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En hälsoekonomisk modellstudie av primärscreening mot livmoderhalscancer med cellprov- och HPV DNA-test
... The Pap smear testing has been determined to be cost effective by countries Social Services [2]. The testing is performed every three years on women between the age of twenty-three and fifty and every five years on women between the age of fifty and sixty [3]. Cells changing to precancerous cells are a relatively slow process and the process does not present external verifiable symptoms [4]. ...
... In this study a qualitative content analysis was performed with an inductive approach according to Graneheim and Lundman [3]. The qualitative method is subjective and the interpretation comes from many realities which are then compared to the theory. ...
Cervical cancer is the second most common type of cancer among women worldwide. In Sweden cervical cancer is the fifteenth most common cancer among women and accounts for 1.9 percent of all female cancers. The Swedish Pap smear screening program is enabling early detection of cell changes in order that treatment may be administered to pre- vent the development of cancerous cells. There are approximately four hundred and fifty cases of cervical cancer de-tected each year in Sweden and of these cases, approximately seventy five percent occur in women who do not partici-pate in the screening and testing program. The purpose of this study was to illustrate and examine the reasons why women did not participate in the program even though they had received a notice that they had an appointment for a Pap smear test. In the study fourteen women from a district in the west of Sweden were interviewed. In order to analyse the interviews a qualitative content analysis according to Lundman and Graneheim was used. The analysis resulted in the development of three categories which were identified as communication, treatment and subterfuge (reasons or excuses for not participating). The theme of the study was the professional treatment of the women’s conditions. In the inter-views the women emphasize the importance of professional treatment that is administered with respectful and sympa-thetic care throughout the whole healthcare system regardless of where and when the visit was conducted. Efficient or-ganization and clear communication would minimize the inconvenience for the women during their visit.
Centrum för utvärdering av medicinsk teknologi (CMT) CMT är en tvärvetenskaplig forskningsenhet som ingår i Institutionen för medicin och hälsa (IMH) vid Linköpings universitet. CMT bedriver kunskaps-och metodutveck-ling samt genomför utvärdering av medicinsk teknologi och hälso-och sjukvård. Besök oss gärna på www.cmt.liu.se Mikael Rahmqvist Rapport 2016:1 i CMT:s rapportserie Centrum för utvärdering av medicinsk teknologi "Hur fungerar punktprevalens-metoden som mätinstrument i sluten sjukhusvård? Kostnader och prevalenser för vård-relaterade infektioner i somatisk slutenvård i Östergötland 2012"
Denna rapport redovisar hur Landstinget i Östergötland, under medverkan av representanter för Institutionen för medicin och hälsa (IMH) vid Linköpings universitet, under åren 2010 till 2012 utvecklade och prövade ett program där forskningsbaserad kunskap sammanställdes och presenterades vid dialogmöten bland kliniska enheter i landstinget. Avsikten var att anpassa ett program som prövats i provinsen Alberta i Kanada, ” The Alberta Ambassador Program”, till svenska förhållanden. Den styrgrupp som under Metodrådet ansvarade för programmet genomförde 2012 sammanlagt 14 dialogmöten vid sjukhuskliniker och vårdcentraler i Östergötland.
Rapportens syfte är att med hjälp av ett ramverk för ”knowledge brokering” - en form för kunskapsöverföring i hälso- och sjukvård - analysera utvecklingen och genomförandet av programmet för ordnat införande av metoder (”Östgötamodellen”) och jämföra med den kanadensiska modellen samt diskutera eventuella skillnader och likheter mellan modellerna.
