- Email: [email protected]
The cervical screening muddle
CORRESPONDENCE
Death by incompetence,2 at which time an inefficient cervical screening programme was rightly put to shame. Although making some reasonable points about misunderstanding of falsenegative and false-positive results, you do not explain that Kent and Canterbury was an exception, publicly identified because of the openness of quality control in this field of medicine. Standards in the programme have improved beyond recognition since the 1980s, although screening had been introduced many years before. Invasive cervical cancer is rare in UK: so it should be when screening aims, and largely succeeds, in the detection and treatment of precancerous disorders which carry a risk of the subsequent development of invasion. Although incidence of invasive cancer has never exceeded 30 per 100 000 women, there was evidence in the early 1980s that incidence was increasing in women born since 1940, that mortality had doubled within 10 years in women aged under 35, and that the frequency of high-grade dyskaryosis was increasing in the same cohort.3 Improved screening has been highly effective for a generation of women who grew up in a climate of greater sexual freedom. We have reported a 57% fall in the incidence of invasive cervical cancer (excluding screen detected stage IA1 cancers) in women born in 1940–54 while they aged from an average of 37·5–47·5 years, the very decade of life when the incidence of symptomatic cancer would be expected to increase most steeply, reaching a peak in women in their late 40s.4 Unlike the situation in Kent and Canterbury, the Southampton experience was not exceptional. The overall incidence of invasive cervical cancer had declined in Southampton from 16·3 to 11·5 per 100 000 women, which is similar to the figures for England as a whole,5 during a period when incidence and mortality were predicted to increase unless screening became more effective. Let us at least have some credit for responding so successfully to the stringent criticism in your 1985 editorial. Amanda Herbert Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK 1 2 3
4
Editorial. The screening muddle. Lancet 1998; 351: 459. Editorial. Cancer of the cervix: death by incompetence. Lancet 1985; ii: 363–64. Osmond C, Gardner MJ, Acheson ED, Adelstein AM. Trends in Cancer Mortality. Analyses by Period of Birth and Death DH1, No 11. HM Stationery Office 1988. Herbert A, Bryant TN, Campbell MJ, Smith J. Investigation of the effect of occult invasive cancer on progress towards
1130
5
successful cervical screening. J Med Screen 1998 (in press). Population and health Monitor 96/2. London: Office for National Statistics, 1996.
Sir—Both Angela Raffle (Jan 24, p 297)1 and your editorial2 highlight the issue of false-negative smear results in the cervical-screening programme, but neither makes the crucial distinction between unavoidable false-negative smears, which are an innate part of the programme, and ones that result from negligent practice. This distinction is further complicated by lawyers who propagate the mistaken belief that cervical screening has a zero error standard and that any error is therefore negligent. Few, if any, legal actions for falsenegative smears have been tested in an English court, and in many instances the accepted standard of proof for negligence is absent. Specifically, that a false-negative smear should not be deemed negligent if it can be shown that the screening had been undertaken with reasonable skill and care. Worthy of particular emphasis is the absence of a legal necessity for reasonable skill and care to equate with perfection.3 Your editorial also addresses the current void in public understanding with regard to false-negative smears. Sir William Wells4 tackled this issue in his first recommendation in the review of cervical-screening services at Kent and Canterbury Hospitals.4 The review states the necessity for a national strategy to provide greater insight into the smear test; particularly, that any screening test, by definition, is imperfect so false reports are bound to occur. Recent guidance emphasises that smear takers have a duty to ensure that women give informed consent for a cervical smear.5 Furthermore, consent could be deemed invalid, if the possibility of false reports has not been explained. Although formal written consent for a smear is rarely obtained, perhaps in the current climate it is now desirable and should be supported by a new national information sheet for patients. The public expect a guarantee that cervical screening will prevent and identify all cases of cervical cancer. The only guarantee on offer, however, is that some cases will not be prevented and that some cases will be missed. The public can be reassured that the inherent fallibilities of cervical screening are more than countered by a high uptake of regular smears, which is indicated by the falling incidence of cervical cancer. Compensation for invasive cervical cancer resulting from any type of falsenegative smear is currently about
£250 000. Such settlements represent a sizeable indirect cost to the screening programme and are adding to the increasing cost-ineffectiveness highlighted by Raffle. A better public understanding of false-negative smears will reduce the current escalation of inappropriate claims for negligence. Whether or not non-negligent cases should be covered by no fault compensation is open for debate. David Slater Department of Histopathology, Rotherham District Hospital, Rotherham Hospitals NHS Trust, Rotherham S60 2UD, UK 1 2 3
4
5
Raffle AE. New tests in cervical screening. Lancet 1998; 351: 297. Editorial. The screening muddle. Lancet 1998; 351: 459–60. Slater DN. False-negative cervical smears: medico-legal fallacies and suggested remedies. Cytopathology (in press). Wells W. Chairman NHS Executive South Thames. Review of cervical screening services at Kent and Canterbury Hospitals NHS Trust. NHS Executive South Thames, Oct, 1997: 1–62. Patnick J, Winder R. A practical guide for health authorities. NHSCSP publication no 7. Sheffield: NHSCSP Publications, Oct, 1997: 34.
