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The strong correlation between smoking and exposure to oncogenic human papillomaviruses (HPVs) has made it difficult to verify the independent role of smoking in cervical carcinogenesis. Thus, the authors evaluated this role. Five large Nordic serum banks containing samples from more than 1,000,000 subjects were linked with nationwide cancer registries (1973-2003). Serum samples were retrieved from 588 women who developed invasive cervical cancer and 2,861 matched controls. The samples were analyzed for cotinine (a biomarker of tobacco exposure) and antibodies to HPV types 16 and 18, herpes simplex virus type 2, and Chlamydia trachomatis. Smoking was associated with the risk of squamous cell carcinoma (SCC) among HPV16- and/or HPV18-seropositive heavy smokers (odds ratio=2.7, 95% confidence interval: 1.7, 4.3). A similar risk of SCC (odds ratio=3.2, 95% confidence interval: 2.6, 4.0) was found in heavy smokers after adjustment for HPV16/18 antibodies. The point estimates increased with increasing age at diagnosis and increasing cotinine level. This study confirms that smoking is an independent risk factor for cervical cancer/SCC in women infected with oncogenic HPVs. These findings emphasize the importance of cervical cancer prevention among women exposed to tobacco smoke. [ABSTRACT FROM AUTHOR]

Presents a correction to the article "Human Papillomavirus Infection As a Risk Factor for Anal and Perianal Skin Cancer in a Prospective Study" that was previously published in "British Journal of Cancer."

Introduction: We report head-to-head comparison of the bivalent and quadrivalent HPV vaccine efficacies against immediate precursors of cervical cancer from 15 years' country-wide cancer registry follow-up of phase III trial cohorts and an age-aligned cohort of unvaccinated women., Methods: These individually and/or clusterrandomized cohorts of HPV6/11/16/18- and HPV16/18-vaccinated and unvaccinated women were enrolled, respectively, in 2002, 2004, and 2003/2005. The trial cohorts comprised initially 16- to 17-year-old HPV6/11/16/18-vaccinated FUTURE II (NCT00092534) participants (866) and HPV16/18-vaccinated PATRICIA (NCT00122681) and 012 trial (NCT00169494) participants (2,465), and 16,526 initially 16- to 19-year-old unvaccinated controls. After active 4-year clinical follow-up, passive, country-wide Finnish Cancer Registry (FCR) follow-up for cervical intraepithelial neoplasia grade 3 (CIN3) and adenocarcinoma in situ (AIS) was based on consented use of unique personal identifiers and started 6 months after the end of the FUTURE II and PATRICIA trials in 2007 and 2009, and ended at the end of 2019. The follow-up with altogether 229,020 follow-up years was age-aligned to ensure that similarly aged cohorts were passively followed up for 15 years post=vaccination for the intention-to-treat analyses of vaccine efficacy., Results: Overall, we identified 5 and 16 CIN3 (no AIS) cases in the HPV6/11/16/18 and HPV16/18 cohorts, respectively, during the FCR-based follow-up. In the unvaccinated cohort, we identified 281 CIN3 cases, 20 AIS cases, and 13 cases with invasive cervical cancer. Vaccine efficacies against CIN3+ were 68.4% and 64.5% for the quadrivalent and the bivalent vaccines, respectively, with overlapping confidence intervals., Discussion: Long-term follow-up of randomized, initially adolescent HPV-vaccinated and unvaccinated cohorts shows, in this head-to-head setting, that the bivalent and quadrivalent HPV vaccines are equally effective against immediate precursors of cervical cancer., Competing Interests: DA, JD, ML, and JPaa have received grants for their HPV vaccination studies from Merck&Co. Inc. DA, JD, ML, and JPaa and GSK Biologicals DA, ML, JPaa. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lehtinen, Gray, Luostarinen, Eriksson, Apter, Bly, Harjula, Heikkilä, Hokkanen, Kuortti, Nieminen, Nummela, Paavonen, Palmroth, Petäjä, Pimenoff, Pukkala and Dillner.)

