Cardiovascular events after elective colorectal cancer surgery in patients with stage I-III disease with no previous cardiovascular disease.

BACKGROUND: The risk of cardiovascular events in patients treated for colorectal cancer is debated due to diverging results in previous studies. Colorectal cancer and cardiovascular disease share several risk factors such as physical inactivity, obesity, and smoking. Information about confounding covariates and follow-up time are therefore essential to address the issue. This study aims to investigate the risk of new-onset cardiovascular events for patients with stage I-III colorectal cancer receiving elective surgery compared to a matched population. MATERIAL AND METHODS: Using a prospective cohort, we compared cardiovascular events among 876 patients treated with elective surgery for incident stage I-III colorectal cancer diagnosed between January 1st, 2001 and December 31st, 2016 to a cancer-free cohort matched by age, sex, and time since enrollment (N = 3504). Regression analyses were adjusted for lifestyle, cardiovascular risk factors, and comorbidity. Multivariable analyses were used to identify risk factors associated with cardiovascular events in the postoperative (<90 days of elective surgery) and long-term phase (>90 days after elective surgery). RESULTS: After a median follow-up of 3.9 years, the hazard ratio (HR) for incident heart failure was 1.53 (95% CI 1.02-2.28) among patients operated for colorectal cancer. The postoperative risk of myocardial infarction or angina pectoris was associated with the use of lipid-lowering drugs. Long-term risks of cardiovascular events were ASA-score of III+IV and lipid-lowering drugs with HRs ranging from 2.20 to 15.8. Further, the use of antihypertensive drugs was associated with an HR of 2.09 (95% CI 1.06-4.13) for angina pectoris or acute myocardial infarction. Heart failure was associated with being overweight, diabetes, and anastomosis leakage. CONCLUSION: We observed an increased hazard of heart failure in patients operated on for stage I-III colorectal cancer compared to cancer-free comparisons. We identified several potential risk factors for cardiovascular events within and beyond 90 days of elective surgery.

In Utero Exposure to Hormonal Contraception and Mortality in Offspring with and without Cancer: A Nationwide Cohort Study.

Approximately 400 million women of reproductive age use hormonal contraceptives worldwide. Eventually, pregnancy sometimes occurs due to irregular use. Use in early pregnancy is found to be associated with child morbidities including cancer, the main reason for disease-related death in children. Here, we add the missing piece about in utero exposure to hormonal contraception and mortality in offspring, including assessments of prognosis in children with cancer. In utero exposure to hormonal contraception may be associated with death since we found a hazard ratio (HR) of 1.22 (95% confidence interval (CI) 1.01-1.48) compared to children of mothers with previous use. The HRs were 1.22 (95% CI 0.99-1.13) for oral combined products and 2.92 (95% CI 1.21-7.04) for non-oral progestin-only products. A poorer prognosis was also found in exposed children with leukemia (3.62 (95% CI: 1.33-9.87)). If causal, hormonal contraception in pregnancy seems detrimental for offspring health and a marker of poorer prognosis in children with leukemia.

High-resolution anoscopy can diagnose precursors to anal cancer.

Anal cancer risk is increased in certain risk groups including people living with HIV (PLWH), especially in men who have sex with men, but also in organ transplant recipients and women with a history of cervical or vulva dysplasia or cancer. High-resolution anoscopy (HRA) is a tool to diagnose anal high-grade squamous intraepithelial lesions (HSIL), and HRA-guided treatment of anal HSIL has been shown to reduce the risk of anal cancer in PLWH. The purpose of this review is to increase the awareness of HRA but also of tertiary prevention by digital anal rectal examination.

Risk of nonovarian cancer in a nationwide-based study of nearly 5000 women with borderline ovarian tumors in Denmark.