Sir—Your editorial1 did not discuss that there is potential for harm in screening programmes other than to the screened. Health information providers are of crucial importance and have ethical responsibilities. They are the windowdressers in the shop window of screening programmes—a reversal of the usual doctor/patient relationship. They aim for a target of 70% uptake to make the programme work. Information providers have to tread an impossibly fine line, which, when it crumbles, ultimately damages not only the health of those with false-negatives and false-positive results, but also of their carers who share their psychological traumas and cope with their physical needs. Ring-fenced funding is no longer available. The stresses that can result from cut-backs in departments, not only damage the health of the screened but also that of the members of the professional screening team who see the quality of their department eroded and the threats or realities of litigation looming. We are now in the collaborative Calman era of commissioning and provision of cancer services where communication and provision of clear information to patients and their families, and consideration of psychological aspects, are written into the general principles.2 By contrast, the screening programme was devised and imposed 10 years ago solely by health
THE LANCET • Vol 351 • April 11, 1998
CORRESPONDENCE
Hazel Thornton
congenital hearing loss will generate controversy and suspicion in a community whose European forefathers had good cause to be wary of geneticists’ motives. Those who are concerned can be reassured that the most immediate and important outcome of this development will be that families can be given accurate scientifically based risks of recurrence rather than widely varying estimates.
Saionara, 31 Regent Street, Rowhedge, Colchester, Essex CO5 7EA, UK
*M Parker, H Fortnum, I D Young
professionals in the Forrest era,3 when even the expert witnesses called were bound to secrecy.4 As Barbara Thomas in the NHS Breast Screening Programme Review 1997 states, “but we must always be looking forward”. It is time we planned to use these resources economically, equitably, efficiently, and effectively.5
1 2
3
4
5
Editorial. The screening muddle. Lancet 1998; 351: 459. Calman K, Hine D. A policy framework for commissioning cancer services. Prepared by an expert advisory group on cancer to the chief medical officers of England and Wales. May, 1994. London: HM Stationery Office, 1994. Forrest P. Breast cancer screening. Report to the health ministers of England, Wales, Scotland and Northern Ireland. London: HM Stationery Office, 1986. Skrabanek P. The debate over mass mammography in Britain: the case against. BMJ 1988; 297: 971–72. Thornton H. Economy, equity, efficiency, effectiveness: the NHS breast screening programme from the patient’s perspective. Clinician Manag 1998 (in press).
Connexin-26 mutations and inherited deafness Sir—The studies by Xavier Estivill and colleagues and Nicholas Lench and coworkers (Feb 7, pp 394, 415)1,2 show that mutations in the connexin-26 gene make a major contribution to nonsyndromal sensorineural hearing loss. In an accompanying commentary, William Reardon (p 383)3 makes the point that hitherto genetic counselling for families with one affected child has relied upon empirical data and goes on to imply that standard practice is to offer a sibling recurrence risk of 1 in 10. Our experience, based on a survey of clinical geneticists in the UK, enables us to comment on the extent to which this advice is offered uniformly and consistently. 63 of 78 UK clinical geneticists responded to a questionnaire on the local genetic services available for families with hearing-impaired children. Respondents were asked to indicate what recurrence risk they would give to the parents of a single affected child and the degree of variation in replies was striking: it ranged from 1 in 4 to 1 in 20. The most common figures quoted were 1 in 10 (44%) and 1 in 6 (20%). Such a degree of disparity among a professional group is disturbing and serves to emphasise the potential value of connexin-26 mutation analysis for accurate genetic counselling. This discovery of the most common cause of
THE LANCET • Vol 351 • April 11, 1998
MRC Institute for Hearing Research, University of Nottingham, Nottingham; and Centre for Medical Genetics, City Hospital, Nottingham, NG5 1PB, UK 1
2
3
Estivill X, Fortina P, Surrey S, et al. Connexin-26 mutations in sporadic and inherited sensorineural deafness. Lancet 1998; 351: 394–98. Lench N, Housemann M, Newton V, Van Camp G, Mueller R. Connexin-26 mutations in sporadic non-syndromal sensorineural deafness. Lancet 1998; 351: 415. Reardon W. Connexin-26 gene mutation and autosomal recessive deafness. Lancet 1998; 351: 383–84.
