Overweight and obesity as risk factors for cervical cancer and detection of precancers among screened women: A nationwide, population-based cohort study.

OBJECTIVE: Obesity is a known risk factor for many types of cancer. However, there is no clear evidence whether overweight and obesity increases the risk of cervical cancer. We investigated the association between body mass index (BMI) and detection of squamous and glandular cervical cancer and precancer. METHODS: Based on the Medical Birth Registry, we conducted a nationwide cohort study in Denmark of 384,559 women with BMI ≥18.5 kg/m2 (pre-pregnancy BMI reported at the start of the pregnancy) having a cervical cytology screening at age 23-49 years within 5 years following the date of childbirth. The cohort was followed for 10 years from the first cervical cytology screening after the childbirth. We assessed absolute risks of cervical lesions according to BMI with the Aalen-Johansen estimator. We conducted Cox proportional hazards regression analyses to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). Analyses were adjusted for age, calendar year, parity, oral contraception use, HPV vaccination, smoking, country of origin, and education. RESULTS: Overweight and obesity were associated with higher rates of cervical cancer (HR = 1.24, 95% CI 1.04-1.49 and HR = 1.14, 95% CI 0.91-1.43, respectively) and lower rates of cervical precancer detection (HR = 0.88, 95% CI 0.84-0.92 and HR = 0.67, 95% CI 0.63-0.71, respectively). CONCLUSIONS: Higher than normal BMI was associated with higher incidence rates of cervical cancer and lower rates of precancer detection, emphasizing the importance of further research in possible mechanisms behind this association.

Factors associated with teenage pregnancy in the Scandinavian countries.

AIMS: Teenage pregnancy may have negative consequences for the mother and the infant. The aim of the study was to examine whether selected individual factors occurring early in life were associated with teenage pregnancy. METHODS: In a population-based, cross-sectional questionnaire study among 34,455 women from Denmark, Norway, and Sweden aged 20-45 years, who had first sexual intercourse (FSI) at age 13-19 years, we assessed the association between early smoking and drinking initiation (i.e., before the age of 13), contraceptive use at FSI, and teenage pregnancy. Log-linear binary regression models were fitted to estimate the relative risk (RR) with 95% confidence intervals (CIs) of teenage pregnancy according to the three exposure variables, overall and by age at FSI. Furthermore, the outcomes of the teenage pregnancies were examined according to age at FSI. RESULTS: Teenage pregnancy occurred in 11% of the population. Both early smoking initiation (RR: 1.6; 95% CI: 1.4-1.8), early drinking initiation (RR: 1.2; 95% CI: 1.0-1.4), and non-use of contraceptives at FSI (RR: 1.9; 95% CI: 1.8-2.0) were associated with teenage pregnancy. The associations for early smoking initiation and non-use of contraceptives remained when analyses were stratified by age at FSI. Almost 60% of all teenage pregnant women had an induced abortion and less than 30% gave birth. CONCLUSIONS: Individual factors, including early smoking and drinking initiation, and non-use of contraceptives at FSI, were associated with teenage pregnancy regardless of age at FSI. This emphasizes the necessity of focusing on early risk-taking behavior as a potential modifier to prevent teenage pregnancy.

Cervical human papillomavirus prevalence according to socioeconomic and demographic characteristics in a large Danish screening population.

AIM: The aim of this study was to investigate high-risk human papillomavirus (hrHPV) prevalence according to socioeconomic and demographic characteristics in a Danish screening population. METHODS: We used data from HPV SCREEN DENMARK, which was an implementation study embedded into the routine cervical cancer screening programme. During 2017-2020, women aged 30-59 years screened in the Region of Southern Denmark were offered HPV testing or cytology. In the HPV group, liquid-based cytology samples were tested for 14 hrHPV types. We obtained registry information on socioeconomic and demographic characteristics and used log-binomial regression to estimate the prevalence ratio (PR) of hrHPV in three age groups (30-39, 40-49, 50-59 years), adjusting for age and marital status. RESULTS: We included 31,124 HPV unvaccinated women. In all age groups, the age-adjusted hrHPV prevalence was higher in women with basic versus higher education (e.g. age 30-39: 11.9% vs. 9.5%; PRage-adjusted=1.24; 95% confidence interval (CI): 1.02-1.50); women who were unemployed vs. employed (e.g. age 30-39: 11.6% vs. 10.4%; PRage-adjusted=1.11; 95% CI: 0.95-1.28); and in women with highest vs. lowest income (e.g. age 30-39: 11.6% vs. 9.5%, PRage-adjusted=1.18, 95% CI: 0.98-1.44). In models adjusted for marital status, these associations largely disappeared. CONCLUSIONS: We found slightly higher hrHPV prevalences in women with basic education, low income and unemployment. The differences largely disappeared when taking into account marital status as a potential proxy for sexual behaviour. Our findings support a need for targeted information on safe sexual practices and promoting socioeconomic equality in HPV vaccination and cervical cancer screening participation.

