Showing papers by "Susanne K. Kjaer published in 2021"
TL;DR: In this paper, the authors determined the real-world effectiveness of vaccination against cervical cancer using Poisson regression with vaccination treated as a time-varying variable and stratified by age at vaccination.
Abstract: Background The primary goal of human papillomavirus (HPV) vaccination is to reduce morbidity and mortality from HPV-associated disease, especially cervical cancer. We determined the real-world effectiveness of HPV vaccination against cervical cancer. Methods The study included women aged 17-30 years living in Denmark October 2006-December 2019. From nationwide registries, information on HPV vaccination and cervical cancer diagnoses were retrieved. Incidence rate ratios (IRRs) with 95% confidence intervals (CIs) for cervical cancer according to vaccination status were estimated using Poisson regression with HPV vaccination treated as a time-varying variable and stratified by age at vaccination. We adjusted for attained age, education, and ethnicity. To address the effect of prevalent disease, different buffer periods were used, with 1-year buffer period as primary analysis. Results The cohort comprised 867 689 women. At baseline, 36.3% were vaccinated at age 16 years and younger, and during follow-up, 19.3% and 2.3% were vaccinated at ages 17-19 years and 20-30 years, respectively. For women vaccinated at ages 16 years and younger or 17-19 years, the IRRs of cervical cancer were 0.14 (95% CI = 0.04 to 0.53) and 0.32 (95% CI = 0.08 to 1.28), respectively, compared with unvaccinated women. In women aged 20-30 years at vaccination, the incidence rate was higher than among unvaccinated women (IRR = 1.19, 95% CI = 0.80 to 1.79) but slightly decreased with increasing buffer period (IRR = 0.85, 95% CI = 0.55 to 1.32, with 4-year buffer period). Conclusion HPV vaccine effectiveness against cervical cancer at the population level is high among girls vaccinated younger than age 20 years. The lack of immediate effect in women vaccinated at age 20-30 years points to the importance of early age at vaccination.
78 citations
University of Cambridge1, University of New South Wales2, QIMR Berghofer Medical Research Institute3, Peter MacCallum Cancer Centre4, University of Melbourne5, New York University6, University of Utah7, Fred Hutchinson Cancer Research Center8, University of Washington9, University of Jena10, Hannover Medical School11, University of Pittsburgh12, Roswell Park Cancer Institute13, University of Texas Health Science Center at Houston14, Cedars-Sinai Medical Center15, University of California, Los Angeles16, University of Copenhagen17, Mayo Clinic18, University of Texas MD Anderson Cancer Center19, Memorial Sloan Kettering Cancer Center20, University of Virginia21, Duke University22, Pomeranian Medical University23, University College London24, University of Michigan25, University of Southern California26, University of Sydney27, Westmead Hospital28, Garvan Institute of Medical Research29
TL;DR: Analysis of coding region of 54 candidate genes found strong evidence that carriers of PALB2 deleterious mutations are at increased risk of high-grade serous ovarian cancer.
Abstract: Purpose The known epithelial ovarian cancer (EOC) susceptibility genes account for less than 50% of the heritable risk of ovarian cancer suggesting that other susceptibility genes exist. The aim of this study was to evaluate the contribution to ovarian cancer susceptibility of rare deleterious germline variants in a set of candidate genes. Methods We sequenced the coding region of 54 candidate genes in 6385 invasive EOC cases and 6115 controls of broad European ancestry. Genes with an increased frequency of putative deleterious variants in cases versus controls were further examined in an independent set of 14 135 EOC cases and 28 655 controls from the Ovarian Cancer Association Consortium and the UK Biobank. For each gene, we estimated the EOC risks and evaluated associations between germline variant status and clinical characteristics. Results The ORs associated for high-grade serous ovarian cancer were 3.01 for PALB2 (95% CI 1.59 to 5.68; p=0.00068), 1.99 for POLK (95% CI 1.15 to 3.43; p=0.014) and 4.07 for SLX4 (95% CI 1.34 to 12.4; p=0.013). Deleterious mutations in FBXO10 were associated with a reduced risk of disease (OR 0.27, 95% CI 0.07 to 1.00, p=0.049). However, based on the Bayes false discovery probability, only the association for PALB2 in high-grade serous ovarian cancer is likely to represent a true positive. Conclusions We have found strong evidence that carriers of PALB2 deleterious mutations are at increased risk of high-grade serous ovarian cancer. Whether the magnitude of risk is sufficiently high to warrant the inclusion of PALB2 in cancer gene panels for ovarian cancer risk testing is unclear; much larger sample sizes will be needed to provide sufficiently precise estimates for clinical counselling.
28 citations
TL;DR: The HPV prevalence appeared to be comparable across subgroups and independent of epithelial dysplasia, and the results did not vary substantially between non-dysplastic and dysplastic samples.
