Publications (32)146.12 Total impact
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Article: Stillbirth, early death and neonatal morbidity among offspring of female cancer survivors.
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ABSTRACT: Background. Increased awareness of the adverse effects of cancer treatments has prompted the development of fertility preserving regimens for the growing population of cancer survivors who desire to have children of their own. Material and methods. We conducted a registry-based study to evaluate the risk of stillbirth, early death and neonatal morbidity among children of female cancer survivors (0-34 years at diagnosis) compared with children of female siblings. A total of 3501 and 16 908 children of female cancer patients and siblings, respectively, were linked to the national medical birth and cause-of-death registers. Results. The risk of stillbirth or early death was not significantly increased among offspring of cancer survivors as compared to offspring of siblings: the risk [Odds Ratio (OR)] of early neonatal death, i.e. mortality within the first week was 1.35, with a 95% confidence interval (CI) of 0.58-3.18, within 28 days 1.40, 95% CI 0.46-4.24 and within the first year of life 1.11, 95% CI 0.64-1.93 after adjustment for the main explanatory variables. All these risk estimates were reduced towards one after further adjustment for duration of pregnancy. Measures of serious neonatal morbidity were not significantly increased among the children of survivors. However, there was a significant increase in the monitoring of children of cancer survivors for neonatal conditions (OR 1.56, 95% CI 1.35-1.80), which persisted even after correcting for duration of pregnancy, that might be related to parental cancer and its treatment or increased surveillance among the children. Conclusion. Offspring of cancer survivors were more likely to require monitoring or care in a neonatal intensive care unit, but the risk of early death or stillbirth was not increased after adjustment for prematurity. Due to the rarity of the mortality outcomes studied, collaborative studies may be helpful in ruling out the possibility of an increased risk among offspring of cancer survivors.Acta oncologica (Stockholm, Sweden) 01/2013; · 2.27 Impact Factor -
Article: Vitamin E serum levels and controlled supplementation and risk of amyotrophic lateral sclerosis.
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ABSTRACT: There are no observational studies or controlled trials of amyotrophic lateral sclerosis (ALS) and circulating α-tocopherol (vitamin E) for prevention of ALS. This study addresses that gap. The study population comprised 29,127 Finnish male smokers, aged 50-69 years, who participated in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, which is both a prospective cohort and a randomized, double-blind, placebo-controlled trial of α-tocopherol (50 mg/day) and β-carotene (20 mg/day). Serum α-tocopherol and β-carotene was assayed at baseline (1985 - 1988). Follow-up (median 16.7 years) continued through 2004. ALS cases were identified through the national Hospital Discharge Register with diagnostic verification by hospital records and death certificates. During 407,260 person-years of follow-up, 50 men were identified with ALS. For males with serum α-tocopherol concentration above the median (≥ 11.6 mg/l), the age-adjusted relative risk (RR) compared to α-tocopherol below the median, was 0.56 (95% confidence interval 0.32 - 0.99), p = 0.046. The RR among α-tocopherol supplement recipients was 0.75 (95% CI 0.32 - 1.79), p = 0.52. Neither serum β-carotene level nor β-carotene supplementation was associated with ALS. In conclusion, the results are consistent with a hypothesized protective effect of α-tocopherol on ALS risk. However, pooled analyses of cohorts with serum and controlled trials are needed to clarify the role of α-tocopherol in ALS risk.Amyotrophic lateral sclerosis and frontotemporal degeneration. 01/2013; -
Article: The HPV test has similar sensitivity but more overdiagnosis than the Pap test-A randomised health services study on cervical cancer screening in Finland.
