Showing papers by "Susanne K. Kjaer published in 2012"

Association between endometriosis and risk of histological subtypes of ovarian cancer: a pooled analysis of case-control studies.

Abstract: Summary Background Endometriosis is a risk factor for epithelial ovarian cancer; however, whether this risk extends to all invasive histological subtypes or borderline tumours is not clear. We undertook an international collaborative study to assess the association between endometriosis and histological subtypes of ovarian cancer. Methods Data from 13 ovarian cancer case–control studies, which were part of the Ovarian Cancer Association Consortium, were pooled and logistic regression analyses were undertaken to assess the association between self-reported endometriosis and risk of ovarian cancer. Analyses of invasive cases were done with respect to histological subtypes, grade, and stage, and analyses of borderline tumours by histological subtype. Age, ethnic origin, study site, parity, and duration of oral contraceptive use were included in all analytical models. Findings 13 226 controls and 7911 women with invasive ovarian cancer were included in this analysis. 818 and 738, respectively, reported a history of endometriosis. 1907 women with borderline ovarian cancer were also included in the analysis, and 168 of these reported a history of endometriosis. Self-reported endometriosis was associated with a significantly increased risk of clear-cell (136 [20·2%] of 674 cases vs 818 [6·2%] of 13 226 controls, odds ratio 3·05, 95% CI 2·43–3·84, p Interpretation Clinicians should be aware of the increased risk of specific subtypes of ovarian cancer in women with endometriosis. Future efforts should focus on understanding the mechanisms that might lead to malignant transformation of endometriosis so as to help identify subsets of women at increased risk of ovarian cancer. Funding Ovarian Cancer Research Fund, National Institutes of Health, California Cancer Research Program, California Department of Health Services, Lon V Smith Foundation, European Community's Seventh Framework Programme, German Federal Ministry of Education and Research of Germany, Programme of Clinical Biomedical Research, German Cancer Research Centre, Eve Appeal, Oak Foundation, UK National Institute of Health Research, National Health and Medical Research Council of Australia, US Army Medical Research and Materiel Command, Cancer Council Tasmania, Cancer Foundation of Western Australia, Mermaid 1, Danish Cancer Society, and Roswell Park Alliance Foundation.

Association Between BRCA1 and BRCA2 Mutations and Survival in Women with Invasive Epithelial Ovarian Cancer

Abstract: Results The 5-year overall survival was 36% (95% CI, 34%-38%) for noncarriers, 44% (95% CI, 40%-48%) for BRCA1 carriers, and 52% (95% CI, 46%-58%) for BRCA2 carriers. After adjusting for study and year of diagnosis, BRCA1 and BRCA2 mutation carriers showed a more favorable survival than noncarriers (for BRCA1: hazard ratio [HR], 0.78; 95% CI, 0.68-0.89; P.001; and for BRCA2: HR, 0.61; 95% CI, 0.50-0.76; P.001). These survival differences remained after additional adjustment for stage, grade, histology, and age at diagnosis (for BRCA1: HR, 0.73; 95% CI, 0.640.84; P.001; and for BRCA2: HR, 0.49; 95% CI, 0.39-0.61; P.001). The BRCA1 HR estimate was significantly different from the HR estimated in the adjusted model (P for heterogeneity=.003). Conclusion Among patients with invasive EOC, having a germline mutation inBRCA1 or BRCA2 was associated with improved 5-year overall survival. BRCA2 carriers had the best prognosis.

Trends in incidence of anal cancer and high-grade anal intraepithelial neoplasia in Denmark, 1978–2008

Abstract: The aim of the study was to determine the incidences of anal cancer and high-grade anal intraepithelial neoplasia (AIN2/3) over time in Danish women and men. Describing the burden of anal cancer and AIN may be valuable in future evaluations of the human papillomavirus (HPV) vaccine. We included all anal cancers in the Danish Cancer Register in the period 1978-2008 and all cases of AIN2/3 in the Danish Registry of Pathology. Overall and age-, period- and histology-specific incidence rates were estimated. During the 30-year period, 2,187 anal cancers were identified, two thirds of which were in women. Between 1978-1982 and 2003-2008, the age-standardized incidence rate of anal cancer increased from 0.68 to 1.48 per 100,000 person-years in women and from 0.45 to 0.80 per 100,000 person-years in men. Although there is no systematic screening for AIN in Denmark, we nevertheless identified 608 cases of AIN2/3 during the study period. The average annual percentage change of 5% between 1998 and 2008 represents a steep increase in the incidence of AIN in both genders. Furthermore, the incidence rate of HPV-associated anal cancers increased significantly, whereas that of non-HPV-associated histological types levelled out or even declined during the 30 years of observation. In women, the increase in HPV-associated cancers was more pronounced among those under 60 years of age. Our findings indicate that vaccines against HPV might play an important role in the prevention of anal cancer and its precursor lesions.

