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Nicholas J. Wald - One of the best experts on this subject based on the ideXlab platform.
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cost and efficacy comparison of prenatal recall and reflex DNA Screening for trisomy 21 18 and 13
2019Co-Authors: Jonathan P. Bestwick, Nicholas J. WaldAbstract:Objective To compare costs and efficacy of reflex and recall prenatal DNA Screening for trisomy 21, 18 and 13 (affected pregnancies). In both methods women have Combined test markers measured. With recall Screening, women with a high Combined test risk are recalled for counselling and offered a DNA blood test or invasive diagnostic testing. With reflex Screening, a DNA analysis is automatically performed on plasma collected when blood was collected for measurement of the Combined test markers. Methods Published data were used to estimate, for each method, using various unit costs and risk cut-offs, the cost per woman screened, cost per affected pregnancy diagnosed, and for a given number of women screened, numbers of affected pregnancies diagnosed, unaffected pregnancies with positive results, and women with unaffected pregnancies having invasive diagnostic testing. Results Cost per woman screened is lower with reflex v recall Screening: £37 v £38, and £11,043 v £11,178 per affected pregnancy diagnosed (DNA £250, Combined test markers risk cut-off 1 in 150). Reflex Screening results in similar numbers of affected pregnancies diagnosed, with 100-fold fewer false-positives and 20-fold fewer women with unaffected pregnancies having invasive diagnostic testing. Conclusions Reflex DNA Screening is less expensive, more cost-effective, and safer than recall Screening.
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prenatal reflex DNA Screening for trisomies 21 18 and 13
2018Co-Authors: Nicholas J. Wald, Jonathan P. Bestwick, Wayne J Huttly, Robert Old, Joan K Morris, Ray Cheng, Joe Aquilina, Elisabeth Peregrine, Devender Roberts, Zarko AlfirevicAbstract:The purpose of the study was to determine the Screening performance of prenatal reflex DNA Screening for trisomies 21 (T21), 18 (T18), and 13 (T13) as part of a routine service at five hospitals. Women who accepted Screening had a first-trimester combined test (pregnancy-associated plasma protein A, free β-human chorionic gonadotropin, nuchal translucency interpreted with maternal age). Those with a risk of having an affected pregnancy ≥1 in 800 were reflexed to a DNA sequencing test using stored plasma from the original blood sample, thereby avoiding the need to recall them. Of 22,812 women screened (including 106 with affected pregnancies), 2,480 (10.9%) were reflexed to DNA testing; 101/106 were detected (69/73 T21, 24/25 T18, and 8/8 T13), a 95% detection rate (95% confidence interval 89–98%) with four false positives (0.02%, 95% confidence interval 0.00–0.05%). The odds of being affected given a positive result were 25:1. Of the 105 screen-positive pregnancies, 91 (87%) had an invasive diagnostic test. Reflex DNA Screening avoided up to 530 invasive diagnostic tests compared with using the combined test. Reflex DNA Screening was successfully implemented in routine care, achieving a high detection rate, low false-positive rate, and, consequently, greater safety with fewer invasive diagnostic tests than other methods of Screening.
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Prenatal maternal plasma DNA Screening for cystic fibrosis: A computer modelling study of Screening performance [version 1; referees: 2 approved]
2017Co-Authors: Robert W. Old, Jonathan P. Bestwick, Nicholas J. WaldAbstract:Background: Prenatal cystic fibrosis (CF) Screening is currently based on determining the carrier status of both parents. We propose a new method based only on the analysis of DNA in maternal plasma. Methods: The method relies on the quantitative amplification of the CF gene to determine the percentage of DNA fragments in maternal plasma at targeted CF mutation sites that carry a CF mutation. Computer modelling was carried out to estimate the distributions of these percentages in pregnancies with and without a fetus affected with CF. This was done according to the number of DNA fragments counted and fetal fraction, using the 23 CF mutations recommended by the American College of Medical Genetics for parental carrier testing. Results: The estimated detection rate (sensitivity) is 70% (100% of those detected using the 23 mutations), the false-positive rate 0.002%, and the odds of being affected given a positive Screening result 14:1, compared with 70%, 0.12%, and 1:3, respectively, with current prenatal Screening based on parental carrier testing. Conclusions: Compared with current Screening practice based on parental carrier testing, the proposed method would substantially reduce the number of invasive diagnostic procedures (amniocentesis or chorionic villus sampling) without reducing the CF detection rate. The expected advantages of the proposed method justify carrying out the necessary test development for use in a clinical validation study
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antenatal reflex DNA Screening for trisomy 18 and trisomy 13 in addition to down s syndrome
2016Co-Authors: Jonathan P. Bestwick, Nicholas J. WaldAbstract:ObjectiveAntenatal reflex DNA Screening for Down’s syndrome has a high Screening performance. We aimed to determine the performance of trisomy 18 and trisomy 13 reflex DNA Screening when added to D...