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ABSTRACT: We compared test sensitivity (in terms of prevented cancers) and overdiagnosis (in terms of non-progressive pre-invasive lesions) between the human papillomavirus test (HPV test, Hybrid Capture 2) and the traditional Pap test in routine screening for cervical cancer. The design was a randomised (1:1) health services study in Finland with intake between 2003 and 2007. We estimated sensitivity by the incidence method within one screening round. Overdiagnosis was based on the rate of cervical intraepithelial Grade 3 (CIN3) lesions diagnosed at screen and during the following interval. Out of 203,788 randomised women 132,298 attended (65% in both study arms) and 600,753 person-years accumulated among attenders up to the end of 2010. In all attenders, 34 invasive cervical cancers and 288 CIN3 lesions were diagnosed at screen or during the following interval. The interval cancer incidence was 2.5/10(5) person-years (sensitivity 0.87) and 1.4 (sensitivity 0.93) in the HPV arm and Pap test arm, respectively. The rate of CIN3 lesions was 57.1 and 38.8, respectively. In conclusion, sensitivity of HPV testing was similar to that of Pap testing but caused more overdiagnosis. Therefore, implementation of HPV testing needs to be reconsidered especially in countries with well organised programmes.International Journal of Cancer 09/2012; · 5.44 Impact Factor -
Article: Evaluation of breast cancer service screening programme with a Bayesian approach: mortality analysis in a Finnish region
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ABSTRACT: Evaluation of long-term effectiveness of population-based breast cancer service screening program in a small geographic area may suffer from self-selection bias and small samples. Under a prospective cohort design with exposed and non-exposed groups classified by whether women attended the screen upon invitation, we proposed a Bayesian acyclic graphic model for correcting self-selection bias with or without incorporation of prior information derived from previous studies with an identical screening program in Sweden by chronological order and applied it to an organized breast cancer service screening program in Pirkanmaa center of Finland. The relative mortality rate of breast cancer was 0.27 (95% CI 0.12–0.61) for the exposed group versus the non-exposed group without adjusting for self-selection bias. With adjustment for selection-bias, the adjusted relative mortality rate without using previous data was 0.76 (95% CI 0.49–1.15), whereas a statistically significant result was achieved [0.73 (95% CI 0.57–0.93)] with incorporation of previous information. With the incorporation of external data sources from Sweden in chronological order, adjusted relative mortality rate was 0.67 (0.55–0.80). We demonstrated how to apply a Bayesian acyclic graphic model with self-selection bias adjustment to evaluating an organized but non-randomized breast cancer screening program in a small geographic area with a significant 27% mortality reduction that is consistent with the previous result but more precise. Around 33% mortality was estimated by taking previous randomized controlled data from Sweden. KeywordsBreast cancer screening-Self-selection bias-Bayesian acyclic graphic model-Mortality reductionBreast Cancer Research and Treatment 04/2012; 121(3):671-678. · 4.43 Impact Factor -
Article: Randomised health services studies.
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ABSTRACT: The randomised controlled (or clinical) trial (RCT) is recognized as the most valid among the study designs. The use of RCT in research is widespread and well formalised. In contrast, implementations of new methods and policies in routine health care are commonly lacking a formalised design, impairing the ability to evaluate and improve health care. Use of experimental designs in health care is possible at the implementation phase of clinical or preventive action or more broad process-of-care. We propose the terminology randomised health services studies (RHS) to denote the use of a randomised design with observations in routine health care, regardless of whether randomisation is done at individual, population or process level. In contrast to RCT, the RHS should be based on the same regulative actions, funding mechanisms and ethical framework as routine health care itself. This commentary discusses the different basis, practicalities, and formalities that distinguish the RHS from the RCT. Development of a formalised framework for RHS, including distinct registration, could contribute to an increased use of valid methods in effectiveness research, thus gaining better and more direct evidence on routine medical practice.International Journal of Cancer 03/2012; 131(12):2898-902. · 5.44 Impact Factor -
Article: Detection rates of precancerous and cancerous cervical lesions within one screening round of primary human papillomavirus DNA testing: prospective randomised trial in Finland.