Genital Warts and Risk of Cancer: A Danish Study of Nearly 50 000 Patients With Genital Warts

Abstract: Background We conducted a large national cohort study to examine the risk of cancer among men and women with genital warts (GW) Methods By use of the Danish National Patient Register, we identified 16,155 men and 32,933 women who received a diagnosis of GW during 1978-2008 Standardized incidence ratios (SIRs) were computed as estimates of the relative risk of specific cancers or sites Results A diagnosis of GW was strongly related to anal (SIR for men, 215; SIR for women, 78), vulvar (SIR, 148), vaginal (SIR, 59), cervical (SIR, 15), penile (SIR, 82), and head and neck cancer (SIR, 28), including subsites of head and neck cancer with confirmed HPV association (SIR for men, 35; SIR for women, 48) The risks remained elevated for >10 years following GW diagnosis In addition, we found moderately increased SIR estimates for nonmelanoma skin cancer, smoking-related cancers, and Hodgkin and non-Hodgkin lymphoma Conclusions Individuals with GW have a long-term increased risk of anogenital cancers and head and neck cancers The elevated risks of nonmelanoma skin cancers might indicate an association with HPV, while excess risks of other cancers could point to differences in other risk factors between individuals with GW and the general population

Thyroid cancer in Denmark 1943-2008, before and after iodine supplementation.

Abstract: 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.

Prevalence and genotype distribution of human papillomavirus infection of the cervix in Spain: the CLEOPATRE study.

Abstract: Human papillomavirus (HPV) infection is a necessary cause of cervical cancer. The aim of this study was to estimate the prevalence of cervical HPV infection and HPV type-specific distribution among women attending cervical cancer screening in Spain during 2007 and 2008. Women aged 18-65 years were recruited according to an age-stratified sampling method. Liquid-based cervical samples were collected and analyzed for cytology, HPV detection, and genotyping. HPV genotyping was determined using the INNO-LiPA HPV Genotyping Extra Reverse Hybridization Line Probe Assay. Prevalence estimates were age-standardized using 2001 Spanish census data. The present study included 3,261 women. Age-standardized HC2-based HPV prevalence was 14.3% (95% CI, 13.1-15.5) among women aged 18-65 years, and 28.8% (26.6-31.1) among women aged 18-25 years. High-risk HPV types were detected in 12.2% (95% CI, 11.1-13.4) of HPV-tested women, representing 84.0% of HPV-positive samples. Multiple infections were present in 4.1% (95% CI, 3.4-4.8) of HPV-tested women (25.0% of HPV-positive samples). The most common high-risk HPV-types among HPV-tested women were 16 (2.9%), 52 (1.8%), 51 (1.6%), 31 (1.3%), and 66 (1.2%). HPV-type 16 was present in 16.9% of HPV-positive samples. One or more of the HPV vaccine types 6/11/16/18 were detected in 3.8% of HPV-tested women (22.1% of HPV-positive samples). Though not a true population-based survey, this study provides valuable baseline data for future assessment of the impact of current HPV vaccination programs in Spain. The high prevalence of HPV infection among young women may reflect recent changes in sexual behavior.

Human Papillomavirus Prevalence and Type Distribution in 3603 HIV-Positive and HIV-Negative Women in the General Population of Tanzania: The PROTECT Study

Abstract: Objective:The aim of the Prevention of Cervical Cancer in Tanzania (PROTECT) study is to assess the prevalence of oncogenic human papillomavirus (HPV) and to determine the type distribution among women in the general population according to human immunodeficiency virus (HIV) status, in preparation f

Increased incidence of penile cancer and high-grade penile intraepithelial neoplasia in Denmark 1978–2008: a nationwide population-based study

Abstract: Objective To assess the trends in incidence of penile cancer during 1978–2008 and high-grade penile intraepithelial neoplasia (PIN2/3) during 1998–2008 in Denmark.