Time trends in prevalence of p16 positivity and combined HPV/p16 positivity in a large cohort of Danish vulvar cancer patients.

Vulvar cancer is rare, but causes substantial morbidity in affected patients. A subset of vulvar cancers is caused by high-risk human papillomavirus (hrHPV), which primarily exerts its oncogenic effect through upregulation of tumor suppressor protein p16. Tumors positive for both hrHPV and p16 (double positive) are assumed to be HPV-driven, but only few large studies have investigated the combined prevalence of hrHPV and p16 positivity in vulvar cancer over time. In this Danish cross-sectional study, we assessed the prevalence of p16 positivity and double positivity for hrHPV and p16 in a large sample of vulvar squamous cell carcinomas (VSCCs) diagnosed during 1990 to 2017. In a nationwide register, we identified VSCCs from 13 hospitals across Denmark, and collected archival tumor tissue for hrHPV testing with INNO-LiPA and immunohistochemical p16 staining. We calculated the prevalence of hrHPV, p16 positivity and double positivity according to time, age and histological subtype and evaluated time trends through estimated annual percentage changes. We included 1278 VSCCs. Overall, 35.0% (95% confidence interval [CI]: 32.4-37.6) were positive for p16 and 31.0% (95% CI: 28.4-33.5) were positive for both hrHPV and p16. The prevalence of p16 positivity and double positivity increased over time, both in women aged ≤59 and ≥60 years. The double positive prevalence was higher in nonkeratinizing (60.7%) and warty/basaloid VSCCs (67.5%) than in keratinizing (16.1%) and verrucous VSCCs (5.0%). These results indicate that approximately one-third of vulvar cancers were caused by hrHPV infection, supporting a substantial preventive potential of the HPV vaccine.

Prevalence of cervical human papillomavirus and the risk of anal co-infection in kidney transplant recipients: Results from a Danish clinical study.

BACKGROUND: Kidney transplant recipients (KTRs) have increased risk of human papillomavirus (HPV)-related cancers, including cervical and anal cancer. In this cross-sectional clinical study, we investigated the prevalence of cervical high-risk HPV (hrHPV) and low-risk (lrHPV), risk factors for cervical hrHPV infection, and the prevalence of cervical and anal hrHPV co-infection in KTRs and immunocompetent controls. METHODS: During 2016-2017, we recruited 125 female KTRs and 125 female immunocompetent controls from one dermatology department (KTRs and controls) and five nephrology departments (KTRs) in Denmark. Liquid-based cervical and anal cytology samples were tested for HPV DNA using the INNO-LiPA test and participants answered a questionnaire on lifestyle. Odds ratios (ORs) were estimated using logistic regression, adjusting for age, lifetime sexual partners, smoking, and (in models concerning anal HPV) receptive anal sex. RESULTS: KTRs had higher prevalence of cervical hrHPV than controls (35.5% vs. 18.2; ORadjusted = 2.9, 95% CI, 1.5-5.5). In contrast, the prevalence of lrHPV was similar in KTRs and controls (25.6% vs. 23.1; ORadjusted = 1.2, 95% CI, 0.7-2.3). KTRs were more likely than controls to have cervical and anal hrHPV co-infection (27.3% vs. 6.6%, ORadjusted = 6.3, 95% CI, 2.7-15.0). CONCLUSIONS: Female KTRs had high prevalence of cervical hrHPV, and co-infection with anal and cervical hrHPV was common. Our results underline that KTRs are an important target group for preventive efforts against HPV-related diseases.