Abstract: Objectives We aimed to provide pooled estimates of human papillomavirus (HPV) prevalence in oral potentially malignant disorders (OPMD) and evaluate the impact of presence of epithelial dysplasia. Methods We searched PubMed, Embase, and Cochrane Library databases for studies that examined the prevalence of HPV DNA in OPMD tested by polymerase chain reaction (PCR). Results Across 52 eligible studies (2,677 cases), we found an overall pooled HPV prevalence of 22.5% (95% confidence interval [CI] 16.6-29.0). Between-study heterogeneity was 93%. When stratified by subgroup, the pooled HPV prevalence in leukoplakia (1,232 cases) was 20.2% (95% CI 11.2-31.1), lichen planus (767 cases) 23.0% (95% CI 15.0-32.2), oral submucous fibrosis (238 cases) 28.6% (95% CI 23.0-34.5), proliferative verrucous leukoplakia (60 cases) 24.7% (95% CI 1.8-62.0), and OPMD unspecified (377 cases) 25.4% (95% CI 16.2-35.8). Information on presence of epithelial dysplasia was available in 19 studies, and the results did not vary substantially between non-dysplastic and dysplastic samples. HPV16 was the predominant genotype among HPV-positive OPMD cases (48.2%, 95% CI 31.4-65.2). Conclusion We found a pooled HPV DNA prevalence of 22.5% in OPMD cases with great between-study heterogeneity. The HPV prevalence appeared to be comparable across subgroups and independent of epithelial dysplasia.
24 citations
TL;DR: Observations show that the 9vHPV vaccine provides continued statistically significant protection through at least 6 years, with indications of continued effectiveness through 8 years.
Abstract: A long-term follow-up (LTFU) of the nine-valent human papillomavirus (9vHPV) vaccine efficacy study in young women aged 16–26 years was initiated to evaluate if vaccine effectiveness for up to 14 y...
19 citations
TL;DR: The results suggest that HPV screening tests in the post-vaccination era might perform better if restricted to the HPV types in the nonavalent vaccine and screening for all 14 HPV types might result in suboptimal balance of harms and benefits.
Abstract: Prevalence of different HPV genotypes is changing after HPV vaccination. The associated risks are needed for optimizing cervical cancer screening.To estimate HPV type-specific prevalence, odds rati...
14 citations
TL;DR: In this paper, the effect of exposure to immunosuppressants on the prognosis of SARS-CoV-2 infection in Denmark was investigated and it was shown that exposure to glucocorticoids was associated with increased risk of hospital admission and death.
Abstract: Background Immunosuppression may worsen SARS-CoV-2 infection. We conducted a nationwide cohort study of the effect of exposure to immunosuppressants on the prognosis of SARS-CoV-2 infection in Denmark. Methods We identified all SARS-CoV-2 test-positive patients from February to October 2020 and linked health care data from nationwide registers, including prescriptions for the exposure, immunosuppressant drugs. We estimated relative risks of hospital admission, intensive care unit (ICU) admission, and death (each studied independently up to 30 days from testing) with a log linear binomial regression adjusted for confounders using a propensity score-based matching weights model. Results A composite immunosuppressant exposure was associated with a significantly increased risk of death (adjusted relative risk 1·56 [95% confidence interval 1.10–2.22]). The increased risk of death was mainly driven by exposure to systemic glucocorticoids (aRR 2.38 [95% CI 1.72–3.30]), which were also associated with an increased risk of hospital admission (aRR 1.34 [95% CI 1.10–1.62]), but not ICU admission (aRR 1.76 [95% CI [0.93–3.35]); these risks were greater for high cumulative doses of glucocorticoids than for moderate doses. Exposure to selective immunosuppressants, tumour necrosis factor inhibitors, or interleukin inhibitors, was not associated with an increased risk of hospitalisation, ICU admission, or death, nor was exposure to calcineurin inhibitors, other immunosuppressants, hydroxychloroquine, or chloroquine. Conclusions Exposure to glucocorticoids was associated with increased risks of hospital admission and death. Further investigation is needed to determine the optimal management of COVID-19 in patients with pre-morbid glucocorticoid usage, specifically whether these patients require altered doses of glucocorticoids.
13 citations
TL;DR: In this paper, the authors report data from the first round of a large Danish pilot implementation of human papillomavirus (HPV)-based screening, and compare colposcopy referrals, detection of high-grade cervical intraepithelial neoplasia (CIN) and cervical cancer, and positive predictive value (PPV) of colposition referral in HPV vs cytology-based screening.
