Cervical screening in the UK and laboratory quality control in the context of the 2007 European guidelines

The first part of this article will provide an overview of cervical cancer screening in the UK during the years before, during and after the introduction of a highly successful centrally organised cervical screening programme in 1988: since then the incidence of invasive cervical cancer has fallen by more than 40%. Screening was introduced in a background of opportunistic screening with poor quality control during a period of time when risk of disease was increasing, which will be demonstrated by national registrations of carcinoma in situ as well as invasive cancer. The programme is still facing new challenges and has recently recorded falling screening coverage in younger women, the causes of which have yet to be established. Liquid-based cytology is in the process of being rolled out nationally but high-risk human papillomavirus testing has yet to be introduced into the National Health Service (NHS) programme. Lessons from our experience may be relevant to countries introducing and maintaining organised programmes elsewhere under similar circumstances. The second part of the article will consider laboratory quality control as practiced in the UK and as recommended in the second edition of the European Guidelines for Quality Assurance in Cervical Cancer Screening. These evidence-based guidelines provide recommendations for organising and monitoring quality control as well as for introducing new technology and standardising terminology, which are equally relevant for new and existing programmes. Invasive cancer audit may highlight areas where procedures could be improved in any programme but also can also demonstrate the effectiveness of screening.     

Cervical cancer screening in Serbia

Cervical cancer is the second most common female malignancy in Serbia, after breast cancer, with 1089 new registered cases and an age-standardized incidence rate of 27.2 per 100,000 women in 2002. It is the fourth leading cause of cancer death with 452 deaths and an age-standardized death rate of 7.2 per 100,000 women. Compared with other European countries, the incidence of cervical cancer in Central Serbia is the highest. Regional differences in incidence are pronounced in Serbia with the lowest age-standardized incidence rate (16.6 per 100,000 women) registered in the Macvanski region and the highest in eastern Serbia and the region of Belgrade where the rates are double at 32.5-38.1 per 100,000 women. Cervical cancer prevention in Serbia has relied on opportunistic screening that is characterized by high coverage in younger and low coverage in middle-aged and older women. Screening of selected groups of women employed in large companies is performed annually by many regional hospitals but this approach has little effect on morbidity and mortality. Recently, the Ministry of Health nominated an Expert Group to develop and implement a national cervical cancer screening program. A number of pilot projects have been undertaken with the results used for development of a national programme for cervical cancer screening. This is expected to be finalized in 2007, and launched over a 3-years period in order to cover all women aged 25-64 in entire Serbia.     

Criteria for organized cervical screening programs. Special emphasis on The Netherlands program

Based on the criteria of Wilson and Jungner and experiences in the population-based organized cervical screening program in the Netherlands, conditions for efficient and effective population screening for cervical cancer are described. The purpose of this paper is to determine if these criteria are met for cervical cancer screening and to give recommendations for improvement. Cervical cancer is still an important health problem; the present incidence reflects both background risk and screening activity during previous decades. A positive effect of screening is reached because of the long development time of the disease and the ability of the Pap smear test to detect precancer and early, symptomatic disease. Considerable reduction in the incidence and mortality of cervical cancers can be reached if all women attend and all detected lesions are adequately followed up. Common terminology and classification criteria for histology and cytology should be used. Whether newly developed techniques that may improve or replace cytology can be used in screening programs should be a multidisciplinary decision after clinical trials have given evidence-based information on the performance, cost-effectiveness and need of these techniques. When cervical cancer screening is undertaken, it should be offered in organized programs at the medical level closest to the patients, the general practitioner. High compliance is the most important factor in reducing cervical cancer incidence. Quality control and assurance must be performed at all levels. In the case of limited resources, the program should use a five-year interval and concentrate on the age range 25-60 years, with special attention to women who have never been screened or were screened > 10 years previously. Evaluation of medical and organizational aspects is mandatory. Cooperation between all involved parties is a prerequisite of creating a successful screening program.     

Cervical cancer screening programs: summary of the 1982. Canadian task force report.