Incidence of cervical precancerous lesions and cervical cancer in Denmark from 2000 to 2019: Population impact of multi-cohort vaccination against human papillomavirus infection.

In Denmark, vaccination against human papillomavirus (HPV) has been implemented in the children's vaccination program (January 2009) and in multiple catch-up cohorts (October 2008 in girls 13-15 years and in August 2012 in women up to 27 years). In the present study we estimate incidence of cervical intraepithelial neoplasia grade 3 (CIN3), adenocarcinoma in situ (AIS), squamous cell carcinoma (SCC) and adenocarcinoma (AC) during 2000-2019. All cases of CIN3 and AIS were identified from the nationwide Pathology Data Bank, while SCC and AC were identified from the Danish Cancer Registry. We calculated age-standardized incidence rates and estimated annual percentage change (EAPC) with corresponding 95% confidence interval (CI) for the periods before vaccination implementation (2000-2005), early after implementation of childhood HPV vaccination and the first catch-up vaccination program (2006-2012), and after implementation of the second catch-up program (2013-2019). For CIN3 and AIS, age-specific incidence rates and EAPCs were calculated. An increasing age-standardized incidence was observed before introduction of HPV vaccination (2000-2005) for CIN3 [EAPCCIN3 : 3.0 (95% CI 1.7 to 4.3)] and AIS [EAPCAIS : 3.5 (95% CI 0.7 to 6.4)]. In the most recent period (2013-2019), following implementation of the second catch-up program, a decrease was observed for both CIN3 [EAPCCIN3 : -6.5 (95% CI -8.3 to -4.8)], AIS [EAPCAIS : -8.7 (95% CI -12.3 to -5.1)] and for SCC [EAPCSCC : -3.9 (95% CI -7.5 to -0.2)]. In this study we document a decrease in the incidence of CIN3, AIS and SCC in the period after implementation of multi-cohort HPV vaccination in Denmark.

Quality Control of Biospecimens in a Danish Clinical Cytology Biobank.

Introduction: Based on the experience from a Swedish biobank, we established a clinical cervical cytology biobank and adapted it to a Danish setting. The aim of the present study was to validate the biobank material regarding quality and quantity, to determine the usefulness of the material for future diagnostics and biomarker testing. Methods: Cervical cytology samples collected in ThinPrep were analyzed before and after biobanking using p16/ki-67 dual staining, a human papillomavirus (HPV) DNA test (Cobas), and a test for HPV messenger RNA (mRNA; Aptima). The concordance of the test results before and after biobanking was assessed. We also evaluated the morphology before and after biobanking and did additional tests on the biobanked material to qualify the usefulness of the material (library preparation for next-generation sequencing [NGS], reverse transcription-polymerase chain reaction [RT-PCR], and the Inno-Lipa HPV genotyping test). Results: For the Cobas HPV test, the concordance was 92% (122/133), and for the Inno-Lipa test (30 samples), it was 100%. For the Aptima assay, the concordance was a little lower, 84% (42/50). The morphology of the cell was well preserved, and the concordance of the p16/ki-67 dual staining was 88% (37/42). The functional tests showed that DNA-based NGS libraries (TST15 panel; Illumina) had good quality parameters. However, with the RT-PCR, 12% of the samples showed poor quality and a too low input amount for the analysis. Conclusion: The quality of the biobanked samples is high, and the material is suitable for testing of DNA, RNA, and protein. However, for testing of specific biomarkers, pilot studies are recommended to ensure sufficient input amount and quality of the material, especially for RNA-based studies.

Comparison of human papillomavirus-based cervical cancer screening strategies in Tanzania among women with and without HIV.