Young age at first intercourse and risk-taking behaviours—a study of nearly 65 000 women in four Nordic countries

Abstract: Background: Risk-taking behaviours such as early initiation of smoking, alcohol drinking and sexual activity often cluster within individuals and could be characteristics of adolescents who in general are risk takers. In the present study, using a large population-based sample of 64 659 women aged 18–45 years in four Nordic countries, we investigate whether young age at first sexual intercourse is associated with subsequent risk-taking behaviours. Methods: We examined the association between young age at first sexual intercourse (age ≤14 years) and subsequent risk-taking behaviours by using multivariate logistic regression by which odds ratios (ORs) and the corresponding 95% confidence intervals (95% CIs) were estimated. Results: The OR of reporting more than 10 lifetime sexual partners was almost four times higher among women who reported a young age at first intercourse (OR = 3.79; 95% CI: 3.60–4.00) in comparison with women >14 years at first intercourse. Furthermore, women who were young at first intercourse were more likely to report two or more recent partners (OR = 1.67; 95% CI: 1.54–1.82) and to have a history of STIs (OR = 2.03; 95% CI: 1.93–2.13). In addition, young age at first intercourse was associated with current smoking (OR = 2.31; 95% CI: 2.20–2.43) and binge drinking (OR = 1.36; 95% CI: 1.28–1.44). All ORs were adjusted for age, years of education and country of residence. Conclusion: Young age at first intercourse is associated with subsequent risk-taking behaviours. Our study emphasizes the importance of targeting prevention efforts towards the complexity of risk-taking behaviours.

Determinants of acceptance of cervical cancer screening in Dar es Salaam, Tanzania

Abstract: Objective To describe how demographic characteristics and knowledge of cervical cancer influence screening acceptance among women living in Dar es Salaam, Tanzania.

Hormone Therapy and Different Ovarian Cancers: A National Cohort Study

Abstract: Postmenopausal hormone therapy use increases the risk of ovarian cancer. In the present study, the authors examined the risks of different histologic types of ovarian cancer associated with hormone therapy. Using Danish national registers, the authors identified 909,946 women who were followed from 1995-2005. The women were 50-79 years of age and had no prior hormone-sensitive cancers or bilateral oophorectomy. Hormone therapy prescription data were obtained from the National Register of Medicinal Product Statistics. The National Cancer and Pathology Register provided data on ovarian cancers, including information about tumor histology. The authors performed Poisson regression analyses that included hormone exposures and confounders as time-dependent covariates. In an average of 8.0 years of follow up, 2,681 cases of epithelial ovarian cancer were detected. Compared with never users, women taking unopposed oral estrogen therapy had increased risks of both serous tumors (incidence rate ratio (IRR) = 1.7, 95% confidence interval: 1.4, 2.2) and endometrioid tumors (IRR = 1.5, 95% confidence interval: 1.0, 2.4) but decreased risk of mucinous tumors (IRR = 0.3, 95% confidence interval: 0.1, 0.8). Similar increased risks of serous and endometrioid tumors were found with estrogen/progestin therapy, whereas no association was found with mucinous tumors. Consistent with results from recent cohort studies, the authors found that ovarian cancer risk varied according to tumor histology. The types of ovarian tumors should be given attention in future studies.

Socioeconomic Position and Stage of Cervical Cancer in Danish Women Diagnosed 2005 to 2009

Abstract: Background: To reduce social disparities in cervical cancer survival, it is important to understand the mechanisms by which social position influence cancer prognosis. We investigated the relations between socioeconomic factors, comorbidity, time since last Papanicolau smear and stage at diagnosis in Danish women with cervical cancer. Methods: We identified 1651 cervical cancer cases diagnosed 2005-2009 from the Danish Gynaecological Cancer Database. Date of diagnosis, clinical cancer stage, tumour histology and treating hospital were retrieved; Pap smear registrations were obtained from the Danish Pathology Register; data on comorbid conditions from the Danish National Patients Register; and data on education, income and cohabitation from Statistics Denmark. Logistic regression models were used to analyse the relations between socioeconomic factors and cancer stage in a four-step model, with stepwise inclusion of mediators. Results: The risk for advanced (stage II-IV) compared with early stage cancer (stage I) was increased for women with short and medium education (OR = 2.40; 1.67-3.45 and 1.76; 1.44-2.16), women living without a partner (OR = 1.31; 1.10-1.55) and older women (OR = 1.07; 1.06-1.08 increase per year). The relations between socioeconomic factors and cancer stage were partly mediated by time since last Pap smear test and to a lesser extent by comorbidity. Conclusions: Shorter education, living alone and older age were related to advanced stage cervical cancer, due partly to Pap smear testing and less to comorbidity. Impact: It is relevant to further investigate how to decrease delay in cervical cancer diagnosis among disadvantaged groups.