The Canadian Task Force on Cervical Cancer Screening Programs, which produced its first report in 1976, was reconvened by the Department of National Health and Welfare in 1980 in response to concerns expressed about the significance of new data, changing sociosexual patterns and wide variations in the implementation of the 1976 recommendations. This article is a summary of the 1982 task force report. In addition to updates of the 1976 material new sections appear on groups at risk, mathematical models of screening, quality control in screening programs, cytologic screening coverage of the Canadian population and management of patients with abnormal smears. The 1982 recommendations deal with frequency of screening, laboratory quality control and follow-up mechanisms. The task force concludes that measures to improve the quality and sensitivity of screening programs and to include women who have never been screened will be more effective in reducing mortality from carcinoma of the cervix than will attempts to increase the frequency of screening. The task force views as unnecessary the annual screening of women over 35 years of age whose previous smears have been normal. Since younger women are sexually more active and tend to have more than one sexual partner they are at high risk. Therefore, the task force recommends annual screening for sexually active women aged 18 to 35 years. Physicians, health care professionals and government health agencies have a role to play in informing women about the recommended intervals for cervical smears and ensuring that screening programs of adequate quality are available. Although women are primarily responsible for entering and continuing in such a program, government-sponsored registries are essential if the full potential of cervical smear programs is to be realized.     

External quality assurance for cervical cytology in developing countries. Experience in Peru and Nicaragua

Given interest from the professionals concerned, an external quality assurance scheme for cervical cytology can successfully be introduced in developing countries. This is a very important precondition if screening programs are to be expanded and decreases in mortality from cervical cancer are to occur in developing countries. Nicaragua and Peru have been experimenting with an external quality assurance system adapted from the Scottish and Northern Ireland scheme. It has been received with enthusiasm and acceptance and has helped cytology laboratories in these countries focusing on quality issues. Nevertheless, a successful quality control scheme that is to result in improvements in the quality of professionals' diagnostic skills needs to be accompanied by a remedial program for subperformers.     

Cervical screening revisited

Some of the achievements of cervical screening in the reduction of morbidity and mortality in different countries are briefly reviewed, along with a consideration of some of the aspects of cervical cancer screening programs. The latter include the organization of the program (e.g., whether it is organized by the national health authorities), the protection afforded by routine screening, the assurance of quality in cervical sampling and in the screening program, the screening interval, the age groups to be screened, the compliance of women to present themselves for screening and of health care personnel to provide appropriate follow-up and/or treatment for the lesions diagnosed, the problem of false positives and its relation to overdiagnosis and overtreatment and, finally, the cost effectiveness. It is concluded that a centrally organized and well supervised cervical screening program, cautiously executed and with all involved parties closely cooperating, can be a cost-effective means of combatting cervical cancer.     

Cervical screening in England and Wales: its effect has been underestimated

Opinions about cervical screening in the UK tend to follow one of two negative lines of thought. The first is that cervical cancer is a rare disease, and too much time and effort are spent on screening. The second is that it has been relatively ineffective, since incidence of invasive carcinoma did not fall until the NHS Cervical Screening Programme (NHSCSP) was introduced in 1988, although it fell by 40% since then. This paper presents publicly available data to demonstrate that neither of these views is true. Registrations of invasive carcinoma of the uterine cervix and carcinoma in situ in England and Wales between 1971 and 1996 show that a substantially increased risk of disease in women born since 1940 has been reversed, almost certainly by greatly improved screening. Cervical carcinoma is now a rare disease because most cases are prevented before they become invasive, mostly by screening young women, aged 20-40, before the decade of life when symptomatic cervical carcinoma most frequently presents.     

Cervical cancer screening: A Slovenian experience

In Slovenia, opportunistic screening was introduced in regular gynaecological practice in 1960. The proportion of population screened was unknown, as well as there were no standards for quality assurance and control. Despite great number of smears read, there were no major changes in invasive cervical cancer incidence in the period 1979 till 1993, but in 1994 the incidence rate started to increase again to reach its peak in 1997 (23,1/100.000, 241 new cases). Based on the experiences from the countries with effectively organised screening programmes, a decision was made in 1996 by the Minister of Health to nominate a group of experts to prepare a proposal for organised cervical cancer screening programme after testing the methodology in pilot study. In the pilot the central computerised information system (Screening Registry) was gradually established to register all smears from the whole country, to identify women who do not attend for screening to send them invitation for screening and to monitor screening activity and its quality. The aim of pilot was also to develop guidelines for quality assurance and control of all procedures involved in cervical cancer screening and treatment of intraepithelial lesions. In three years since the beginning of the national programme, nearly 70% of women in the target age group were registered with at least one smear. All other results are presented in regular programme reports. There is still place for further development of the programme, but the incidence of cervical cancer already started to decline especially among younger women, who attend for screening more often than those aged over 50.     

Cancer screening in older adults.

Adults aged 65 and older represent an increasingly important segment of the US population. Cancer is an important cause of death in this group. Screening for cancer can significantly reduce cancer incidence and mortality. In this review I address screening for breast, cervical, prostate, lung, colorectal, and ovarian cancer in older Americans. Decisions about screening for cancer must consider the effects of screening, diagnostic evaluations, and treatments on the quality of life of each person.     