Abstract: Introduction Human papillomavirus (HPV) testing as the primary cervical cancer screening method is implemented in several countries. We report data from the first round of a large Danish pilot implementation of HPV-based screening. Our aim was to compare colposcopy referrals, detection of high-grade cervical intraepithelial neoplasia (CIN) and cervical cancer, and positive predictive value (PPV) of colposcopy referral in HPV vs cytology-based screening. Material and methods From May 2017 to October 2018, women aged 30-59 years attending cervical cancer screening in the uptake area of the Department of Pathology, Vejle Hospital, Region of Southern Denmark were screened by primary HPV testing (n = 16 067) or primary cytology (n = 23 981) depending on municipality of residence. In the HPV group, women with HPV16/18, or other high-risk HPV types and abnormal cytology, were referred to immediate colposcopy. Women with other high-risk HPV types and normal cytology were invited for repeat screening with HPV test and cytology after 12 months. From a nationwide pathology register, we obtained information on screening results and subsequent histological diagnoses during up to 2.9 years after the first screen. PPVs included diagnoses within 1 year after referral. Results In the HPV group, 3.7% were referred to immediate colposcopy and 2.8% were referred at the 12-month repeat screening. The total referral to colposcopy was higher in the HPV (6.6%) than cytology group (2.1%) (age-adjusted relative referral = 3.05, 95% confidence interval [CI] 2.75-3.38). The detection of CIN3+ was higher in the HPV (1.5%) than the cytology group (0.8%) (age-adjusted relative detection = 1.88, 95% CI 1.56-2.28). The probability of CIN3+ among women referred to colposcopy (= PPV) was lower in the HPV (21.1%; 95% CI 18.7%-23.7%) than the cytology group (34.6%; 95% CI 30.7%-38.9%). In the HPV group, the PPV was lower among women referred at repeat screening (12.1%) than among women referred immediately (27.8%). Conclusions Compared with cytology-based screening, HPV-based screening provided a 90% increased CIN3+ detection at the cost of a threefold increase in colposcopy referrals, when considering complete data from the prevalence round. Our findings support implementation of HPV-based screening in Denmark, but modifications of screening algorithms may be warranted to decrease unnecessary colposcopy referrals.
13 citations
TL;DR: The incidence of most anogenital precancers and cancers were increased in women with diabetes, however, women with Diabetes had lower incidence of cervical precancer.
Abstract: In this register-based cohort study, we estimated the incidence of human papillomavirus (HPV)-related anogenital precancer and cancer in women with diabetes compared with women without diabetes. We followed all women living in Denmark born 1916 to 2001 (n = 2 508 321) for individual-level information on diabetes (Type 1 or 2 [T1D or T2D]), diagnoses of cervical, vaginal, vulvar and anal intraepithelial neoplasia Grade 2 or 3 (IN2/3) and cancer and other covariates from nationwide registries. We used Poisson regression to model the incidence rates of anogenital IN2/3 and cancer as a function of diabetes status, age, HPV vaccination, education, calendar year, and cervical cancer screening status. Incidence rate ratios (IRRs) were estimated for diabetes overall, and separately for T1D and T2D, compared with women without diabetes. Women with diabetes had higher rates of vulvar IN2/3 (IRR = 1.63; 95% confidence interval [CI]: 1.41-1.88), vulvar cancer (IRR = 1.61; 95% CI: 1.36-1.91) and vaginal cancer (IRR = 1.79; 95% CI: 1.27-1.91) than women without diabetes. Similar patterns were observed for anal IN2/3, anal cancer and cervical cancer, although not statistically significant. In contrast, women with diabetes had lower rates of cervical IN2/3 (IRR = 0.74; 95% CI: 0.69-0.79) than women without diabetes. Patterns were generally similar in women with T1D and T2D, although cancer rates were higher in women with T2D. In conclusion, the incidence of most anogenital precancers and cancers were increased in women with diabetes. However, women with diabetes had lower incidence of cervical precancer. Our findings could be explained by biological mechanisms and/or behavioral factors, such as smoking and less frequent cervical screening participation.
13 citations
TL;DR: In this paper, the determinants of uptake and completion of a 3-dose human papillomavirus vaccination program by adult women in a European context were estimated, using multilevel logistic models in 2019.
12 citations
University of Bristol1, University of Cambridge2, Cedars-Sinai Medical Center3, University of Chicago4, University of Virginia5, Hospital Clínico San Carlos6, German Cancer Research Center7, University of Hamburg8, QIMR Berghofer Medical Research Institute9, University of Sydney10, Westmead Hospital11, Hannover Medical School12, University of Erlangen-Nuremberg13, University of Edinburgh14, Aristotle University of Thessaloniki15, Mayo Clinic16, National University of Singapore17, Charité18, University of Copenhagen19, University of Zielona Góra20, Pomeranian Medical University21, University of California, Los Angeles22, Bashkir State University23, Russian Academy of Sciences24, Radboud University Nijmegen25, University of Calgary26, Genome Institute of Singapore27, University Health Network28, Lund University29, University of New South Wales30, Duke University31, Yale University32, Laval University33, University of Southern Maine34, Case Western Reserve University35, Vanderbilt University36, Huntsman Cancer Institute37, Emory University38
TL;DR: The 22 genes identified by the cross-cancer analysis represent promising candidates that further elucidate the role of the transcriptome in mediating germline breast and ovarian cancer risk.
