Kirsten Frederiksen

Long-term Absolute Risk of Cervical Intraepithelial Neoplasia Grade 3 or Worse Following Human Papillomavirus Infection: Role of Persistence

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.

Atypical cancer pattern in patients with Parkinson's disease

Among 14 088 patients, with a primary diagnosis of Parkinsons disease during the period 1977–98 identified from the National Register of Patients, 1282 cancers were subsequently recorded in the Danish Cancer Registry, compared with 1464 expected, with a standardised incidence ratio (SIR) of 0.88 (95% confidence interval (CI), 0.8–0.9). Significantly reduced risks were found for smoking-related cancers, for example, cancers of the lung (SIR, 0.38), larynx (0.47) and urinary bladder (0.52), although moderate reductions in risk were also seen for several nonsmoking-related cancers. In contrast, increased risks were seen for malignant melanoma (SIR, 1.95; 95% CI, 1.4–2.6), nonmelanocytic skin cancer (1.25; 1.1–1.4) and breast cancer (1.24; 1.0–1.5). The observed cancer pattern supports the hypothesis that constituents of tobacco smoke inhibit or delay the development of Parkinsons disease, but a low smoking prevalence appears to be only part of the explanation for the decreased cancer incidence. The increased relative risks of melanoma and nonmelanoma skin cancer are not likely to be artefactual, but further investigations of potential mechanisms are warranted.

Acrylamide exposure and incidence of breast cancer among postmenopausal women in the Danish Diet, Cancer and Health Study.

Acrylamide, a probable human carcinogen, is formed in several foods during high‐temperature processing. So far, epidemiological studies have not shown any association between human cancer risk and dietary exposure to acrylamide. The purpose of this study was to conduct a nested case control study within a prospective cohort study on the association between breast cancer and exposure to acrylamide using biomarkers. N‐terminal hemoglobin adduct levels of acrylamide and its genotoxic metabolite, glycidamide in red blood cells were analyzed (by LC/MS/MS) as biomarkers of exposure on 374 breast cancer cases and 374 controls from a cohort of postmenopausal women. The adduct levels of acrylamide and glycidamide were similar in cases and controls, with smokers having much higher levels (∼3 times) than nonsmokers. No association was seen between acrylamide‐hemoglobin levels and breast cancer risk neither unadjusted nor adjusted for the potential confounders HRT duration, parity, BMI, alcohol intake and education. After adjustment for smoking behavior, however, a positive association was seen between acrylamide‐hemoglobin levels and estrogen receptor positive breast cancer with an estimated incidence rate ratio (95% CI) of 2.7 (1.1–6.6) per 10‐fold increase in acrylamide‐hemoglobin level. A weak association between glycidamide hemoglobin levels and incidence of estrogen receptor positive breast cancer was also found, this association, however, entirely disappeared when acrylamide and glycidamide hemoglobin levels were mutually adjusted.

Malignant Melanoma and Other Types of Cancer Preceding Parkinson Disease

Background: A large follow-up study in Denmark showed a two-fold higher incidence of malignant melanoma in patients with Parkinson disease than in the general population. Using a population-based case–control approach, we investigated the prevalence of malignant melanoma, skin carcinoma, and other cancers before a first hospitalization or outpatient visit for Parkinson disease. Methods: We used the national Danish Hospital Register to identify 8090 patients with a primary diagnosis of Parkinson disease during the period of 1986–1998. Each case was matched with 4 population controls selected at random from among inhabitants alive at the date of first hospital contact with the patient. Incident cases of cancer since 1943 were ascertained by linkage to the Danish Cancer Registry, and the cancer histories of patients with Parkinson disease were compared with those of population controls. Results: We observed an increased prevalence of malignant melanoma and skin carcinoma prior to the first hospital contact for Parkinson disease, with overall odds ratios of 1.44 (95% confidence intervals = 1.03–2.01) and 1.26 (1.11–1.43), respectively. To the contrary, we observed a reduced prevalence of cancers at smoking-related sites in patients before their first hospital contact for Parkinson disease. Conclusions: Our finding of an increased prevalence of malignant melanoma and skin carcinoma before the diagnosis of Parkinson disease weakens the suggested hypothesis that these cancers are caused by the treatment of Parkinson disease. The finding of a decreased prevalence of smoking-related cancers preceding Parkinson disease is consistent with the well-known higher risk of Parkinson disease among nonsmokers.