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performance of antenatal reflex DNA Screening for down s syndrome
2015Co-Authors: Nicholas J. Wald, Jonathan P. BestwickAbstract:ObjectiveMaternal plasma DNA analysis has a high but imperfect antenatal Down’s syndrome Screening performance. We aimed to determine the effect of combining DNA testing with current tests.MethodsIn our modelled Screening protocol, women provide two samples, one serum sample for a Combined test, and a plasma sample for a possible DNA test. Women with a Combined test risk above a specified level have a DNA test using the plasma sample without the need to recall them for another sample and counselling (ie. in a reflex manner). Women with a failed DNA test after a second attempt using a fresh plasma sample have an Integrated test. Screening performance was estimated according to the proportion of women reflexed to DNA testing and compared with universal DNA testing.ResultsReflexing 10% of women to a DNA test yields a 91% detection rate (DR) for a 0.025% false-positive rate (FPR) and no failed tests, compared with a 98% DR, 0.2% FPR and a 2.5% test failure rate with universal DNA testing (94% for 0.046% if 20...
Jonathan P. Bestwick - One of the best experts on this subject based on the ideXlab platform.
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cost and efficacy comparison of prenatal recall and reflex DNA Screening for trisomy 21 18 and 13
2019Co-Authors: Jonathan P. Bestwick, Nicholas J. WaldAbstract:Objective To compare costs and efficacy of reflex and recall prenatal DNA Screening for trisomy 21, 18 and 13 (affected pregnancies). In both methods women have Combined test markers measured. With recall Screening, women with a high Combined test risk are recalled for counselling and offered a DNA blood test or invasive diagnostic testing. With reflex Screening, a DNA analysis is automatically performed on plasma collected when blood was collected for measurement of the Combined test markers. Methods Published data were used to estimate, for each method, using various unit costs and risk cut-offs, the cost per woman screened, cost per affected pregnancy diagnosed, and for a given number of women screened, numbers of affected pregnancies diagnosed, unaffected pregnancies with positive results, and women with unaffected pregnancies having invasive diagnostic testing. Results Cost per woman screened is lower with reflex v recall Screening: £37 v £38, and £11,043 v £11,178 per affected pregnancy diagnosed (DNA £250, Combined test markers risk cut-off 1 in 150). Reflex Screening results in similar numbers of affected pregnancies diagnosed, with 100-fold fewer false-positives and 20-fold fewer women with unaffected pregnancies having invasive diagnostic testing. Conclusions Reflex DNA Screening is less expensive, more cost-effective, and safer than recall Screening.