Effectiveness of VIA, Pap, and HPV DNA testing in a cervical cancer screening program in a peri-urban community in Andhra Pradesh, India

Background

While many studies have compared the efficacy of Pap cytology, visual inspection with acetic acid (VIA) and human papillomavirus (HPV) DNA assays for the detection cervical intraepithelial neoplasia and cancer, few have evaluated the program effectiveness.

Methods and Findings

A population-based sample of 5603 women from Medchal Mandal in Andhra Pradesh, India were invited to participate in a study comparing Pap cytology, VIA, and HPV DNA screening for the detection of CIN3+. Participation in primary screening and all subsequent follow-up visits was rigorously tracked. A 20% random sample of all women screened, in addition to all women with a positive screening test result underwent colposcopy with directed biopsy for final diagnosis. Sensitivity, specificity, positive and negative predictive values were adjusted for verification bias. HPV testing had a higher sensitivity (100%) and specificity (90.6%) compared to Pap cytology (sensitivity  =  78.2%; specificity = 86.0%) and VIA (sensitivity = 31.6%; specificity = 87.5%). Since 58% of the sample refused involvement and another 28% refused colposcopy or biopsy, we estimated that potentially 87.6% of the total underlying cases of CIN3 and cancer may have been missed due to program failures.

Conclusions

We conclude that despite our use of available resources, infrastructure, and guidelines for cervical cancer screening implementation in resource limited areas, community participation and non-compliance remain the major obstacles to successful reduction in cervical cancer mortality in this Indian population. HPV DNA testing was both more sensitive and specific than Pap cytology and VIA. The use of a less invasive and more user-friendly primary screening strategy (such as self-collected swabs for HPV DNA testing) may be required to achieve the coverage necessary for effective reduction in cervical cancer mortality.     

Cervical cancer in Osijek-Baranja County--possibilities for prevention

In Osijek-Baranja County, there was a rise in the number of non-invasive and fall of invasive cervical cancer in the period 2000-2008, but cervical cancer still represents an important public health problem in Osijek-Baranja County. Cervical cancer in 2008 was the ninth female cancer site and represents 3.5% of all malignant diseases in women. In the same year it was also at the ninth place of all cancer deaths in women with a share of 3.3%. The large number of women cervical cancer was detected at an advanced stage of the disease so that there is an pincrease in mortality from cervical cancer. Although the incidence of cervical cancer is lower in relation to Croatia and other countries in the region, the mortality rate is still higher than in the countries of Western Europe. In order to reduce the incidence and mortality of cervical cancer primary task of the public health system is the introduction of secondary prevention through properly organized screening program. The program should be tailored to the financial and human resources and local specificities, with the agreement on a strategy that will give the best results.     

European trends in cervical cancer mortality in relation to national screening programs, 1985–2014

BackgroundCervical cancer is the fourth leading oncological cause of death in women. Variable trends in cervical cancer mortality have been observed across Europe, despite the widespread adoption of screening programs. This variability has previously been attributed to heterogeneity in the quality of screening programs.MethodsAge-standardized cervical cancer death rates for European countries between 1985 and 2014 were analyzed using Joinpoint regression. Countries were dichotomized based on year of implementation and population invitational coverage of national population-based cervical cancer screening programs. National cervical cancer mortality trends during the study period were compared based on this classification.ResultsDecreasing trends in mortality were observed in all European countries with the specific exceptions of Bulgaria, Greece and Latvia. The highest rates of cervical cancer mortality throughout the study period were in Romania (16.0-14.9/100,000) and the lowest rates in Italy (1.4-1.2/100,000). The greatest percentage decline in mortality was observed in the United Kingdom and the greatest absolute reduction in mortality was seen in Hungary. European countries which implemented a national population-based cervical cancer screening program prior to 2009 demonstrated greater improvements in cervical cancer mortality outcomes compared to those that did not (p = 0.016).ConclusionCervical cancer mortality is improving in most European countries; however, substantial variation remains. Trends in mortality were associated with the time of implementation of national population-based cervical screening programs.     

Cost effectiveness of population screening and rescreening for cervical cancer in the Netherlands

In a screening program for cervical cancer held in the western part of the Netherlands in 1978, it was shown that the incidence of positive cases dropped from 8.0% to 1.4% when repeat screening was performed within two years; however, the incidence of mild dysplasia remained the same (13.0%). Forty percent of the allocated funds were used for canvassing. Recanvassing of the no-response group did not result in the finding of positive cases. Of the ten positive cases in the rescreened group, four had had inadequate negative smears previously, and two had had adequate negative smears; in two cases the previous smears were reclassified as dysplasias, and in the two remaining cases endocervical carcinoma cells were found in the additional endocervical smear. In light of the high canvassing costs of population screening and the low detection rate of positive cases in the rescreened group, as described in this paper, it appears overly costly to repeat population screening with two years.     