Health economic assessment is a tool for estimating cost-effectiveness ofresource uses in health care. Information on cost-effectiveness constitutes onepart of the foundation on which priority setting decisions are made, in order tomake the best possible use of available resources. The aim of this report is to describe the methods, meaning, and implications ofhealth economic assessments. Methodological issues are discussed, and thereport is formulated to reflect the standpoints of health economists working at CMT. The theoretical foundation of health economic assessments is in welfare theory,prescribing a societal perspective of the analyses. A societal perspectiveprescribes that all relevant costs and effects are to be included in the analysis.Direct costs are dominated by the use of health care resources and indirect costsmainly consist of production losses, due to the fact that unhealthy people areunable to perform their work. The theory also prescribes that resourcesconsumed are to be valued according to the opportunity cost approach, i.e. thevalue of a resource in its best alternative use. In practice health economicassessments contain some deviations from what is prescribed by welfare theory,for instance when it comes to costing it is often necessary to settle with rougherestimates. Below are examples of questions that are dealt with in this report: What theoretical foundation should form the basis of our analyses? What perspective should be taken in the analysis, that of the society orthat of the health care sector? Should costs associated with informal care be included in the analysis,and if so how should they be valued? How should costs associated with production losses be valued? Should costs of added life years be included in the analysis? What alternative ways are there for measuring quality of life (QALYweights),and which of these is the most appropriate? Which level of discount rate should be used in analyses stretching overlonger times than one year? Further questions related to the analysis are described, such as the appropriatetime-frame of the analysis, simulation of future costs and consequences, andsensitivity analyses. Hälsoekonomisk utvärdering är ett viktigt instrument för att bedömakostnadseffektivitet av resursanvändning inom hälso- och sjukvården. Kostnadseffektivitetenutgör en del av beslutsunderlaget vid prioriteringar, syftande tillatt vårdens ändliga resurser används på bästa möjliga sätt. Syftet med denna rapport är att ge en beskrivning av hur hälsoekonomiskautvärderingar utförs och vad de står för. Rapporten berör även metodologiskaöverväganden och betydelser av dessa, och speglar det dominerande synsättetbland hälsoekonomer verksamma vid CMT. Hälsoekonomiska utvärderingar har sin teoretiska grund i välfärdsteori vilketföreskriver att analyser utförs med ett samhällsperspektiv. Detta innebär att allarelevanta kostnader (och effekter) ska vägas in i analysen, såväl direkta somindirekta kostnader. Direkta kostnader domineras av förbrukning av hälso- ochsjukvårdsresurser medan indirekta kostnader huvudsakligen består avproduktionsförluster, d v s oförmåga att arbeta till följd av sjukdom. Teorin föreskriverockså att förbrukade resurser värderas enligt en alternativkostnadsprincip,d v s värdet av resurserna i dess mest värdefulla alternativa användning.I praktiken innehåller hälsoekonomiska utvärderingar en del avsteg frånvälfärdsteori, man får t ex ofta nöja sig med mer schablonmässiga kostnader. I rapporten behandlas bland annat följande frågor: Vilken teoretisk grund bör vi utgå ifrån? Vilket perspektiv ska analysen göras utifrån, samhällets eller sjukvårdens? Ska kostnader för informell vård inkluderas i analysen, och hur ska de i såfall värderas? Hur ska kostnader för produktionsförluster värderas? Ska kostnader för adderade levnadsår ingå i analysen? Vilka alternativa sätt finns för att mäta livskvalitet (QALY-vikter), ochvilket av dessa är det lämpligaste? Vilken diskonteringsränta är lämplig att använda vid analyser över längretid än ett år? Dessutom behandlas analysfrågor såsom vilken tidshorisont som är lämplig attanvända, simulering av framtida kostnader och effekter, samt känslighetsanalyser.
Beslut om införande av nya behandlingsmetoder och arbetssätt i sjukvården präglas alltid av en viss grad av osäkerhet. De studier som gjorts av metodens för- och nackdelar kan vara av olika god kvalitet och därmed ge mer eller mindre säkra resultat. Efter att användningen av systematiska litteraturstudier vid medicinsk teknologiutvärdering tog fart på 1980-talet började man efterfråga ett beslutsunderlag som även tar hänsyn till olika studiers kvalitet. Detta initierade utvecklingen av flera olika system för evidensgradering.