Risk for cervical intraepithelial neoplasia grade 3 or worse in relation to smoking among women with persistent human papillomavirus infection

Abstract: Background: Smoking has been associated with cervical cancer. We examined whether smoking increases the risk for high-grade cervical lesions in women with high-risk human papillomavirus (HPV) infection. Methods: In a population-based cohort study, 8,656 women underwent a structured interview, and subsequently cervical cells were obtained for HPV DNA testing. Women with high-risk HPV infection and no prevalent cervical disease at baseline ( n = 1,353) were followed through the Pathology Data Bank for cervical lesions for up to 13 years. Separate analyses of women with persistent high-risk HPV infection ( n = 312) were also conducted. HRs for a diagnosis of cervical intraepithelial neoplasia grade 3 or worse/high-grade squamous intraepithelial lesions or worse (CIN3+) and the corresponding 95% confidence intervals (CI) were calculated in the two groups. Results: Among high-risk HPV-positive women, an increased risk for CIN3+ was associated with long-term smoking (≥10 years) and heavy smoking (≥20 cigarettes/d). In the subgroup of women with persistent HPV infection, heavy smoking was also associated with a statistically significantly higher risk for CIN3+ than never smoking (HR, 1.85; 95% CI, 1.05–3.22, adjusted for length of schooling, parity, and HPV type at baseline). The average number of cervical cytology screening tests per year during follow-up did not explain the differences in risk in relation to smoking ( P = 0.4). Conclusions: Smoking is associated with an increased risk for subsequent high-grade cervical lesions in women with persistent high-risk HPV infection. Impact: Our study adds to the understanding of the role of smoking in the natural history of HPV and cervical carcinogenesis. Cancer Epidemiol Biomarkers Prev; 21(11); 1949–55. ©2012 AACR . This article is featured in Highlights of This Issue, [p. 1891][1] [1]: /lookup/volpage/21/1891?iss=11

Predictors of human papillomavirus infection in women undergoing routine cervical cancer screening in Spain: the CLEOPATRE study

Abstract: Human papillomavirus (HPV) is a sexually transmitted infection that may lead to development of precancerous and cancerous lesions of the cervix. The aim of the current study was to investigate socio-demographic, lifestyle, and medical factors for potential associations with cervical HPV infection in women undergoing cervical cancer screening in Spain. The CLEOPATRE Spain study enrolled 3 261 women aged 18–65 years attending cervical cancer screening across the 17 Autonomous Communities. Liquid-based cervical samples underwent cytological examination and HPV testing. HPV positivity was determined using the Hybrid Capture II assay, and HPV genotyping was conducted using the INNO-LiPA HPV Genotyping Extra assay. Multivariate logistic regression was used to identify putative risk factors for HPV infection. A lifetime number of two or more sexual partners, young age (18–25 years), a history of genital warts, and unmarried status were the strongest independent risk factors for HPV infection of any type. Living in an urban community, country of birth other than Spain, low level of education, and current smoking status were also independent risk factors for HPV infection. A weak inverse association between condom use and HPV infection was observed. Unlike monogamous women, women with two or more lifetime sexual partners showed a lower risk of infection if their current partner was circumcised (P for interaction, 0.005) and a higher risk of infection if they were current smokers (P for interaction, 0.01). This is the first large-scale, country-wide study exploring risk factors for cervical HPV infection in Spain. The data strongly indicate that variables related to sexual behavior are the main risk factors for HPV infection. In addition, in non-monogamous women, circumcision of the partner is associated with a reduced risk and smoking with an increased risk of HPV infection.

Use of dairy products, lactose, and calcium and risk of ovarian cancer - results from a Danish case-control study.

Abstract: Background. A number of epidemiological studies have examined the association between use of dairy products and risk of ovarian cancer, but results are conflicting. Using data from a large Danish population-based case-control study we here further examined the association between dairy consumption, lactose, and calcium and risk of overall ovarian cancer and histological types of ovarian cancer. Material and methods. In the period 1995–1999 we included 554 women with epithelial ovarian cancer and 1554 randomly selected age-matched controls (35–79 years). All women participated in a detailed personal interview that included questions about dairy consumption. Data were analysed using multiple logistic regression models. Results. Total dairy intake was associated with ovarian cancer risk (OR = 1.11; 95% CI: 1.07–1.15 per 100 ml/day). The association was strongest for milk [OR = 1.14; 95% CI: 1.03–1.27 per glass (200 ml)/day], soured milk products [OR = 1.49; 95% CI: 1.22–1.81 per portion (250 ml)/day]...