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ABSTRACT: To compare the detection rates of precancerous and cancerous cervical lesions by human papillomavirus (HPV) DNA testing and by conventional cytology screening. Prospective randomised trial. Two cohorts were followed over one screening round of five years, screened initially by primary HPV DNA testing or by primary Pap test. Population based programme for cervical cancer screening in Finland. Women aged 25-65 years invited for screening in 2003-07 (101 678 in HPV arm; 101 747 in conventional cytology arm). INTERVENTION : Women were randomly allocated (1:1) to primary HPV DNA screening followed by cytology triage if they had positive results, or to primary cytology screening. Screening method was disclosed at the screening visit. Trial personnel involved were aware of all test results. Cumulative detection rates of cervical intraepithelial neoplasia (CIN), adenocarcinoma in situ (AIS), and invasive cervical cancer before the second screening (after five years) or before 31 December 2008. Lesions detected at screening and during the five year interval were included. 1010 and 701 precancerous or cancerous lesions were detected during an average follow-up of 3.6 years in the HPV and cytology arms, respectively. Among invited women, the hazard ratio was 1.53 (95% confidence interval l.28 to 1.84) for CIN grade 1, 1.54 (1.33 to 1.78) for CIN 2, 1.32 (1.09 to 1.59) for CIN 3 or AIS, and 0.81 (0.48 to 1.37) for cervical cancer. In 25-34 year old participants, the cumulative hazard (or cumulative detection rate) was 0.0057 (0.0045 to 0.0072) for HPV screening versus 0.0046 (0.0035 to 0.0059) for conventional screening; corresponding data for women aged 35 years and older were 0.0022 (0.0019 to 0.0026) and 0.0017 (0.0014 to 0.0021), respectively. Primary HPV DNA screening detects more cervical lesions than primary cytology within one screening round of five years. Even if the detection rate of CIN 3 or AIS increased in the HPV arm in both age groups, the absolute difference in cumulative rates in women aged 35 years or older was small. By carefully selecting age groups and screening intervals, HPV screening could increase the overall detection rate of cervical precancerous lesions only slightly. However, these findings should be interpreted in the context of the high level of opportunistic screening that occurs in Finland. International Standard Randomised Controlled Trial ISRCTN23885553.BMJ (Clinical research ed.). 01/2012; 345:e7789. -
Article: Validation of histological diagnoses in a national cervical screening register.
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ABSTRACT: Monitoring and evaluation of cancer screening programmes require accurate data on invitations, visits, test results, diagnoses and management. The purpose of this study was to evaluate the completeness and accuracy of histological diagnoses (cervical precancerous lesions and cancer) in the Finnish cervical cancer screening register by comparing data with the cancer register and the administrative hospital discharge register. Screening data covering all 16 353 screening episodes that resulted in a referral for colposcopy over the period of 1998-2007 were individually linked with hospital discharge and cancer register data using the unique personal identifier. Agreement between registers, as well as sensitivity, coverage and positive predictive values (PPV) for the screening register and the hospital discharge register diagnosis, were estimated. Invasive cases in the cancer register and pooled cases of precancerous lesions were used as reference case populations. The sensitivity of the screening register for cervical cancer was 69%, the coverage 100% and the PPV 77%. Corresponding values for the hospital discharge register were 81%, 100% and 83%, respectively. Sensitivity of the screening register for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) against the pooled case population was 89% and coverage 99%. Corresponding values for the hospital discharge register were 78% and 93%. Kappa-values for pair-wise agreement between the three registers ranged between 0.73 and 0.79, often the lesion grade was lower in the screening register than in the other two registers. The data in the screening register has high coverage and is thus useful for statistical and evaluation purposes. However, in order to improve the accuracy of diagnostic information, there are grounds to consider data retrieval through systematic linkage to other health care registers.Acta oncologica (Stockholm, Sweden) 08/2011; 51(1):37-44. · 2.27 Impact Factor -
Article: Cervical cancer patterns with automation-assisted and conventional cytological screening: a randomized study.