Gradering av evidens innebär att det samlade beslutsunderlaget tillmäts en evidensstyrka (bevisvärde) som baseras framför allt på kvalitet, kvantitet och inbördes samstämmighet mellan olika studier. Enskilda studiers kvalitet bedöms och deras beslutsvärde sammanvägs med övrig information till ett samlat beslutsunderlag.
GRADE presenterades första gången 2004 i British Medical Journal (BMJ) och är idag det mest spridda systemet för evidensgradering. Ett flertal internationella organisationer samt utvärderingsenheter i Europa, Nordamerika och Asien använder GRADE och i Sverige har Statens beredning för medicinsk utvärdering (SBU) och Socialstyrelsen studerat systemet och integrerat delar av arbetssättet i sin verksamhet. Förutom evidensgradering innehåller GRADE även en del som utgår från det vetenskapliga underlaget för att beskriva med hur stor säkerhet man kan rekommendera att använda eller inte använda en metod.
På Centrum för utvärdering av medicinsk teknologi (CMT) har vi studerat flera system för evidensgradering. Ett antal system studerades initialt men då dessa tydligt konvergerade mot det system som formulerats i GRADE inriktades arbetet på att detaljstudera detta och ta fram ett diskussionsunderlag på svenska för att belysa frågan hur GRADE kan användas i Sverige i ett utvärderings- och prioriteringsarbete, lokalt, regionalt och nationellt. Målgrupper för rapporten är beslutsfattare, sjukvårdspersonal och akademiskt verksamma med intresse för utvärdering och införande av nya metoder i sjukvården.
Rapporten inleds med historiken bakom utvecklingen av GRADE. Därefter ges en beskrivning av GRADEs arbetsmetod och grundläggande principer. Kapitel 3 innehåller en kritisk granskning av systemet och en diskussion av för- och nackdelar samt användbarheten i ett svenskt utvärderingsperspektiv. Vidare innehåller rapporten bilagor med GRADEs arbetsblad och ett flertal exempel på utvärderingar enligt detta arbetssätt.
En GRADE-bedömning består av två delar: en evidensprofil för den undersökta metoden samt en rekommendation om användandet.
Evidensprofilen innehåller en kvalitetsbedömning (Quality assessment) och en summering av resultat (Summary of findings). Samtliga betydelsefulla effektmått ska redovisas i resultatsummeringen och bakomliggande studier ska graderas avseende design, studiekvalitet mm. Evidensprofilens roll är att ge underlag för beslut om praxisförändringar men ger endast vägledning vad gäller klinisk effekt av en intervention.
I Sverige finns en tradition av allsidiga utvärderingar, med vilket avses att metoder granskas ur ett medicinskt, ekonomiskt, socialt och etiskt perspektiv. Därför ger inte GRADEs evidensprofil tillräcklig information för beslut om praxisförändringar i ett svenskt perspektiv.
Rekommendationen om användandet av den undersökta metoden är del två och det avslutande steget i GRADE. Detta steg utförs av en kommitté av experter i det sjukvårdssystem där metoden är tänkt att användas. En rekommendation att använda en metod ska spegla gruppens övertygelse att önskade effekter överväger över oönskade effekter och graden av övertygelse, att det mest fördelaktiga agerandet rekommenderas, kan anges som stark eller svag. Tillvägagångssättet är strukturerat men lämnar mycket utrymme för subjektiva bedömningar. Rekommendationen ska grundas på information i evidens-profilen och utöver detta på gällande normer och preferenser i samhället samt ekonomiska aspekter. De senare bedömningsgrunderna varierar i hög grad beroende på i vilket land bedömningen görs. Bland annat är bedömning av kostnadseffektivitet inget uttalat krav för beslutsfattande i alla länder men i praktiken går det inte att arbeta fram en rekommendation utan ett moment av prioritering.
SBU har beslutat att använda Grade, med viss modifikation, men endast för att ta fram en evidensprofil. Dock strävar man efter att göra utvärderingar som analyserar alla relevanta aspekter som kan ha betydelse för ett beslut och kompletterar därför evidensprofilen med t.ex. kostnadseffektivitet i förekommande fall.
