Impact of cervical screening by human papillomavirus genotype: Population-based estimations.

BACKGROUND: Cervical screening programs use testing for human papillomavirus (HPV) genotypes. Different HPV types differ greatly in prevalence and oncogenicity. We estimated the impact of cervical screening and follow-up for each HPV type. METHODS AND FINDINGS: For each type of HPV, we calculated the number of women needed to screen (NNS) and number of women needing follow-up (NNF) to detect or prevent one cervical cancer case, using the following individual level input data (i) screening and cancer data for all women aged 25 to 80 years, resident in Sweden during 2004 to 2011 (N = 3,568,938); (ii) HPV type-specific prevalences and screening histories among women with cervical cancer in Sweden in 2002 to 2011(N = 4,254); (iii) HPV 16/18/other HPV prevalences in the population-based HPV screening program (N = 656,607); and (iv) exact HPV genotyping in a population-based cohort (n = 12,527). Historical screening attendance was associated with a 72% reduction of cervical cancer incidence caused by HPV16 (71.6%, 95% confidence interval (CI) [69.1%, 73.9%]) and a 54% reduction of cancer caused by HPV18 (53.8%, 95% CI [40.6%, 63.1%]). One case of HPV16-caused cervical cancer could be prevented for every 5,527 women attending screening (number needed to screen, NNS). Prevention of one case of HPV16-caused cervical cancer required follow-up of 147 HPV16-positive women (number needed to follow-up, NNF). The NNS and NNF were up to 40 to 500 times higher for HPV types commonly screened for with lower oncogenic potential (HPV35,39,51,56,59,66,68). For women below 30 years of age, NNS and NNF for HPV16 were 4,747 and 289, respectively, but >220,000 and >16,000 for HPV35,39,51,56,59,66,68. All estimates were either age-standarized or age-stratified. The primary limitation of our study is that NNS is dependent on the HPV prevalence that can differ between populations and over time. However, it can readily be recalculated in other settings and monitored when HPV type-specific prevalence changes. Other limitations include that in some age groups, there was little data and extrapolations had to be made. Finally, there were very few cervical cancer cases associated with certain HPV types in young age group. CONCLUSIONS: In this study, we observed that the impact of cervical cancer screening varies depending on the HPV type screened for. Estimating and monitoring the impact of screening by HPV type can facilitate the design of effective and efficient HPV-based cervical screening programs. TRIAL REGISTRATION: ClinicalTrials.gov with numbers NCT00479375, NCT01511328.

HPV Vaccination and the Risk of Invasive Cervical Cancer.

BACKGROUND: The efficacy and effectiveness of the quadrivalent human papillomavirus (HPV) vaccine in preventing high-grade cervical lesions have been shown. However, data to inform the relationship between quadrivalent HPV vaccination and the subsequent risk of invasive cervical cancer are lacking. METHODS: We used nationwide Swedish demographic and health registers to follow an open population of 1,672,983 girls and women who were 10 to 30 years of age from 2006 through 2017. We assessed the association between HPV vaccination and the risk of invasive cervical cancer, controlling for age at follow-up, calendar year, county of residence, and parental characteristics, including education, household income, mother's country of birth, and maternal disease history. RESULTS: During the study period, we evaluated girls and women for cervical cancer until their 31st birthday. Cervical cancer was diagnosed in 19 women who had received the quadrivalent HPV vaccine and in 538 women who had not received the vaccine. The cumulative incidence of cervical cancer was 47 cases per 100,000 persons among women who had been vaccinated and 94 cases per 100,000 persons among those who had not been vaccinated. After adjustment for age at follow-up, the incidence rate ratio for the comparison of the vaccinated population with the unvaccinated population was 0.51 (95% confidence interval [CI], 0.32 to 0.82). After additional adjustment for other covariates, the incidence rate ratio was 0.37 (95% CI, 0.21 to 0.57). After adjustment for all covariates, the incidence rate ratio was 0.12 (95% CI, 0.00 to 0.34) among women who had been vaccinated before the age of 17 years and 0.47 (95% CI, 0.27 to 0.75) among women who had been vaccinated at the age of 17 to 30 years. CONCLUSIONS: Among Swedish girls and women 10 to 30 years old, quadrivalent HPV vaccination was associated with a substantially reduced risk of invasive cervical cancer at the population level. (Funded by the Swedish Foundation for Strategic Research and others.).