Molecular genetic tests in surgical management of familial adenomatous polyposis Sir—D G R Evans and colleagues (Dec 13, p 1777)1 raise important questions about the implications of the results of our earlier study..2 Our report on 225 polyposis patients with colectomy and ileorectal anastomosis showed that half the patients would need rectal excision later in life because of uncontrollable polyps or rectal cancer. Earlier work indicated that the course of the disease is correlated with the site of mutations within the APC gene.3,4 For example, families with polyposis due to mutations located in a region distal to codon 1250, especially mutations at codon 1309, are characterised both by the development of thousands of polyps, and by early age of onset of disease.3 In the same way, it might be expected that patients with polyposis caused by mutations associated with a severe phenotype are at higher risk of rectal excision after ileorectal anastomosis. Our study confirmed that, both by years of follow-up as well as by age, patients with mutations in this region had a substantially increased risk of rectal excision. At the time we completed our study (1995), the recorded mutations in the APC gene were limited to exons 1–14 and the 5' part of exon 15. The mutations we reported were also at the
5' part of codon 1462. Later on, mutations were reported at the 3' part of exon 15.4,5 Many of the families harbouring such mutations, including those described by Evans and colleagues, show an atypical phenotype, which clearly differs from the phenotype of families with mutations located between codon 1250 and 1462. We agree with Evans that decisions about surgical management of polyposis patients should not be based solely on the site of the mutations, which is why we said that “the results of DNA-testing in relation to the phenotypic expression in the patient and family could be helpful in surgical decision making”.2 Thus we believe that a patient with a rectum free of adenomas from a family with polyposis due to a codon 1309 mutation that includes several relatives with a severe phenotype of polyposis is a good candidate for restorative protocolectomy, especially with the good results of this type of surgery. Of course, after the patient has been fully informed about the natural history of the disease and the pros and cons of the main surgical options, the final decision lies with the patient. *Hans F A Vasen, Rob B van der Luijt, Carli Tops, J Frederik M Slors *Netherlands Foundation for the Detection of Hereditary Tumours, 2333 AA, Leiden, Netherlands; Department of Human Genetics and Clinical Genetics at the Universities of Leiden and Utrecht; and the Department of Surgery, Amsterdam Medical Centre, Amsterdam 1
2
3
4
5
Evans DGR, Hill J, Dudding T, Burn J, Maher ER. Molecular genetic tests in surgical management of familial adenomatous polyposis. Lancet 1998; 350: 1777. Vasen HFA, van der Luijt RB, Slors JFM, et al. Molecular genetic tests as a guide to surgical management of familial adenomatous polyposis. Lancet 1996; 348: 433–35. Caspari R, Friedl W, Mandl M, et al. Familial adenomatous polyposis: mutation at codon 1309 and early onset of colon cancer. Lancet 1994; 343: 629–32. Scott RJ, van der Luijt RB, Spycher M, et al. Novel germline APC mutation in a large familial adenomatous polyposis kindred displaying variables phenotypes. Gut 1995; 36: 731–36. Friedl W, Meuschel S, Caspari R, et al. Attenuated familial adenomatous polyposis due to a mutation in the 3' part of the APC gene. A clue for understanding the function of the APC protein. Hum Genet 1996; 97: 579–84.