Evidence regarding cancer risk after borderline ovarian tumors (BOTs) is limited. We conducted a nationwide cohort study examining the incidence of nonovarian cancers in women with serous or mucinous BOTs compared with the general female population with up to 41 years of follow-up. Through the nationwide Pathology Registry, we identified nearly 5000 women with BOTs (2506 serous and 2493 mucinous) in Denmark, 1978 to 2018. We computed standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) as relative risk estimates of specific nonovarian cancers. Compared with general female population rates, women with serous BOTs had increased rates of particularly malignant melanoma (SIR = 1.9; 95% CI: 1.3-2.6), thyroid cancer (SIR = 3.0; 95% CI: 1.4-5.4) and myeloid leukemia (SIR = 3.2; 95% CI: 1.5-5.8), and women with mucinous BOTs had elevated rates of lung cancer (SIR = 1.7; 95% CI: 1.3-2.1), pancreatic cancer (SIR = 1.9; 95% CI: 1.2-2.9) and myeloid leukemia (SIR = 2.3; 95% CI: 0.9-4.7). We found no convincing association with neither breast nor colorectal cancer in women with BOTs. This is the first large nationwide study showing that women with specific types of BOTs have increased risks of several nonovarian cancers, likely due to some shared risk factors or genetic characteristics.

Base of tongue/tonsillar and laryngeal cancer in Denmark 1994-2018: Temporal trends in incidence according to education and age.

OBJECTIVES: Base-of-tongue (BOT)/tonsillar cancer incidence is rising, primarily due to human papillomavirus; meanwhile, rates of the mainly smoking-associated laryngeal cancer is declining. Little is known about whether these trends are seen in all socioeconomic levels and age-groups. We describe incidence trends of BOT/tonsillar and laryngeal cancer in Denmark 1994-2018 by educational level and age. METHODS: BOT/tonsillar and laryngeal cancer cases diagnosed 1994-2018 were identified from the Danish Cancer Registry. We obtained individual-level educational information from nationwide registries. We estimated age-standardized incidence rates of BOT/tonsillar and laryngeal cancer according to sex, education and age. Temporal incidence trends were evaluated by the average annual percentage change (AAPC) with corresponding 95% confidence intervals (CIs) using linear and Poisson regression models for age-standardized incidence rates. RESULTS: We identified 4245 individuals with BOT/tonsillar cancer and 6123 with laryngeal cancer. BOT/tonsillar cancer incidence increased among men with short (AAPC:3.4, 95% CI 2.1;4.6) and long (AAPC:5.1, 95% CI 3.2;7.1) education, and all age-groups, while decreased from 2012 among men with medium education (AAPC:-4.3, 95 %CI -7.6;-1.0). Laryngeal cancer incidence decreased from 2007 in men with medium (AAPC:-4.7, 95% CI -6.7;-2.7) and long (AAPC:-2.4, 95% CI -3.4;-1.4) education, and all age-groups, whereas increased in men with short education (AAPC:1.0, 95% CI 0.2;1.8). Similar trends were seen among women. CONCLUSIONS: Over the last 25 years, BOT/tonsillar cancer incidence in Denmark has generally increased in all age-groups and educational levels. In contrast, social inequality was seen in laryngeal cancer trends as incidence decreased in individuals with medium and long education, while incidence increased in individuals with short education.

Incidence of HPV-related Anogenital Intraepithelial Neoplasia and Cancer in Men With Diabetes Compared With the General Population.

BACKGROUND: Diabetes may increase risk of human papillomavirus (HPV)-related precancer and cancer. We estimated incidence of penile and anal high-grade intraepithelial neoplasia (hgPeIN, hgAIN) and squamous cell carcinoma (SCC) in men with diabetes compared with the entire Danish male population without diabetes. METHODS: In this registry-based cohort study, we included all men born 1916-2001 and residing in Denmark (n = 2,528,756). From nationwide registries, we retrieved individual-level information on diabetes, educational level, and diagnoses of hgPeIN, hgAIN, penile SCC, and anal SCC. We used Poisson regression models to estimate incidence of hgPeIN, hgAIN, penile SCC, and anal SCC as a function of diabetes status, attained age, calendar period, and education. We estimated incidence rate ratios (IRRs) of each outcome in men with diabetes compared with nondiabetic men, both for diabetes overall and separately for type 1 (T1D) and type 2 diabetes (T2D). RESULTS: Men with diabetes had increased incidence rate of penile SCC compared with nondiabetic men (IRR = 1.5, 95% CI = 1.2, 1.9). We saw similar trends for anal SCC, hgPeIN, and hgAIN. The combined incidence rate of penile and anal SCC was increased in men with T2D (IRR = 1.5, 95% CI = 1.3, 1.8), but not with T1D (IRR = 0.53, 95% CI = 0.20, 1.4) compared with men without diabetes. CONCLUSION: The incidence of penile and anal high-grade intraepithelial neoplasia and SCC in men with diabetes was increased compared with men without diabetes. For penile and anal SCCs, this was primarily due to an increased risk in men with T2D.