Evaluation of co-testing with cytology and human papillomavirus testing in cervical screening.

Cervical screening is increasingly switching to human papillomavirus (HPV) testing. In many settings, the switch has involved one or several co-tests (testing using both cytology and HPV) in the screening guidelines, to ensure safety. When Sweden switched to HPV testing in 2015 the guidelines included a co-test at age 41. To evaluate the effect of co-testing, we identified all 208,701 women resident in Sweden who in 2019 were 40-42 years old and thus eligible for co-testing. All cervical samples, the results of the test and of the subsequent biopsies were identified in the Swedish National Cervical Screening Registry. Out of the 10,643 women with co-testing in screening, there were 197 women with a subsequent biopsy with high-grade cervical neoplasia or worse (CIN2+). Among these 197 women, 189 had a screening test positive for both HPV and cytology, 6 women were HPV+/Cyt- and 2 women were HPV-/Cyt+. There were 7115 women with a co-test outside of the screening program. Among these, 325 women had a CIN2+ in histopathology, 290 were double positive, 13 women were cyt+/HPV-, and 11 women each were HPV+/cyt- and HPV-/Cyt-. In summary, the additional yield of CIN2+ with co-testing was 2 cases per 10,643 women as compared with 195/10,643 CIN2+ cases detected with HPV screening alone. However, for cervical samples taken outside the screening program (e.g. taken on a clinical indication) there was an increased yield (314 CIN2+ cases detected with co-testing as compared to 301 cases with HPV screening).

High Amounts of SARS-CoV-2 Precede Sickness Among Asymptomatic Health Care Workers.

BACKGROUND: Whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positivity among asymptomatic subjects reflects past or future disease may be difficult to ascertain. METHODS: We tested 9449 employees at Karolinska University Hospital, Stockholm, Sweden for SARS-CoV-2 RNA and antibodies, linked the results to sick leave records, and determined associations with past or future sick leave using multinomial logistic regression. RESULTS: Subjects with high amounts of SARS-CoV-2 virus, indicated by polymerase chain reaction (PCR) cycle threshold (Ct) value, had the highest risk for sick leave in the 2 weeks after testing (odds ratio [OR], 11.97; 95% confidence interval [CI], 6.29-22.80) whereas subjects with low amounts of virus had the highest risk for sick leave in the 3 weeks before testing (OR, 6.31; 95% CI, 4.38-9.08). Only 2.5% of employees were SARS-CoV-2 positive while 10.5% were positive by serology and 1.2% were positive in both tests. Serology-positive subjects were not at excess risk for future sick leave (OR, 1.06; 95% CI, .71-1.57). CONCLUSIONS: High amounts of SARS-CoV-2 virus, as determined using PCR Ct values, was associated with development of sickness in the next few weeks. Results support the concept that PCR Ct may be informative when testing for SARS-CoV-2. Clinical Trials Registration. NCT04411576.

Organized primary human papillomavirus-based cervical screening: A randomized healthcare policy trial.

BACKGROUND: Clinical trials in the research setting have demonstrated that primary human papillomavirus (HPV)-based screening results in greater protection against cervical cancer compared with cytology, but evidence from real-life implementation was missing. To evaluate the effectiveness of HPV-based cervical screening within a real-life screening program, the organized, population-based cervical screening program in the capital region of Sweden offered either HPV- or cytology-based screening in a randomized manner through a randomized healthcare policy (RHP). METHODS AND FINDINGS: A total of 395,725 women aged 30 to 64 years that were invited for their routine cervical screening visit were randomized without blinding to either cytology-based screening with HPV triage (n = 183,309) or HPV-based screening, with cytology triage (n = 212,416 women) between September 1, 2014 and September 30, 2016 and follow-up through June 30, 2017. The main outcome was non-inferior detection rate of cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Secondary outcomes included superiority in CIN2+ detection, screening attendance, and referral to histology. In total, 120,240 had a cervical screening sample on record in the study period in the HPV arm and 99,340 in the cytology arm and were followed for the outcomes of interest. In per-protocol (PP) analyses, the detection rate of CIN2+ was 1.03% (95% confidence interval (CI) 0.98 to 1.10) in the HPV arm and 0.93% (0.87 to 0.99) in the cytology arm (p for non-inferiority <0.0001; odds ratio (OR) 1.11 (95% CI 1.02 to 1.22)). There were 46 cervical cancers detected in the HPV arm (0.04% (0.03 to 0.06)) and 48 cancers detected in the cytology arm (0.05% (0.04 to 0.07)) (p for non-inferiority <0.0001; OR 0.79 (0.53 to 1.18)). Intention-to-screen (ITS) analyses found few differences. In the HPV arm, there was a modestly increased attendance after new invitations (68.56% (68.31 to 68.80) vs. 67.71% (67.43 to 67.98); OR 1.02 (1.00 to 1.03)) and increased rate of referral with completed biopsy (3.89% (3.79 to 4.00) vs. 3.53% (3.42 to 3.65); OR 1.10 (1.05 to 1.15)). The main limitations of this analysis are that only the baseline results are presented, and there was an imbalance in invitations between the study arms. CONCLUSIONS: In this study, we observed that a real-life RHP of primary HPV-based screening was acceptable and effective when evaluated against cytology-based screening, as indicated by comparable participation, referral, and detection rates. TRIAL REGISTRATION: ClinicalTrials.gov NCT01511328.