Abstract: Familial, sequencing, and genome-wide association studies (GWASs) and genetic correlation analyses have progressively unraveled the shared or pleiotropic germline genetics of breast and ovarian cancer. In this study, we aimed to leverage this shared germline genetics to improve the power of transcriptome-wide association studies (TWASs) to identify candidate breast cancer and ovarian cancer susceptibility genes. We built gene expression prediction models using the PrediXcan method in 681 breast and 295 ovarian tumors from The Cancer Genome Atlas and 211 breast and 99 ovarian normal tissue samples from the Genotype-Tissue Expression project and integrated these with GWAS meta-analysis data from the Breast Cancer Association Consortium (122,977 cases/105,974 controls) and the Ovarian Cancer Association Consortium (22,406 cases/40,941 controls). The integration was achieved through application of a pleiotropy-guided conditional/conjunction false discovery rate (FDR) approach in the setting of a TWASs. This identified 14 candidate breast cancer susceptibility genes spanning 11 genomic regions and 8 candidate ovarian cancer susceptibility genes spanning 5 genomic regions at conjunction FDR 1 Mb away from known breast and/or ovarian cancer susceptibility loci. We also identified 38 candidate breast cancer susceptibility genes and 17 candidate ovarian cancer susceptibility genes at conjunction FDR < 0.05 at known breast and/or ovarian susceptibility loci. The 22 genes identified by our cross-cancer analysis represent promising candidates that further elucidate the role of the transcriptome in mediating germline breast and ovarian cancer risk.
12 citations
TL;DR: 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.
Abstract: 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 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.
01 Jun 2021
TL;DR: PURPOSECervical cancer screening is one of the strategies to prevent the disease among women at risk as discussed by the authors, and Human Papillomavirus (HPV) DNA testing is increasingly used as the cervical cancer screening.
Abstract: PURPOSECervical cancer screening is one of the strategies to prevent the disease among women at risk. Human papillomavirus (HPV) DNA testing is increasingly used as the cervical cancer screening me...
TL;DR: Risks were particularly elevated for affective and stress-related disorders and parents of deceased children and children diagnosed at a younger age were at particular risk of hospital contacts for psychiatric disorders.
Abstract: Background Having a child diagnosed with cancer is a devastating experience that may affect parents' mental health. We aimed to assess the risk of hospital contacts for psychiatric disorders in parents of children with cancer. Methods We conducted a nationwide population-based cohort study using Danish registry data. Parents of children diagnosed with cancer between 1982 and 2014 (n = 6689 mothers, n = 5509 fathers) were matched with comparison parents of cancer-free children (n = 67 544 mothers, n = 55 756 fathers). We used Cox proportional hazards models to estimate the risk of hospital contacts for any psychiatric disorder and specific disorders. Cox models were also used to investigate sociodemographic and cancer-related risk factors for psychiatric disorders. Results Incidence rates of hospital contacts for any psychiatric disorder were 426 per 100 000 person-years in mothers of children with cancer and 345 per 100 000 person-years in comparison mothers. For fathers, the respective incidence rates were 260 and 262 cases per 100 000 person-years. Compared with parents of cancer-free children, mothers of children with cancer were at an increased risk of hospital contacts for any psychiatric disorder (hazard ratio = 1.23, 95% confidence interval = 1.12 to 1.36), whereas no elevated risk was seen in fathers (hazard ratio = 0.99, 95% confidence interval = 0.87 to 1.13). Among mothers, risks were particularly elevated for affective and stress-related disorders. Parents of deceased children and children diagnosed at a younger age were at particular risk of hospital contacts for psychiatric disorders. Conclusion Hospital contacts for psychiatric disorders were overall rare. Health-care professionals should draw attention to subgroups of vulnerable parents to meet their needs of support and adequate treatment.
TL;DR: A systematic review of studies on the prognostic significance of human papillomavirus (HPV) and immunohistochemical expression of p16 and p53 among women with vaginal cancer is presented in this paper.
Abstract: INTRODUCTION Human papillomavirus (HPV), p16, and p53 have been investigated as prognostic markers in various HPV-related cancers. Within the field of vaginal cancer, however, the evidence remains sparse. In this systematic review, we have compiled the presently published studies on the prognostic significance of HPV and immunohistochemical expression of p16 and p53 among women with vaginal cancer. MATERIAL AND METHODS We conducted a systematic search of PubMed, Embase, and Cochrane Library to identify relevant studies published until April 2021. We included studies reporting survival after histologically verified vaginal cancers tested for HPV, p16, and/or p53. Survival outcomes included overall survival, disease-free survival, disease-specific survival, and progression-free survival. RESULTS We included a total of 12 studies. The vast majority of vaginal cancer cases included in each study were squamous cell carcinomas (84%-100%). Seven studies reported survival after vaginal cancer according to HPV status, and the majority of these studies found a tendency towards improved survival for women with HPV-positive vaginal cancer. Three out of four studies reporting survival according to p16 status found an improved survival among women with p16-positive vaginal cancer. For p53, only one of six studies reported an association between p53 expression and survival. CONCLUSIONS This systematic review suggests that women with HPV- and p16-positive vaginal cancer have an improved prognosis compared with those with HPV- or p16-negative vaginal cancer. Results for p53 were varied, and no conclusion could be reached. Only 12 studies could be included in the review, of which most were based on small populations. Hence, further and larger studies on the prognostic impact of HPV, p16, and p53 in vaginal cancer are warranted.