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ABSTRACT: The purpose was to evaluate alternative cytological screening methods in population-based screening for cervical cancer up to cancer incidence and mortality outcome. Automation-assisted screening was compared to conventional cytological screening in a randomized design. The study was based on follow-up of 503,391 women invited in the Finnish cervical cancer screening program during 1999-2003. The endpoints were incident cervical cancer, severe intraepithelial neoplasia and deaths from cervical cancer. One third of the women had been randomly allocated to automation-assisted screening and two thirds to conventional cytology. Information on cervical cancer and severe neoplasia were obtained through 1999-2007 from a linkage between screening and cancer registry files. There were altogether 3.2 million woman-years at risk, and the average follow-up time was 6.3 years. There was no difference in the risk of cervical cancer between the automation-assisted and conventional screening methods; the relative risk (RR) of cervical cancer between the study and control arm was 1.00 (95% confidence interval [CI] = 0.76-1.29) among all invited and 1.08 (95% CI = 0.76-1.51) among women who were test negative at entry. Comparing women who were test negative with nonscreened, RR of cervical cancer incidence was 0.26, 95% CI = 0.19-0.36 and of mortality 0.24 (0.13-0.43). Both methods were valid for screening. Because cervical cancer is rare in our country, we cannot rule out small differences between methods. Evidence on alternative methods for cervical cancer screening is increasing and it is thus feasible to evaluate new methods in large-scale population-based screening programs up to cancer outcome.International Journal of Cancer 03/2011; 128(5):1204-12. · 5.44 Impact Factor -
Article: Analytical decision model for sample size and effectiveness projections for use in planning a population-based randomized controlled trial of colorectal cancer screening.
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ABSTRACT: Population-based randomized controlled trials (RCTs) often involve enormous costs and long-term follow-up to evaluate primary end points. Analytical decision-simulated model for sample size and effectiveness projections based on primary and surrogate end points are necessary before planning a population-based RCT. Based on the study design similar to two previous RCTs, transition rates were estimated using a five-state natural history model [normal, preclinical detection phase (PCDP) Dukes' A/B, PCDP Dukes' C/D, Clinical Dukes' A/B and Clinical Dukes' C/D]. The Markov cycle tree was assigned transition parameters, variables related to screening and survival rate that simulated results of 10-year follow-up in the absence of screening for a hypothetical cohort aged 45-74 years. The corresponding screened arm was to simulate the results after the introduction of population-based screening for colorectal cancer with fecal occult blood test with stop screen design. The natural course of mean sojourn time for five-state Markov model were estimated as 2.75 years for preclinical Dukes' A/B and 1.38 years for preclinical Dukes' C/D. The expected reductions in mortality and Dukes' C/D were 13% (95% confidence intervals: 7-19%) and 26% (95% confidence intervals: 20-32%), respectively, given a 70% acceptance rate and a 90% colonoscopy referral rate. Sample sizes required were 86,150 and 65,592 subjects for the primary end point and the surrogate end point, respectively, given an incidence rate up to 0.0020 per year. The sample sizes required for primary and surrogate end points and the projection of effectiveness of fecal occult blood test for colorectal cancer screening were developed. Both are very important to plan a population-based RCT.Journal of Evaluation in Clinical Practice 02/2011; 17(1):123-9. · 1.23 Impact Factor -
Article: Response to dr braillon.
Journal of Medical Screening 01/2011; 18(2):103-4. · 1.69 Impact Factor -
Article: Intensified screening among high risk women within the organised screening programme for cervical cancer in Finland.
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ABSTRACT: Based on a five-year follow-up of 130 692 women who participated in the five-yearly organised screening in Finland in 1995, we estimated the risk for incident invasive cervical cancer and severe precancerous lesion for groups of women with different combinations of high-risk determinants at baseline. Compared to women with normal cytology and no symptoms at the index screen, the risk of developing invasive cervical cancer during the next screening interval was significantly elevated in women with abnormal cytology at baseline screen (RR 5.8, 95% CI 2.6-13.1); additionally, the risk of cervical intraepithelial neoplasia grade 3 (CIN3) lesions was even higher (RR 9.4, 95% CI 6.9-12.5), both results after removing respective screen detected cases at index screen. Among women with symptoms of vaginal bleeding or abnormal vaginal discharge but normal cytology the risk of invasive cervical cancer was increased but not significantly (RR 2.4, 95% CI 0.9-6.3) and the risk of CIN3 lesions was only slightly elevated (RR 1.5, 95% CI 0.95-2.4). In women less than 40 years of age, the risk of cervical cancer was 50% higher than in women 40 years or more in those with normal cytology and no symptoms, however not significantly. Symptoms indicated a similarly elevated risk for cancer in both age groups. After abnormal cytology there was a nine-fold risk for cancer in young women (under 40 years) and a six-fold risk in old women (40 years or more) when compared to women aged 40 or more with no symptoms and normal cytology. In young women CIN3 lesions were found in great excess, three times more often, compared to those aged 40 and over. In all, selective intensified screening for cervical cancer complementing the five-yearly unselective programme is feasible for women with abnormal cytological findings at an acceptable level of incremental cost.Acta oncologica (Stockholm, Sweden) 01/2011; 50(1):106-11. · 2.27 Impact Factor -
Article: Coverage and performance of colorectal cancer screening with the faecal occult blood test in Finland.