Från många håll efterfrågas explicita rekommendationer till stöd för ett beslutsfattande. GRADEs metodologi underlättar inte framtagning av rekommendationer i någon högre grad. Medan arbetssättet för att ta fram evidensprofilen är väl genomarbetat återstår mycket utvecklingsarbete vad gäller rekommendationsdelen.
Användning av GRADEs metodologi kan bidra till ett mer strukturerat arbetssätt vid bedömning av nya teknologier i hälso- och sjukvården. Metoden behöver dock vidareutvecklas lokalt för att komma ett steg närmare själva beslutsfattandet. Analyser av kostnadseffektivitet och andra kriterier som kan ligga till grund för prioriteringar behövs, då vi lever i en verklighet där sjukvårdsresurserna är starkt begränsade. Vidare bör utveckling ske mot en mer objektiv bedömning av kriterierna i rekommendationsdelen.
GRADE-systemet ger ett bra utgångsläge för att ta fram ett sammanvägt evidensmaterial och användningen av systemet kan leda till diskussioner och utveckling som kan resultera i ett mer komplett arbetssätt. En intressant utveckling vore att testa systemet för att syntetisera olika typer av kunskap, forsknings- såväl som praktikerbaserad, vilket skulle göra arbetssättet användbart som utvärderingsmetod även vid införande av vissa ickefarmakologiska metoder där traditionell studiedesign inte alltid går att använda.
Decision on the introduction of new treatments and practices in healthcare are always characterized by uncertainty. The studies carried out to evaluate the pros and cons of a new method can be of different quality and thus provide more or less certain results. When the use of systematic literature reviews on health technologies took off in the 1980s, decision makers began to ask for guidance documents, which also took into account individual study quality. This initiated the development of several systems for grading of evidence.
Grading of evidence means that the overall decision material is assigned a strength of evidence, based primarily on quality, quantity and consistency between ifferent studies. The quality of individual studies are assessed and their decision values are weighted together with additional information to obtain an overall decision making material.
GRADE (Grading of Recommendations Assessment, Development and Evaluation) is an approach developed internationally. It started as an informal collaboration between different groups interested in how to assess the value of different studies and the credibility of the overall decision basis for deciding on the introduction of new medical technologies.
GRADE was first presented in 2004 in the British Medical Journal (BMJ), and is today the most widespread system for grading of evidence. Several international organizations, and assessment units in Europe, North America and Asia are using GRADE and in Sweden, the Swedish Council on Technology Assessment in Health Care (SBU) and the National Board of Health and Welfare have studied the system and integrated parts of the approach in their work. In addition to assessment of evidence quality the GRADE approach also covers development and presentation of recommendations to use or not to use the assessed methods that, based on the scientific basis, also describe the degree of confidence with which a recommendation can be given.
At the Centre for Medical Technology Assessment (CMT), several systems of evidence-grading have been studied. However, as the systems under study clearly converged towards the GRADE approach, a sharper focus was set on a detailed study of this system and to develop a discussion paper in Swedish in order to highlight the issue of how GRADE can be used in the Swedish context for evaluation and priority setting, locally, regionally and nationally. Target groups for the report are policy makers, healthcare professionals and academic researchers with an interest in issues of evaluation and implementation of health technologies.
The report begins with the historical background behind the development of GRADE. In Chapter 2 a description of GRADE’s working method and underlying principles is given. Chapter 3 contains a critical review of the system and a discussion of the advantages and disadvantages, and usefulness in a Swedish evaluation perspective. Furthermore, the report contains appendices with GRADE worksheets and numerous examples of assessments using the GRADE approach.
A GRADE-assessment consists of two parts: an evidence profile for the method in question and a recommendation regarding its use.
The evidence profile contains a ”Quality assessment” and a ”Summary of findings.” All the important outcomes are shown in the summary and the underlying studies are graded according to design, study quality, etc. The role of the evidence profile is to inform policy and practice but it does only give guidance regarding the clinical efficacy of the interventions.