California State University, Fullerton1, University of Michigan2, University of New South Wales3, University College London4, University of California, Irvine5, Stanford University6, Icahn School of Medicine at Mount Sinai7, Rutgers University8, Harvard University9, Brigham and Women's Hospital10, University of Southern Maine11, Emory University12, Duke University13, Mayo Clinic14, University of Copenhagen15, University of Queensland16, University of Texas Health Science Center at Houston17, University of Pittsburgh18, Roswell Park Cancer Institute19, Cedars-Sinai Medical Center20, University of Hawaii at Manoa21, University of Hamburg22, German Cancer Research Center23, Fred Hutchinson Cancer Research Center24, University of Washington25, Huntsman Cancer Institute26, Yale University27, University of Cambridge28, University of Southern California29, Memorial Sloan Kettering Cancer Center30, QIMR Berghofer Medical Research Institute31
TL;DR: Incomplete pregnancies are associated with a reduced risk of invasive epithelial ovarian cancer, and an inverse association was observed for all major histotypes; it was strongest for clear cell ovarian cancer.
Abstract: Author(s): Lee, Alice W; Rosenzweig, Stacey; Wiensch, Ashley; Australian Ovarian Cancer Study Group; Ramus, Susan J; Menon, Usha; Gentry-Maharaj, Aleksandra; Ziogas, Argyrios; Anton-Culver, Hoda; Whittemore, Alice S; Sieh, Weiva; Rothstein, Joseph H; McGuire, Valerie; Wentzensen, Nicolas; Bandera, Elisa V; Qin, Bo; Terry, Kathryn L; Cramer, Daniel W; Titus, Linda; Schildkraut, Joellen M; Berchuck, Andrew; Goode, Ellen L; Kjaer, Susanne K; Jensen, Allan; Jordan, Susan J; Ness, Roberta B; Modugno, Francesmary; Moysich, Kirsten; Thompson, Pamela J; Goodman, Marc T; Carney, Michael E; Chang-Claude, Jenny; Rossing, Mary Anne; Harris, Holly R; Doherty, Jennifer Anne; Risch, Harvey A; Khoja, Lilah; Alimujiang, Aliya; Phung, Minh Tung; Brieger, Katharine; Mukherjee, Bhramar; Pharoah, Paul DP; Wu, Anna H; Pike, Malcolm C; Webb, Penelope M; Pearce, Celeste Leigh | Abstract: BackgroundParity is associated with decreased risk of invasive ovarian cancer; however, the relationship between incomplete pregnancies and invasive ovarian cancer risk is unclear. This relationship was examined using 15 case-control studies from the Ovarian Cancer Association Consortium (OCAC). Histotype-specific associations, which have not been examined previously with large sample sizes, were also evaluated.MethodsA pooled analysis of 10 470 invasive epithelial ovarian cancer cases and 16 942 controls was conducted. Odds ratios (ORs) and 95% confidence intervals (CIs) for the association between incomplete pregnancies and invasive epithelial ovarian cancer were estimated using logistic regression. All models were conditioned on OCAC study, race and ethnicity, age, and education level and adjusted for number of complete pregnancies, oral contraceptive use, and history of breastfeeding. The same approach was used for histotype-specific analyses.ResultsEver having an incomplete pregnancy was associated with a 16% reduction in ovarian cancer risk (OR = 0.84, 95% CI = 0.79 to 0.89). There was a trend of decreasing risk with increasing number of incomplete pregnancies (2-sided Ptrend l .001). An inverse association was observed for all major histotypes; it was strongest for clear cell ovarian cancer.ConclusionsIncomplete pregnancies are associated with a reduced risk of invasive epithelial ovarian cancer. Pregnancy, including incomplete pregnancy, was associated with a greater reduction in risk of clear cell ovarian cancer, but the result was broadly consistent across histotypes. Future work should focus on understanding the mechanisms underlying this reduced risk.
TL;DR: 1 or 2 doses of quadrivalent HPV vaccine was associated with substantial protection against genital warts in girls vaccinated at age ≤16 years, and the 1-dose VE approached that of 3 or 3 doses over calendar time, probably reflecting the impact of herd protection.
Abstract: BACKGROUND Increasing evidence suggests that 1-dose human papillomavirus (HPV) vaccination may protect significantly against HPV-related disease. We provide nationwide, real-world data on the risk of genital warts (GWs) after <3 vaccine doses. METHODS All Danish women born in 1985-2003 were identified, and individual-level vaccination data were retrieved. The cohort was followed up for first occurrence of GWs until 31 December 2016. Using Poisson regression, we calculated incidence rates (IRs) of GWs per 100 000 person-years and IR ratios (IRRs) with corresponding 95% confidence intervals (CIs) for GWs, according to vaccination status, age at first dose, and calendar time. RESULTS The cohort comprised 1 076 945 girls and women, of whom 485 408 were vaccinated. For girls initiating vaccination at age 12-14 years and 15-16 years, 1-dose vaccine effectiveness (VE) was 71% (IRR = 0.29; 95% CI, .22-.38) and 62% (0.38; .29-.49), respectively, compared with unvaccinated girls. In the same age groups, 2-dose VE was 78% (IRR, 0.22; 95% CI, .18-.26) and 68% (0.32; .26-.38), respectively. After 2009, the IRRs for 3 versus 1 dose and 2 versus 1 dose increased towards unity over calendar time, being 0.69 (95% CI, .57-.84) and 0.86 (.68-1.08) in 2016, respectively. CONCLUSIONS In this study, 1 or 2 doses of quadrivalent HPV vaccine was associated with substantial protection against GWs in girls vaccinated at age ≤16 years. The 1-dose VE approached that of 3 or 2 doses over calendar time, probably reflecting the impact of herd protection.