Cervical cancer is the most common female cancer in Eastern Africa, and the World Health Organization (WHO) recommends human papillomavirus (HPV)-based screening as a key element to eliminate the disease. In this cross-sectional study from Tanzania, we compared nine HPV-based cervical cancer screening strategies, including HPV testing at standard cut-off; HPV testing at increased viral load cut-offs; HPV testing with partial/extended genotyping, and HPV testing with visual inspection with acetic acid (VIA). We pooled data collected during 2008 to 2009 and 2015 to 2017 from 6851 women aged 25 to 65. Cervical cytology samples were HPV tested with Hybrid Capture 2, and HPV positive samples were genotyped with INNO-LiPA Extra II. Human immunodeficiency virus (HIV) testing and VIA were done according to local standards. We calculated sensitivity, specificity, positive and negative predictive value of screening strategies, with high-grade cytological lesions as reference, separately for women with and without HIV. HPV testing at standard cut-off (1.0 relative light units [RLU]) had highest sensitivity (HIV+: 97.8%; HIV-: 91.5%), but moderate specificity (HIV+: 68.1%; HIV-: 85.7%). Increasing the cut-off for HPV positivity to higher viral loads (5.0/10.0 RLU) increased specificity (HIV+: 74.2%-76.5%; HIV-: 89.5%-91.2%), with modest sensitivity reductions (HIV+: 91.3%-95.7%; HIV-: 83.5%-87.8%). Limiting test positivity to HPV types 16/18/31/33/35/45/52/58 improved specificity while maintaining high sensitivity (HIV+: 90.2%; HIV-: 81.1%). Triage with VIA and/or partial genotyping for HPV16/18 or HPV16/18/45 had low sensitivities (≤65%). In conclusion, HPV testing alone, or HPV testing with extended genotyping or increased viral load cut-offs, may improve cervical cancer screening in Sub-Saharan Africa.

Changes in HPV prevalence in Danish women with vulvar cancer during 28 years - A nationwide study of >1300 cancer cases.

OBJECTIVE: A substantial proportion of vulvar cancers are caused by high-risk human papillomavirus (hrHPV), but hrHPV prevalence in vulvar cancer has mainly been investigated in smaller studies which did not evaluate time trends. Our aim was to assess hrHPV prevalence in >1300 Danish vulvar cancers diagnosed during 1990-2017, including changes in hrHPV prevalence over time. METHODS: In a nationwide pathology register, we identified women diagnosed with vulvar cancer at thirteen hospitals from all Danish regions. Archival tumor tissue was collected from local repositories and, upon pathology review, sent to a central laboratory for HPV testing using INNO-LiPA. We calculated hrHPV prevalence according to time, age and histology, and evaluated the overall and age-specific estimated annual percentage change (EAPC). RESULTS: We included 1308 vulvar cancer cases, with a median age of 72 years at diagnosis. The overall hrHPV prevalence was 52.0% (95% CI: 49.3-54.7). HPV types 16/18 were found in 39.6% of cases, whereas nine-valent HPV (9vHPV) vaccine types 16, 18, 31, 33, 45, 52, and 58 were found in 50.8%. The hrHPV prevalence showed an increasing trend over time, with an EAPC of 0.35% (95% CI: 0.00-0.71). The hrHPV prevalence was higher in younger women throughout the study period, and increasing trends over time were seen in both older (age ≥ 60) and younger (age < 60) women. The hrHPV prevalence was higher in non-keratinizing (71.0%) and warty/basaloid (78.0%) carcinomas than in keratinizing (39.4%) and verrucous (36.4%) carcinomas. CONCLUSIONS: Our results indicate that the 9vHPV vaccine could potentially prevent a substantial proportion of vulvar cancers in Denmark.

Women with obesity participate less in cervical cancer screening and are more likely to have unsatisfactory smears: Results from a nationwide Danish cohort study.

Some studies found an association between obesity and increased cervical cancer risk, but potential mechanisms are unknown. In this nationwide register-based cohort study, we investigated the association between overweight/obesity and cervical cancer screening participation and risk of unsatisfactory smears. The study population was identified in the Danish Medical Birth Registry. We included 342,526 women aged 23-49 years with pre-pregnancy body mass index (BMI) registered during 2004-2013. Screening participation and unsatisfactory smears during up to four years after child birth were identified in a nationwide pathology register. We used absolute risk regression to estimate the relative absolute risk (RAR) with 95% confidence intervals (CIs) of screening participation according to BMI, adjusted for age, calendar year, sociodemographic characteristics, parity and previous high-grade cervical intraepithelial neoplasia. Among those who were screened (n = 295,482), we used log-binomial regression to investigate the relative risk (RR) of an unsatisfactory smear according to BMI, adjusted for age, year, parity, oral contraceptive use and pathology department. A lower proportion of obese women (79.3%) than women of normal weight (85.8%) were screened, and obese women had lower adjusted probability of being screened than women of normal weight (RARadjusted = 0.94, 95% CI, 0.93-0.95). A higher proportion of obese women (2.4%) than women of normal weight (1.7%) had an unsatisfactory smear, and this association remained after adjustments (RRadjusted = 1.28, 95% CI, 1.19-1.38). In conclusion, women with obesity were less likely to participate in cervical cancer screening and more likely to have an unsatisfactory smear than women of normal weight.