Objective -Direct oral anticoagulants (DOAC) are replacing vitamin K antagonists (VKA) for the prevention of ischemic stroke and venous thromboembolism. We set out to assess the effect of prior treatment with DOAC and VKA in patients with aneurysmal subarachnoid hemorrhage (SAH). Methods -Consecutive SAH patients treated at two (Aachen, Germany and Helsinki, Finland) university hospitals were considered for inclusion. To assess the association between anticoagulant treatments on SAH severity measure by modified Fisher grading (mFisher) and outcome as measured by the Glasgow outcome scale (GOS, 6 months), DOAC- and VKA-treated patients were compared against age- and sex-matched SAH controls without anticoagulants. Results -During the inclusion timeframes, 964 SAH patients were treated in both centers. At the time point of aneurysm rupture, nine patients (0.93%) were on DOAC treatment, and 15 (1.6%) patients were on VKA. These were matched to 34 and 55 SAH age- and sex-matched controls, re-spectively. Overall, 55.6% of DOAC-treated patients suffered poor-grade (WFNS 4-5 ) SAH compared to 38.2% among their respective controls ( p = 0.35); 53.3% of patients on VKA suffered poor-grade SAH compared to 36.4% in their respective controls ( p = 0.23). Neither treatment with DOAC (aOR 2.70, 95%CI 0.30 to 24.23; p = 0.38), nor VKA (aOR 2.78, 95%CI 0.63 to 12.23; p = 0.18) were inde-pendently associated with unfavorable outcome (GOS 1-3 ) after 12 months. Conclusions -Iatrogenic coagulopathy caused by DOAC or VKA was not associated with more severe radiological or clinical subarachnoid hemorrhage or worse clinical outcome in hospitalized SAH patients.

•Our study did not support the hypothesis that small AVMs lead to larger hematoma volumes in the event of a rupture.•AVM size did not correlate with the clinical severity of the bleeding as measured with HH and WFNS scores.•Larger supratentorial hematomas were associated with a more severe clinical manifestation and a poorer outcome.•In the event of a rupture, the AVM size did not correlate with the 2-4-month GOS.•AVICH score showed a good correlation with the 2-4-month GOS score., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Published by Elsevier B.V. on behalf of EUROSPINE, the Spine Society of Europe, EANS, the European Association of Neurosurgical Societies.)

Intensive care for patients with traumatic brain injury (TBI) aims to optimize intracranial pressure (ICP) and cerebral perfusion pressure (CPP). The transformation of ICP and CPP time-series data into a dynamic prediction model could aid clinicians to make more data-driven treatment decisions. We retrained and externally validated a machine learning model to dynamically predict the risk of mortality in patients with TBI. Retraining was done in 686 patients with 62,000 h of data and validation was done in two international cohorts including 638 patients with 60,000 h of data. The area under the receiver operating characteristic curve increased with time to 0.79 and 0.73 and the precision recall curve increased with time to 0.57 and 0.64 in the Swedish and American validation cohorts, respectively. The rate of false positives decreased to ≤2.5%. The algorithm provides dynamic mortality predictions during intensive care that improved with increasing data and may have a role as a clinical decision support tool., (© 2022. The Author(s).)