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ABSTRACT: Mortality from colorectal cancer has been shown to decrease by repeated screening using faecal occult blood (FOB) testing in randomized screening trials. This report presents coverage and performance of organized screening among the general population in Finland. In 2004-2007, people aged 60-69 years were randomized into biennial screening and control arms. The screening test was a guaiac-based FOB test (Hemoccult) with dietary restriction and three test cards for six consecutive samples. Test positives were referred for full colonoscopy. The programme was launched in 2004 and subsequently it expanded over regions and age-cohorts. In 2007, the programme covered one-third of the target population and 74,592 people had been invited for screening, of them 26,866 for the second round. Uptakes for the first and second rounds, respectively, were 62% and 68% in men and 77% and 80% in women. The proportion of test positives increased from 2.4% to 2.9% from the first to the second round and the positive predictive value for cancers decreased from 7.5% to 4.3%. By 2007, organized colorectal cancer screening covered one-third of the target population in Finland. Implementation of screening measured with response rate was successful and met the criteria for a public health programme, but performance in terms of positive predictive value needs monitoring.Journal of Medical Screening 01/2011; 18(1):18-23. · 1.69 Impact Factor -
Article: Preterm delivery among female survivors of childhood, adolescent and young adulthood cancer.
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ABSTRACT: We studied the deliveries of female cancer survivors and female siblings in a population-based setting in Finland. Nationwide cancer and birth registries were merged to identify 1,309 first postdiagnosis deliveries of early-onset (diagnosed under age 35) female patients with cancer and 5,916 first deliveries of female siblings occurring in 1987-2006. Multiple logistic regression models were used to estimate risk of preterm (<37 weeks), low birth weight (<2500 g) and small-for-gestational-age deliveries. The risk of preterm delivery among cancer survivors compared with siblings was overall increased [odds ratio (OR) 1.46, 95% confidence interval (CI) 1.14-1.85], the increase in risk being visible in all diagnostic age groups. Risk of low birth weight (LBW) was also significantly increased (OR 1.68; 95% CI 1.29-2.18) but not after adjustment for duration of pregnancy (OR 1.11; 95% CI 0.76-1.64). Neither was the risk of small-for-gestational-age (SGA) increased. The risk of preterm delivery was most pronounced in survivors delivering 10 years or more after diagnosis. Site-specific analyses indicated that survivors of germ cell tumors and central nervous system (CNS) tumors were at increased risk of preterm delivery, although numbers were small. In childhood survivors, kidney tumors formed the main cause of preterm delivery. Pediatric, adolescent and young adult cancer survivors are at risk for preterm delivery. Heightened surveillance is recommended especially for Wilms', germ cell and CNS tumor survivors. Such adverse pregnancy outcomes can occur a decade or more after cancer diagnosis, indicating a continued need for obstetric awareness, surveillance and counseling in former patients with cancer.International Journal of Cancer 10/2010; 127(7):1669-79. · 5.44 Impact Factor -
Article: Estimation of natural history parameters of breast cancer based on non-randomized organized screening data: subsidiary analysis of effects of inter-screening interval, sensitivity, and attendance rate on reduction of advanced cancer.