HPV types, cervical high-grade lesions and risk factors for oncogenic human papillomavirus infection among 3416 Tanzanian women.

OBJECTIVE: The objective of the present study was to assess the prevalence and type-specific distribution of cervical high-risk (HR) human papillomavirus (HPV) among women with normal and abnormal cytology, and to describe risk factors for HR HPV among HIV-positive and HIV-negative women in Tanzania. METHODOLOGY: A cross-sectional study was conducted in existing cervical cancer screening clinics in Kilimanjaro and Dar es Salaam. Cervical specimens were obtained from women aged 25-60 years. Samples were shipped to Denmark for cytological examination, and to Germany for HR HPV testing (using Hybrid Capture 2) and genotyping (using LiPaExtra). Risk factors associated with HPV were assessed by multivariable logistic regression analysis. RESULT: Altogether, 4080 women were recruited with 3416 women contributing data for the present paper, including 609 HIV-positive women and 2807 HIV-negative women. The overall HR HPV prevalence was 18.9%, whereas the HR HPV prevalence in women with high-grade squamous intraepithelial lesions (HSILs) was 92.7%. Among HPV-positive women with HSIL, HPV16 (32.5%) and HPV58 (19.3%) were the the most common types followed by HPV18 (16.7%) and HPV52 (16.7%). Factors associated with HR HPV included younger age, increasing number of partners and early age at first intercourse. Similar risk factors were found among HIV-positive and HIV-negative women. In addition, among HIV-positive women, those with CD4 counts <200 cells/mm3 had an increased risk of HR HPV (OR 2.2; 95% CI 1.2 to 4.8) compared with individuals with CD4 count ≥500 cells/mm3. CONCLUSION: Given the HPV distribution among Tanzanian women, the current HPV vaccination in Tanzania using quadrivalent vaccine may be considered replaced by the nonavalent vaccine in the future. In addition, appropriate antiretroviral treatment management including monitoring of viremia may decrease the burden of HR HPV in HIV-positive women.

Prevalence of human papillomavirus in oral epithelial dysplasia: Systematic review and meta-analysis.

The purpose of this systematic review and meta-analysis was to estimate the overall and type-specific prevalence of human papillomavirus (HPV) DNA in oral epithelial dysplasia and assess p16INK4a overexpression in relation to HPV-status. A systematic literature search identified 31 eligible studies (832 cases) evaluating the presence of HPV DNA in oral epithelial dysplasia cases by PCR. Of these, six studies evaluated p16INK4a overexpression in relation to HPV-status. The overall pooled prevalence of HPV DNA in oral epithelial dysplasia was 27.2% (95% CI: 17.6-38.1). We observed substantial interstudy heterogeneity, which could not be explained by differences in continent, tissue type, or severity of epithelial dysplasia. HPV16 was the predominant genotype detected. Moreover, 62.2% of HPV positive and 17.8% of HPV negative oral epithelial dysplasia samples stained intensively positive for p16INK4a . This meta-analysis found that 27% of oral epithelial dysplasia harbor HPV DNA. Whether this represents a transient infection or has a carcinogenic role is unknown.

High-risk human papillomavirus infection in female and subsequent risk of infertility: a population-based cohort study.