Sweden has built a tradition of comprehensive assessment, meaning that methods are examined from a medical, economic, social and ethical perspective. Therefore, GRADE’s evidence profile is not sufficient to inform policy and practice in a Swedish perspective.
The recommendation on the use of the investigated method is the final step in GRADE. This step is performed by a committee of experts in the healthcare system in which the method is intended to be used. A recommendation to use a method shall reflect the committee's belief that the desired effects outweigh the undesirable effects. The degree of confidence, that the most advantageous behaviour is recommended, shall also be indicated as strong or weak. The approach is structured but leaves room for subjective judgments. The recommendation is based on information in the evidence profile, and beyond that on current norms and preferences in the society, and economic aspects. The latter evaluation criteria will vary greatly depending on the country where the evaluation is made. Among other things, assessment of cost-effectiveness is not explicitly required for decision making in all countries but in reality it is not possible to work out recommendations without an element of priority setting.
SBU has decided to use GRADE, with some modification, but only to develop an evidence profile. However, SBU attempts to make assessments that analyze all relevant aspects that may be important in decision making and therefore supplements the evidence profile with for example a cost-effectiveness analysis in some cases.
Explicit recommendations in support of decision making are asked for in many quarters. GRADE’s methodology does not, to any great extent, facilitate the development of such recommendations. While the working method for developing the evidence profile is comprehensive, significant development efforts still remain regarding the recommendation part of the GRADE system.
GRADE’s methodology can contribute to a more structured approach in the assessment of new technologies in health care. However, the methodology needs to approach the actual decision making a bit closer through the development of more objective assessments of values and preferences. Further, methods for priority setting are needed, as we live in a reality where resources for healthcare are limited. GRADE can be used as a platform for discussions and development towards a more comprehensive approach. An interesting progression would be to test the system for synthesis of more different types of knowledge, research as well as practitioner-based, which would make the working method useful for the evaluation and introduction of certain non-pharmacological methods where the traditional study design is not always possible to use.
Fotsår och andra fotkomplikationer vid diabetes orsakar stort lidande och tar stora sjukvårdsresurser i anspråk. Mycket talar för att frekvensen och svårig-hetsgraden av fotkomplikationer kan minskas med god förebyggande vård och effektiva metoder för att diagnostisera problemen i ett tidigt stadium. I rapporten redovisas resultatet av en systematisk genomgång av den vetenskapliga litteraturen om värmemätning som metod för prevention av fotproblem hos personer med diabetes. Rapporten innehåller också resultat som inte publicerats tidigare från en försöksanvändning av fotplattan SpectraSole Pro 1000, en ny bildgenererande teknologi som baseras på värmekänsliga flytande kristaller och som visualiserar värmefördelningen i fötterna. Målgrupper för rapporten är beslutsfattare, vårdpersonal samt patienter.
Inledningsvis beskrivs epidemiologi samt riktlinjer och vårdpraxis för prevention och behandling av fotkomplikationer vid diabetes. En redogörelse ges för samhällets kostnader för fotsår samt värdet av en tidig diagnos för prevention av allvarliga komplikationer. Därefter beskrivs kunskapsläget vad gäller sambandet mellan värmeförändringar och fotproblem. Vidare ges en beskrivning av utveckling och användning av olika teknologier för värme-mätning, varefter SpectraSole-studien avrapporteras.
Baserat på litteraturgenomgången har kostnaden för diabetiska fotsår beräknats. Men variationen i ingångsvärdena har varit stor eftersom de ingående studierna utförts i olika länder och med olika studiepopulationer. Detta har lett till en hög osäkerhet i de estimerade värdena, särskilt vad gäller medelkostnaden generellt för ett fotsår, där populationer med mycket varierande sjukdomsgrad använts. Totalkostnaden för diabetiska fotsår i Sverige kan uppskattas ligga i intervallet 851 - 1625 miljoner SEK per år och medelkostnaden för ett fall av fotsår som lett till amputation är 249 000 - 462 000 SEK. Sjukhusvård är det som kostar mest, medan förebyggande vård och diagnostik har relativt låga kostnader. Att reducera antalet dagar på sjukhus borde därför ha förutsättning att vara lönsamt. Preventiva insatser och ett förbättrat omhändertagande av patienterna i multi-disciplinära fotteam har reducerat amputationsfrekvensen betydligt under senare år men litteraturen pekar på att det fortfarande finns mycket att vinna på en intensifierad förebyggande vård och ett tidigt omhändertagande. Ett uppskattat antal fotsår per år i Sverige är idag 8600, vilket med en amputationsincidens på 15 procent innebär att cirka 1300 fotsår leder till amputation. Kostnaden för dessa beräknas till 324 - 601 miljoner SEK per år.