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ABSTRACT: Estimating the natural history parameters of breast cancer not only elucidates the disease progression but also make contributions to assessing the impact of inter-screening interval, sensitivity, and attendance rate on reducing advanced breast cancer. We applied three-state and five-state Markov models to data on a two-yearly routine mammography screening in Finland between 1988 and 2000. The mean sojourn time (MST) was computed from estimated transition parameters. Computer simulation was implemented to examine the effect of inter-screening interval, sensitivity, and attendance rate on reducing advanced breast cancers. In three-state model, the MST was 2.02 years, and the sensitivity for detecting preclinical breast cancer was 84.83%. In five-state model, the MST was 2.21 years for localized tumor and 0.82 year for non-localized tumor. Annual, biennial, and triennial screening programs can reduce 53, 37, and 28% of advanced cancer. The effectiveness of intensive screening with poor attendance is the same as that of infrequent screening with high attendance rate. We demonstrated how to estimate the natural history parameters using a service screening program and applied these parameters to assess the impact of inter-screening interval, sensitivity, and attendance rate on reducing advanced cancer. The proposed method makes contribution to further cost-effectiveness analysis. However, these findings had better be validated by using a further long-term follow-up data.Breast Cancer Research and Treatment 07/2010; 122(2):553-66. · 4.43 Impact Factor -
Article: Rate of cervical cancer, severe intraepithelial neoplasia, and adenocarcinoma in situ in primary HPV DNA screening with cytology triage: randomised study within organised screening programme.
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ABSTRACT: To assess the performance and impact of primary human papillomavirus (HPV) DNA screening with cytology triage compared with conventional cytology on cervical cancer and severe pre-cancerous lesions. Randomised trial. Population based screening programme for cervical cancer in southern Finland in 2003-5. 58 076 women, aged 30-60, invited to the routine population based screening programme for cervical cancer. Primary HPV DNA test (hybrid capture II) with cytology triage if the result was positive or conventional cytological screening (reference). Rate of cervical cancer, cervical intraepithelial neoplasia (CIN) grade III, and adenocarcinoma in situ (as a composite outcome referred to as CIN III+) during 2003-7 through record linkage between files from the screening registry and the national cancer registry. In the HPV and conventional arms there were 95 600 and 95 700 woman years of follow-up and 76 and 53 cases of CIN III+, respectively (of which six and eight were cervical cancers). The relative rate of CIN III+ in the HPV arm versus the conventional arm was 1.44 (95% confidence interval 1.01 to 2.05) among all women invited for screening and 1.77 (1.16 to 2.74) among those who attended. Among women with a normal or negative test result, the relative rate of subsequent CIN III+ was 0.28 (0.04 to 1.17). The rate of cervical cancer between arms was 0.75 (0.25 to 2.16) among women invited for screening and 1.98 (0.52 to 9.38) among those who attended. When incorporated into a well established organised screening programme, primary HPV screening with cytology triage was more sensitive than conventional cytology in detecting CIN III+ lesions. The number of cases of cervical cancer was small, but considering the high probability of progression of CIN III the findings are of importance regarding cancer prevention. Current Controlled Trials ISRCTN23885553.BMJ (Clinical research ed.). 01/2010; 340:c1804. -
Article: Socioeconomic differences in incidence of cervical cancer in Finland by cell type.
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ABSTRACT: We studied variation in incidence of cervix cancer during 1971-1995 among Finnish women born in 1906 to 1945 by social class and cell type. The Finnish Cancer Registry data were linked to the 1970 Population Census, which included social class data. There were 0.8 million individuals in the cohort under follow-up, with 5,102 squamous cell cancers and 573 cases of cervical adenocarcinoma diagnosed after the census date. Incidence of squamous cell cancer was more than two-fold in the lowest social class (standardized incidence ratio (SIR) 1.29, 95% CI 1.21-1.36) as compared with the highest one (SIR 0.59, 0.51-0.66), while there was no association between social class and risk on adenocarcinoma (SIR 1.07, 0.87-1.28 and 1.08, 0.79-1.45, respectively). Oncogenic HPV is regarded as the necessary cause of all types of cervix cancer. Sexually transmitted diseases and social status are correlated. Lack of association between adenocarcinoma and social class makes the HPV-etiology of this cell type less credible than that of squamous cell cancer.Acta oncologica (Stockholm, Sweden) 12/2009; 49(2):180-4. · 2.27 Impact Factor -
Article: Age-specific evaluation of primary human papillomavirus screening vs conventional cytology in a randomized setting.