OBJECTIVE: To study whether infection with high-risk human papillomavirus (HPV), registered both as a single HPV positive test and as HPV persistence, increases the risk of female factor infertility in later reproductive life. DESIGN: Population-based cohort study. SETTING: Not applicable. PATIENT(S): A random sample of 11,088 women (20-29 years of age at enrollment) tested for cervical HPV at enrollment during 1991-93 and again after 2 years. Information on female factor infertility was obtained by linkage to the Danish Infertility Cohort. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Follow-up for each study participant was the period from the date of enrollment or date of the second visit until diagnosis of female factor infertility (main outcome), conception, death, emigration, disappearance, or end of study period. Data were analyzed by means of a Cox proportional hazards regression model. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between HPV status and female factor infertility after adjustment for potentially confounding factors were determined. RESULT(S): After relevant exclusions, 10,595 women were eligible for analysis, 1,861 (17.6%) of whom were high-risk HPV positive at the first visit. There was no association between a positive HPV test at first visit (HR = 0.88; 95% CI, 0.75-1.02) or positivity for the same high-risk HPV type at the first and second visit (persistence; HR = 0.97; 95% CI, 0.66-1.44) and subsequent risk of female factor infertility in reproductive life. CONCLUSION(S): We found no association between a high-risk HPV infection and risk of female factor infertility, neither for a single HPV positive test nor for a persistent HPV infection.

Prevalence of human papillomavirus DNA and p16INK4a in penile cancer and penile intraepithelial neoplasia: a systematic review and meta-analysis.

BACKGROUND: Although previous meta-analyses have examined human papillomavirus (HPV) DNA prevalence in penile cancer, none, to our knowledge, have assessed pooled HPV DNA prevalence in penile intraepithelial neoplasia or p16INK4a percent positivity in penile cancer and penile intraepithelial neoplasia. Therefore, we aimed to examine the prevalence of HPV DNA and p16INK4a positivity in penile cancer and penile intraepithelial neoplasia worldwide. METHODS: In this systematic review and meta-analysis, we searched PubMed, Embase, and the Cochrane Library until July 24, 2017, for English-language articles published from Jan 1, 1986, onwards reporting the prevalence of HPV DNA and p16INK4a positivity, either alone or in combination, in at least five cases of penile cancer or penile intraepithelial neoplasia. Only studies that used PCR or hybrid capture for the detection of HPV DNA and immunohistochemical staining or methylation for the detection of p16INK4a were included. Data were extracted and subsequently crosschecked, and inconsistencies were discussed to reach consensus. Using random-effects models, we estimated the pooled prevalence and 95% CI of HPV DNA and p16INK4a positivity in penile cancer and penile intraepithelial neoplasia, stratifying by histological subtype and HPV DNA or p16INK4a detection method. Type-specific prevalence of HPV6, HPV11, HPV16, HPV18, HPV31, HPV33, and HPV45 in penile cancer was estimated. FINDINGS: Our searches identified 1836 non-duplicate records, of which 73 relevant papers (71 studies) were found to be eligible. The pooled HPV DNA prevalence in penile cancer (52 studies; n=4199) was 50·8% (95% CI 44·8-56·7; I2=92·6%, pheterogeneity<0·0001). A high pooled HPV DNA prevalence was seen in basaloid squamous cell carcinomas (84·0%, 95% CI 71·0-93·6; I2=48·0%, pheterogeneity=0·0197) and in warty-basaloid carcinoma (75·7%, 70·1-81·0; I2=0%, pheterogeneity=0·52). The predominant oncogenic HPV type in penile cancer was HPV16 (68·3%, 95% CI 58·9-77·1), followed by HPV6 (8·1%, 4·0-13·7) and HPV18 (6·9%, 2·9-12·4). The pooled HPV DNA prevalence in penile intraepithelial neoplasia (19 studies; n=445) was 79·8% (95% CI 69·3-88·6; I2=83·2%, pheterogeneity<0·0001). The pooled p16INK4a percent positivity in penile cancer (24 studies; n=2295) was 41·6% (95% CI 36·2-47·0; I2=80·6%, pheterogeneity<0·0001), with a high pooled p16INK4a percent positivity in HPV-related squamous cell carcinoma (85·8%, 95% CI 72·1-95·4; I2=56·4%, pheterogeneity=0·0011) as compared with non-HPV-related squamous cell carcinoma (17·1%, 7·9-29·1; I2=78·3%, pheterogeneity<0·0001). Moreover, among HPV-positive cases of penile cancer, the p16INK4a percent positivity was 79·6% (95% CI 65·7-90·7; I2=89·9%, pheterogeneity<0·0001), compared with 18·5% (9·6-29·6; I2=89·3%, pheterogeneity<0·0001) in HPV-negative penile cancers. The pooled p16INK4a percent positivity in penile intraepithelial neoplasia (six studies; n=167) was 49·5% (95% CI 18·6-80·7). INTERPRETATION: A large proportion of penile cancers and penile intraepithelial neoplasias are associated with infection with HPV DNA (predominantly HPV16), emphasising the possible benefits of HPV vaccination in men and boys. FUNDING: None.