Prospects for accelerated elimination of cervical cancer.

Human Papillomavirus (HPV) infection is a necessary risk factor for cervical cancer. If HPV is no longer spread, no new cervical cancer precursors will occur. The timepoint for control of the HPV infection will therefore be a rate-limiting step for cervical cancer elimination. We used a validated dynamic HPV transmission model to estimate the age-specific HPV16 incidences and basic reproductive numbers (R0) with input data from Sweden. If R0 is below 1, a fade-out resulting in extinction is expected. Above age 35, we found an R0 of 0.4. Thus, when younger birth cohorts no longer transmit HPV to women >35 years of age, we predict that the HPV infection will no longer be sustained among the older women. Given adequate resources, campaigns to eliminate HPV that are designed based on the R0 measurements followed by screening to detect and treat pre-existing cervical cancer precursors could achieve accelerated cervical cancer elimination.

Elimination of HPV-associated oropharyngeal cancers in Nordic countries.

Incidence of human papillomavirus (HPV, most notably HPV type 16) associated oropharyngeal squamous cell carcinoma (OPSCC) among middle-aged (50-69 year-old) males has tripled in four high income Nordic countries (Denmark, Finland, Norway and Sweden) over the last 30 years. In Finland and Sweden, this increase was preceded by an HPV16 epidemic in fertile-aged populations in the 1980's. The recent implementation of school-based prophylactic HPV vaccination in early adolescent boys and girls will gradually decrease the incidence, and eventually eliminate the HPV-associated OPSCCs (especially tonsillar and base of tongue carcinomas) in the Nordic countries. However, beyond the adolescent and young adult birth cohorts vaccinated, there are approximately 50 birth cohorts (born in 1995 or before) that would benefit from screening for HPV-associated OPSCC. This article reviews the need, prerequisites, proof-of-concept trial and prospects of preventing HPV-associated OPSCC in the Nordic countries.

Early assessment of the first wave of the COVID-19 pandemic on cancer screening services: The International Cancer Screening Network COVID-19 survey.

Screening can decrease the burden of breast, cervical, and colorectal cancers. The COVID-19 pandemic led many countries to suspend cancer screening services as part of their response to the pandemic. The International Cancer Screening Network (ICSN) carried out an online survey to assess the effects of the first wave of the COVID-19 pandemic on cancer screening. A 33-item survey was distributed to 834 email addresses to gather information about settings and assess decision-making processes that led to cancer screening suspension. Information about communication, impact on resources, and patient follow-up was collected. Quantitative data was analyzed as frequencies overall and by setting, while a comment section under each survey item captured nuanced details. Responses were recategorized into 66 settings, representing 35 countries. Most settings suspended cancer screening services (n = 60, 90.9%) in March 2020 (n = 45, 68.2%), guided by a government decision (n = 51, 77.3%). Few settings made the decision whether to suspend services based on a preparedness plan (n = 17, 25.8%). In most settings, professionals were reassigned (n = 41, 62.1%) and infrastructure repurposed (n = 35, 53.0%). The first wave of the COVID-19 pandemic has had profound effects on cancer screening worldwide, including the suspension of services in almost all settings. Most settings were unprepared to deal with the scale of the pandemic but demonstrated flexibility in the response. These results contribute to inform, through experiences and lessons learned, the next steps for the global cancer screening community to further evaluate the impact of COVID-19 and prepare for future disruptions.