Screening for the prevention of cervical cancer in the era of human papillomavirus vaccination: an Australian perspective

Australia has a unique and highly successful screening program for cervical cancer which is based on the conventional Pap smear. Since its introduction in 1991 there has been a decline in both the incidence of and mortality from this disease. Part of the success of this program has been the introduction of Pap test registers and strict quality assurance measures for cervical cytology, including compulsory key performance indicators for laboratories. Using these measures, nationwide calculations give cervical cytology in Australia a sensitivity of 78% for high-grade lesions and a positive predictive value (PPV) of 78%. Australia was the first country to introduce a widespread government-funded human papillomavirus (HPV) vaccination program in 2007. Because of the high accuracy of Australian cytology, HPV testing alone, given its low PPV and high cost, is unlikely to be a viable alternative to cytology for primary screening in this country. Australia therefore faces unique issues and choices in integrating its extensive vaccination program with a successful cervical screening program.     

Cervical cancer screening programme in Finland with an example on implementing alternative screening methods

In Finland (population 5 million) the organised Pap screening programme for preventing cervical cancer has been in action already for 45 years. Women aged 30 to 64 are targeted (N 1.25 million) and the screening interval is five years. The programme invites women seven times in a lifetime; the attendance rate per one screening invitational round is 73%. The programme has affected markedly the cervical cancer rates in our country. During the decennia of its action there has been about 80% decrease in the age-adjusted cervical cancer incidence and mortality rates. The current age-standardised incidence rate is 4 and mortality rate 1 per 100,000 woman-years. In the current article we describe the organisational aspects of the programme; and pay attention to renovation of the programme taken place during the last decade when novel technological alternatives have been started to be used as the screening tests. By expanding the coverage and compliance of screening we still expect to increase the impact of the programme. Same time, efforts are needed to avoid overuse of services due to spontaneous screening, in order to decrease potential adverse effects and improve overall cost-effectiveness. A large-scale public health policy trial on Human papillomavirus (HPV) screening is on-going. Cross-sectional information available thus far suggests promising results. Follow-up of cancer rates after screening episodes are still required to evaluate optimal screening policies (e.g., screening intervals by age groups, and starting and stopping ages). We propose speeding up the use of modern technological alternatives in organised screening programmes.     

Cervical cancer screening in Middle Eastern and Asian migrants to Australia: A record linkage study

Background. Australia's organized cervical screening program recommends two-yearly screening for women aged 18–69 years and reminder letters are sent at 27 months. Cervical screening registers hold comprehensive information on screening, but not country of birth. A linkage study was performed in order to assess cervical screening behavior in migrants. Methods. To assess screening participation, we linked year 2000 records for 12,541 Middle Eastern/Asian-born women 20–54 years of age, and an age and area matched random sample of 12,143 Australian-born women in the New South Wales (NSW) Midwives Data Collection (MDC), which records country of birth, to screening register records. Screening behavior after 2000 was assessed in women without a recorded prior cervical abnormality. Results. The odds ratios for being screened at least once within a 3 year period, with reference to Australian-born women and adjusted for age, parity, socioeconomic status and smoking, were 0.88 (95% CI: 0.81–0.97) and 0.74 (95% CI: 0.70–0.79) in women born in the Middle East and Asia, respectively. Screening increased with increasing socioeconomic status (SES), absence of smoking and greater parity in Australian-born women but little, if at all, in migrant women. In a sensitivity analysis in which hospital admitted patients were the source of population samples, some patterns were sufficiently different to suggest that selection for illness can affect the strength and direction of associations in linked data. Conclusion. Migrant women from Asian and Middle-eastern countries are less likely than Australian-born women to participate in cervical screening at the recommended interval. Their likelihood of screening is also less related to socioeconomic status, smoking and parity than that in Australian-born women.     

Cervical cancer screening in the Czech Republic

Cytological diagnosis of atypical cells of cervix uteri by the Papanicolaou method was introduced in the Czech Republic (CR) very early - in 1947. The first data on the incidence of cervical cancer in CR are available from 1960 when the rate was 32.3 cases/10(5) women. In 1966 the Czech National Health Law was passed that guaranteed women a yearly preventive examination by a gynaecologist including screening for cervical carcinoma that would be covered by the compulsory health insurance. Notwithstanding high frequency of screening visits and the fact that all women are eligible, the incidence of CC has not changed in the last 34 years. The reasons for this include the coverage of Czech women, which is estimated to be low (50% at the most), and that none of the cytology laboratories are accredited for screening, there are no national registries for any aspect of screening and there are no mechanisms for evaluation of the screening process. As a result, it is likely that the majority of cervical screening activity that is undertaken is ineffective and the implementation of an organised and quality controlled screening programme, in compliance with the recommendations of many European Institutions, is urgently required to ensure that Czech women are properly protected against this disease and that scarce healthcare resources are used in the most cost-effective manner.     