Does hormone replacement therapy and use of oral contraceptives increase the risk of non-melanoma skin cancer?

Abstract: We aimed to examine whether use of hormone replacement therapy (HRT) and oral contraceptives (OC) affect the risk of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) in women. Using data from 29,875 women enrolled in the prospective “Diet, Cancer, and Health” study between 1993 and 1997, women with available information on HRT and OC use at baseline were identified. Statistical analyses were based on the Cox’s proportional hazards model. The mean age at enrollment in the study was 56.7 years, whereas the mean age at the end of follow-up was 67.5 years. 1,175 cases of BCC and 76 cases of SCC were identified in the cohort during follow-up through 2007. The BCC incidence rate ratio was 1.15 (95% CI: 1.07–1.37) for ever users of HRT at baseline compared to never users, whereas risk of BCC was unaffected by duration of HRT use. Ever use of HRT was not associated with SCC risk but a significantly increased risk of 1.35 (95% CI: 1.05–1.72) associated with every 5 years of HRT use was observed. No convincing associations between OC use and BCC or SCC risk were observed. The findings indicated that HRT but not OC may increase the risk of NMSC. However, further studies are warranted as risk estimates for SCC had relatively low precision due to a limited number of SCC cases.

Physical state and viral load as predictive biomarkers for persistence and progression of HPV16-positive cervical lesions: results from a population based long-term prospective cohort study

Abstract: Persistent infection with a high risk (hr) human papillomavirus (HPV) has been established as the main cause of cervical cancer and high-grade cervical intraepithelial neoplasia (CIN3). Because most infections are transient, testing for hrHPV lacks specificity and has a low positive predictive value. It has been suggested that additional parameters like viral load and physical status of the viral genome could improve the effectiveness of HPV-based screening. We investigated the association between HPV16 viral load and physical state with viral persistence or risk of incident CIN3 or worse in a population-based prospective cohort study comprising 8656 women (20-29 years). All participants had two gynecological examinations two years apart and were followed through the nationwide Danish Pathology Data Bank (median follow-up: 12.9 yrs). Seventynine cervical swabs from women with a persistent HPV16 infection were available for analysis. For comparison we selected a random age-matched sample of transiently HPV16 infected women (N=91). Persistently infected women with incident CIN3 or cancer (CIN3+; N=31) were compared to women with normal cytology during follow up (non-progressors; N=39). Quantitative real-time PCR for HPV16E6, E2 and IFNb1 was done to determine the HPV16 viral load and the E2/E6 ratio was used as a surrogate marker for integration. Women with normal cytology who became persistently HPV16 infected had a significantly lower HPV16 load at baseline than women who cleared the infection (median 4.72 copies/cell versus median 20.0 copies/cell, respectively; p=0.0003). There was no difference in viral load at enrollment between women who progressed to CIN3+ and women who stayed cytologically normal (p=0.85). At the second examination viral load tended to be higher in women who progressed, but the difference was not statistically significant (p=0.39). The E2/E6 ratio was shown to be lower in the persistently infected group (p<0.0001) already at the first examination, but no difference between non-progressors and CIN3+ cases was observed at any of the two examinations (p=0.61 and 0.86). Lower viral load and integration of the viral genome are predictive for the persistence of HPV16 DNA, but not for the progression of a persistent HPV16 infection to CIN3+ in women with normal cytology.

