Harms and benefits of screening to prevent cervical cancer

Harms and benefits of screening to prevent cervical cancer

Harms and benefits of screening to prevent cervical cancer Julian Peto and colleagues (July 17, p 249)1 present an excellent review of trends in cervic...

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Harms and benefits of screening to prevent cervical cancer Julian Peto and colleagues (July 17, p 249)1 present an excellent review of trends in cervical cancer mortality, and warn about the high rates observed in British women. However, both their projection of a hypothetical cervical cancer epidemic without screening and their calculated costs per life saved are an unscientific exercise in screening advocacy. First, Peto and colleagues assume that “by 1978, about 40% of cervical cancers in women younger than 40 years were already being prevented”. The selective reference to a single paper from 19852 turns a weak hypothesis, based on a short time series of 15-year cancer incidence (1963–78), into a fact. The actual report presents a time series of mortality of 50 years (1953–2002); figure 2 suggests little change before 1988. This finding is confirmed by another article3 referenced by Peto and colleagues, sadly omitting the fact that screening had had no impact on mortality before 1988. To obtain a 40% incidence reduction, screening needs to be very effective, with a high coverage and a good quality of Papanicolaou (Pap) testing. Opportunistic screening overscreens women at low risk, misses women at high risk, and shows a high variability in the quality of Pap test. Second, Peto and co-workers assume that cervical cancer risk in the future is a constant, unchanging one. The cohort born in 1952 was aged 16 years in 1968, the beginning of the sexual revolution. The advent of AIDS changed sexual behaviour radically. Female gonorrhoea dropped from about 25 000 at the end of the 1970s to 4000 in 1995.4 Peto and colleagues refer to the recent doubling of gonorrhoea. It increased again to 6000, which is less than a quarter of what it was 25 years ago; half of these new cases arise in black ethnic groups.4 Third, Peto and colleagues ignore the considerable costs of overdiagnosis and www.thelancet.com Vol 364 October 23, 2004

overtreatment, which are part of cervical cancer screening.5 1% of the women might be saved, at the costs of overdiagnosing and overtreatment in 40%. While The Lancet attacks the pharmaceutical industry for only giving the good news and withholding the bad news, the bad news of cancer screening is rarely published. That the screening industry still withholds correct information on both the benefits and the harms of cancer screening, stated as number needed to treat (mortality averted) and number needed to harm (additional diagnostic and therapeutic interventions generated), is unacceptable. Peto and co-workers correctly point to a serious failure of public health in the past: a failure to maintain sexual hygiene. But, they further assume that public health remains ignorant and impotent. A-B-C campaigns (Abstain, Be faithful, use Condoms) are not only for Africans; residents of the UK did make good use of sensible sexual health promotion, witnessed by the steep decline of sexually transmitted diseases. A rational cervical cancer prevention programme would be ABCD, with the added D for Detect those at high risk. Such a programme would save resources, prevent anxiety and unnecessary treatment in many women, improve primary prevention of all sexually transmitted diseases, including AIDS, and improve detection, surveillance, and treatment of women who are truly at risk.

Luc Bonneux [email protected] Belgian Healthcare Knowledge Center (KCE), Residence Palace, 10de verdieping, Wetstraat 155, B-1040 Brussels, Belgium 1

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Peto J, Gilham C, Fletcher O, Matthews FE. The cervical cancer epidemic that screening has prevented in the UK. Lancet 2004; 364: 249–56. Parkin DM, Nguyen-Dinh X, Day NE. The impact of screening on the incidence of cervical cancer in England and Wales. Br J Obstet Gynaecol 1985; 92: 150–57. Sasieni P, Adams J. Effect of screening on cervical cancer mortality in England and Wales: analysis of trends with an age period cohort model. BMJ 1999; 318: 1244–45. PHLS; DHSS & PS and the Scottish ISD(D)5 collaboration group. Sexually transmitted infections in the UK: new episodes seen at

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genitourinary medicine clinics, 1991 to 2001. London: Public Health Laboratory Service, 2002. Raffle AE, Alden B, Quinn M, Babb PJ, Brett MT. Outcomes of screening to prevent cancer: analysis of cumulative incidence of cervical abnormality and modelling of cases and deaths prevented. BMJ 2003; 326: 901.

Julian Peto and colleagues1 dismiss the fact that before relaunch of cervical cancer screening as a quality assured national programme, for every death prevented, 57 000 tests had to be done and almost 2000 women had abnormal screening results.2 Their article takes us back to the days when effectiveness of screening was seen as a yes/no question, and anyone advocating a more sophisticated approach was attacked as a heretic.3 We believe that the lessons of the past are crucially important, and they are being ignored. Men need to be protected from the damage that the first 20 years of cervical screening inflicted on women;4 haphazard prostate screening, not backed by evidence, is already being delivered to 5–10% of men older than age 50 years and is resulting in considerable harm. We agree with Peto and colleagues that the cervical screening programme is successful, and will be more so in the future, but their estimates of future deaths prevented are probably somewhat high because of their 1·67 inflation factor based on an outdated report.5 Peto and colleagues confuse past, present, and future benefit, make simplistic estimates of cervical intraepithelial neoplasia (CIN) progression, cost per life saved, and numbers needed to screen, and omit the possibility of screening related harm. The age period cohort model used by Peto and colleagues is essentially the same as that used by us and by others.6,7 That they dismiss the results of our analysis of true-life screening records in a quarter of a million women during 1976–96 is, therefore, strange. Their estimates do not contradict ours, since they relate to a different period and to younger women, who might have a higher risk than the women in our cohort. Their estimate of CIN progression is not