Objective: We assessed the relationship between Chlamydia trachomatis infection, duration of oral contraceptive (OC) use and cervical atypia among young adult Finnish women., Design: A longitudinal study., Setting and Participants: Women who were included in this study participated in a community-randomised trial on the effectiveness of human papillomavirus (HPV) vaccination and C. trachomatis screening at ages 18.5 and 22 years in Finland. They completed questionnaires on both visits about sexual behaviours. The cytology test results at age 18.5 and 22 years were also available for those women. The total number of participants in this study at 18.5 years of age were 11 701 and at 22 years of age were 6618., Main Outcome Measure: ORs with 95% CIs using univariable and multivariable logistic regression were used to assess the association between C. trachomatis infection, duration of OC and squamous intraepithelial lesions (SIL)., Results: There were 940 cytological SIL cases at the first screening visit and 129 cytological SIL cases at the second screening visit. Among the 22 years old, more than fourfold adjusted risk of SIL was associated with C. trachomatis positivity. The HPV16/18, condom use, smoking and number of sexual partners adjusted joint effect of prolonged OC use and C. trachomatis was significantly increased (OR 4.7, 95% CI 1.7 to 12.8) in the 22-year-old women. This observed joint effect was 1.6 times higher than expected on a multiplicative scale. On additive scale, the observed relative excess risk from interaction was 1.8., Conclusion: The risk of SIL in HPV vaccinated women is significantly increased if they are C. trachomatis positive and have used OC for 5 or more years. The biological basis may be lack of condom facilitated protection against sexually transmitted diseases., Trial Registration Number: NCT00534638., Competing Interests: Competing interests: ML and DA have grants from Merck & Co Inc and GSK for HPV vaccination trials through their employers (Tampere University, ML; Family Federation Finland, DA)., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Human papillomavirus (HPV) vaccination protects against HPV, a necessary risk factor for cervical cancer. We now report results from population-based follow-up of randomised cohorts that vaccination provides HPV-type-specific protection against invasive cancer., Methods: Individually and/or cluster randomised cohorts of HPV-vaccinated and non-vaccinated women were enrolled in 2002-2005. HPV vaccine cohorts comprised originally 16-17 year-old HPV 16/18-vaccinated PATRICIA (NCT00122681) and 012 trial (NCT00169494) participants (2465) and HPV6/11/16/18-vaccinated FUTURE II (NCT00092534) participants (866). Altogether, 3341 vaccines were followed by the Finnish Cancer Registry in the same way as 16 526 non-HPV-vaccinated controls. The control cohort stemmed from 15 665 originally 18-19 years-old women enrolled in 2003 (6499) or 2005 (9166) and 861 placebo recipients of the FUTURE II trial. The follow-up started 6 months after the clinical trials in 2007 and 2009 and ended in 2019. It was age aligned for the cohorts., Findings: During a follow-up time of up to 11 years, we identified 17 HPV-positive invasive cancer cases (14 cervical cancers, 1 vaginal cancer, 1 vulvar cancer and 1 tongue cancer) in the non-HPV-vaccinated cohorts and no cases in the HPV-vaccinated cohorts. HPV typing of diagnostic tumour blocks found HPV16 in nine cervical cancer cases, HPV18, HPV33 and HPV52 each in two cases and HPV45 in one cervical cancer case. The vaginal, vulvar and tongue cancer cases were, respectively, positive for HPV16, HPV52/66 and HPV213. Intention-to-treat vaccine efficacy against all HPV-positive cancers was 100% (95% CI 2 to 100, p<0.05)., Interpretation: Vaccination is effective against invasive HPV-positive cancer., Trial Registration Number: NCT00122681, Post-results; NCT00169494, Post-results; NCT00092534, Post-results., Competing Interests: Competing interests: We declare that ML, DA, JD and JPaa have received grants from Merck & Co. Inc. and/or from the GSK group of companies through their respective employers. GSK Biologicals SA was provided the opportunity to review this manuscript but the authors are solely responsible for final content and interpretation., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Cervical cancer elimination through human papillomavirus (HPV) vaccination programs requires the attainment of herd effect. Due to its uniquely high basic reproduction number, the vaccination coverage required to achieve herd effect against HPV type 16 exceeds what is attainable in most populations. We have compared how gender-neutral and girls-only vaccination strategies create herd effect against HPV16 under moderate vaccination coverage achieved in a population-based, community-randomized trial., Methods and Findings: In 2007-2010, the 1992-1995 birth cohorts of 33 Finnish communities were randomized to receive gender-neutral HPV vaccination (Arm A), girls-only HPV vaccination (Arm B), or no HPV vaccination (Arm C) (11 communities per trial arm). HPV16/18/31/33/35/45 seroprevalence differences between the pre-vaccination era (2005-2010) and post-vaccination era (2011-2016) were compared between all 8,022 unvaccinated women <23 years old and resident in the 33 communities during 2005-2016 (2,657, 2,691, and 2,674 in Arms A, B, and C, respectively). Post- versus pre-vaccination-era HPV seroprevalence ratios (PRs) were compared by arm. Possible outcome misclassification was quantified via probabilistic bias analysis. An HPV16 and HPV18 seroprevalence reduction was observed post-vaccination in the gender-neutral vaccination arm in the entire study population (PR16 = 0.64, 95% CI 0.10-0.85; PR18 = 0.72, 95% CI 0.22-0.96) and for HPV16 also in the herpes simplex virus type 2 seropositive core group (PR16 = 0.64, 95% CI 0.50-0.81). Observed reductions in HPV31/33/35/45 seroprevalence (PR31/33/35/45 = 0.88, 95% CI 0.81-0.97) were replicated in Arm C (PR31/33/35/45 = 0.79, 95% CI 0.69-0.90)., Conclusions: In this study we only observed herd effect against HPV16/18 after gender-neutral vaccination with moderate vaccination coverage. With only moderate vaccination coverage, a gender-neutral vaccination strategy can facilitate the control of even HPV16. Our findings may have limited transportability to other vaccination coverage levels., Trial Registration: ClinicalTrials.gov number NCT00534638, https://clinicaltrials.gov/ct2/show/NCT00534638., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: M.L. has previously received grants from Merck & Co. and GSK Biologicals through his employers the Finnish Institute of Health and Welfare (THL) and the University of Tampere for HPV vaccination studies.