The importance of low-risk HPV infection for the risk of abnormal cervical cytology/histology in more than 40 000 Danish women

Abstract: Objectives To estimate the age and type-specific distribution of low-risk (LR) human papillomavirus (HPV) types in cervical samples from women in the general population and to assess the distribution of LR-HPV without the coexistence of high-risk HPV types in different cytology and histology categories. Methods In a cross-sectional study, liquid-based cytology samples (SurePath) were collected over a 3-year period. The samples were HPV tested by Hybrid Capture II (HC2; Digene) and genotyped using a PCR-based assay (INNO-LiPAv2; Innogenetics Inc.). A total of 40 382 women (14–95 years of age) were included in the study. By linkage with the nationwide Pathology Data Bank, the HPV test results were directly linked to cytological diagnoses made from the same samples and to subsequent histology results. Results Overall, 2790 women (6.9%) tested positive for LR-HPV types, with HPV6 and HPV70 being the most frequent types detected, whereas HPV11 was uncommon. The highest prevalence was observed in the youngest age group (≤19 years). The LR-HPV prevalence was 6.3% in women with normal cytology, 33.1% in atypical squamous cells of undetermined significance (ASCUS), 19.6% in low-grade squamous intraepithelial lesion and 12.7% in those with high-grade squamous intraepithelial lesion. When considering women with LR-HPV alone, the prevalence was 2.0% (normal cytology), 11.3% (ASCUS), 2.6% (low-grade squamous intraepithelial lesion) and 0.7% in women with high-grade squamous intraepithelial lesion, respectively. A similar pattern was observed in relation to the histological diagnoses with the majority of LR-HPV infections detected in CIN1 lesions (24.7%). Conclusions LR-HPV types alone are relatively common in ASCUS, whereas LR-HPV types without coexisting high-risk HPV types are virtually never detected in severe cervical lesions.

Use of analgesic drugs and risk of ovarian cancer: results from a Danish case-control study

Abstract: Objective.Theroleofanalgesicdruguseindevelopmentofovariancancerisnotfully understood. We examinedtheassociationbetweenanalgesicuse andrisk ofovarian cancer. In addition, we examined whether the association differed according to histologicaltypes.Design.Population-basedcase–controlstudy.Setting.Denmarkin the period 1995–1999. Population. We included 756 women with epithelial ovarian cancer and 1564 randomly selected control women aged 35–79 years. Methods. Informationonanalgesicdrugusewascollectedfrompersonalinterviews.Analgesic drugsweredividedintothefollowingcategories:anyanalgesics;aspirin;non-aspirin non-steroidal anti-inflammatory drugs; paracetamol; and other analgesic drugs. The association between analgesic drug use and ovarian cancer risk was analysed using multiple logistic regression models. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. Main outcome measures. Epithelial ovarian cancer. Results. Women with a regular use of any analgesics (OR = 0.79; 95% CI 0.62 − 1.01) or aspirin (OR = 0.68; 95% CI 0.46 − 1.02) had a decreased risk of ovarian cancer, although not statistically significant. Regular use of non-aspirin non-steroidal anti-inflammatory drugs, paracetamol or other analgesics did not decrease ovarian cancer risk. Use of any analgesics (OR = 0.72; 95% CI 0.53–0.98) or aspirin (OR = 0.60; 95% CI 0.36–1.00) resulted in a statistically significant decreased risk of serous ovarian cancer but not mucinous or other ovarian tumors. Conclusion.Inaccordancewithmostpreviousstudies,ourresultsindicateapossible inverse association between analgesic use, particularly aspirin, and ovarian cancer risk. Abbreviations: CI, confidence interval; COX, cyclo-oxygenase; NSAID, nonsteroidal anti-inflammatory drug; OR, odds ratio.

Risk factors for VIA positivity and determinants of screening attendances in Dar es Salaam, Tanzania

Abstract: Tanzania is among the countries in the world where the cervical cancer incidence is estimated to be highest. Acknowledging an increase in the burden of cervical cancer, VIA was implemented as a regional cervical cancer screening strategy in Tanzania in 2002. With the aim of describing risk factors for VIA positivity and determinants of screening attendances in Tanzania, this paper present the results from a comparative analysis performed among women who are reached and not reached by the screening program”. 14 107 women aged 25–59 enrolled in a cervical cancer screening program in Dar es Salaam in the period 2002 – 2008. The women underwent VIA examination and took part in a structured questionnaire interview. Socioeconomic characteristics, sexual behavior, HIV status and high-risk (HR) HPV infection were determined in a subpopulation of 890 who participated and 845 who did not participate in the screening. Being widowed/separated OR=1.41 (95% CI: 1.17-1.66), of high parity OR=3.19 (95% CI: 1.84-5.48) of low education OR= 4.30 (95% CI: 3.50-5.31) and married at a young age OR=2.17 (95% CI: 1.37-3.07) were associated with being VIA positive. Women who participated in the screening were more likely to be HIV positive OR= 1.59 (95% CI. 1.14-2.25) in comparison with women who had never attended screening, while no difference was found in the prevalence of HR-HPV infection among women who had attended screening and women who had not attended screening. Women who are widowed/separated, of high parity, of low education and married at a young age are more likely to be VIA positive and thus at risk of developing cervical cancer. The study further documents that a referral linkage between the HIV care and treatment program and the cervical cancer screening program is in place in the setting studied, where HIV positive were more likely to participate in the cervical cancer screening program than HIV negative women.