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ABSTRACT: Human papillomavirus (HPV) DNA testing has shown higher sensitivity than cytology for detecting cervical lesions, but it is uncertain whether the higher sensitivity is dependent on the age of the woman being screened. We compared the age-specific performance of primary HPV DNA screening with that of conventional cytology screening in the setting of an organized population-based cervical cancer screening program in Finland. From January 1, 2003, to December 31, 2005, randomized invitations were sent to women aged 25-65 years for routine cervical cancer screening by primary high-risk HPV DNA testing (n = 54 207) with a Hybrid Capture 2 assay followed by cytology triage for women who were HPV DNA positive or by conventional cytology screening (n = 54 218). In both screening arms, cytology results of low-grade squamous intraepithelial lesion or worse triggered a referral for colposcopy. Relative rates (RRs) of detection to assess test sensitivity, specificity, and positive predictive values (PPVs) with 95% confidence intervals (CIs) were calculated for the histological endpoints of cervical intraepithelial neoplasia (CIN) grade 1 or higher (CIN 1+), CIN grade 2 or higher (CIN 2+), and CIN grade 3 or higher (CIN 3+). All statistical tests were two-sided. The overall frequency of colposcopy referrals was 1.2% in both screening arms. Women younger than 35 years were referred more often in the HPV DNA screening vs the conventional screening arm (RR = 1.27, 95% CI = 1.01 to 1.60). The prevalence of histologically confirmed CIN or cancer was 0.59% in the HPV DNA screening arm vs 0.43% in the conventional screening arm. The relative rates of detection for CIN 1, CIN 2, and CIN 3+ for HPV DNA screening with cytology triage vs conventional screening were 1.44 (95% CI = 0.99 to 2.10), 1.39 (95% CI = 1.03 to 1.88), and 1.22 (95% CI = 0.78 to 1.92), respectively. The specificity of the HPV DNA test with cytology triage was equal to that of conventional screening for all age groups (99.2% vs 99.1% for CIN 2+, P = .13). Among women aged 35 years or older, the HPV DNA test with cytology triage tended to have higher specificity than conventional screening. The PPVs for HPV DNA screening with cytology triage were consistently higher than those for conventional screening. In both screening arms, the test specificities increased with increasing age of the women being screening, whereas the highest PPVs were observed among the youngest women being screened. Overall, 7.2% of women in the HPV DNA screening arm vs 6.6% of women in the conventional screening arm were recommended for intensified follow-up, and the percentages were highest among 25- to 29-year-olds (21.9% vs 10.0%, respectively). Primary HPV DNA screening with cytology triage is more sensitive than conventional screening. Among women aged 35 years or older, primary HPV DNA screening with cytology triage is also more specific than conventional screening and decreases colposcopy referrals and follow-up tests.CancerSpectrum Knowledge Environment 11/2009; 101(23):1612-23. · 14.07 Impact Factor -
Article: Risk of cancer among children of cancer patients - a nationwide study in Finland.
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ABSTRACT: Cancer treatments have the potential to cause germline mutations that might increase the risk of cancer in the offspring of former cancer patients. This risk was evaluated in a population-based study of early onset cancer patients in Finland. Using the nationwide registry data, 26,331 children of pediatric and early onset cancer patients (diagnosed under age 35 between 1953 and 2004) were compared to 58,155 children of siblings. Cancer occurrence among the children was determined by linkage with the cancer registry, and the standardized incidence ratios (SIRs) were calculated comparing the observed number of cancers with that expected, based on rates in the general population of Finland. Among the 9,877 children born after their parent's diagnosis, cancer risk was increased (SIR 1.67; 95% CI 1.29-2.12). However, after removing those with hereditary cancer syndromes, this increase disappeared (SIR 1.03; 95% CI 0.74-1.40). The overall risk of cancer among the offspring of siblings (SIR 1.07; 95% CI 0.94-1.21) was the same as among the offspring of the patients with non hereditary cancer. Risk of cancer in offspring, born before their parents cancer diagnosis, was elevated (SIR 1.37, 95% CI 1.20-1.54), but removing hereditary syndromes resulted in a diminished and nonsignificant association (SIR 1.08, 95% CI 0.93-1.25). This study shows that offspring of cancer patients are not at an increased risk of cancer except when the patient has a cancer-predisposing syndrome. These findings are directly relevant to counseling cancer survivors with regard to family planning.International Journal of Cancer 10/2009; 126(5):1196-205. · 5.44 Impact Factor -
Article: Probability of parenthood after early onset cancer: a population-based study.