The elimination of cervical cancer rests on high efficacy of human papillomavirus (HPV) vaccines. The HPV type distribution among cases of invasive cervical cancer (ICC) is used to make predictions about the impact of eliminating different types of HPV, but accumulating evidence of differences in age-specific cancer incidence by HPV type exists. We used one of the largest population-based series of HPV genotyping of ICCs (n = 2,850; Sweden, 2002-2011) to estimate age-specific ICC incidence by HPV type and obtain estimates of the cancer-protective impact of the removal of different HPV types. In the base case, the age-specific ICC incidence had 2 peaks, and the standardized lifetime risk (SLTR, the lifetime number of cases per birth cohort of 100,000 females) for HPV-positive ICC was 651 per 100,000 female births. In the absence of vaccine types HPV 16 and HPV 18, the SLTR for ICC was reduced to 157 per 100,000 female births (24% of HPV-positive SLTR). Elimination of all 9 types that can currently be vaccinated against reduced the remaining SLTR to 47 per 100,000 female births (7%), the remaining ICC incidence only slowly increasing with age. In conclusion, after elimination of vaccine-protected HPV types, very few cases of ICC will be left, especially among fertile, reproductive-age women., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Our aim was to create simple and largely scalable machine learning-based algorithms that could predict mortality in a real-time fashion during intensive care after traumatic brain injury. We performed an observational multicenter study including adult TBI patients that were monitored for intracranial pressure (ICP) for at least 24 h in three ICUs. We used machine learning-based logistic regression modeling to create two algorithms (based on ICP, mean arterial pressure [MAP], cerebral perfusion pressure [CPP] and Glasgow Coma Scale [GCS]) to predict 30-day mortality. We used a stratified cross-validation technique for internal validation. Of 472 included patients, 92 patients (19%) died within 30 days. Following cross-validation, the ICP-MAP-CPP algorithm's area under the receiver operating characteristic curve (AUC) increased from 0.67 (95% confidence interval [CI] 0.60-0.74) on day 1 to 0.81 (95% CI 0.75-0.87) on day 5. The ICP-MAP-CPP-GCS algorithm's AUC increased from 0.72 (95% CI 0.64-0.78) on day 1 to 0.84 (95% CI 0.78-0.90) on day 5. Algorithm misclassification was seen among patients undergoing decompressive craniectomy. In conclusion, we present a new concept of dynamic prognostication for patients with TBI treated in the ICU. Our simple algorithms, based on only three and four main variables, discriminated between survivors and non-survivors with accuracies up to 81% and 84%. These open-sourced simple algorithms can likely be further developed, also in low and middle-income countries.