Self-perceived risk of STIs in a population-based study of Scandinavian women.

OBJECTIVE: This study examined the associations between current behaviours/characteristics and self-perceived risk for STIs, among randomly selected women aged 18-45 years from Denmark, Norway and Sweden. METHOD: A population-based, cross-sectional, questionnaire study (paper based, web based and telephone based) was conducted during 2011-2012. We compared medium-high STI risk perception with no/low risk perception. The associations were explored for women who had ever had sexual intercourse and for women with a new partner in the last 6 months using multivariable logistic regression. RESULT: The overall prevalence of medium-high STI risk perception was 7.4%. It was highest among women aged 18-24 years (16.2%) and among the Danish women (8.8%). Number of new sexual partners in the last 6 months (≥3vs 0 partners, OR 14.94, 95% CI 13.20 to 16.94) was strongly associated with medium-high STI risk perception. Among women with a new partner in the last 6 months, lack of condom use increased medium-high STI risk perception (OR 1.73, 95% CI 1.52 to 1.96). Genital warts in the last year, binge drinking and being single were associated with increased risk perception and remained statistically significant after additional adjustments were made for number of new partners and condom use with new partners in the last 6 months. CONCLUSION: Subjective perception of risk for STI was associated with women's current risk-taking behaviours, indicating women generally are able to assess their risks for STIs. However, a considerable proportion of women with multiple new partners in the last 6 months and no condom use still considered themselves at no/low risk for STI.

Analyses of germline variants associated with ovarian cancer survival identify functional candidates at the 1q22 and 19p12 outcome loci.

We previously identified associations with ovarian cancer outcome at five genetic loci. To identify putatively causal genetic variants and target genes, we prioritized two ovarian outcome loci (1q22 and 19p12) for further study. Bioinformatic and functional genetic analyses indicated that MEF2D and ZNF100 are targets of candidate outcome variants at 1q22 and 19p12, respectively. At 19p12, the chromatin interaction of a putative regulatory element with the ZNF100 promoter region correlated with candidate outcome variants. At 1q22, putative regulatory elements enhanced MEF2D promoter activity and haplotypes containing candidate outcome variants modulated these effects. In a public dataset, MEF2D and ZNF100 expression were both associated with ovarian cancer progression-free or overall survival time. In an extended set of 6,162 epithelial ovarian cancer patients, we found that functional candidates at the 1q22 and 19p12 loci, as well as other regional variants, were nominally associated with patient outcome; however, no associations reached our threshold for statistical significance (p<1×10-5). Larger patient numbers will be needed to convincingly identify any true associations at these loci.

Maternal fertility problems and risk for transient neonatal diabetes mellitus.