Studier har visat att det finns ett samband mellan ökad temperatur och begynnande fotproblem hos patienter med diabetes. Smärta förekommer sällan på grund av perifer neuropati hos patienten och förhöjd temperatur kan därför vara en viktig indikator för fotkomplikationer som inte kan observeras på annat sätt. Rekommendationer om temperaturundersökning av diabetesfötter ges i konsensusdokument och riktlinjer, både i Sverige och utomlands, men mätning med något instrument utförs mycket sporadiskt. Skanning med IR-termometer är en möjlig metod men detta är tidsödande och praxis idag är att man med handen känner av fotens hudtemperatur.
Försök har gjorts med daglig monitorering av fottemperaturen i hemmet och dessa studier indikerar att frekvensen fotsår skulle kunna minskas med över 60 procent. Det finns dock inget i den studerade litteraturen som tyder på att metoden införts som standard någonstans. Det är främst två metoder för värmemätning som fått klinisk tillämpning på experimentell basis. Dessa är skanning med IR-termometer samt termografi med flytande kristaller (LCT). Båda teknikerna har en låg kostnad och är okomplicerade att använda.
Vid försöksanvändningen av fotindikatorn SpectraSole Pro 1000 har patienterna först undersökts enligt nuvarande praxis för fotundersökning och därefter med fotindikatorn. Fynd från undersökningen med fotindikatorn jämfördes sedan med den information som framkommit i standard-undersökningen. I studien gjordes 69 mätningar och antalet patienter var 65. En undersökning med fotindikatorn upplevdes som enkel och snabb att utföra och de bilder som genereras av problemområden kan eventuellt göra patienterna mer delaktiga i vård och inspektion av sina fötter.
SpectraSole Pro 1000 detekterade 75 procent av förväntade problemområden bland de fall som hade sämst fotstatus och i hela materialet upptäcktes sex temperaturskillnader som missats i den ordinarie undersökningen. Av detta kan man dra slutsatsen att instrumentet tillför information, men att det inte kan ersätta den inspektion som är standard idag. För att kunna avgöra i vilken grad fotsårs- och amputationsfrekvensen påverkas, samt betydelsen av detta för livskvalitet och överlevnad, krävs en större studie med långtidsuppföljning av fotkomplikationer i studiepopulationen.
Baserat på den undersökta litteraturen kan man konstatera att det idag finns indikatorer på att regelbunden värmemätning av diabetikers fötter är av värde. Värmemätning kan dock endast utgöra ett komplement till nuvarande under-sökningspraxis. Vid en eventuellt ändrad praxis, där värmemätning ingår som standard, kommer resursanvändningen för att fastställa fotstatus hos patienterna att öka, medan eventuellt sparade kostnader står att finna längre fram i vårdkedjan. Snabba insatser är avgörande för den vidare utvecklingen av nyupptäckta skador på fötterna och en omfördelning av resurser till diagnostik och tidigt omhändertagande skulle sannolikt bli nödvändig.
Diabetic foot complications impose a major economic burden to society and lead to decreased quality of life for the patients. Preventive measures and effective diagnostic methods are necessary to limit the incidence of foot ulcers and lower limb amputations. This report covers a systematic review of the scientific literature on temperature measurements for prevention of diabetic foot disorders and a feasibility study of a new LCT-technology that shows the warmth distribution of the feet. The target readers for the report are decision makers, medical professionals and patients.