Objective: We investigated whether the risk of cervical atypia is associated with a short interval between the age at first sexual intercourse (FSI) or age at the start of oral contraceptive (OC) use and menarche., Design: A population-based cohort study., Setting: Finnish women in the age range of 16-17 years old were enrolled in the PATRICIA trial of human papillomavirus (HPV) 16/18 vaccine efficacy., Participants: The association of cervical atypia with the interval between FSI or start of OC use and menarche was assessed in the control arm (hepatitis A vaccinated) who had participated in biannual clinical follow-up visits for 4 years. Altogether, 913 women had normal baseline cervical cytology and answered behavioural questionnaires at enrolment and end of the follow-up., Main Outcome Measure: ORs with 95% CIs using univariate and multivariable logistic regression were used to assess the association between cervical atypia and the interval between FSI or the start of OC use and menarche., Results: The mean ages at menarche, FSI and the start of OC use were 12.4, 16.0 and 16.4. Chlamydia trachomatis infection was associated with an increased risk of cervical atypia in women with a short (<3 years) interval between menarche and FSI/start of OC use (OR 1.8, 95% CI 1.0 to 3.6 and OR 2.2, 95% CI 1.0 to 5.1). Whereas HPV 16/18 infection was associated with increased atypia risk estimates in women with a longer (≥3 years) interval (OR 1.8, 95% CI 1.1 to 2.7 and OR 1.4, 95% CI 1.0 to 2.1). In women with a short interval between menarche and FSI, early age at the start of OC use was not associated with an increased risk of cervical atypia in the univariate (OR 0.7) nor multivariable analyses., Conclusion: Short interval between menarche and the age at start of sexual activity does not increase the risk of HPV-associated cervical atypia., Trial Registration Number: NCT00122681., Competing Interests: Competing interests: ML and DA have grants from Merck & Co. Inc. and GSK for HPV vaccination trials through their employers (Tampere University, ML; Family Federation Finland, DA)., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: We assessed population-level changes in glioblastoma survival between 2000 and 2013 in Finland, with focus on elderly patients (>70 y) in order to assess if changes in treatment of glioblastoma are reflected also in population-based survival rates., Methods: We identified all patients (age ≥18 y) from the Finnish Cancer Registry (FCR) with a histopathological diagnosis of primary glioblastoma in 2000-2013. Patients were followed up until December 2015. The accuracy of register-based search of glioblastoma patients was internally validated. We report age-standardized relative survival ratios and relative excess risks (RERs) of death in 2000-2006 (pre-period) and 2007-2013 (post-period)., Results: We identified 2045 glioblastoma patients from the FCR. The accuracy of the FCR-based search was 97%. Median age was 63.3 years, and 42% were women. Incidence increased on average by 1.6% (P = 0.004) and median age by 0.4 years per calendar year. Between the pre- and post-periods, the proportion of patients >70 years increased from 24% to 27%. In >70-year-old patients, the median survival time increased from 3.6 months in 2000-2006 to 4.5 months in 2007-2013 (RER 0.82, 95% CI: 0.68-0.98). In ≤70-year-old patients, the median survival time increased from 9.3 months in 2000-2006 to 11.7 months in 2007-2013 (RER 0.74, 95% CI: 0.67-0.82)., Conclusion: Despite the increased proportion of elderly glioblastoma patients, population-level survival of glioblastoma patients has improved since the year 2000. However, increasing incidence, increasing age of patients, and poor survival in elderly are alarming, and future studies should perhaps focus more on elderly., (© The Author(s) 2018. