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Booth N.,University of Tampere | Rissanen P.,University of Tampere | Tammela T.L.J.,University of Tampere | Maattanen L.,Mass Screening Registry | And 2 more authors.
European Urology

Background: Evidence of the potential impact of systematic screening for prostate cancer (PCa) on health-related quality of life (HRQoL) at a population-based level is currently scarce. Objective: This study aims to quantify the long-term HRQoL impact associated with screening for PCa. Design, setting, and participants: Postal questionnaire surveys were conducted in 1998, 2000, 2004, and 2011 among men in the Finnish PCa screening trial diagnosed with PCa (total n = 7011) and among a random subsample of the trial population (n = 2200). In 2011, for example, 1587 responses were received from men with PCa in the screening arm and 1706 from men in the control arm. In addition, from the trial subsample, 549 men in the screening arm and 539 in the control arm provided responses. Outcome measurements and statistical analysis: Health-state-value scores were compared between the intervention and control arms using three distinct HRQoL measures (15D, EQ-5D, and SF-6D), and statistical significance was assessed using t tests. In addition, differences over repeated assessments of HRQoL between groups were evaluated using generalised estimating equations. Results and limitations: In the 2011 survey, a small but statistically significant difference emerged between the trial arms among men diagnosed with PCa (mean scores, screening vs control arm: 15D: 0.872 vs 0.866, p = 0.14; EQ-5D: 0.852 vs 0.831, p = 0.03; and SF-6D: 0.763 vs 0.756, p = 0.06). Such differences in favour of the screening arm were not found among the sample of men from the trial (15D: 0.889 vs 0.892, p = 0.62; EQ-5D: 0.831 vs 0.852, p = 0.08; and SF-6D: 0.775 vs 0.777, p = 0.88). The slight advantage with screening among men with PCa was reasonably consistent across time in the longitudinal analysis and was strongest among men with early-stage disease. Conclusions: These results show some long-term HRQoL benefit from screening for men with PCa but suggest little impact overall in the trial population. © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved. Source

Arbyn M.,Scientific Institute of Public Health | Arbyn M.,A+ Network | Ronco G.,Centro per la Prevenzione Oncologica | Anttila A.,Mass Screening Registry | And 7 more authors.

More than ever, clinicians need regularly updated reviews given the continuously increasing amount of new information regarding innovative cervical cancer prevention methods. A summary is given from recent meta-analyses and systematic reviews on 3 possible clinical applications of human papillomavirus (HPV) testing: triage of women with equivocal or low-grade cytologic abnormalities; prediction of the therapeutic outcome after treatment of cervical intraepithelial neoplasia (CIN) lesions, and last not but not least, primary screening for cervical cancer and pre-cancer. Consistent evidence is available indicating that HPV-triage with the Hybrid Capture® 2 assay (Qiagen Gaithersburg, Inc., MD, USA [previously Digene Corp.] (HC2) is more accurate (higher sensitivity, similar specificity) than repeat cytology to triage women with equivocal Pap smear results. Several other tests show at least similar accuracy but mRNA testing with the APTIMA® (Gen-Probe Inc., San Diego, CA, USA) test is similarly sensitive but more specific compared to HC2. In triage of low-grade squamous intraepithelial lesions (LSIL), HC2 is more sensitive but its specificity is substantially lower compared to repeat cytology. The APTIMA® test is more specific than HC2 without showing a loss in sensitivity. Identification of DNA of HPV types 16 and/or 18, or RNA from the five most carcinogenic HPV types allow selecting women at highest risk for CIN3+ but the sensitivity and negative predictive value of these markers are lower than full-range high-risk HPV (hrHPV) testing. After conservative treatment of cervical pre-cancer, HPV testing picks up more quickly, with higher sensitivity and not lower specificity, residual or recurrent high-grade CIN than follow-up cytology. Primary screening for hrHPV generally detects more CIN2, CIN3 or cancer compared to cytology at cut-off atypical squamous cells of undetermined significance (ASC-US) or LSIL, but is less specific. Combined HPV and cytology screening provides a further small gain in sensitivity at the expense of a considerable loss in specificity if positive by either test is referred to colposcopy, in comparison with HPV testing only. Randomised trials and follow-up of cohort studies consistently demonstrate a significantly lower cumulative incidence of CIN3+ and even of cancer, in women aged 30 years or older, who were at enrollment hrHPV DNA negative compared to those who were cytologically negative. The difference in cumulative risk of CIN3+ or cancer for double negative (cytology & HPV) versus only HPV-negative women is small. HC2, GP5+/6+ PCR (polymerase chain reaction), cobas® 4800 PCR (Roche Molecular Systems Inc., Alameda, CA, USA) and Real Time PCR (Abbott Molecular, Des Plaines, IL, USA) can be considered as clinically validated for use in primary screening. The loss in specificity associated with primary HPV-based screening can be compensated by appropriate algorithms involving reflex cytology and/or HPV genotyping for HPV16 or 18. There exists a substantial evidence base to support that HPV testing is advantageous both in triage of women with equivocal abnormal cytology, in surveillance after treatment of CIN lesions and in primary screening of women aged 30 years or older. However, the possible advantages offered by HPV-based screening require a well organised program with good compliance with screening and triage policies. © 2012 Marc Arbyn. Source