AIMS: The study of imprinting disorders in the context of infertility and its treatment is important, as studies have indicated an increased risk. In this study, we evaluated the risk of transient neonatal diabetes mellitus (TNDM), defined here as diabetes mellitus presenting within the first six weeks of life, in children born to women with fertility problems. METHODS: This nationwide register-based cohort study comprised all 2,107,837 children born in Denmark between 1977 and 2010. Of these, 121,044 (5.7%) children were born to women with fertility problems. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between maternal fertility status and the risk for TNDM. RESULTS: A total of 103 children developed TNDM during the follow-up period. Children born to women with fertility problems had an elevated risk for TNDM, after adjustment for birth year, maternal age at birth and parental history of diabetes, although this was not statistically significant (HR = 1.49; 95% CI 0.73-3.03). The risk of children born in the period 1994-2010 (a period with more comprehensive information on maternal fertility problems and with more invasive fertility treatment procedures) was increased almost twofold (HR = 1.92; 95% CI 0.92-4.00) but was still not statistically significant. CONCLUSIONS: Our results indicate that children born to women with fertility problems, particularly after 1993, may be at an elevated risk for TNDM. As the increased risks were not statistically significant, however, the finding may be due to chance.

Does stage of cancer, comorbidity or lifestyle factors explain educational differences in survival after endometrial cancer? A cohort study among Danish women diagnosed 2005-2009.

BACKGROUND: Several studies have documented an association between socioeconomic position and survival from gynaecological cancer, but the mechanisms are unclear. OBJECTIVE: The aim of this study was to examine the association between level of education and survival after endometrial cancer among Danish women; and whether differences in stage at diagnosis and comorbidity contribute to the educational differences in survival. METHODS: Women with endometrial cancer diagnosed between 2005 and 2009 were identified in the Danish Gynaecological Cancer Database, with information on clinical characteristics, surgery, body mass index (BMI) and smoking status. Information on highest attained education, cohabitation and comorbidity was obtained from nationwide administrative registries. Logistic regression models were used to determine the association between level of education and cancer stage and Cox proportional hazards model for analyses of overall survival. RESULTS: Of the 3638 patients identified during the study period, 787 had died by the end of 2011. The group of patients with short education had a higher odds ratio (OR) for advanced stage at diagnosis, but this was not statistically significant (adjusted OR 1.20; 95% CI 0.97-1.49). The age-adjusted hazard ratio (HR) for dying of patients with short education was 1.47 (CI 95% 1.17-1.80). Adjustment for cohabitation status, BMI, smoking and comorbidity did not change HRs, but further adjustment for cancer stage yielded a HR of 1.36 (1.11-1.67). CONCLUSION: Early detection in all educational groups might reduce social inequalities in survival, however, the unexplained increased risk for death after adjustment for prognostic factors, warrants increased attention to patients with short education in all age groups throughout treatment and rehabilitation.

Use of the nonavalent HPV vaccine in individuals previously fully or partially vaccinated with bivalent or quadrivalent HPV vaccines.

With the availability of the nonavalent human papillomavirus (HPV) vaccine, vaccinees, parents and healthcare providers need guidance on how to complete an immunization course started with the bi- or quadrivalent vaccine and whether to revaccinate individuals who have completed a full immunization course with the bi- or quadrivalent vaccine. To answer these questions three parameters should be considered: age at the start of vaccination (9 to 14 years of age versus 15 years and older, the cut-off for 2 or 3 doses schedule), the number of doses already received and the time interval between doses. Based on a number of scenarios, we propose that the 9-valent vaccine can be used to complete an incomplete vaccination regimen or might be added to a previous completed schedule to extend protection.

The influence of hormone therapies on colon and rectal cancer.

Exogenous sex hormones seem to play a role in colorectal carcinogenesis. Little is known about the influence of different types or durations of postmenopausal hormone therapy (HT) on colorectal cancer risk. A nationwide cohort of women 50-79 years old without previous cancer (n = 1,006,219) were followed 1995-2009. Information on HT exposures was from the National Prescription Register and updated daily, while information on colon (n = 8377) and rectal cancers (n = 4742) were from the National Cancer Registry. Potential confounders were obtained from other national registers. Poisson regression analyses with 5-year age bands included hormone exposures as time-dependent covariates. Use of estrogen-only therapy and combined therapy were associated with decreased risks of colon cancer (adjusted incidence rate ratio 0.77, 95 % confidence interval 0.68-0.86 and 0.88, 0.80-0.96) and rectal cancer (0.83, 0.72-0.96 and 0.89, 0.80-1.00), compared to never users. Transdermal estrogen-only therapy implied more protection than oral administration, while no significant influence was found of regimen, progestin type, nor of tibolone. The benefit of HT was stronger for long-term hormone users; and hormone users were at lower risk of advanced stage of colorectal cancer, which seems supportive for a causal association between hormone therapy and colorectal cancer.