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Due to long lag time between infection/cancer diagnoses human papillomavirus (HPV) vaccination programs will deliver vaccine efficacy (VE) estimates against cancer end-points late. Cancer registry follow-up of population-based, randomised trial cohorts of vaccinated and unvaccinated women was undertaken for the estimation of VE against cervical intraepithelial neoplasia grade three and invasive cancer (CIN3+)., Methods: We report interim results with 98 561 person years of Finnish Cancer Registry -based follow-up of individually and/or cluster randomised cohorts of HPV-16/18 vaccinated and unvaccinated adolescent women enrolled in June 2003/2005, and between May 2004 and April 2005, respectively. The cohorts comprised 15 627 18- to 19-year-old unvaccinated women (NCT01393470), and 2 401 and 64 16- to 17-year-old HPV-16/18 vaccinated women participating the PATRICIA (NCT00122681) and HPV-012 (NCT00169494) trials, respectively. The age-aligned passive follow-up started 6 months after the clinical trials' end., Results: During the follow-up of 4.5 to 10 years post enrolment we identified 75 cases of cervical intraepithelial neoplasia grade 3 (CIN3) and 4 cases of invasive cervical cancer (ICC) in the unvaccinated cohort, and 4 CIN3 cases in the HPV-16/18 vaccinated women. Diagnostic blocks were available for HPV typing from 87% of the cases. CIN3+ lesions were detectable in 54 cases. HPV16 was found in 26 of 50 unvaccinated CIN3+ cases, and in 3 CIN3+ cases in the HPV-16/18 vaccinated women. The latter were all baseline positive for cervical HPV16 DNA. Baseline data was not available for the unvaccinated women. Intention-to-treat VE against any CIN3+ was 66% (95% CI 8, 88)., Conclusions: Ten years post vaccination the AS04-adjuvanted HPV-16/18 vaccine shows continued efficacy against CIN3+ irrespectively of HPV type. Vaccine efficacy was not observed in baseline HPV16 DNA positive subjects., Trial Registration Number: NCT01393470., Competing Interests: Competing interests: DA, ML, JP and JD have received grants from GSK group of companies and/or Merck & Co. Inc. through their employers (DA, Family Federation Finland; ML; University of Tampere; JP and PN University of Helsinki; JD and ML, Karolinska Institute) for HPV vaccination studies. GD was and FS is employee of GSK group of companies. FS has received shares and stock options from the GSK group of companies., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Cutaneous human papillomavirus (HPV) types have been associated with non-melanoma skin cancer (NMSC), including a previous nested case-control study using HPV serology with bacterially derived fusion proteins with the major HPV capsid protein L1 (GST-L1). However, HPV serology using conformationally intact pseudovirions has been shown to correlate better with natural infection. Prospective studies using a more valid marker of infection are therefore warranted., Methods: Cancer registry follow-up of large Nordic biobanks identified prediagnostic serum samples from 633 subjects who later developed SCC, 1,990 subjects who developed basal cell carcinoma (BCC). The samples from cases and matched controls were tested for IgG to pseudovirions to 16 different HPV types (3, 5, 6, 11, 15: , 16, 18, 31, 32, 33, 38: , 45, 52, 58, 68, and 76: ) and two polyomaviruses (MCPyV and JCPyV)., Results: Baseline seropositivity was not associated with SCC risk, and there were only weak associations with BCC risk [HPV-5 (OR, 1.1; 95% confidence interval [CI], 1.0-1.3), HPV-15 (OR, 1.2; 95% CI, 1.0-1.4), HPV-38 (OR, 1.2; 95% CI, 1.0-1.3), and MCPyV (OR, 1.1; 95% CI, 1.0-1.3)]. Acquisition of HPV-5 seropositivity during follow-up was associated with SCC risk (OR, 3.2; 95% CI, 1.3-7.6). Persistent seropositivity for HPV-15 was weakly associated with BCC (OR, 1.4; 95% CI, 1.0-1.9) and HPV-6 antibody persistence was weakly associated with SCC (OR, 2.2; 95% CI, 1.0-4.8)., Conclusion: Considering the large number of viruses tested, the weak associations found do not support any strong links between studied HPV and NMSC, with the possible exception of HPV-5 seroconversion and SCC., Impact: Known alpha and beta papillomaviruses do not appear to be risk factors for NMSC. Cancer Epidemiol Biomarkers Prev; 25(4); 721-4. ©2016 AACR., (©2016 American Association for Cancer Research.)