Significance tests for cancer screening trials

The goal of a cancer screening program is to reduce cancer mortality by detecting tumors at earlier stages of their development. For some types of cancer, screening tests may allow the preclinical detection of benign precursors of a tumor, and thus a screening program could result in reductions in both cancer incidence and mortality. For other types of cancer, a screening program will not reduce cancer incidence, and thus the expected outcome in a randomized cancer screening trial would be equal cancer incidence rates in control and study groups, but reduced cancer mortality in the study group. For the latter situation, we employ a variety of Poisson models for cancer incidence and mortality to derive optimal tests for equality of cancer mortality rates in a cancer screening trial, and we compare the asymptotic relative efficiencies of the test statistics under various alternatives. We demonstrate that testing equality of case mortality rates using Fisher's exact test or its Pearson chi-square approximation is nearly optimal when cancer incidence rates are equal and is fully efficient when cancer incidence rates are unequal. When valid, this comparison of case mortality rates in the study and control groups can be considerably more powerful than the standard comparison of population mortality rates. We illustrate the results using data from a clinical trial of a breast cancer screening program.     

Trends in incidence of,and mortality from,cervical lesions in Ireland: Baseline data for future evaluation of the national cervical screening programme

AimTo investigate incidence and mortality trends for cervical lesions in Ireland in the period 1994–2008.MethodsWe used data from the National Cancer Registry, Ireland and national death registration data to calculate age-standardised rates for the periods of interest. We used standardised rate ratios to test whether incidence was associated with socio-demographic variables and used Joinpoint to examine trends by morphology grouping.ResultsIncidence of cervical cancer and cervical intraepithelial neoplasia (CIN3) rose over the period 1994–2008. The annual percentage change for cervical cancer was 1.8% and that for CIN3 was 3.8%. Women resident in the most deprived areas had invasive cervical cancer incidence almost twice as high as those resident in the least deprived areas (standardised rate ratio (SRR) = 1.8). Comparing incidence in Ireland to England and Wales, Northern Ireland and Scotland in the three years 2005–2007, the SRRs (other areas vs. Ireland) were 0.70, 0.88 and 0.84 respectively. Cervical cancer rates have fallen in these countries in the same period that there is a rise demonstrated in Ireland.ConclusionIncidence rates of cervical cancer rose in Ireland steadily, albeit modestly, during 1994–2008, most likely due to long-term changes in patterns of sexual behaviour and contraceptive use. A more pronounced rise in CIN3 rates point to considerable levels of opportunistic screening during this period. Mortality rates have changed little over the past four decades, in contrast to trends in countries with well-organised screening programmes.     

The burden of cervical cancer in Vietnam: Synthesis of the evidence

There is currently no national cervical screening or HPV immunization program in Vietnam. This study aims to synthesize available data on the burden of disease and to project the burden of cervical cancer to 2049 if no major interventions are implemented. We reviewed published data sources on risk factors for HPV prevalence, high-grade lesions, cervical cancer incidence and mortality in Vietnam from 1990 to 2017. We then used the available data to project the number of new cervical cancer cases for the period 2013–2049. Data on cervical cancer incidence and mortality in Vietnam are limited; two Vietnamese cancer registries have been reported on by the International Agency for Research on Cancer, which cover urban populations representing ∼20% of the national population. The reported age-standardized cervical cancer incidence in Hanoi was 6.7 (1993–1997), compared to 28.8 and 14.1 per 100,000 women in Ho Chi Minh City (1995–1998 and 2009–2012, respectively). Cancer mortality data are not uniformly available from cancer registries or mortality surveys in Vietnam because cause of death has not been routinely ascertained. Based on available urban population registry data, estimated rates in the rural population, and forward projection of existing trends, we estimate that without any further intervention, the number of new cases will increase from 6930 (range 5671–8493) in 2012 to 8562 (range 5775–12,762) in 2049, giving a total of 379,617 (range 276,879–542,941) new cases over the period 2013–2049. These findings help underpin the case for the delivery of HPV vaccination and cervical screening in Vietnam, and support similar initiatives in other low- and middle-income countries.