Cost-Effectiveness of Magnetic Resonance Imaging in Prostate Cancer Screening: A Microsimulation Study.

OBJECTIVE: This study aimed to assess the cost-effectiveness of magnetic resonance imaging (MRI) with combinations of targeted biopsy (TBx) and systematic biopsy (SBx) for early prostate cancer detection in Sweden. METHODS: A cost-utility analysis was conducted from a lifetime societal perspective using a microsimulation model. Five strategies included no screening and quadrennial screening for men aged 55 to 69 years using SBx alone, TBx on positive MRI (MRI + TBx), combined TBx/SBx on positive MRI (MRI + TBx/SBx), and SBx on negative MRI with TBx/SBx on positive MRI (MRI - SBx, MRI + TBx/SBx). Test characteristics were based on a recent Cochrane review. We predicted the number of biopsies, costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios. RESULTS: The screening strategies were classified in Sweden as high costs per QALY gained compared with no screening. Using MRI + TBx and MRI + TBx/SBx reduced the number of biopsy episodes across a lifetime by approximately 40% compared with SBx alone. Both strategies showed strong dominance over SBx alone and MRI - SBx, MRI + TBx. Compared with MRI + TBx, the MRI + TBx/SBx strategy had an incremental cost-effectiveness ratio of more than €200 000 per QALY gained, which was classified in Sweden as a very high cost. These predictions were robust in the probabilistic sensitivity analysis. Limitations included generalizability of the model assumptions and uncertainty regarding the health-state values and study heterogeneity from the Cochrane review. CONCLUSIONS: MRI + TBx and MRI + TBx/SBx showed strong dominance over alternative screening strategies. MRI + TBx resulted in similar or marginally lower gains in QALYs and lower costs than MRI + TBx/SBx. MRI + TBx was considered the optimal choice among the screening strategies.

Risk of SARS-CoV-2 exposure among hospital healthcare workers in relation to patient contact and type of care.

AIM: We aimed to assess prevalence of IgG antibodies to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and factors associated with seropositivity in a large cohort of healthcare workers (HCWs). METHODS: From 11 May until 11 June 2020, 3981 HCWs at a large Swedish emergency care hospital provided serum samples and questionnaire data. Presence of IgG antibodies to SARS-CoV-2 was measured as an indicator of SARS-CoV-2 exposure. RESULTS: The total seroprevalence was 18% and increased during the study period. Among the seropositive HCWs, 11% had been entirely asymptomatic. Participants who worked with COVID-19 patients had higher odds for seropositivity: adjusted odds ratio 1.96 (95% confidence intervals 1.59-2.42). HCWs from three of the departments managing COVID-19 patients had significantly higher seroprevalences, whereas the prevalence among HCWs from the intensive care unit (also managing COVID-19 patients) was significantly lower. CONCLUSIONS: HCWs in contact with SARS-CoV-2 infected patients had a variable, but on average higher, likelihood for SARS-CoV-2 infections.

Cervical cancer case-control audit: Results from routine evaluation of a nationwide cervical screening program.

Our study used a refined case-control cervical cancer Audit framework to investigate effectiveness of cervical screening, with measures of three screening failures: irregular-participation, cervical cancer developed after cytological abnormalities and after normal screening results. The register-based study included 4,254 cervical cancer cases diagnosed in Sweden during 2002-2011, and 30 population-based controls per case. We used conditional logistic regression models to examine relative risks of cervical cancer in relation to screening participation and screening results in the past two screening rounds from 6 months before cancer diagnosis. We found that women unscreened in past two screening rounds showed four times increased risk of cervical cancer compared to women screened in time (OR = 4.1, 95% CI = 3.8-4.5), and women unscreened in the previous round but screened in the most recent round also showed a statistically significantly elevated risk (OR = 1.6, 95% CI = 1.5-1.8). Women having abnormality in previous two rounds exhibited higher risk of cervical cancer compared to women screened with normal results, while having normal results in the subsequent round after the abnormality also yielded an increased risk (OR = 4.0, 95% CI = 3.2-5.1). Being screened with only normal results was associated with 89% risk reduction for squamous cell cancer, compared to women unscreened, but only 60% reduction for adenocarcinoma. Our findings emphasize the importance of routine participation in cervical screening and suggest that management of abnormalities, as well as sensitivity of the test, warrants improvement especially for preventing cervical adenocarcinoma. The Audit framework serves as routine evaluation model and the findings benchmark for future evaluation of changes in screening practice.