The epidemiology of the diabetic foot is explored as well as guidelines and current practices for prevention and treatment. Further are the costs of diabetic foot ulcers estimated, based on the literature, and the value of early diagnosis is discussed. There is, however, a large variation in the basic data, depending on variations in study populations and country of origin in the included literature, which has lead to fairly indefinite estimates. Foot ulcer costs in Sweden are estimated to 851 - 1625 million SEK each year. The average cost for a case of foot ulcer, from diagnosis to healing, is 99 000 - 189 000 SEK. The highest costs are for hospitalisation, while prevention and diagnostic measures incur relatively small expenses. This means that reduction of hospital admissions through preventive care has a potential to be cost effective. Implementation of multi-disciplinary foot-care teams during the past years has led to dramatic reductions in the frequency of lower limb amputations, but there is still a lot to be gained by early diagnosis and prevention. The estimated number of foot ulcers in Sweden today is 8600. With an amputation incidence of 15 % this indicates that 1300 ulcers each year will result in an amputation, incurring costs estimated to be 324 - 601 million SEK.
Studies show that increased temperature can be used as a predictive sign of future ulceration of the diabetic foot. The patient seldom feels pain because of peripheral neuropathy, and thus, temperature can be an important indicator of foot disorders that otherwise would have passed undetected. Recommendations about temperature evaluation are given in consensus statements and guidelines, in Sweden and elsewhere, but instrumental measurements are seldom performed. Scanning with an IR-thermometer is one available, but time consuming, method and today's practice is palpation of the foot temperature.
Studies of daily home monitoring of foot temperature points at a more than 60 % decreased incidence of ulcers. There is, however, nothing in the studied literature to indicate that the method has been adopted for standard use anywhere. There are mainly two technologies for temperature measurement that have had an experimental clinical application. They are scanning with IR-thermometer and liquid crystal thermography (LCT). Both technologies have low costs and are easy to use.
Results that have not been published previously are reported from the feasibility study of the new LCT foot indicator SpectraSole Pro 1000. The patients initially had their foot status determined in a standard examination, according to current practice, and were thereafter examined with the LCT instrument. Findings from the examinations with SpectraSole Pro 1000 were then analysed and compared to the preceding ordinary examinations. 69 examinations were performed in 65 patients. An examination with SpectraSole Pro 1000 was considered easy and quick to perform and the instrument clearly visualised problem areas of the foot, which might motivate patients to a higher compliance and contribute to a better foot-related behaviour.
SpectraSole Pro 1000 detected 75 % of the foot problems among the patients in the three groups with the worst foot status. Among all patients the instrument detected six cases that had been missed in the ordinary examination. This leads to the conclusion that the foot indicator gives additional information, but cannot replace the standard inspection of the foot. To be able to assess how the incidence of ulcers and amputations is influenced, a larger trial must be performed in the primary care setting, preferably with a long term follow up to assess the outcome of prevented foot complications.
Based on the studied literature, the conclusion can be drawn that regular temperature monitoring of diabetic feet probably is of value. However, temperature monitoring can only be a complement to the current practice for foot examination. If temperature monitoring was to be included in a regular practice, costs for determination of foot status and primary foot care would increase, while potential savings would be on specialist care and hospitalisation. A rapid diagnosis and early intervention is crucial for the healing of lesions of the diabetic foot and a redistribution of resources to early interventions might be necessary.
Studiens syfte var att undersöka effektivitet och kostnadseffektivitet för nyförskrivning av hörapparater, inkluderande jämförelse mellan ”enkel” apparat (analog) och ”avancerad” (digital). Studien var randomiserad ”cross-over”- studie, enkelblind genom att apparaternas höljen gjorts likartade och utan beteckningar. Som utfallsmått användes dels ett primärt utfallsmått, ”tal i brus”, dels generiska mått relaterade till problemlösningsförmåga (IPPA, PIRS) och hälsorelaterad livskvalitet (EQ-5D, HUI3). Vidare studerades brukarnas preferenser vad gäller apparat såväl utan som med kännedom om kostnader. Studien gjordes i samverkan med hörcentraler vid landstingen i Östergötlands, Kalmar och Jönköpings län. Under 2002 och 2003 rekryterades 161 brukare till studien; medelåldern var ca 70 år, 60 procent män och 40 procent kvinnor.