Relationship of benign gynecologic diseases to subsequent risk of ovarian and uterine tumors

Objective: Although endometriosis and uterine leiomyomas are common conditions, the extent to which either is associated with certain types of malignancies remains uncertain. Methods: Using record linkage techniques, we assessed the relationships between hospital and outpatient admissions for endometriosis or leiomyomas and the development of ovarian and uterine cancers in Denmark between 1978 and 1998. Based on a population-based cohort exceeding 99,000 women, including 2,491 ovarian cancers, 860 borderline ovarian tumors, and 1,398 uterine cancers, we derived relative risks (RR) and 95% confidence intervals (95% CI) associated with overall and histology-specific tumor risks after adjustment for calendar time and reproductive characteristics. Results: Endometriosis seemed to predispose to the development of ovarian cancer, with the association restricted to endometrioid or clear cell malignancies. Five or more years after the diagnosis of endometriosis, the RRs (95% CIs) were 2.53 (1.19-5.38) for endometrioid (7 exposed cases) and 3.37 (1.24-9.14) for clear cell (4 exposed cases) malignancies. Uterine leiomyomas were associated with increases in the risk of uterine malignancies, particularly sarcomas, where the RRs (95% CIs) were 20.80 (11.32-38.22) for women with 1 to 4 years of follow-up (11 exposed cases) and 5.70 (2.27-14.32) for those with more extended follow-up (5 exposed cases). Conclusion: In combination with clinical, pathologic, and molecular data, our results support that some endometriotic lesions may predispose to clear cell and endometrioid ovarian cancers. Uterine leiomyomas also showed a strong connection with subsequent uterine sarcomas, although it was difficult to decipher whether this reflected detection bias, shared risk factors, or an etiologic relationship. (Cancer Epidemiol Biomarkers Prev 2005;14(12):2929–35)

Association of adherence to lifestyle recommendations and risk of colorectal cancer: a prospective Danish cohort study

Objectives To evaluate the association between a simple lifestyle index based on the recommendations for five lifestyle factors and the incidence of colorectal cancer, and to estimate the proportion of colorectal cancer cases attributable to lack of adherence to the recommendations. Design Prospective cohort study. Setting General population of Copenhagen and Aarhus, Denmark. Participants 55 487 men and women aged 50-64 years at baseline (1993-7), not previously diagnosed with cancer. Main outcome measure Risk of colorectal cancer in relation to points achieved in the lifestyle index (based on physical activity, waist circumference, smoking, alcohol intake, and diet (dietary fibre, energy percentage from fat, red and processed meat, and fruits and vegetables)) modelled through Cox regression. Results During a median follow-up of 9.9 years, 678 men and women had colorectal cancer diagnosed. After adjustment for potential confounders, each additional point achieved on the lifestyle index, corresponding to one additional recommendation that was met, was associated with a lower risk of colorectal cancer (incidence rate ratio 0.89 (95% confidence interval 0.82 to 0.96). In this population an estimated total of 13% (95% CI 4% to 22%) of the colorectal cancer cases were attributable to lack of adherence to merely one additional recommendation among all participants except the healthiest. If all participants had followed the five recommendations 23% (9% to 37%) of the colorectal cancer cases might have been prevented. Results were similar for colon and rectal cancer, but only statistically significant for colon cancer. Conclusions Adherence to the recommendations for physical activity, waist circumference, smoking, alcohol intake, and diet may reduce colorectal cancer risk considerably, and in this population 23% of the cases might be attributable to lack of adherence to the five lifestyle recommendations. The simple structure of the lifestyle index facilitates its use in public health practice.

Family‐centred care of children in hospital – a concept analysis

AIM This paper reports a concept analysis of family-centred nursing care of hospitalized children. BACKGROUND Family-centred care describes a practice aimed towards involving the family in all aspects of care. Previous analyses explore the colloquial use of the concept. An increasing amount of scientific papers apply the concept with seemingly little consistency in use. DATA SOURCES A systematic literature search including articles from 1951 to 2009 resulted in a sample of 25 research articles. REVIEW METHODS A theoretical concept analysis influenced by Risjords distinction between theoretical and colloquial analyses and based on the principles developed by Morse, Hupcey and Penrod was used to examine the structure and scientific maturity of the concept. FINDINGS There is good agreement on the defining attributes of the concept, but they are described by sub concepts in need of clarification. The relationship between family and professionals is characterized by a mutual dependency and shared responsibility for the childs care, which may have both positive and negative consequences and holds potential areas of conflict not fully explained by the attribute of partnership. The nature of partnership remains unclear and it may therefore not yet be a relevant attribute. The concept is defined from the perspective of professionals and families, mostly represented by mothers. Few attempts have been made to operationalize the concept. CONCLUSION Family-centred care is a partially mature and highly abstract concept. Developing a theory of family-centred care could position the concept in a theoretical context and should also include the perspective of the sick child.