TL;DR: In this paper, the influence of socioeconomic status (SES) on long-term survival of non-localized ovarian cancer was examined, and the authors found that higher personal income is associated with slightly higher probability of longterm survival, whereas education and marital status did not affect the probability of survival.
TL;DR: The incidence of borderline ovarian tumors in Denmark 1997‐2018 is described by histology, age at diagnosis and educational level to describe the trend in incidence over the past 20 years.
Abstract: INTRODUCTION After some decades with an increasing incidence of borderline ovarian tumors, more recent studies have observed that the incidence rate seems to be leveling off or declining. In this study, we describe the incidence of borderline ovarian tumors in Denmark 1997-2018 by histology, age at diagnosis and educational level. MATERIAL AND METHODS All borderline ovarian tumors registered in the Danish Pathology Registry during 1997-2018 were identified and individual-level educational information was retrieved from nationwide registers. Age-standardized incidence rates were estimated according to histology, age at diagnosis and educational level. To investigate incidence trends over time, the average annual percentage change and corresponding 95% confidence intervals (CIs) were estimated using Poisson regression. RESULTS We identified 3927 women with borderline ovarian tumors during the study period, of which 1997 (50.9%) were serous and 1743 (44.4%) were mucinous. The age-standardized incidence rate of serous borderline ovarian tumors did not change significantly over calendar time (average annual percentage change = -0.13, 95% confidence interval [CI] -1.13 to 0.88). For mucinous tumors, the age-standardized incidence rate was also relatively stable during the first half of the study period, followed by a decrease from 2.56 to 1.25 per 100 000 person-years between 2007-2011 and 2017-2018. Over the entire study period, the incidence rate of mucinous borderline tumors declined on average by 2.91% (95% CI -4.24 to -1.51) per year. The incidence of both types of borderline ovarian tumors seemed to be highest among women with a low educational level. Over calendar time, the incidence of mucinous tumors decreased in all educational groups, whereas the incidence of serous tumors decreased exclusively in women with a high educational level. Time trends did not differ markedly by age at diagnosis. CONCLUSIONS In Denmark, the incidence of serous borderline ovarian tumors was stable during 1997-2018, whereas the incidence of mucinous borderline ovarian tumors decreased. The incidence rates of both types of borderline ovarian tumors tended to be highest among women with a low educational level throughout the study period.
TL;DR: In this article, the authors used Poisson regression models to estimate incidence of penile and anal high-grade intraepithelial neoplasia (hgPeIN, hgAIN, penile SCC, and anal SCC as a function of diabetes status, attained age, calendar period, and education.
Abstract: Introduction 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. Materials and 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 non-diabetic 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 non-diabetic 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.
TL;DR: A recent meeting, conducted by the HPV Prevention and Control Board (HPV-PCB), reviewed the current status of adult human papillomavirus vaccination of adults, discussed limitations, challenges and benefits of adult HPV vaccination, evaluated the effectiveness of HPV vaccination after treatment of post cervical cancer and precancerous lesions, and discussed the potential impact of adult vaccination on cervical cancer elimination strategies in light of the current and future vaccine shortage as discussed by the authors.
Abstract: For more than a decade human papillomavirus (HPV) vaccine have been implemented in most high-income countries, and more recently also in several low- and middle-income countries. The vaccines are safe and their impact and effectiveness in preventing HPV vaccine type infection and associated diseases has been thoroughly established. Currently, the primary recommended cohorts for immunisation are adolescents, 9-15 years of age but HPV is an ubiquitous infection that is mainly (but not exclusively) sexually transmitted. Sexually active adults remain susceptible to infection and continued transmission of the virus, representing a reservoir of infection in the population. A recent meeting, conducted by the HPV Prevention and Control Board (HPV-PCB), reviewed the current status of HPV vaccination of adults, discussed limitations, challenges and benefits of HPV vaccination of adults, evaluated the effectiveness of HPV vaccination after treatment of post cervical cancer and precancerous lesions, and discussed the potential impact of adult vaccination on cervical cancer elimination strategies in light of the current and future HPV vaccine shortage. HPV-PCB is an independent multidisciplinary board of international experts that disseminates relevant information on HPV to a broad array of stakeholders and provides guidance on strategic, technical and policy issues in the implementation of HPV prevention and control programs. The HPV-PCB concluded that, given the current data available on adult HPV vaccination and the ongoing vaccine supply constraints, it is too early to implement routine vaccination of adults. Many research gaps need to be filled before we have a better understanding of the efficacy and broader public health impact of HPV vaccination in adult women.
TL;DR: In this paper, risk factors for Type I and Type II endometrial cancer (EC) and directly compare the influence of risk factors on the risk of Type II with Type I tumors were examined.