Background: High coverage and attendance is essential for cervical cancer screening success. We investigated whether the previous positive experiences on increasing screening attendance by self-sampling in Finland are sampler device dependent., Methods: All women identified to cervical cancer screening in 2013 in 28 Finnish municipalities were randomised to receive a lavage- (n = 6030) or a brush type of self-sampling device (n = 6045) in case of non-attendance after two invitation letters. Seven hundred seventy non-attending women in the lavage device group and 734 in the brush group received the self-sampling offer. Women's experiences were enquired with an enclosed questionnaire., Results: Total attendance in the lavage group increased from 71.0 to 77.7% by reminder letters and further to 80.5% by self-sampling. Respective increase in the brush group was from 72.2 to 78.6% and then to 81.5%. The participation by self-sampling was 21.7% (95% CI 18.8-24.6) in the lavage group and 23.8% (95% CI 20.8-26.9) in the brush group. Women's self-sampling experiences were mainly positive and the sampler devices were equally well accepted by the women., Conclusion: Our study shows that the lavage device and brush device perform similarly in terms of uptake by non-attending women and user comfort. If self-sampling is integrated to the routine screening program in Finland, either of the devices can be chosen without the fear of losing participants due to a less acceptable device.

Purpose: Associations between population-based screening, breast carcinoma detection modes and breast carcinoma death have not been studied using nationwide data at individual level. We evaluated these in Finland, where invitational age is gradually expanding from 50-59 to 50-69 years in 2008-2017. We also predicted breast carcinoma patterns in 2020 to assess the impact of changing invitational policy on breast carcinoma incidence and mortality., Methods: The data included breast carcinomas in 2000-2010 (n = 48 040), and deaths due to these carcinomas (n = 4722). We divided carcinomas into those detected before or after the screening age, and those detected at the screening age. The latter was further divided into screen-detected and interval carcinomas, and carcinomas in the non-attendees. The prediction of future patterns was based on incidence data from the ten-year period 1998-2007 preceding the period of expanding invitational age in the national programme., Results: Approximately 13% of in situ carcinomas were detected before, 29% after, and 57% at the screening age. In invasive cancers, the percentages were 16%, 42%, and 42%, respectively. At the screening age, more than half of invasive cancers were screening-detected, one quarter interval cancers, and one out of six cancers in the non-attendees. Almost 60% of breast cancer deaths were due to cancers detected after the screening age. By 2020, breast cancers detected at the screening age will increase from 42% to 65%, and breast cancers detected by screening from 23% to 38%., Conclusions: The study demonstrates a novel approach to examine associations between breast carcinoma incidence and mortality within and outside population-based screening. The results show mammography screening having a distinct role in overall breast carcinoma incidence and mortality.

Background: There is currently some uncertainty about the effectiveness of screening outside the established core ages of 30 to 60. We audited the screening histories of cervical cancers and conducted a case-control evaluation of the effectiveness of organized screening in different ages., Methods: Screening histories for 1,546 cervical cancer cases and 9,276 age-matched controls were derived by linkage to the screening register. ORs and 95% confidence intervals (CI) for the association of participation in a program screen and cervical cancer diagnosis in the following screening interval were estimated using conditional logistic regression and corrected for self-selection bias., Results: Participation in a single screen was associated with a 47% decrease in cervical cancers, but this effect was age-dependent. Screening at 25 showed little or no impact on the risk of cervical cancer in the next interval, whereas screens at 40 to 65 showed protective effects of 51% to 66%., Conclusions: Program screening at the age of 25 is not associated with a reduced risk of cervical cancer in the following screening interval. Additional analyses are needed that also take opportunistic screening of women during the first rounds of organized screening into consideration. In contrast, screening yields substantial risk reductions in older ages at least up to the age of 60. This study also provides moderate indication of a long-lasting risk reduction associated with screening at the age of 65., Impact: Cervical cancer screening effectiveness is for the first time evaluated at different ages up to 65 with correction for self-selection bias of participation in organized screening., (©2012 AACR.)

Background: Several sexually transmitted infections (STI) have been reported to interact with human papillomavirus (HPV) in the etiology of cervical cancer. A large cohort study is required to obtain a both unbiased and stable estimate of their effects., Methods: Four major biobanks in the Nordic Countries containing samples from about 1,000,000 subjects were linked with nation-wide cancer registries. Serum samples from 604 women with invasive cervical cancer (ICC) diagnosed on average 10 years after sampling and 2,980 matched control women were retrieved and analyzed with serology for key STI., Results: Exposure to HPV16 was the strongest risk factor for cervical cancer [OR = 2.4; 95% confidence interval (CI), 2.0-3.0], particularly for squamous cell carcinoma (OR = 2.9; 95% CI, 2.2-3.7). HPV18 was strongly associated with increased risk for adenocarcinoma (OR = 2.3; 95% CI, 1.3-4.1). Baseline seropositivity for HPV16 did not confer any increased risk for HPV18 DNA-positive cancer and conversely HPV18 seropositivity had no association with HPV16 DNA-positive cancers. HPV6 had no effect on its own (OR = 1.1; 95% CI, 0.9-1.3), but had an antagonistic effect on the risk conferred by HPV16 (P < 0.01). Herpes simplex virus 2 had little or no association (OR = 1.1; 95% CI, 0.8-1.4). Previous exposure to Chlamydia trachomatis, as indicated by serum antibodies, had a strongly increased risk for cervical cancer (OR = 1.9; 95% CI, 1.5-2.3)., Conclusions: A large prospective study has assessed the role of different STIs in cervical cancer., Impact: Prospective evidence supports cofactor role of some STI in cervical cancer.