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ABSTRACT: We evaluated in a population-based setting the postdiagnosis parenthood among survivors compared with the fertility patterns of siblings. Cancer patients aged 0-34 years at diagnosis were identified from the Finnish Cancer Registry (N = 25,784), and their siblings (N = 44,611) by registry linkage. Further linkage identified the offspring of the patient and sibling cohorts. The relative probabilities of parenthood for first and second births separately were estimated for male and female survivors in different diagnostic age-groups and subsites using a Cox proportional hazards model, with age as the time variable and adjusting for the birth cohort of parents. In addition, estimates were calculated for 5 diagnostic eras in all subsites combined. Compared to siblings, both female and male cancer survivors were less likely to parent at least 1 child (RR 0.46, 95% CI 0.44-0.48 and RR 0.57, 95% CI 0.54-0.60, respectively). The relative probability of parenthood was especially low in male childhood cancer survivors and female young adult cancer survivors. However, cancer patients were only slightly less likely than siblings to parent a second child, with RR 0.91, 95% CI 0.86-0.97 and RR 0.95, 95% CI 0.89-1.01 for females and males, respectively. The relative probability of parenthood increased over calendar time among young adult cancer patients. The relative probability of parenthood following early onset cancer was overall significantly reduced by approximately 50%. Parenting a second child, however, was not reduced among pediatric and adolescent survivors, and only slightly reduced among early adulthood cancer survivors compared to siblings.International Journal of Cancer 10/2008; 123(12):2891-8. · 5.44 Impact Factor -
Article: Test positivity cutoff level of a high risk human papillomavirus test could be increased in routine cervical cancer screening.
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ABSTRACT: We present data on test positivity, relative sensitivity, rates of detection and relative specificity for primary human papillomavirus (HPV) testing with different cutoff levels for test positivity, in comparison to conventional cytology. In 2003-2004, 18,438 women were screened primarily with Hybrid Capture 2 (HC 2) assay, a test for oncogenic HPV DNA, and 21,446 with conventional cytology within the organised screening programme in Finland. A cytological triage test was performed for the HPV positives. Women with cytology equal to low grade squamous intraepithelial lesion (LSIL) or worse were referred for colposcopy. The relative sensitivity measured as relative risk (RR) of any cervical intraepithelial neoplasia (CIN) or cancer was 1.58 for the HPV test at the relative light units (rlu) ratio cutoff 1.00, in comparison to cytology. With the cutoff 3.00, all CIN 2+ lesions were detected. With cutoff 10.00, 2 of the 22 CIN 3+ lesions were missed. Relative specificity for HPV screening for any CIN was 92.6% at cutoff 1.00, 94.6% at cutoff 3.00 and 96.3% at cutoff 10.00. For CIN 3+ specificity estimates for these cutoffs were 92.1%, 94.1% and 95.8%, respectively. Used for routine screening as the sole test, the HPV test cutoff can be increased from the level recommended for clinical use. With HC 2, the detection rate at rlu ratio cutoff 10.00 is still at the level of high-quality conventional screening. At that level, the false positive rate is reduced by about half and the specificity of the HPV test becomes equal to the average specificity of conventional cytology.International Journal of Cancer 10/2008; 123(12):2902-6. · 5.44 Impact Factor
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2003–2013
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Finnish Cancer Registry, Helsinki
Helsinki, Province of Southern Finland, Finland
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2002
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National Public Health Institute
Helsinki, Province of Southern Finland, Finland
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