Authors’ reply Sir—Hans Vasen and colleagues acknowledge the continued evolution of our knowledge of the relation between specific mutations in the APC
1131
Death by incompetence,2 at which time an inefficient cervical screening programme was rightly put to shame. Although making some reasonable points about misunderstanding of falsenegative and false-positive results, you do not explain that Kent and Canterbury was an exception, publicly identified because of the openness of quality control in this field of medicine. Standards in the programme have improved beyond recognition since the 1980s, although screening had been introduced many years before. Invasive cervical cancer is rare in UK: so it should be when screening aims, and largely succeeds, in the detection and treatment of precancerous disorders which carry a risk of the subsequent development of invasion. Although incidence of invasive cancer has never exceeded 30 per 100 000 women, there was evidence in the early 1980s that incidence was increasing in women born since 1940, that mortality had doubled within 10 years in women aged under 35, and that the frequency of high-grade dyskaryosis was increasing in the same cohort.3 Improved screening has been highly effective for a generation of women who grew up in a climate of greater sexual freedom. We have reported a 57% fall in the incidence of invasive cervical cancer (excluding screen detected stage IA1 cancers) in women born in 1940–54 while they aged from an average of 37·5–47·5 years, the very decade of life when the incidence of symptomatic cancer would be expected to increase most steeply, reaching a peak in women in their late 40s.4 Unlike the situation in Kent and Canterbury, the Southampton experience was not exceptional. The overall incidence of invasive cervical cancer had declined in Southampton from 16·3 to 11·5 per 100 000 women, which is similar to the figures for England as a whole,5 during a period when incidence and mortality were predicted to increase unless screening became more effective. Let us at least have some credit for responding so successfully to the stringent criticism in your 1985 editorial. Amanda Herbert Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK 1 2 3
4
Editorial. The screening muddle. Lancet 1998; 351: 459. Editorial. Cancer of the cervix: death by incompetence. Lancet 1985; ii: 363–64. Osmond C, Gardner MJ, Acheson ED, Adelstein AM. Trends in Cancer Mortality. Analyses by Period of Birth and Death DH1, No 11. HM Stationery Office 1988. Herbert A, Bryant TN, Campbell MJ, Smith J. Investigation of the effect of occult invasive cancer on progress towards
1130
5
successful cervical screening. J Med Screen 1998 (in press). Population and health Monitor 96/2. London: Office for National Statistics, 1996.
Sir—Both Angela Raffle (Jan 24, p 297)1 and your editorial2 highlight the issue of false-negative smear results in the cervical-screening programme, but neither makes the crucial distinction between unavoidable false-negative smears, which are an innate part of the programme, and ones that result from negligent practice. This distinction is further complicated by lawyers who propagate the mistaken belief that cervical screening has a zero error standard and that any error is therefore negligent. Few, if any, legal actions for falsenegative smears have been tested in an English court, and in many instances the accepted standard of proof for negligence is absent. Specifically, that a false-negative smear should not be deemed negligent if it can be shown that the screening had been undertaken with reasonable skill and care. Worthy of particular emphasis is the absence of a legal necessity for reasonable skill and care to equate with perfection.3 Your editorial also addresses the current void in public understanding with regard to false-negative smears. Sir William Wells4 tackled this issue in his first recommendation in the review of cervical-screening services at Kent and Canterbury Hospitals.4 The review states the necessity for a national strategy to provide greater insight into the smear test; particularly, that any screening test, by definition, is imperfect so false reports are bound to occur. Recent guidance emphasises that smear takers have a duty to ensure that women give informed consent for a cervical smear.5 Furthermore, consent could be deemed invalid, if the possibility of false reports has not been explained. Although formal written consent for a smear is rarely obtained, perhaps in the current climate it is now desirable and should be supported by a new national information sheet for patients. The public expect a guarantee that cervical screening will prevent and identify all cases of cervical cancer. The only guarantee on offer, however, is that some cases will not be prevented and that some cases will be missed. The public can be reassured that the inherent fallibilities of cervical screening are more than countered by a high uptake of regular smears, which is indicated by the falling incidence of cervical cancer. Compensation for invasive cervical cancer resulting from any type of falsenegative smear is currently about
£250 000. Such settlements represent a sizeable indirect cost to the screening programme and are adding to the increasing cost-ineffectiveness highlighted by Raffle. A better public understanding of false-negative smears will reduce the current escalation of inappropriate claims for negligence. Whether or not non-negligent cases should be covered by no fault compensation is open for debate. David Slater Department of Histopathology, Rotherham District Hospital, Rotherham Hospitals NHS Trust, Rotherham S60 2UD, UK 1 2 3
4
5
Raffle AE. New tests in cervical screening. Lancet 1998; 351: 297. Editorial. The screening muddle. Lancet 1998; 351: 459–60. Slater DN. False-negative cervical smears: medico-legal fallacies and suggested remedies. Cytopathology (in press). Wells W. Chairman NHS Executive South Thames. Review of cervical screening services at Kent and Canterbury Hospitals NHS Trust. NHS Executive South Thames, Oct, 1997: 1–62. Patnick J, Winder R. A practical guide for health authorities. NHSCSP publication no 7. Sheffield: NHSCSP Publications, Oct, 1997: 34.