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prenatal reflex DNA Screening for trisomies 21 18 and 13
2018Co-Authors: Nicholas J. Wald, Jonathan P. Bestwick, Wayne J Huttly, Robert Old, Joan K Morris, Ray Cheng, Joe Aquilina, Elisabeth Peregrine, Devender Roberts, Zarko AlfirevicAbstract:The purpose of the study was to determine the Screening performance of prenatal reflex DNA Screening for trisomies 21 (T21), 18 (T18), and 13 (T13) as part of a routine service at five hospitals. Women who accepted Screening had a first-trimester combined test (pregnancy-associated plasma protein A, free β-human chorionic gonadotropin, nuchal translucency interpreted with maternal age). Those with a risk of having an affected pregnancy ≥1 in 800 were reflexed to a DNA sequencing test using stored plasma from the original blood sample, thereby avoiding the need to recall them. Of 22,812 women screened (including 106 with affected pregnancies), 2,480 (10.9%) were reflexed to DNA testing; 101/106 were detected (69/73 T21, 24/25 T18, and 8/8 T13), a 95% detection rate (95% confidence interval 89–98%) with four false positives (0.02%, 95% confidence interval 0.00–0.05%). The odds of being affected given a positive result were 25:1. Of the 105 screen-positive pregnancies, 91 (87%) had an invasive diagnostic test. Reflex DNA Screening avoided up to 530 invasive diagnostic tests compared with using the combined test. Reflex DNA Screening was successfully implemented in routine care, achieving a high detection rate, low false-positive rate, and, consequently, greater safety with fewer invasive diagnostic tests than other methods of Screening.
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Prenatal maternal plasma DNA Screening for cystic fibrosis: A computer modelling study of Screening performance [version 1; referees: 2 approved]
2017Co-Authors: Robert W. Old, Jonathan P. Bestwick, Nicholas J. WaldAbstract:Background: Prenatal cystic fibrosis (CF) Screening is currently based on determining the carrier status of both parents. We propose a new method based only on the analysis of DNA in maternal plasma. Methods: The method relies on the quantitative amplification of the CF gene to determine the percentage of DNA fragments in maternal plasma at targeted CF mutation sites that carry a CF mutation. Computer modelling was carried out to estimate the distributions of these percentages in pregnancies with and without a fetus affected with CF. This was done according to the number of DNA fragments counted and fetal fraction, using the 23 CF mutations recommended by the American College of Medical Genetics for parental carrier testing. Results: The estimated detection rate (sensitivity) is 70% (100% of those detected using the 23 mutations), the false-positive rate 0.002%, and the odds of being affected given a positive Screening result 14:1, compared with 70%, 0.12%, and 1:3, respectively, with current prenatal Screening based on parental carrier testing. Conclusions: Compared with current Screening practice based on parental carrier testing, the proposed method would substantially reduce the number of invasive diagnostic procedures (amniocentesis or chorionic villus sampling) without reducing the CF detection rate. The expected advantages of the proposed method justify carrying out the necessary test development for use in a clinical validation study
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Prenatal maternal plasma DNA Screening for cystic fibrosis: A computer modelling study of Screening performance.
2017Co-Authors: Rw Old, Jonathan P. Bestwick, Nj WaldAbstract:Background: Prenatal cystic fibrosis (CF) Screening is currently based on determining the carrier status of both parents. We propose a new method based only on the analysis of DNA in maternal plasma. Methods: The method relies on the quantitative amplification of the CF gene to determine the percentage of DNA fragments in maternal plasma at targeted CF mutation sites that carry a CF mutation. Computer modelling was carried out to estimate the distributions of these percentages in pregnancies with and without a fetus affected with CF. This was done according to the number of DNA fragments counted and fetal fraction, using the 23 CF mutations recommended by the American College of Medical Genetics for parental carrier testing. Results: The estimated detection rate (sensitivity) is 70% (100% of those detected using the 23 mutations), the false-positive rate 0.002%, and the odds of being affected given a positive Screening result 14:1, compared with 70%, 0.12%, and 1:3, respectively, with current prenatal Screening based on parental carrier testing. Conclusions: Compared with current Screening practice based on parental carrier testing, the proposed method would substantially reduce the number of invasive diagnostic procedures (amniocentesis or chorionic villus sampling) without reducing the CF detection rate. The expected advantages of the proposed method justify carrying out the necessary test development for use in a clinical validation study.The author(s) declared that no grants were involved in supporting this work
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antenatal reflex DNA Screening for trisomy 18 and trisomy 13 in addition to down s syndrome
2016Co-Authors: Jonathan P. Bestwick, Nicholas J. WaldAbstract:ObjectiveAntenatal reflex DNA Screening for Down’s syndrome has a high Screening performance. We aimed to determine the performance of trisomy 18 and trisomy 13 reflex DNA Screening when added to D...