Advances in cervical cancer prevention: Efficacy, effectiveness, elimination?

With major advances in understanding the infectious etiology of cervical cancer, preventive medicine has obtained highly promising new tools. Human papillomavirus (HPV) vaccines, together with a growing arsenal of HPV-based screening tests, have the potential to radically change public health but require diligent, large-scale implementation to reach the final goal: the elimination of cervical cancer. We reflect here upon the state of cervical cancer prevention globally as there have been several recent developments that will inform this implementation process.

Impact of HPV vaccination on cervical screening performance: a population-based cohort study.

BACKGROUND: Human papillomavirus (HPV) vaccination is predicted to lower the positive predictive value (PPV) of cytology. METHODS: We included 153,250 girls born between 1989 and 1993, resident in Sweden since the introduction of HPV vaccines (October 2006) and attending cervical screening at age 23 years. We assessed their first cytology and following histopathological diagnosis using Swedish National Cervical Screening Registry (NKCx). By linkage with the national Swedish HPV vaccination registry, we determined PPV of abnormal cytology for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and the differences with 95% confidence intervals (CIs) according to vaccination status. RESULTS: The PPV of high-grade cytology for CIN2+ was 69.9% (95% CI, 67.9-71.9), 64.9% (95% CI, 59.8-69.8) and 57.4% (95% CI, 50.9-63.7) among women unvaccinated, initiating vaccination at age 17-22 years and initiating vaccination before age 17 years, corresponding to reduction in PPV by 8% (95% CI, 0-15%) and 17% (95% CI, 7-26%) in vaccinated groups after adjustment for birth cohort, respectively. CONCLUSION: The PPV of cytology for CIN2+ decreased among vaccinated women, and the decrease was stronger for girls vaccinated at younger ages. A switch from cytology to HPV testing might potentially improve the screening performance.

Colposcopic and histopathologic evaluation of women with HPV persistence exiting an organized screening program.

BACKGROUND: Human papillomavirus-based screening has a higher sensitivity for precursors of cervical cancer compared with cytology-based screening. However, more evidence is needed on optimal management of human papillomavirus-positive women. OBJECTIVE: The objective of the study was to compare the risk of histopathologically confirmed cervical intraepithelial lesions grade 2 or worse after 1 and 3 years of human papillomavirus persistence, respectively, and evaluate the clinical management of human papillomavirus-positive women in the 56-60 year age group. STUDY DESIGN: This was a randomized health care policy offering human papillomavirus screening to 50% of resident women aged 56-60 years in the Stockholm/Gotland region of Sweden during January 2012 through May 2014. Women who were human papillomavirus positive/cytology negative at baseline were referred for a repeat test after 1 or 3 years. In case of human papillomavirus persistence, women were referred for colposcopy, including biopsies and endocervical sampling. RESULTS: The human papillomavirus prevalence was 5.5% (405 women of 7325 attending). Among the 405 human papillomavirus-positive women, 313 were reflex test cytology negative at baseline and were referred for a repeat human papillomavirus test, 176 women after 1 year and 137 women after 3 years. After 1 year, 91 of 176 (52%) were persistently human papillomavirus positive and after 3 years 55 of 137 (40%) (P = .042). In repeat cytology, 10 of the 91 (12%) were positive after 1 year and 15 of 55 (33%) after 3 years (P = .005). The attendance rates for colposcopy were similar: 82 of 91 (90%) in the 1 year group and 45 of 55 (82%) in the 3 year group. All women attending colposcopy were postmenopausal, and endocervical sampling and punch biopsies were performed to facilitate colposcopic management, with a positive predictive value of 43-50% and 28-31%, respectively. Histopathologically confirmed cervical intraepithelial lesions grade 2 or worse was found in 19 of 82 women (23%) and 9 of 45 women (20%) in the 1 year and 3 year groups, respectively, and registry linkage follow-up found no cancers in either group. Human papillomavirus genotyping was predictive of cervical intraepithelial lesions grade 2 or worse, and human papillomavirus 16 was the most common genotype at human papillomavirus persistence, occurring in 18% of the cases in the 1 year group and 20% in the 3 year group. CONCLUSION: It was safe to postpone repeat human papillomavirus tests for 3 years in postmenopausal women attending the organized cervical screening program. There was a high risk for cervical intraepithelial lesions grade 2 or worse at follow-up and noteworthy yields from human papillomavirus genotyping as well as endocervical sampling and random biopsies in the absence of visible colposcopic lesions.