Sir—Your editorial1 did not discuss that there is potential for harm in screening programmes other than to the screened. Health information providers are of crucial importance and have ethical responsibilities. They are the windowdressers in the shop window of screening programmes—a reversal of the usual doctor/patient relationship. They aim for a target of 70% uptake to make the programme work. Information providers have to tread an impossibly fine line, which, when it crumbles, ultimately damages not only the health of those with false-negatives and false-positive results, but also of their carers who share their psychological traumas and cope with their physical needs. Ring-fenced funding is no longer available. The stresses that can result from cut-backs in departments, not only damage the health of the screened but also that of the members of the professional screening team who see the quality of their department eroded and the threats or realities of litigation looming. We are now in the collaborative Calman era of commissioning and provision of cancer services where communication and provision of clear information to patients and their families, and consideration of psychological aspects, are written into the general principles.2 By contrast, the screening programme was devised and imposed 10 years ago solely by health
THE LANCET • Vol 351 • April 11, 1998
CORRESPONDENCE
Hazel Thornton
congenital hearing loss will generate controversy and suspicion in a community whose European forefathers had good cause to be wary of geneticists’ motives. Those who are concerned can be reassured that the most immediate and important outcome of this development will be that families can be given accurate scientifically based risks of recurrence rather than widely varying estimates.
Saionara, 31 Regent Street, Rowhedge, Colchester, Essex CO5 7EA, UK
*M Parker, H Fortnum, I D Young
professionals in the Forrest era,3 when even the expert witnesses called were bound to secrecy.4 As Barbara Thomas in the NHS Breast Screening Programme Review 1997 states, “but we must always be looking forward”. It is time we planned to use these resources economically, equitably, efficiently, and effectively.5
1 2
3
4
5
Editorial. The screening muddle. Lancet 1998; 351: 459. Calman K, Hine D. A policy framework for commissioning cancer services. Prepared by an expert advisory group on cancer to the chief medical officers of England and Wales. May, 1994. London: HM Stationery Office, 1994. Forrest P. Breast cancer screening. Report to the health ministers of England, Wales, Scotland and Northern Ireland. London: HM Stationery Office, 1986. Skrabanek P. The debate over mass mammography in Britain: the case against. BMJ 1988; 297: 971–72. Thornton H. Economy, equity, efficiency, effectiveness: the NHS breast screening programme from the patient’s perspective. Clinician Manag 1998 (in press).
Connexin-26 mutations and inherited deafness Sir—The studies by Xavier Estivill and colleagues and Nicholas Lench and coworkers (Feb 7, pp 394, 415)1,2 show that mutations in the connexin-26 gene make a major contribution to nonsyndromal sensorineural hearing loss. In an accompanying commentary, William Reardon (p 383)3 makes the point that hitherto genetic counselling for families with one affected child has relied upon empirical data and goes on to imply that standard practice is to offer a sibling recurrence risk of 1 in 10. Our experience, based on a survey of clinical geneticists in the UK, enables us to comment on the extent to which this advice is offered uniformly and consistently. 63 of 78 UK clinical geneticists responded to a questionnaire on the local genetic services available for families with hearing-impaired children. Respondents were asked to indicate what recurrence risk they would give to the parents of a single affected child and the degree of variation in replies was striking: it ranged from 1 in 4 to 1 in 20. The most common figures quoted were 1 in 10 (44%) and 1 in 6 (20%). Such a degree of disparity among a professional group is disturbing and serves to emphasise the potential value of connexin-26 mutation analysis for accurate genetic counselling. This discovery of the most common cause of
THE LANCET • Vol 351 • April 11, 1998
MRC Institute for Hearing Research, University of Nottingham, Nottingham; and Centre for Medical Genetics, City Hospital, Nottingham, NG5 1PB, UK 1
2
3
Estivill X, Fortina P, Surrey S, et al. Connexin-26 mutations in sporadic and inherited sensorineural deafness. Lancet 1998; 351: 394–98. Lench N, Housemann M, Newton V, Van Camp G, Mueller R. Connexin-26 mutations in sporadic non-syndromal sensorineural deafness. Lancet 1998; 351: 415. Reardon W. Connexin-26 gene mutation and autosomal recessive deafness. Lancet 1998; 351: 383–84.