Anne Marie Comeau - One of the best experts on this subject based on the ideXlab platform.
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diagnostic dilemmas resulting from the immunoreactive trypsinogen DNA cystic fibrosis newborn Screening algorithm
2005Co-Authors: Richard B. Parad, Anne Marie ComeauAbstract:Objective To quantitate the proportion of infants identified through cystic fibrosis (CF) newborn Screening (NBS) by an immunoreactive trypsinogen (IRT)/DNA Screening algorithm who have an unclear diagnosis as defined by the findings of an elevated IRT level and either 1) 2 CF gene (CFTR) mutations detected and sweat chloride level Study design Using the 4-year cohort of CF-affected infants recently described by the Massachusetts CF NBS program, we identified and described the number of infants with the diagnostic characteristics (diagnostic dilemmas) aforementioned. Results Of infants with positive results on CF NBS who had 1 CFTR mutation detected and a borderline sweat chloride concentration, nearly 20% displayed a second CFTR mutation on further evaluation. Of all infants with positive CF NBS results considered affected with CF, 11% had a diagnosis that fell into 1 of the diagnostic dilemma categories aforementioned. Conclusions Four problematic diagnostic categories generated by CF NBS are defined. In the absence of data on the natural history of such infants, careful follow-up is recommended for infants in whom a definitive diagnosis is elusive.
Johannes Berkhof - One of the best experts on this subject based on the ideXlab platform.
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cost effectiveness of cervical cancer prevention in central and eastern europe and central asia
2013Co-Authors: Johannes Berkhof, Johannes A Bogaards, Erhan Demirel, Mireia Diaz, Monisha Sharma, Jane J KimAbstract:We studied the cost-effectiveness of cervical cancer prevention strategies in the Central and Eastern Europe and Central Asia (CEECA) region. The cost-effectiveness of human papillomavirus (HPV)16/18 vaccination of 12 year-old girls was calculated for 28 countries, under the assumption that vaccination prevents 70% of all cervical cancer cases and that cervical cancer and all-cause mortality rates are stable without vaccination. At three-dose vaccination costs of I$ 100 per vaccinated girl (currency 2005 international dollars), HPV16/18 vaccination was very cost-effective in 25 out of 28 countries using the country's gross domestic product (GDP) per capita as cost-effectiveness threshold (criterion by World Health Organization). A three-dose vaccination cost of I$ 100 is within the current range of vaccine costs in European immunization programs, and therefore our results indicate that HPV vaccination may be good value for money. To evaluate the cost-effectiveness of cervical cancer Screening combined with vaccination, we calibrated a published simulation model to HPV genotype data collected in Slovenia, Poland, and Georgia. The Screening interval was varied at 3, 6, and 10 years starting at age 25 or 30 and ending at age 60. In Slovenia and Poland, combined vaccination and 10-yearly HPV (DNA) Screening (vaccination coverage 70%, Screening coverage per round 70%) was very cost-effective when the cost of three-dose vaccination was I$ 100 per vaccinated girl. More intensive Screening was very cost-effective when the Screening coverage per round was 30% or 50%. In Georgia, 10-yearly Pap Screening was very cost-effective in unvaccinated women. Vaccination combined with 10-yearly HPV Screening was likely to be cost-effective if the three-dose vaccination cost was I$ 50 per vaccinated girl. To conclude, cervical cancer prevention strategies utilizing both HPV16/18 vaccination and HPV Screening are very cost-effective in countries with sufficient resources. In low-resource settings, low vaccine pricing is essential for strategies of combined vaccination and Screening to be cost-effective. This article forms part of a regional report entitled "Comprehensive Control of HPV Infections and Related Diseases in the Central and Eastern Europe and Central Asia Region" Vaccine Volume 31, Supplement 7, 2013. Updates of the progress in the field are presented in a separate monograph entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012.