Anal Human Papillomavirus Infection in Kidney Transplant Recipients Compared With Immunocompetent Controls.

BACKGROUND: Kidney transplant recipients (KTRs) have increased risk of human papillomavirus (HPV)-related anogenital (pre)cancers, including anal high-grade intraepithelial lesions and cancer. Previous studies on anal high-risk HPV (hrHPV) among KTRs are sparse. METHODS: In a cross-sectional study, we included 247 KTRs and 248 controls from a dermatology department and 5 nephrology departments in Denmark during 2016-2017. All participants provided an anal cytobrush sample that was tested for HPV DNA. Participants completed a questionnaire on lifestyle and sexual habits. We used logistic regression to estimate odds ratios (ORs) of anal hrHPV in KTRs compared with controls and risk factors for anal hrHPV in KTRs. RESULTS: The anal hrHPV prevalence was higher in female KTRs (45.5%) than in controls (27.2%). Female KTRs had almost 3-fold higher adjusted odds of anal hrHPV than controls (adjusted OR, 2.87 [95% confidence interval, 1.57-5.22]). In contrast, among men we did not observe increased prevalence or odds of anal hrHPV in KTRs compared with controls (prevalence, 19.4% vs 23.6%; adjusted OR, 0.85 [95% 95% confidence interval, .44-1.64]). Among hrHPV-positive KTRs, 63% and 52% of men and women, respectively, were infected with hrHPV types covered by the nonavalent HPV vaccine (type 16, 18, 31, 33, 45, 52, or 58). Current smoking, >10 lifetime sexual partners, history of genital warts, and among men having had receptive anal sex were risk factors for anal hrHPV in KTRs. CONCLUSIONS: Female KTRs had an increased risk of anal hrHPV compared with immunocompetent controls. Our findings indicate that pretransplant HPV vaccination should be considered to prevent anal high-grade intraepithelial lesions and cancer caused by anal hrHPV infection in KTRs. CLINICAL TRIALS REGISTRATION: NCT03018327.

Increased risk of genital warts in inflammatory bowel disease: A Danish registry-based cohort study (1996-2018).

BACKGROUND: Patients with inflammatory bowel disease (IBD) are at increased risk of human papillomavirus (HPV) related cancers such as anal squamous cell carcinoma. However, risk of non-malignant HPV infection has never been systematically studied in IBD. This study aims to assess the risk of genital warts (GW) in IBD patients. METHODS: Using the Danish nationwide registries, we identified 49,163 patients with IBD between 1996 and 2018 and matched them to 491,665 individuals from the general population by age, sex, and HPV immunisation. Cumulative incidence rates for GW in IBD and non-IBD patients were calculated by age. Cox proportional regression analysis was used to calculate hazard ratios (HR) for GW in IBD compared to matched population and in Crohn's disease (CD) compared to ulcerative colitis (UC). We undertook subgroup analysis for risk of GW by sex, year of IBD diagnosis, contraceptive exposure and IBD treatment exposure. RESULTS: The fully adjusted HR for GW in IBD patients compared to the matched non-IBD population was 1.33 (95% CI: 1.19-1.49) and 1.13 (95% CI: 1.01, 1.27) in CD as compared to UC. This increased risk was particularly observed in female (HR: 1.54, 95% CI: 1.33-1.79) over male (HR: 1.14, 95% CI: 0.97-1.34) IBD patients, but was also found across all periods of diagnosis with IBD, regardless of contraceptive treatment exposure, and also seen in IBD patients who had never been exposed to immunosuppressive treatment (HR: 1.33, 95% CI: 1.19-1.49). CONCLUSION: In this nationwide, population-representative cohort study, we observed a 33% increased risk of GW in patients with IBD compared to the matched population and a 13% increased risk of GW in CD compared with UC. This risk was particularly increased in female over male IBD patients and seen independent of IBD treatment exposure.