Leinonen M.K.,Finnish Cancer Registry | Anttila A.,Mass Screening Registry | Malila N.,Finnish Cancer Registry | Malila N.,University of Tampere | And 4 more authors.
British Journal of Cancer

Background: Large-scale data on type-specific HPV prevalences and disease burden are needed to monitor the impact of HPV vaccination and to plan for HPV-based cervical screening. Methods: 33 043 women (aged 25-65) were screened for HPV by a Hybrid Capture 2 (HC2) in a population-based programme. HPV-positive women (n = 2574) were triaged by cytology and HPV genotyped using PCR-Luminex. Type-specific prevalence of HPV infection and its correlation to findings in cytology triage and histology as well as Population Attributable Fractions for a referral to colposcopy and findings in histology were calculated. Results: Among HC2-positive women, 61.5% had normal, 23.1% had ASC-US and 15.5% had LSIL or more severe (LSIL+) results in cytology. Out of HC2-positive samples, 57% contained the 13 Group 1/2A HPV types, which were targeted by the HC2, 15% contained Group 2B types, 8.5% Group 3 types and 30% were found to be negative in HPV genotyping. The proportion of samples positive for HPV by the HC2, but negative in HPV genotyping increased with age and decreased with increasing cytological abnormality. The most frequent types were HPV 16 (0.9% of screened women and 12.1% of the HC2-positive women), HPV 31 (0.7% and 8.9%, respectively) and HPV 52 (0.5% and 6.3%, respectively). The prevalence of Group 1/2A HPV types increased with increasing CIN grade and attributed 78.3% (95% CI 53.4-89.9) of the CIN 3+ lesions, while HPV 16 attributed 55.8% (40.0-67.5) of them. Conclusion: The type-specific prevalence of HPV were slightly lower than the average in international meta-analyses. Genotyping for HPV 16 better identified women with CIN 3+ than cytology triage at the threshold of LSIL+. The high proportion of women that were HC2-positive but HPV-negative in genotyping suggests that HPV genotyping may be useful also for validation of results in HPV screening. The large-scale HPV genotyping data were found to be directly useful for planning further preventive efforts for cervical cancer. Copyright © 2013 Cancer Research UK. Source

Kalliala I.,Mass Screening Registry | Dyba T.,Mass Screening Registry | Nieminen P.,University of Helsinki | Hakulinen T.,Mass Screening Registry | Anttila A.,Mass Screening Registry
International Journal of Cancer

After treatment of the cervical intraepithelial neoplasia (CIN) cervical cancer incidence remains elevated at least for 20 years. Whether the overall or cervical cancer mortality after treatment of CIN is elevated is unknown. The aim of this study was to determine the long-term survival and cause-specific mortality among women treated for CIN. The study population consisted of 7,104 women treated for CIN between 1974 and 2001 and 35,437 individually matched controls. The follow-up of mortality was based on nationwide registries and closed at death, emigration or December 31, 2005. The possible differences in mortality were assessed using Cox proportional hazard model. With follow-up time of approximately 630,000 woman-years, overall 2,781 deaths were observed, 530 among women treated for CIN and 2,251 among reference population (HR 1.1, 95% CI 1.0-1.3). Mortality from any cancer (HR 1.4, 95% CI 1.2-1.7), lung cancer (HR 2.7, 95% CI 1.8-4.1) and HPV-related anogenital cancer (HR 3.1, 95% CI 1.1-8.6) was higher among CIN patients, but mortality from cervical cancer was not (HR 1.0, 95% CI 0.3-4.0). Elevated cervical cancer incidence after treatment of CIN, documented earlier, did not predict elevation in cervical cancer mortality. This suggests high effectiveness of CIN management. Most of the excess mortality observed among CIN patients was due to increased risk of other cancers. These long-term mortality patterns should be considered when planning and evaluating the management of CIN lesions and related cervical or other cancer prevention activity. © 2009 UICC. Source

Virtanen A.,Mass Screening Registry | Anttila A.,Mass Screening Registry | Nieminen P.,University of Helsinki
BMC Women's Health

Background: Offering self-sampling to non-attendees of cervical screening increases screening attendance. Methods: We used observations from two Finnish studies on the use of self-sampling among the non-attendees to estimate in a hypothetical screening population of 100,000 women the possible costs per extra screened woman and costs per extra detected and treated CIN2+ with three intervention strategies; 1) a primary invitation and a reminder letter, 2) a primary invitation and a mailed self-sampling kit and 3) two invitation letters and a self-sampling kit. The program costs were derived from actual performance and costs in the original studies and a national estimate on management costs of HPV related diseases. Results: The price per extra participant and price per detected and treated CIN2+ lesion was lower with a reminder letter than by self-sampling as a first reminder. When self-sampling was used as a second reminder with a low sampler price and a triage Pap-smear as a follow-up test for HPV-positive women instead of direct colposcopy referral, the eradication of a CIN2+ lesion by self-sampling was not more expensive than in routine screening, and the addition of two reminders to the invitation protocol did not increase the price of an treated CIN2+ lesion in the entire screened population. Conclusions: As a first reminder, a reminder letter is most likely a better choice. As second reminder, the higher costs of self-sampling might be compensated by the higher prevalence of CIN2+ in the originally non-attending population. © 2015 Virtanen et al. Source

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