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impact of vaccine protection against multiple hpv types on the cost effectiveness of cervical Screening
2012Co-Authors: Veerle M H Coupe, Johannes A Bogaards, Chris J L M Meijer, Johannes BerkhofAbstract:Cross-protection against non-HPV16/18 types and the emergence of broad spectrum vaccines protecting against multiple HPV types will influence the cost-effectiveness of future Screening. To assess this influence we used an individual-based simulation model describing the relation between 14 HPV types and cervical disease, allowing the occurrence of multiple type infections. Screening scenarios for vaccinated women were evaluated, firstly for HPV16/18 vaccination with partial cross-protection against HPV 31, 33, 45 and 58 and secondly, for broad spectrum vaccination against 5-13 HPV types. The vaccine-induced incidence reduction of type-specific infection was varied from 0 to 95% in the cross-protection setting and set at 100% in the setting of broad spectrum vaccines. Scenarios of either cytology or HPV DNA Screening were considered under varying lifetime number of Screening rounds. At a cost-effectiveness threshold of €20,000/QALY, four times HPV DNA Screening between 30 and 60 years was the selected scenario in addition to HPV16/18 vaccination, whether or not cross-protection was conferred (€6707 and €9994/QALY, respectively). In the absence of cross-protection, a fifth Screening round might be considered (ICER €22,967/QALY). In addition to broad spectrum vaccination, one screen during lifetime was cost-effective up to an 11-valent vaccine. If the vaccine-induced type-specific incidence reduction was lowered to 99%, one screen during lifetime was cost-effective even in addition to 13-valent vaccination. In conclusion, in a cohort of HPV16/18 vaccinated women, four rounds of HPV DNA Screening is cost-effective. One screen during lifetime remains cost-effective in addition to broad spectrum vaccination offering protection against many high-risk HPV types.
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human papillomavirus testing for the detection of high grade cervical intraepithelial neoplasia and cancer final results of the pobascam randomised controlled trial
2012Co-Authors: Dorien Rijkaart, Johannes Berkhof, Folkert J Van Kemenade, Lawrence Rozendaal, N W J Bulkmans, Danielle A M Heideman, Gemma G Kenter, Jack Cuzick, Peter J F Snijders, Chris J L M MeijerAbstract:Summary Background Human papillomavirus (HPV) testing is more sensitive for the detection of high-grade cervical lesions than is cytology, but detection of HPV by DNA Screening in two Screening rounds 5 years apart has not been assessed. The aim of this study was to assess whether HPV DNA testing in the first screen decreases detection of cervical intraepithelial neoplasia (CIN) grade 3 or worse, CIN grade 2 or worse, and cervical cancer in the second Screening. Methods In this randomised trial, women aged 29–56 years participating in the cervical Screening programme in the Netherlands were randomly assigned to receive HPV DNA (GP5+/6+-PCR method) and cytology co-testing or cytology testing alone, from January, 1999, to September, 2002. Randomisation (in a 1:1 ratio) was done with computer-generated random numbers after the cervical specimen had been taken. At the second Screening 5 years later, HPV DNA and cytology co-testing was done in both groups; researchers were masked to the patient's assignment. The primary endpoint was the number of CIN grade 3 or worse detected. Analysis was done by intention to screen. The trial is now finished and is registered, number ISRCTN20781131. Findings 22 420 women were randomly assigned to the intervention group and 22 518 to the control group; 19 999 in the intervention group and 20 106 in the control group were eligible for analysis at the first screen. At the second screen, 19 579 women in the intervention group and 19 731 in the control group were eligible, of whom 16 750 and 16 743, respectively, attended the second screen. In the second round, CIN grade 3 or worse was less common in the intervention group than in the control group (88 of 19 579 in the intervention group vs 122 of 19 731 in the control group; relative risk 0·73, 95% CI 0·55–0·96; p=0·023). Cervical cancer was also less common in the intervention group than in the control group (four of 19 579 in the intervention group vs 14 of 19 731; 0·29, 0·10–0·87; p=0·031). In the baseline round, detection of CIN grade 3 or worse did not differ significantly between groups (171 of 