The prognostic significance of HPV, p16, and p53 protein expression in vaginal cancer: A systematic review.

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.

Follow-up after abnormal cervical cancer screening in immigrants compared with Danish-born women - A nationwide register study.

Cervical cancer screening is offered free-of-charge to women aged 23-64 years in Denmark. Immigrants participate less in screening than Danish-born women, but little is known about their participation in follow-up after abnormal screening results. In this registry-based cohort study, we examined the likelihood of timely follow-up after an abnormal cervical cytology in immigrants from different countries and regions compared with Danish-born women. In nationwide registers, we identified women aged 23-64 years with high-grade (n = 74,335) or low-grade (n = 174,038) abnormal cytology during 1997-2017. Timely follow-up was defined as a new examination within six months for high-grade and 18 months for low-grade abnormalities. We calculated the probability of timely follow-up by country and region of origin and estimated odds ratios (ORs) of timely follow-up between immigrants and Danish-born women. The proportions with timely follow-up after high-grade abnormalities ranged from 90.6%-95.1% in immigrants from different countries or regions, compared with 95.5% in Danish-born women. For low-grade abnormalities, follow-up ranged from 75.2%-92.8% in immigrants, compared with 90.6% in Danish-born women. Women from Sub-Saharan Africa had low probability of timely follow-up after both high-grade (90.9%) and low-grade (75.2%) abnormalities. The differences between immigrants and Danish-born women remained when adjusting for age, year, income, employment and marital status. In conclusion, immigrants from most countries and regions were slightly less likely than Danish-born women to receive timely follow-up after abnormal cervical cytology, also after adjusting for socioeconomic differences. Efforts should be made to improve follow-up of abnormal screening results in immigrant groups with low attendance.

Risk of Anogenital Warts in Renal Transplant Recipients Compared with Immunocompetent Controls: A Cross-sectional Clinical Study.

Renal transplant recipients have increased risk of human papilloma virus-related anogenital (pre)cancers. Less is known about their risk of anogenital warts. The aim of this study was to estimate the prevalence and odds of anogenital warts in renal transplant recipients compared with immunocompetent controls, and to assess risk factors for intra- and perianal warts in renal transplant recipients. The study examined 248 renal transplant recipients and 250 controls for cutaneous and mucosal anogenital warts. Participants completed a questionnaire on lifestyle and sexual habits. For external anogenital warts (including penile, vulvar and perianal warts), renal transplant recipients had higher prevalence and odds than controls, both in men (8.1% vs 1.6%, adjusted odds ratio (ORadjusted)=5.09, 95% confidence interval (95% CI), 1.03-25.04) and women (11.3% vs 1.6%, ORadjusted=8.09, 95% CI 1.69-38.82). For intra-anal warts, there was no clear pattern of higher odds in renal transplant recipients than controls. Current smoking and having had receptive anal sex increased the risk of intra-/perianal warts in renal transplant recipients. In conclusion, renal transplant recipients in this study had higher odds of external anogenital warts than controls.

Benefits and potential harms of human papillomavirus (HPV)-based cervical cancer screening: A real-world comparison of HPV testing versus cytology.

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.

Risk of Anal High-grade Squamous Intraepithelial Lesions Among Renal Transplant Recipients Compared With Immunocompetent Controls.