TL;DR: In this paper, an individual patient data meta-analysis was conducted to determine the prognostic value of hrHPV DNA and p16 in patients with anal squamous cell carcinoma (ASCC) while controlling for major clinical and tumour covariates.
TL;DR: In this paper, the authors evaluated the associations between genital human papillomavirus (HPV) infection and circumcision, smoking, and alcohol use after accounting for sexual behavior, and found no association with alcohol use in the analysis adjusted for sexual behaviour.
Abstract: It is crucial to understand the natural history of genital human papillomavirus (HPV) infection in men to prevent the increasing male HPV-related disease burden. We evaluated the associations between HPV infection and circumcision, smoking, and alcohol use after accounting for sexual behavior. The study included 2331 male personnel from Danish barracks. Penile swabs were tested for HPV DNA with a polymerase chain reaction assay, INNO-LiPA. All men completed a self-administered questionnaire providing data on potential risk factors for HPV such as lifestyle and sexual habits. Using multivariable logistic regression, associations between potential risk factors and HPV infection were estimated and expressed as odds ratios (ORs) with 95% confidence intervals (CI). Current cigarette smoking was associated with increased odds of HPV detection (OR = 1.2; 95% CI: 1.0-1.4), but we found no association with alcohol use in the analysis adjusted for sexual behavior. Circumcision reduced the odds of a prevalent HPV infection (OR = 0.7; 95% CI: 0.5-1.0) although not statistically significantly. Strong associations with lifetime and recent number of female sex partners were observed, but in contrast to uncircumcised men, increasing number of sex partners was not associated with higher HPV prevalence in circumcised men. In conclusion, smoking was associated with increased odds of penile HPV in men from the general population in Denmark, whereas circumcision seemed to reduce the risk. Moreover, our results indicated that there might be differences in the viral susceptibility between circumcised and uncircumcised men.
QIMR Berghofer Medical Research Institute1, University of Cambridge2, Mayo Clinic3, Westmead Hospital4, University of California, Los Angeles5, University of Erlangen-Nuremberg6, Katholieke Universiteit Leuven7, Vanderbilt University8, Cedars-Sinai Medical Center9, Hannover Medical School10, University of Jena11, University of Pittsburgh12, Roswell Park Cancer Institute13, University of Marburg14, University of Copenhagen15, Emory University16, Duke University17, Brigham and Women's Hospital18, Harvard University19, University of Bergen20, Haukeland University Hospital21, University of New South Wales22, Oregon Health & Science University23, Beatson West of Scotland Cancer Centre24, University Health Network25, University of Hawaii at Manoa26, University of Glasgow27, Humboldt University of Berlin28, Peter MacCallum Cancer Centre29, University of Sydney30
TL;DR: The authors carried out a genome-wide association study (GWAS) of progression-free survival (PFS) in 2352 women with EOC who had undergone cytoreductive surgery and standard carboplatin/paclitaxel chemotherapy.
Abstract: Many loci have been found to be associated with risk of epithelial ovarian cancer (EOC). However, although there is considerable variation in progression-free survival (PFS), no loci have been found to be associated with outcome at genome-wide levels of significance. We carried out a genome-wide association study (GWAS) of PFS in 2352 women with EOC who had undergone cytoreductive surgery and standard carboplatin/paclitaxel chemotherapy. We found seven single nucleotide polymorphisms (SNPs) at 12q24.33 associated with PFS (P The locus at 12q24.33 represents one of the first genome-wide significant loci for survival for any cancer. ULK1 is a plausible candidate for the target of this association. This finding provides insight into genetic markers associated with EOC outcome and potential treatment options.
University of California, Irvine1, University of Michigan2, University of Southern California3, Duke University4, Cancer Registry of Norway5, Memorial Sloan Kettering Cancer Center6, QIMR Berghofer Medical Research Institute7, University of Queensland8, Danish Cancer Society9, German Cancer Research Center10, University of Copenhagen11, Yale University12, Huntsman Cancer Institute13, Fred Hutchinson Cancer Research Center14, Cedars-Sinai Medical Center15, University of Pittsburgh16, Roswell Park Cancer Institute17, Emory University18, Brigham and Women's Hospital19, University of British Columbia20, California State University, Fullerton21
TL;DR: In this paper, a pooled analysis of self-reported data from 11 case-control studies in the Ovarian Cancer Association Consortium (OCAC) was conducted to evaluate the association between hysterectomy and ovarian cancer, and to understand how hormone therapy use and endometriosis affect this association.
TL;DR: Men with prostate cancer who experience symptoms of depression or anxiety should seek professional help early on, and patient education could aid in raising awareness and reducing the stigma associated with mental disorders.