19 999 vs 150 of 20 106; 1·15, 0·92–1·43; p=0·239) but was significantly more common in women with normal cytology (34 of 19 286 vs 12 of 19 373; 2·85, 1·47–5·49; p=0·001). Furthermore, significantly more cases of CIN grade 2 or worse were detected in the intervention group than in the control group (267 of 19 999 vs 215 of 20 106; 1·25, 1·05–1·50; p=0·015). In the second screen, fewer HPV16-positive CIN grade 3 or worse were detected in the intervention group than in the control group (17 of 9481 vs 35 of 9354; 0·48, 0·27–0·85; p=0·012); detection of non-HPV16-positive CIN grade 3 or worse did not differ between groups (25 of 9481 vs 25 of 9354; 0·99, 0·57–1·72; p=1·00). The cumulative detection of CIN grade 3 or worse and CIN grade 2 or worse did not differ significantly between study arms, neither for the whole study group (CIN grade 3 or worse: 259 of 19 999 vs 272 of 20 106; 0·96, 0·81–1·14, p=0·631; CIN grade 2 or worse: 427 of 19 999 vs 399 of 20 106; 1·08, 0·94–1·24; p=0·292), nor for subgroups of women invited for the first time (CIN grade 3 or worse in women aged 29–33 years: 102 of 3139 vs 105 of 3128; 0·97, 0·74–1·27; CIN grade 2 or worse in women aged 29–33 years: 153 of 3139 vs 151 of 3128; 1·01, 0·81–1·26; CIN grade 3 or worse in women aged 34–56 years: 157 of 16 860 vs 167 of 16 978; 0·95, 0·76–1·18; CIN grade 2 or worse in women aged 34–56 years: 274 of 16 860 vs 248 of 16 978; 1·11, 0·94–1·32). Interpretation Implementation of HPV DNA testing in cervical Screening leads to earlier detection of clinically relevant CIN grade 2 or worse, which when adequately treated, improves protection against CIN grade 3 or worse and cervical cancer. Early detection of high-grade cervical legions caused by HPV16 was a major component of this benefit. Our results lend support to the use of HPV DNA testing for all women aged 29 years and older. Funding Zorg Onderzoek Nederland (Netherlands Organisation for Health Research and Development).
Ahti Anttila - One of the best experts on this subject based on the ideXlab platform.
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detection rates of precancerous and cancerous cervical lesions within one Screening round of primary human papillomavirus DNA testing prospective randomised trial in finland
2012Co-Authors: Maarit K Leinonen, Matti Hakama, Jussi Tarkkanen, Nea Malila, Pekka Juhani Nieminen, Stefan Lonnberg, Arun Pokhrel, Pirkkapekka Laurila, Ahti AnttilaAbstract:Objective To compare the detection rates of precancerous and cancerous cervical lesions by human papillomavirus (HPV) DNA testing and by conventional cytology Screening. Design 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. Setting Population based programme for cervical cancer Screening in Finland. Participants 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. Main outcome measures 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. Results 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. Conclusions 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. Trial registration International Standard Randomised Controlled Trial ISRCTN23885553.
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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
2010Co-Authors: Ahti Anttila, Laura Kotaniemitalonen, Maarit K Leinonen, Matti Hakama, Pekka Laurila, Jussi Tarkkanen, Nea Malila, Pekka NieminenAbstract:Objective 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. Design Randomised trial. Setting Population based Screening programme for cervical cancer in southern Finland in 2003-5. Participants 58 076 women, aged 30-60, invited to the routine population based Screening programme for cervical cancer. Interventions Primary HPV DNA test (hybrid capture II) with cytology triage if the result was positive or conventional cytological Screening (reference). Main outcome measures 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. Results 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. Conclusions 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. Trial registration Current Controlled Trials ISRCTN23885553.
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age specific evaluation of primary human papillomavirus Screening vs conventional cytology in a randomized setting
2009Co-Authors: Maarit K Leinonen, Laura Kotaniemitalonen, Pekka Laurila, Jussi Tarkkanen, Nea Malila, Pekka Nieminen, Ahti AnttilaAbstract: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). Conclusions 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. J Natl Cancer Inst 2009;101:1612–1623