Emergency contraceptive pill use among women in Denmark, Norway and Sweden: Population-based survey.

INTRODUCTION: Emergency contraceptive pill (ECP) use is reported to have increased in several countries over time. In this multi-country population-based questionnaire study, we aimed to describe the patterns of ECP use and identify factors associated with its use. MATERIAL AND METHODS: In 2011-2012, women aged 18-45 years were randomly selected from national registers in Denmark, Norway and Sweden and invited to respond to questions related to lifestyle and contraceptive use. We used generalized logistic models to estimate odds ratios (ORs) and 95% confidence intervals (CI) comparing women who had used ECP with women who had never used ECP. RESULTS: Of the 45 445 women, 33.9% (Denmark = 32.3%, Norway = 35.1%, Sweden = 34.6%) had used ECP at least once in their lifetime. Among ECP users, 15.8% had used ECP within the last year and 50.0% had used ECP more than once in their life. After adjusting for country, age at response and response type, ECP use was associated with higher education (OR 2.09, 95% CI 1.54-2.84) and being single, divorced or widowed (OR 3.17, 95% CI 2.87-3.49). Binge drinking and smoking increased the odds of ECP use. Furthermore, early age at first intercourse (OR 1.29, 95% CI 1.08-1.55), having a new partner in the last 6 months (≥3 partners: OR 6.44, 95% CI 5.46-7.60) and lack of condom use with a recent new partner (OR 1.42, 95% CI 1.22-1.66) were found to be associated with ECP use. CONCLUSIONS: Our study shows that ECP use is common among Scandinavian women. Higher education and being single were associated with increased odds of ECP use. Risk behaviors such as smoking and early age at first sex were also associated with increased odds of ECP use. Since ECP use is not protective against sexually transmitted infections, our findings highlight the need to encourage awareness and regular use of condoms to prevent sexually transmitted diseases in women.

Age at first intercourse, number of partners and sexually transmitted infection prevalence among Danish, Norwegian and Swedish women: estimates and trends from nationally representative cross-sectional surveys of more than 100 000 women.

INTRODUCTION: Sexual behavior at the population level impacts on public health. Recent representative sexual behavior data are lacking. MATERIAL AND METHODS: Cross-sectional surveys in 2005 and 2012 on women age 18-45 years randomly selected from the general population in Denmark (n = 40 804), Norway (n = 30 331) and Sweden (n = 32 114). RESULTS: Median (interquartile range) age at first intercourse was 16 (15-18) years in Denmark, 17 (16-18) years in Norway, and 17 (15-18) years in Sweden. Women in the most recent birth cohort had sexual debut at the lowest age, and were most likely to have sexual debut before the legal age of consent. Proportions with debut age ≤14 years among women born 1989-1994 vs 1971-1976, odds ratio (95% confidence interval) were: 18.4% vs 10.9%, 1.95 (1.74-2.18) in Denmark, 12.9% vs 6.3%, 2.38 (2.01-2.82) in Norway, 17.8% vs 11.4%, 1.75 (1.55-1.98) in Sweden. Median (interquartile range) number of lifetime sexual partners was 6 (3-10) in Denmark, 5 (2-10) in Norway, and 6 (3-11) in Sweden. The proportion of women reporting >10 sexual partners was also highest in the most recent survey. The percentage with odds ratio (95% confidence interval) in 2012 vs 2005 surveys were: 24.9% vs 22.8%, 1.13 (1.07-1.18) for Denmark; 23.8% vs 19.8%, 1.27 (1.19-1.34) for Norway; and 28.3% vs 23.8%, 1.31 (1.24-1.38) for Sweden. Similarly, the proportion of women reporting ever having had a sexually transmitted infection among women age <30 years were: 29.4% vs 26.4%, 1.21 (1.13-1.31) in Denmark, 28.9% vs 25.0%, 1.20 (1.10-1.31) in Norway, and 29.4% vs 22.2%, 1.45 (1.33-1.58) in Sweden. CONCLUSIONS: Scandinavian women reported lower age at first intercourse in younger birth cohorts. Moreover, they reported more lifetime sexual partners and a higher prevalence of ever having a sexually transmitted infection in 2012 than in 2005. Our findings may inform the interpretation of trends in outcomes associated with sexual health, and public health policies.