Hormone therapy and ovarian borderline tumors: a national cohort study

Abstract: Little is known about the influence of postmenopausal hormone therapy on the risk of ovarian borderline tumors. We aimed at assessing the influence of different hormone therapies on this risk. A total of 909,875 Danish women 50–79 years old without previous hormone-sensitive cancers or bilateral oophorectomy were followed in this nationwide cohort study 1995–2005. The National Register of Medicinal Product Statistics provided exposure information on all women who redeemed prescriptions on hormone therapy. The National Cancer and Pathology Register provided data on borderline ovarian tumors. Information on confounding factors was available from other national registers. Poisson regression analyses provided risk estimates with hormone exposures as time-dependent covariates. In an average of 8.0 years of follow-up, 703 incident ovarian borderline tumors were detected. Compared with never users, hormone use for more than 4 years increased the risk of borderline tumors: relative risk (RR) 1.40; 95% confidence interval (CI), 1.09–1.81. Combined estrogen and progestin therapy for more than 4 years increased the risk: RR 1.49 (1.10–2.01), with no difference between cyclic and continuous combined therapy (p = 0.83); RR 1.56 (1.08–2.25) and 1.45 (0.87–2.43), respectively. The RR with estrogen therapy did not differ significantly from RR with combined therapy (p = 0.58): RR 1.27 (0.82–1.98). Disregarding the type of hormone therapy, hormone use for 4 years or less did not increase the risk of borderline tumors. Combined hormone therapy for more than 4 years increases the risk of ovarian borderline tumors.

Genital warts in men: a large population-based cross-sectional survey of Danish men

Abstract: Objectives To estimate the occurrence of and risk factors associated with genital warts in Danish men Methods We conducted a cross-sectional, questionnaire-based study among almost 23 000 men aged 18–45 years, randomly sampled from the general population of Denmark. Data was collected on self-reported clinically diagnosed genital warts, and various lifestyle habits. Results Ever having had clinically diagnosed genital warts was reported by 7.9% of the men. The median age at first occurrence was 22 years. Genital warts within the previous 12 months were reported by 0.92% of the men, with a peak of 1.83% among men aged 21–24 years. The likelihood of reporting genital warts was strongly correlated with the lifetime number of sex partners (OR 8.0; 95% CI 6.0 to 10.8 for ≥15 partners vs 1–2 partners). Other factors associated with an increased risk for genital warts included ever having smoked and having had other sexually transmitted infections. Conclusions Almost 8% of Danish men aged 18–45 years reported having had a diagnosis of genital warts. The results provide baseline information for developing and monitoring prevention strategies against genital warts, such as vaccination against human papillomavirus types 6 and 11.

Limited prognostic value of tissue protein expression levels of cyclin E in Danish ovarian cancer patients: from the Danish 'MALOVA' ovarian cancer study.

Abstract: The primary objective of this study was to assess the expression of cyclin E in tumour tissues from 661 patients with epithelial ovarian tumours. The second was to evaluate whether cyclin E tissue expression levels correlate with clinico-pathological parameters and prognosis of the disease. Using tissue arrays (TA), we analysed the cyclin E expression levels in tissues from 168 women with borderline ovarian tumours (BOT) (147 stage I, 4 stage II, 17 stage III) and 493 Ovarian cancer (OC) patients (127 stage I, 45 stage II, 276 stage III, 45 stage IV). Using a 10% cut-off level for cyclin E overexpression, 20% of the BOTs were positive with a higher proportion of serous than mucinous tumours. Sixty-two per cent of the OCs were positive for cyclin E expression with the highest percentage found in clear cell carcinomas. Results based on univariate and multivariate survival analyses with a 10% cut-off value showed that cyclin E had no independent prognostic value. In conclusion, we found cyclin E expression in tumour tissue to be of limited prognostic value to Danish OC patients.

Genome-wide association study for ovarian cancer susceptibility using pooled DNA.