Abstract: To estimate the risk of first-time antidepressant prescriptions as a proxy for depression or anxiety and associated risk factors in patients with prostate cancer and their female partners. We followed all men (n = 25,126) and their female cohabiting partners (n = 8785) without a history of cancer or antidepressants from the Danish Diet, Cancer and Health cohort from 1997 to 2014 or 2010, respectively. We estimated the cumulative incidence of first-time antidepressant prescriptions in men with prostate cancer compared with cancer-free men and their respective female partners, using the Danish National Prescription Registry. Sociodemographic, lifestyle-related, and clinical risk factors were assessed using Cox regression models. A total of 1828 men were diagnosed with prostate cancer of whom 15% received antidepressants. The unadjusted hazard ratio of antidepressant prescription was 2.18 (95%CI, 1.92, 2.48) for men with prostate cancer and 1.27 (95%CI, 0.87, 1.85) for their partners, compared with cancer-free men and their partners, respectively. After adjusting for sociodemographic, lifestyle-related, and comorbidity factors, this risk was 2-fold to 4-fold increased among patients, but not significantly increased among partners. Significant risk factors among patients were curative and palliative treatment (vs. active surveillance and watchful waiting), nonlocalized disease, and short education. Men with prostate cancer have a higher risk of receiving antidepressant medication than cancer-free men. Clinical characteristics can help clinicians in identifying patients at a high risk of depression or anxiety. Men with prostate cancer who experience symptoms of depression or anxiety should seek professional help early on. Patient education could aid in raising awareness and reducing the stigma associated with mental disorders.
TL;DR: In this article, the authors examined the association between use of antidepressants and endometrial cancer risk with a particular focus on selective serotonin reuptake inhibitors (SSRIs), using conditional logistic regression.
Abstract: BACKGROUND Preclinical studies have suggested that antidepressant drugs may possess antineoplastic properties. In a nationwide case-control study, we examined the association between use of antidepressants and endometrial-cancer risk with a particular focus on selective serotonin reuptake inhibitors (SSRIs). METHODS From the Danish Cancer Registry, we identified all women with a histologically verified diagnosis of endometrial cancer between 2000 and 2016, and, for each woman, 15 age-matched controls. We obtained information on use of SSRIs, tricyclic antidepressants (TCAs) and other antidepressants based on records of filled prescriptions from the National Prescription Register. Using conditional logistic regression, we calculated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for associations between use of antidepressants and endometrial-cancer risk compared with non-use. In active comparator analyses, SSRI use was compared with TCA use. RESULTS The study population comprised 8164 cases and 122 432 controls. Compared with non-use, SSRI use was associated with an OR of 0.88 (95% CI 0.82-0.96) for endometrial cancer, whereas the association with TCA use was close to unity (OR 1.05, 95% CI 0.90-1.22). Use of other antidepressants yielded an OR of 0.86 (95% CI 0.71-1.03). We observed no apparent trends in associations according to cumulative amount. The inverse association with SSRI use persisted when compared with TCA use (OR 0.81, 95% CI 0.66-0.99). CONCLUSIONS Use of SSRIs was associated with a decreased risk of endometrial cancer, whereas no inverse association appeared with use of TCAs. The antineoplastic potential of SSRIs should be investigated in future studies.
TL;DR: In this paper, the authors examined time trends in ovarian/tubal cancer relative survival, excess mortality, and all-cause mortality for different histological types and levels of socioeconomic position.
TL;DR: In this article, a prospective study among women (25-60 years) attending cervical cancer screening in Tanzania, the authors conducted a multivariable regression analysis, factors associated with increased odds of HPV acquisition included HIV positivity, low CD4 count, younger age, and multiple sex partners.
TL;DR: In this article, the authors examined the incidence of high-grade penile intraepithelial neoplasia (PeIN), the incidence and 5-year relative survival as well as mortality of penile SCC in Denmark over the latest 20 years.
Abstract: Purpose Squamous cell carcinoma (SCC) of the penis is rare. Some studies have suggested that the incidence is increasing but the available literature is equivocal. We examined the incidence of high-grade penile intraepithelial neoplasia (PeIN), the incidence and 5-year relative survival as well as mortality of penile SCC in Denmark over the latest 20 years. Methods New cases of high-grade PeIN and penile cancer were identified from high-quality nationwide registries. Age-standardized (World) incidence rates per 100,000 person-years and average annual percentage change (AAPC) were estimated. For penile SCC, 5-year relative survival was calculated, and Cox regression was used to examine the effect of selected characteristics on mortality. Results Altogether, 1,070 new cases of high-grade PeIN were diagnosed (1997-2018) and the incidence increased from 0.87 to 1.84 per 100,000 person-years from 1997-1998 to 2017-2018 (AAPC = 4.73; 95% CI: 3.54-5.94). We identified 1,216 penile cancer cases (1997-2018) (95.7% SCC). The incidence of penile SCC increased slightly from 0.85 per 100,000 person-years in 1997-1998 to 1.13 per 100,000 person-years in 2017-2018 (AAPC = 1.01; 95% CI: 0.24-1.79). The 5-year relative survival of penile SCC did not change substantially, whereas the mortality tended to decrease. Conclusion Penile SCC is increasing slightly in Denmark, while a pronounced increase in the incidence of high-grade PeIN is seen. The 5-year relative survival from penile cancer was relatively stable over time. Increasing exposure to HPV infection at the population level may have contributed to the observed increase in PeIN and penile SCC. Awareness of HPV may also have contributed to the increased detection of PeIN.