Background: Attendance in screening is an important determinant of cervical cancer. Previous experience on high-risk human papillomavirus (hrHPV) DNA testing on patient-obtained samples suggests a good effect among nonattendees of screening. We assessed the effects of self-sampling on attendance in the Finnish screening program., Methods: Nonattendees after the primary invitation in one municipality (Espoo) were randomized to receive either a self-sampling kit (2,397 women) or an extra invitation (6,302 women). One fourth (1,315 women) of reminder letter arm nonattendees also received a self-sampling kit as a third intervention. Main outcomes were increases in screening attendance and coverage., Results: The adjusted relative risk for participation by self-sampling as a second intervention in comparison to a reminder letter arm was 1.21 (95% CI: 1.13-1.30). Total attendance increased from 65% to 76% by self-sampling and from 65% to 74% with a reminder letter. Combining the interventions (reminder letter and then self-sampling) increased total attendance from 63% to 78%. One fifth of the participants in all three groups increased screening coverage (previous Pap smear ≥5 years ago or never). Self-obtained samples were more often HPV positive than provider-obtained ones (participants after primary invitation and reminder letter), 12% to 13% versus 7%., Conclusions: Self-sampling is a feasible option in enhancing the attendance at organized screening, particularly as an addition to a reminder letter., Impact: If self-sampling is used as a third intervention after two written invitations, the overall attendance in Finland could most likely reach the desired 80% to 85%.

Background: We assessed the performance and validity of cytology in the Finnish screening program by considering high-grade neoplasia and cervical cancer (CIN3+) rates as detected in the program and by reevaluating cases observed after a negative screening test., Methods: This retrospective study included 915 screen-detected CIN3+ cases and 421 cases observed after a negative screen. Randomized and blinded reevaluation of potential false-negative screening tests covered 345 archival case smears from women without a referral to colposcopy, as well as 689 control smears for estimating performance and validity measures., Results: The false-negative rate at the cutoff of low-grade squamous intraepithelial lesion or worse was 35% (95% confidence interval, 30-40%). In the subpopulation with original screening result of Pap I, the false-negative rate was 23% (18-28%). Sensitivity of screening laboratory rereading for detecting low-grade lesions or worse as atypical was 75% (67-82%) and specificity 93% (91-94%). Reproducibility of specific cytologic diagnoses was only fair. False negatives constituted 11% of all CIN3+ diagnoses in the screened population; those false negatives with an original Pap I screening result constituted 5%., Conclusions: Although screen failures in the form of diagnostic false negatives occur within the Finnish screening program, their effect on cancer incidence is fairly small and cannot be readily decreased without sacrificing the high specificity of screening or without high incremental costs. Feedback for the screening laboratories is needed, however, to improve the reproducibility of cytologic diagnoses to optimize the burden of intensified follow-up and treatment of precancerous lesions.

We performed a large nested case-control study within the Finnish and Icelandic maternity cohorts to verify/falsify the association of maternal EBV infection with an increased risk of acute lymphoblastic leukemia (ALL) in the offspring found in previous studies. All hematologic malignancies diagnosed among children born during 1983 to 2006 in Finland and 1997 to 2005 in Iceland were identified through national cancer registries. For each index mother of a leukemia case, three matched control mothers with cancer-free offspring were identified. First trimester sera from 561 ALL and 144 non-ALL index mothers and from 2,105 control mothers were analyzed for antibodies to EBV viral capsid antigen (IgG and IgM), early antigen (IgG) and ZEBRA protein (IgG). Conditional logistic regression-based estimates of odds ratios and 95% confidence intervals adjusted for birth order and sib-ship size were calculated. Overall, there was no evidence of increased risk of ALL associated to EBV viral capsid antigen IgM (odds ratio, 0.9; 95% confidence interval, 0.5-1.8). The early antigen and ZEBRA antibodies (EBV reactivation markers) were also not associated with risk. The data argue against a role of EBV in ALL.