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robust, since it is based on national laboratory data for 1 year, during which time only about a third of women have a test. This method is no proxy for analysing cumulative detection rates as we have done. The number needed to screen to prevent a death will improve considerably in the future, but their estimate is not reliable; it ignores competing mortality, assumes 100% uptake of, and 100% protection by, screening, and is based on an inflated estimate of lifetime risk. Cost-effectiveness will also improve, but it is not realistic to use an historical National Audit Office estimate of annual national cost and relate this to deaths prevented in 2030. The article and associated media reports created the impression that already 5000 fewer cervical cancer deaths are occurring annually because of screening, yet the article is describing estimates for 2030 not 2004. The statistical models are based on small numbers of cases and deaths in younger women before national call and recall began in 1988. Whether the higher rates in these younger women represent a shifting of the curve of agespecific rates to the left because of earlier onset of sexual activity, or whether, as Peto and colleagues assume, it translates to equivalent multiplication of risk at every age for that cohort, is unknown. Their projections extend 50 years ahead on only 35 years’ data, which inevitably involves uncertainty. Their assumption of 40% higher rates before 1988 without screening does not fit the facts about previous trends, improvements in survival, or contemporary uptake. It shifts the cumulative lifetime risk from the model we used8 to the higher rates shown by the dotted line in figure 3 of the article. Our conclusion is that it is hard to know who is more shortsighted, Peto and colleagues for misinterpreting the message of our outcomes analysis, or The Lancet for publishing an unbalanced article despite our detailed referees’ comments. Cervical screening is remarkably successful now and will be more so in the 1484

future. In the past, when there was haphazard screening without policy or standards and cervical cancer was a rare disease, it did a considerable amount of harm, as well as some good, at very high cost per cervical cancer death avoided. We clearly have not learned from the past, since the same mistake is being repeated with prostate screening.

*A E Raffle, M Quinn angela.raffl[email protected] *Bristol North Primary Care Trust, King Square House, Bristol BS2 8EE, UK (AER); and National Cancer Intelligence Centre, Office for National Statistics, London, UK (MQ) 1

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Peto J, Gilham C, Fletcher O, Matthews FE. The cervical cancer epidemic that screening has prevented in the UK. Lancet 2004; 364: 249–56. Raffle AE, Alden B, Quinn M, Babb PJ, Brett MT. Outcomes of screening to prevent cancer: analysis of cumulative incidence of cervical abnormality and modelling of cases and deaths prevented. BMJ 2003; 326: 901. Slater D. The cervical screening muddle. Lancet 1998; 351: 1130. Frankel S, Smith GD, Donovan J, Neal D. Screening for prostate cancer. Lancet 2003; 361: 1122–28. Parkin DM, Nguyen-Dinh X, Day NE. The impact of screening on the incidence of cervical cancer in England and Wales. Br J Obstet Gynaecol 1985; 92: 150–57. Quinn M, Babb P, Jones J, Allen E. Effect of screening on incidence of and mortality from cancer of cervix in England: evaluation based on routinely collected statistics. BMJ 1999; 318: 904–08. Sasieni P, Adams J. Effect of screening on cervical cancer mortality in England and Wales: analysis of trends with an age period cohort model. BMJ 1999; 318: 1244–45. Quinn M, Babb P, Brock A, Kirby L, Jones J. Cancer trends in England and Wales. London: Office for National Statistics, 2001.

Julian Peto and colleagues1 provide evidence of the true benefits of the UK cervical cancer screening programme.A central feature of their analysis is to compare observed and expected occurrence of cervical cancer with a simple age and birth cohort model. One of their three crucial assumptions concerns the number of cases already being prevented by screening by 1988, failure to allow for which in similar studies could have underestimated the real benefits of screening reorganisation since that time.2,3 However, their analysis does not highlight period effects, which might indicate subgroups of the population in

whom further screening benefits might be obtained. As our figure shows, using data obtained from the Office for National Statistics, overall mortality attributed to cancer of the uterine cervix declined in England and Wales between 1950 and 2000, but there are clear differences by marital status; ageadjusted mortality (at age 15–74 years where the data are most accurate) among the ever married declined substantially, but in the never married it has increased steadily since the 1970s until the most recent past. We had to use this method of analysis because of the aggregated form in which the Office for National Statistics made available the data to maintain confidentiality. We could not examine detailed age-specific rates over the past 10 years. However, detailed inspection is unlikely to alter the finding of a striking difference in trends for single and other women. Peto and colleagues provide refined estimates of the gap between observed and predicted mortality over the past decade.2,3 Their analysis suggests that overall reductions in (sexual) risk behaviours, or the reorganisation of the screening programme, or both, are having a beneficial effect. We believe the divergent trends suggest that the balance of those forces among single women is producing a different outcome. After review of the marital status cervical cancer mortality pattern to 1990, we concluded that profound changes and remaining differences in the pattern of sexual risk behaviour most probably accounted for the observations to that time, and that differential participation in the screening programme, patterns of hysterectomy, or other risk factors played a much smaller part.4 We are unable to find data for current participation in the UK screening programme by marital status. However, before reorganisation of the programme this issue received a considerable amount of attention.4 Certainly, sexual risk behaviours differ by marital status and these differences could now be more pronounced than www.thelancet.com Vol 364 October 23, 2004