Abstract: Recent Genome-Wide Association Studies (GWAS) have identified four low-penetrance ovarian cancer susceptibility loci. We hypothesized that further moderate- or low-penetrance variants exist among the subset of single-nucleotide polymorphisms (SNPs) not well tagged by the genotyping arrays used in the previous studies, which would account for some of the remaining risk. We therefore conducted a time- and cost-effective stage 1 GWAS on 342 invasive serous cases and 643 controls genotyped on pooled DNA using the high-density Illumina 1M-Duo array. We followed up 20 of the most significantly associated SNPs, which are not well tagged by the lower density arrays used by the published GWAS, and genotyping them on individual DNA. Most of the top 20 SNPs were clearly validated by individually genotyping the samples used in the pools. However, none of the 20 SNPs replicated when tested for association in a much larger stage 2 set of 4,651 cases and 6,966 controls from the Ovarian Cancer Association Consortium. Given that most of the top 20 SNPs from pooling were validated in the same samples by individual genotyping, the lack of replication is likely to be due to the relatively small sample size in our stage 1 GWAS rather than due to problems with the pooling approach. We conclude that there are unlikely to be any moderate or large effects on ovarian cancer risk untagged by less dense arrays. However, our study lacked power to make clear statements on the existence of hitherto untagged small-effect variants.

[HPV infection might play a role in the development of non-melanoma skin cancer in immunocompetent individuals].

Abstract: Human papillomavirus (HPV) is necessary for the development of cervical cancer and is also involved in vulvar, anus, penis and head and neck cancer. Little is known about the role of HPV infection in non-melanoma skin cancer (NMSC). Through a systematic review of the literature, we studied the HPV prevalence in immunocompetent individuals in relation to NMSC. We found that HPV, including multiple HPV types, tended to be more prevalent in NMSC, especially in squamous cell carcinoma (SCC) compared to basal cell carcinoma and healthy skin, indicating a potential link between HPV and SCC in immunocompetent individuals.

Questionable evidence of increasing incidence of invasive penile cancer in Denmark: authors reply

Abstract: We appreciate the interest and comments of Dr. Frisch et al. on our paper about the incidence of penile cancer and high-grade penile intraepithelial neoplasia grades 2 and 3 (PIN 2/3) in Denmark. As they correctly pointed out, we conducted the study using data from the Danish Cancer Registry as well as from the Danish Pathology Data Bank (PDB). Even though we have previously published incidence studies including only data from the Danish Cancer Registry, the addition of data from the PDB is based on our recent observation that at least for some cancers this will add a number of incident cases not identified in the Danish Cancer Registry. As penile cancer is a rare cancer, we found it important to take advantage of the existence of multiple data sources. With this rare cancer, the analyses may be especially vulnerable to underreporting and by including several data sources, we tried to reduce this potential bias. In stead of only displaying the combined results, we chose to present the data separately to be as transparent as possible. We fully agree with Dr. Frisch et al. that the PDB also has underreporting in the initial period and is most likely not complete until around the mid-1990s, and we also agree that there may be too much focus on the trend going all the way back from 1978 in our paper and that the main interpretation of the incidence of penile cancer should focus on the more recent years in the analyses in our paper. As mentioned by Dr. Frisch et al., a Dutch study has also looked at incidence of penile carcinoma and carcinoma in situ [1]. We have performed additional analyses so that comparison between the two studies is straighter forward. In line with that study, we looked at all penile carcinomas, all invasive penile carcinomas and all non-invasive (in situ) penile carcinomas, and we found that the incidence of all penile carcinomas increased from 1.2 in 1997–1998 to 1.8 in 2007–2008. However, the increase was mostly pronounced for the noninvasive penile carcinomas with an estimated average annual percentage change of 1.2 % (p = 0.03), whereas the estimated annual percentage change for invasive carcinomas in this period (0.9 %) did not reach statistical significance (p = 0.34) pointing to an increase in incidence especially of carcinoma in situ. These results are in line with the results of the Dutch study [1]. In our study, we calculated the incidence of the PIN 2/3 lesions as lesions with [2-year interval and found that the incidence increased from 0.5 to 0.9 per 100,000 men-years in the study period. A more conservative way to assess the incidence of these pre-invasive lesions is, of course, to count only the first episode of PIN 2/3 in each man. When we performed this analysis, we found virtually the same result with the incidence increasing from 0.47 to 0.82 per 100,000 men-years (Fig. 1). We again thank Dr. Frisch et al. for bringing some of their insightful thoughts to our paper.