual field in 80%, 79% and 100%, respectively. The predominance of visual field progressions at all stages was still apparent when using narrower (3‐dB) MD intervals for staging. Conclusion In the EMGT material on eyes with manifest open‐angle glaucoma, the initial progression was detected much more often in the visual field series than in the optic disc photographs at all stages of disease.

Abstract Aim of the study To analyse late morbidity and mortality in pre and post-menopausal breast cancer patients treated with postmastectomy radiotherapy, with emphasis on side-effects from the heart, cerebrovascular and respiratory systems. Methods Long term follow-up of two randomised, clinical trials with 1100 patients was carried out. Pre-menopausal women were allocated to radiotherapy (RT), RT + oral cyclophosphamide (RT + C) or cyclophosphamide only (C). Post-menopausal women were allocated to RT, RT + Tamoxifen for one year (RT + Tam) or tamoxifen only (Tam). Information on admission to hospital, mortality and causes of death was obtained from national registers. Results After 25 years, adding RT to cyclophosphamide in pre-menopausal women raised the mortality from heart disease from zero to 0.8% ( p = 0.04). In post-menopausal women, adding RT to Tam raised the mortality from heart disease from 10.5% to 18.4% ( p = 0.005). In post-menopausal women mortality due to cerebrovascular disease increased from 3.4% to 8.7% by adding RT to Tam ( p = 0.015). The differences were not evident until in the second decade of follow-up. In spite of differences in specific causes of death, there were no significant differences between the treatment arms concerning morbidity or overall mortality. Conclusion Postmastectomy radiotherapy to the chest wall and loco-regional lymph nodes including the parasternal lymph nodes as delivered in the end of the seventies did not reduce overall mortality, but gave a significantly increased risk of death from heart and cerebrovascular disease, which appeared during the second decade after radiotherapy.

Summary Background Several studies have shown the efficacy of endocrine therapy in combination with radiotherapy in high-risk prostate cancer. To assess the effect of radiotherapy, we did an open phase III study comparing endocrine therapy with and without local radiotherapy, followed by castration on progression. Methods This randomised trial included men from 47 centres in Norway, Sweden, and Denmark. Between February, 1996, and December, 2002, 875 patients with locally advanced prostate cancer (T3; 78%; PSA

The lifetime risk for cardiovascular disease in a large cohort of childhood cancer survivors has not been fully assessed. In a retrospective population‐based cohort study predicated on comprehensive national health registers, we identified a cohort of 32,308 one‐year survivors of cancer diagnosed before the age of 20 in the five Nordic countries between the start of cancer registration in the 1940s and 1950s to 2008; 211,489 population comparison subjects were selected from national population registers. Study subjects were linked to national hospital registers, and the observed numbers of first hospital admission for cardiovascular disease among survivors were compared with the expected numbers derived from the population comparison cohort. Cardiovascular disease was diagnosed in 2,632 childhood cancer survivors (8.1%), yielding a standardized hospitalization rate ratio (RR) of 2.1 (95% CI 2.0–2.2) and an overall absolute excess risk (AER) of 324 per 100,000 person‐years. At the end of follow‐up 12% of the survivors were ≥ 50 years of age and 4.5% ≥ 60 years of age. Risk estimates were significantly increased throughout life, with an AER of ∼500–600 per 100,000 person‐years at age ≥ 40. The highest relative risks were seen for heart failure (RR, 5.2; 95% CI 4.5–5.9), valvular dysfunction (4.6; 3.8–5.5) and cerebrovascular diseases (3.7; 3.4–4.1). Survivors of hepatic tumor, Hodgkin lymphoma and leukemia had the highest overall risks for cardiovascular disease, although each main type of childhood cancer had increased risk with different risk profiles. Nordic childhood cancer survivors are at markedly increased risk for cardiovascular disorders throughout life. These findings indicate the need for preventive interventions and continuous follow‐up for this rapidly growing population. What's new? The long‐term effects of cancer treatment in childhood cancer survivors can be serious, and more research is needed to fully investigate the relationship between treatment and chronic disease in aging survivors. This retrospective population‐based cohort study focused on cardiovascular late effects among childhood cancer survivors in the five Nordic countries. Survivors were found to be at significantly increased risk for cardiovascular disease throughout their lives. Relative risk was highest for heart failure, valvular dysfunction, and cerebrovascular diseases. Overall, survivors had a twofold increased lifetime risk for hospitalization for cardiovascular disease.

Abstract Conclusion: This study shows a persistent trend of an increase in the incidence of carcinoma of the tongue into the twenty-first century for both sexes and all age groups except for young males. Objectives: During the last decades increased incidence of squamous cell carcinoma (SCC) of the tongue in young adults has been reported. We previously showed an increased incidence in SCC of the tongue in Scandinavia in 1960-1994, most pronounced in patients aged 20-39 years. The aim of this study was to investigate whether the trend of increased incidence of tongue cancer continued into the twenty-first century in a population-based study in the Nordic countries. Methods: Data for all reported SCCs of the tongue and base of tongue in patients aged 20-79 years during 1960-2008 were extracted from the NORDCAN registry, based on the National Cancer registries in the Nordic countries. Data from Sweden, Norway, Finland, Denmark, and Iceland were analyzed. The age groups 20-39, 40-64, and 65-79 years were studied separately as well as male and female figures. Results: In all, 12 280 cases were reported, of which 673 were diagnosed in patients aged 20-39 years. The trend of an increase persisted after 1994 in both sexes and all three age groups except in young males.