Molecular genetic tests in surgical management of familial adenomatous polyposis Sir—D G R Evans and colleagues (Dec 13, p 1777)1 raise important questions about the implications of the results of our earlier study..2 Our report on 225 polyposis patients with colectomy and ileorectal anastomosis showed that half the patients would need rectal excision later in life because of uncontrollable polyps or rectal cancer. Earlier work indicated that the course of the disease is correlated with the site of mutations within the APC gene.3,4 For example, families with polyposis due to mutations located in a region distal to codon 1250, especially mutations at codon 1309, are characterised both by the development of thousands of polyps, and by early age of onset of disease.3 In the same way, it might be expected that patients with polyposis caused by mutations associated with a severe phenotype are at higher risk of rectal excision after ileorectal anastomosis. Our study confirmed that, both by years of follow-up as well as by age, patients with mutations in this region had a substantially increased risk of rectal excision. At the time we completed our study (1995), the recorded mutations in the APC gene were limited to exons 1–14 and the 5' part of exon 15. The mutations we reported were also at the
5' part of codon 1462. Later on, mutations were reported at the 3' part of exon 15.4,5 Many of the families harbouring such mutations, including those described by Evans and colleagues, show an atypical phenotype, which clearly differs from the phenotype of families with mutations located between codon 1250 and 1462. We agree with Evans that decisions about surgical management of polyposis patients should not be based solely on the site of the mutations, which is why we said that “the results of DNA-testing in relation to the phenotypic expression in the patient and family could be helpful in surgical decision making”.2 Thus we believe that a patient with a rectum free of adenomas from a family with polyposis due to a codon 1309 mutation that includes several relatives with a severe phenotype of polyposis is a good candidate for restorative protocolectomy, especially with the good results of this type of surgery. Of course, after the patient has been fully informed about the natural history of the disease and the pros and cons of the main surgical options, the final decision lies with the patient. *Hans F A Vasen, Rob B van der Luijt, Carli Tops, J Frederik M Slors *Netherlands Foundation for the Detection of Hereditary Tumours, 2333 AA, Leiden, Netherlands; Department of Human Genetics and Clinical Genetics at the Universities of Leiden and Utrecht; and the Department of Surgery, Amsterdam Medical Centre, Amsterdam 1
2
3
4
5
Evans DGR, Hill J, Dudding T, Burn J, Maher ER. Molecular genetic tests in surgical management of familial adenomatous polyposis. Lancet 1998; 350: 1777. Vasen HFA, van der Luijt RB, Slors JFM, et al. Molecular genetic tests as a guide to surgical management of familial adenomatous polyposis. Lancet 1996; 348: 433–35. Caspari R, Friedl W, Mandl M, et al. Familial adenomatous polyposis: mutation at codon 1309 and early onset of colon cancer. Lancet 1994; 343: 629–32. Scott RJ, van der Luijt RB, Spycher M, et al. Novel germline APC mutation in a large familial adenomatous polyposis kindred displaying variables phenotypes. Gut 1995; 36: 731–36. Friedl W, Meuschel S, Caspari R, et al. Attenuated familial adenomatous polyposis due to a mutation in the 3' part of the APC gene. A clue for understanding the function of the APC protein. Hum Genet 1996; 97: 579–84.
Authors’ reply Sir—Hans Vasen and colleagues acknowledge the continued evolution of our knowledge of the relation between specific mutations in the APC
1131