Use of fertility drugs and risk of ovarian cancer: Danish population based cohort study

Objective To examine the effects of fertility drugs on overall risk of ovarian cancer using data from a large cohort of infertile women. Design Population based cohort study. Setting Danish hospitals and private fertility clinics. Participants 54 362 women with infertility problems referred to all Danish fertility clinics during 1963-98. The median age at first evaluation of infertility was 30 years (range 16-55 years), and the median age at the end of follow-up was 47 (range 18-81) years. Included in the analysis were 156 women with invasive epithelial ovarian cancer (cases) and 1241 subcohort members identified in the cohort during follow-up in 2006. Main outcome measure Effect of four groups of fertility drugs (gonadotrophins, clomifene citrate, human chorionic gonadotrophin, and gonadotrophin releasing hormone) on overall risk of ovarian cancer after adjustment for potential confounding factors. Results Analyses within cohort showed no overall increased risk of ovarian cancer after any use of gonadotrophins (rate ratio 0.83, 95% confidence interval 0.50 to 1.37), clomifene (1.14, 0.79 to 1.64), human chorionic gonadotrophin (0.89, 0.62 to 1.29), or gonadotrophin releasing hormone (0.80, 0.42 to 1.51). Furthermore, no associations were found between all four groups of fertility drugs and number of cycles of use, length of follow-up, or parity. Conclusion No convincing association was found between use of fertility drugs and risk of ovarian cancer.

Depth of Cervical Cone Removed by Loop Electrosurgical Excision Procedure and Subsequent Risk of Spontaneous Preterm Delivery

OBJECTIVE: To investigate the association between cone depth of the loop electrosurgical excision procedure (LEEP) of the cervix and subsequent risk of spontaneous preterm delivery. METHODS: The study included all deliveries in Denmark over a 9-year period, 1997-2005, with information obtained from various public health registries. Of the 552,678 singleton deliveries included in the study, 19,049 were preterm and 8,180 were subsequent to LEEP. Of the 8,180 deliveries with prior LEEP, 273 were subsequent to two or more LEEPs. Of the deliveries subsequent to only one LEEP, we extracted information about cone depth on 3,605 deliveries, of which 223 were preterm (6.2%). Logistic regression analyses were used to evaluate association between cone characteristics and the subsequent risk of preterm delivery, with simultaneous adjustment for potential confounders. RESULTS: Increasing cone depth was associated with a significant increase in the risk of preterm delivery, with an estimated 6% increase in risk per each additional millimeter of tissue excised (odds ratio 1.06, 95% confidence interval 1.03-1.09). Severity of the cone histology and time since LEEP were not associated with the risk of preterm delivery. Having had two or more LEEPs increased the risk almost fourfold for subsequent preterm delivery when compared with no LEEP before delivery, and almost doubled the risk when compared with one LEEP before delivery. CONCLUSION: Increasing cone depth of LEEP is directly associated with an increasing risk of preterm delivery, even after adjustment for several confounding factors. LEVEL OF EVIDENCE: II

Arsenic in Drinking-Water and Risk for Cancer in Denmark

Background Arsenic is a well-known carcinogen, which is often found in drinking-water. Epidemiologic studies have shown increased cancer risks among individuals exposed to high concentrations of arsenic in drinking-water, whereas studies of the carcinogenic effect of low doses have had inconsistent results. Objective Our aim was to determine if exposure to low levels of arsenic in drinking-water in Denmark is associated with an increased risk for cancer. Methods The study was based on a prospective Danish cohort of 57,053 persons in the Copenhagen and Aarhus areas. Cancer cases were identified in the Danish Cancer Registry, and the Danish civil registration system was used to trace and geocode residential addresses of the cohort members. We used a geographic information system to link addresses with water supply areas, then estimated individual exposure to arsenic using residential addresses back to 1970. Average exposure for the cohort ranged between 0.05 and 25.3 μg/L (mean = 1.2 μg/L). Cox’s regression models were used to analyze possible relationships between arsenic and cancer. Results We found no significant association between exposure to arsenic and risk for cancers of the lung, bladder, liver, kidney, prostate, or colorectum, or melanoma skin cancer; however, the risk for non-melanoma skin cancer decreased with increasing exposure (incidence rate ratio = 0.88/μg/L average exposure; 95% confidence interval, 0.84–0.94). Results adjusted for enrollment area showed no association with non-melanoma skin cancer. Conclusions The results indicate that exposure to low doses of arsenic might be associated with a reduced risk for skin cancer.