High-risk human papillomavirus status and prognosis in invasive cervical cancer: A nationwide cohort study.

BACKGROUND: High-risk human papillomavirus (hrHPV) infection is established as the major cause of invasive cervical cancer (ICC). However, whether hrHPV status in the tumor is associated with subsequent prognosis of ICC is controversial. We aim to evaluate the association between tumor hrHPV status and ICC prognosis using national registers and comprehensive human papillomavirus (HPV) genotyping. METHODS AND FINDINGS: In this nationwide population-based cohort study, we identified all ICC diagnosed in Sweden during the years 2002-2011 (4,254 confirmed cases), requested all archival formalin-fixed paraffin-embedded blocks, and performed HPV genotyping. Twenty out of 25 pathology biobanks agreed to the study, yielding a total of 2,845 confirmed cases with valid HPV results. Cases were prospectively followed up from date of cancer diagnosis to 31 December 2015, migration from Sweden, or death, whichever occurred first. The main exposure was tumor hrHPV status classified as hrHPV-positive and hrHPV-negative. The primary outcome was all-cause mortality by 31 December 2015. Five-year relative survival ratios (RSRs) were calculated, and excess hazard ratios (EHRs) with 95% confidence intervals (CIs) were estimated using Poisson regression, adjusting for education, time since cancer diagnosis, and clinical factors including age at cancer diagnosis and International Federation of Gynecology and Obstetrics (FIGO) stage. Of the 2,845 included cases, hrHPV was detected in 2,293 (80.6%), and we observed 1,131 (39.8%) deaths during an average of 6.2 years follow-up. The majority of ICC cases were diagnosed at age 30-59 years (57.5%) and classified as stage IB (40.7%). hrHPV positivity was significantly associated with screen-detected tumors, young age, high education level, and early stage at diagnosis (p < 0.001). The 5-year RSR compared to the general female population was 0.74 (95% CI 0.72-0.76) for hrHPV-positive cases and 0.54 (95% CI 0.50-0.59) for hrHPV-negative cases, yielding a crude EHR of 0.45 (95% CI 0.38-0.52) and an adjusted EHR of 0.61 (95% CI 0.52-0.71). Risk of all-cause mortality as measured by EHR was consistently and statistically significantly lower for cases with hrHPV-positive tumors for each age group above 29 years and each FIGO stage above IA. The difference in prognosis by hrHPV status was highly robust, regardless of the clinical, histological, and educational characteristics of the cases. The main limitation was that, except for education, we were not able to adjust for lifestyle factors or other unmeasured confounders. CONCLUSIONS: In this study, women with hrHPV-positive cervical tumors had a substantially better prognosis than women with hrHPV-negative tumors. hrHPV appears to be a biomarker for better prognosis in cervical cancer independent of age, FIGO stage, and histological type, extending information from already established prognostic factors. The underlying biological mechanisms relating lack of detectable tumor hrHPV to considerably worse prognosis are not known and should be further investigated.

Nationwide comprehensive human papillomavirus (HPV) genotyping of invasive cervical cancer.

BACKGROUND: The Swedish National Cervical Screening Registry collects and evaluates comprehensive, nationwide health data to optimise organised cervical cancer prevention. Since all cervical cancer specimens are saved in biobanks, population-based data from the specimens should be available for analysis and linkage with other health information. METHODS: We identified all cervical cancers diagnosed in Sweden during 2002-2011 (4254 confirmed cases) and requested the tissue blocks to retrieve human papillomavirus (HPV) genotype data using general primer PCR with Luminex genotyping and real-time PCR targeting the E6/E7 regions of HPV16/18. RESULTS: We obtained blocks from 2932/4254 (69%) of cases. Valid HPV genotyping data was retrieved for 2850 cases (97%). The most common type was HPV16 (60%), followed by HPV18 (19%), HPV45 (7%), HPV31 (3%), HPV33 (2%), HPV52 (2%), HPV39 (1%), HPV70 (1%), HPV56 (1%), HPV35 (1%), HPV58 (1%) and HPV59 (1%). Ninety-six percent of all HPV-positive cases had a single infection. Eighty-nine cases were HPV-positive only when testing for the HPV16/18-E6/E7 region. CONCLUSIONS: We present one of the largest series of HPV-genotyped cervical cancers to date. The systematic collection of cervical cancer HPV genotyping data by the screening registry will facilitate prevention and monitoring of HPV type-specific disease burden.