BACKGROUND: Renal transplant recipients (RTRs) have increased risk of human papillomavirus (HPV)-related cancers, including anal cancer. We investigated the prevalence of anal high-grade intraepithelial lesions (HSILs) in RTRs compared with immunocompetent controls and risk factors for anal HSIL in RTRs. METHODS: We included 247 RTRs and 248 controls in this cross-sectional study. We obtained anal samples for HPV testing with INNO-LiPA and performed high-resolution anoscopy on all participants. The participants completed a questionnaire on lifestyle and sexual habits. We used logistic regression to estimate odds ratios (ORs) of histologically confirmed anal HSIL in RTRs vs controls and risk factors for anal HSIL in RTRs, stratified by sex and anal high-risk (hr) HPV status, adjusting for age, smoking, lifetime sexual partners, and receptive anal sex. RESULTS: RTRs had higher anal HSIL prevalence than controls, both among men (6.5% vs 0.8%; adjusted OR [aOR], 11.21 [95% confidence interval {CI}, 1.46-291.17]) and women (15.4% vs 4.0%; aOR, 6.41 [95% CI, 2.14-24.10]). Among those with anal hrHPV, RTRs had higher anal HSIL prevalence than controls (33.8% vs 9.5%; aOR, 6.06 [95% CI, 2.16-20.27]). Having had receptive anal sex (aOR, 6.23 [95% CI, 2.23-19.08]) or genital warts (aOR, 4.21 [95% CI, 1.53-11.48]) were risk factors for anal HSIL in RTRs. All HSIL cases occurred in individuals with anal hrHPV. CONCLUSIONS: RTRs had increased risk of anal HSIL compared with immunocompetent controls, with particularly high prevalence in female RTRs. Receptive anal sex, previous genital warts, and anal hrHPV infection were risk factors for anal HSIL in RTRs. Screening for anal HSIL in RTRs should be considered. CLINICAL TRIALS REGISTRATION: NCT03018927.

The role of body mass index in incidence and persistence of cervical human papillomavirus infection.

PURPOSE: This study aimed to assess the association between body mass index and incident or persistent cervical high-risk human papillomavirus (hrHPV) infection. METHODS: This cohort study included 6809 women from the general Danish population who participated in two clinical visits (in 1991-1993 and in 1993-1995). Height and weight were measured by nurses, lifestyle data were obtained by structured interviews, and cervical cytology samples were obtained for hrHPV DNA testing. We conducted log-binomial regression to estimate risk ratios (RRs) with 95% confidence intervals (CIs) of incident and type-specific persistent hrHPV infection according to body mass index, adjusting for age, education, smoking, and the number of sexual partners in the past year. RESULTS: We found no increased risk of incident hrHPV infection in women who were underweight (RRadjusted, 0.97; 95% CI, 0.64-1.48), overweight (RRadjusted, 0.98, 95% CI, 0.82-1.17), or obese (RRadjusted, 0.93; 95% CI, 0.63-1.36) compared with women of normal weight. The risk of hrHPV persistence was similar in overweight (RRadjusted, 0.98; 95% CI, 0.71-1.34) and obese (RRadjusted, 1.00; 95% CI, 0.56-1.79) women compared with women of normal weight, whereas underweight women had a lower risk (RRadjusted, 0.32; 95% CI, 0.11-0.95). CONCLUSIONS: Overweight and obesity were not associated with HPV incidence or persistence when adjusting for sexual behavior.

Time trends in the incidence and survival of vaginal squamous cell carcinoma and high-grade vaginal intraepithelial neoplasia in Denmark - A nationwide population-based study.

OBJECTIVE: To describe trends in incidence of high-grade vaginal intraepithelial neoplasia (VaIN) and vaginal squamous cell carcinoma (SCC) in Denmark. For vaginal SCC, we also examine 5-year relative survival and mortality. METHODS: All high-grade VaIN cases diagnosed 1997-2017 and vaginal SCCs during 1978-2017 were identified in two high-quality nationwide registers. Age-standardized incidence rates and average annual percentage change (AAPC) were assessed. For vaginal SCC, 5-year relative survival was calculated, and Cox regression was applied to study the effect of selected characteristics on mortality. RESULTS: Altogether, 831 cases of high-grade VaIN and 721 vaginal SCCs were identified. The age-standardized incidence rate of high-grade VaIN showed no clear trend over time. However, when we stratified by age and divided the study period according to HPV vaccine licensure in Denmark (2006), the incidence of high-grade VaIN decreased significantly by 15.6% per year (95% CI: -23.2, -7.3%) after 2007 onwards among the youngest women (<30 years). For vaginal SCC, the incidence decreased from 0.5 (1978-1982) to 0.3 (2013-2017) per 100,000 woman-years. The 5-year relative survival improved over time and was 67.9% (95% CI: 54.9, 84.1%) in the most recent time period. Mortality was significantly associated with calendar year, age, and stage at diagnosis. CONCLUSIONS: The overall incidence of high-grade VaIN showed no clear trend over time, but a significant decline was observed in women younger than 30 years after HPV vaccine licensure. The incidence of vaginal SCC was reduced by approximately 50% and survival after vaginal SCC improved over time.