Contribution of Germline Mutations in the RAD51B, RAD51C, and RAD51D Genes to Ovarian Cancer in the Population.

PURPOSE: The aim of this study was to estimate the contribution of deleterious mutations in the RAD51B, RAD51C, and RAD51D genes to invasive epithelial ovarian cancer (EOC) in the population and in a screening trial of individuals at high risk of ovarian cancer. PATIENTS AND METHODS: The coding sequence and splice site boundaries of the three RAD51 genes were sequenced and analyzed in germline DNA from a case-control study of 3,429 patients with invasive EOC and 2,772 controls as well as in 2,000 unaffected women who were BRCA1/BRCA2 negative from the United Kingdom Familial Ovarian Cancer Screening Study (UK_FOCSS) after quality-control analysis. RESULTS: In the case-control study, we identified predicted deleterious mutations in 28 EOC cases (0.82%) compared with three controls (0.11%; P < .001). Mutations in EOC cases were more frequent in RAD51C (14 occurrences, 0.41%) and RAD51D (12 occurrences, 0.35%) than in RAD51B (two occurrences, 0.06%). RAD51C mutations were associated with an odds ratio of 5.2 (95% CI, 1.1 to 24; P = .035), and RAD51D mutations conferred an odds ratio of 12 (95% CI, 1.5 to 90; P = .019). We identified 13 RAD51 mutations (0.65%) in unaffected UK_FOCSS participants (RAD51C, n = 7; RAD51D, n = 5; and RAD51B, n = 1), which was a significantly greater rate than in controls (P < .001); furthermore, RAD51 mutation carriers were more likely than noncarriers to have a family history of ovarian cancer (P < .001). CONCLUSION: These results confirm that RAD51C and RAD51D are moderate ovarian cancer susceptibility genes and suggest that they confer levels of risk of EOC that may warrant their use alongside BRCA1 and BRCA2 in routine clinical genetic testing.

Human Papillomavirus Infection Among 2460 Men in Denmark: Prevalence in Relation to Age Using 2 Human Papillomavirus DNA Testing Methods.

BACKGROUND: It is crucial to understand the epidemiology and natural history of human papillomavirus (HPV) infection in both men and women, to prevent the increasing HPV-related disease burden in men. Data on HPV prevalence among men in the general population are limited. In this cross-sectional population-based study, we aimed to estimate genital HPV infection prevalence in Danish men using 2 different test methods. METHODS: Penile swab samples from 2460 male employees and conscripts at military barracks in Denmark were tested for HPV DNA with the hybrid capture 2 (HC2) method, and a polymerase chain reaction (PCR) assay, Inno-LiPA. The overall and age- and type-specific prevalence of HPV infection with 95% confidence intervals (CIs) were estimated, and the correlation between the 2 assays was assessed. RESULTS: The overall HPV prevalence was 22.2% (95% CI, 20.6-23.9) in the HC2 test and 41.8% (95% CI, 39.9-43.8) with PCR. Of the PCR-positive samples, 50.9% were negative in the HC2 test. Of 183 PCR-positive samples that could not be genotyped (HPVX), 88.0% (95% CI, 83.2-92.7) were HC2 negative. The most prevalent types were HPV-51, HPV-16, HPV-66, HPV-53, and HPV-6. The prevalence of high-risk and low-risk HPV peaked among men aged 20 to 29 years, whereas the HPVX prevalence increased with age. CONCLUSIONS: Human papillomavirus is highly prevalent in the general male population of Denmark, with HPV-16 and HPV-51 being the most prevalent. Polymerase chain reaction detects twice as many positive samples as HC2 but includes HPVX, possibly representing cutaneous HPV types found on normal genital skin.