Determinants of the presence of human papillomaviruses in the anal canal of Russian men.

Knowledge of determinants of anal human papillomavirus (HPV) infections among men is still limited as most of the studies are focused on high-risk populations and geographically narrowed. Such knowledge obtained in different populations is essential for better understanding of HPV natural history, transmission dynamics, and its role in the development and prevention of anogenital malignancies in different regions. Here we tested anal canal swab samples from 359 Russian heterosexual (323 human immunodeficiency virus [HIV]-negative and 27 HIV-positive, aged 18-67 years) men attending a sexually transmitted infection clinic 36 HPV types using a proficient Luminex assay. HPV-positivity in anal samples was common for 332 HIV-negative heterosexual men for overall HPV (15.7%, n = 52), oncogenic HPV (9.6%, n = 32), nononcogenic HPV (8.1%, n = 27), and multiple HPV infections (4.5%, n = 14). The most common anal HPV types were HPV16 (5.7%), HPV45, and HPV51 (1.8% each), HPV66, and HPV87 (1.8% each). No association was found with the number of lifetime sexual partners, age of participants at the time of the study, or their sexual debut. Although anal HPV positivity was more common among HIV-positive men, the current study provides additional evidence that anal HPV can be frequently detected in heterosexual HIV-negative men favoring further studies on transmission routes to discriminate between contamination and true HPV infection.

Effectiveness of cervical screening after age 60 years according to screening history: Nationwide cohort study in Sweden.

BACKGROUND: The relatively high incidence of cervical cancer in women at older ages is a continuing concern in countries with long-established cervical screening. Controversy remains on when and how to cease screening. Existing population-based studies on the effectiveness of cervical screening at older ages have not considered women's screening history. We performed a nationwide cohort study to investigate the incidence of cervical cancer after age 60 years and its association with cervical screening at age 61-65, stratified by screening history at age 51-60. METHODS AND FINDINGS: Using the Total Population Register, we identified 569,132 women born between 1 January 1919 and 31 December 1945, resident in Sweden since age 51. Women's cytological screening records, cervical cancer occurrence, and FIGO stage (for those diagnosed with cancer) were retrieved from national registers and medical charts. We calculated the cumulative incidence of cervical cancer from age 61 to age 80 using a survival function considering competing risk, and estimated the hazard ratio (HR) of cervical cancer in relation to screening status at age 61-65 from Cox models, adjusted for birth cohort and level of education, conditioning on women's screening history in their 50s. In women unscreened in their 50s, the cumulative incidence up to age 80 was 5.0 per 1,000 women, and screening at age 61-65 was associated with a lower risk for cervical cancer (HR = 0.42, 95% CI 0.24-0.72), corresponding to a decrease of 3.3 cancer cases per 1,000 women. A higher cumulative incidence and similarly statistically significant risk decrease was seen for women with abnormal smears in their 50s. In women adequately or inadequately screened with only normal results between age 51 and age 60, the cumulative incidence of cervical cancer from age 61 to 80 was 1.6 and 2.5 per 1,000 women, respectively, and further screening at age 61-65 was not associated with statistically significant decreases of cervical cancer risk up to age 80, but with fewer cancer cases of advanced stages at age 61-65. Adjustment for potential lifestyle confounders was limited. CONCLUSIONS: In this study, cervical screening with cytology at age 61-65 was associated with a statistically significant reduction of subsequent cervical cancer risk for women who were unscreened, or screened with abnormalities, in their 50s. In women screened with normal results in their 50s, the risk for future cancer was not sizeable, and the risk reduction associated with continued screening appeared limited. These findings should inform the current debate regarding age and criteria to discontinue cervical screening.