Nyförskrivning av hörapparat, ”bakom örat”-modell bilateralt om ej kontraindikation för detta förelåg, ger för samtliga ovan nämnda utfallsmått en avsevärd förbättring. Förskrivningens kostnadseffektivitet, med fritt val mellan apparattyperna (ungefärligen lika många väljer enkel som avancerad), ger en kostnad per vunnet kvalitetsjusterat levnadsår av 80 000 kronor mätt med EQ-5D och 17 300 kronor mätt med HUI3. Härvid har vi antagit att livskvalitetsförhöjningen står sig över fem år, vidare har kostnader inkluderats för läkarbesök, audiogram, utprovning, tillverkning av två insatser samt apparatkostnader.
I en jämförelse mellan apparattyperna ger den avancerade apparaten signifikant högre andel uppfattade ord i ”tal i brus”-testet samt signifikant bättre problemlösningsförmåga (IPPA), dock endast något svagare förbättring enlig PIRS. Livskvaliteten (EQ-5D) skattades något högre för den enkla apparaten.
När brukaren genomgått testperioder med respektive apparattyp erbjöds han/hon att välja apparat. Utan kännedom om egenavgifterna valde 62 procent den avancerade apparaten. Med kostnadskännedom ändrade sig 11 personer och valde enkel apparat, en valde unilateral anpassning men bibehöll avancerad apparat. Med kostnadskännedom var således fördelningen mellan apparattyperna lika. Betalningsviljan är således för många brukare betydande och kan uppgå till en merkostnad av ca 8000 kronor för att få den avancerade apparaten i stället för den enkla. Utan kostnadskännedom valde 88% dubbelsidig anpassning och 12% hörapparat till enbart ett öra. Med kostnadskännedom ändrades detta till 87% respektive 13%.
Studien har visat att hörapparatförskrivning för förstagångsanvändare har hög kostnadseffektivitet. Avancerad apparat ger signifikant förbättrad taluppfattning jämfört med enkel apparat. Livskvalitetsmätningarna i studien tyder på att det är svårt att utifrån dessa avgöra värdet av specifika olikheter mellan apparattyper.
Skin cancer is one of the most rapidly increasing cancers among the Swedish population and a significant cause of illness and death. The aim of this study was to from a societal perspective estimate the total cost of skin cancer in Sweden in 2005, using a combined top-down and bottom- up, prevalence based cost of illness approach. The total cost of skin cancer was estimated to 1,25 billion SEK (1 €= 9,3 SEK). The direct costs were estimated to 665 million SEK and constituted 53 percent of the total cost. Indirect costs were estimated to 583 million SEK and constituted 47 percent of the total cost. The main cost driver was production lost caused by premature death, amounting to 39 percent of the total cost.
In addition, this study compares the cost of skin cancer with the costs arising from road traffic accidents. Focusing on the methodological differences that arise when comparing economic cost founded on similar but yet different methods when conducting cost analysis. We demonstrate that the seemingly large difference between the cost of skin cancer and the cost arising from road traffic accident, in reality is not as large as it first appear.
Studier av prioriteringar i primärvården är särskilt intressanta eftersom det är där de allra flesta av oss kommer i kontakt med hälso- och sjukvården. Det är också i primärvården prioriteringar och olika former av ransonering på grund av begränsade resurser är vanliga. De allra flesta av oss förstår och accepterar att vi inte omedelbart kan få träffa en läkare om det inte rör sig om akuta och allvarliga sjukdomstillstånd. Vi finner många gånger ett råd om egenvård som en tillfredställande lösning för tillfället. Hur olika prioriteringar görs ”bakom kulisserna” är dock många gånger oklart för oss. Vi kan ibland t.ex. undra varför vi får betala för vissa vårdtjänster medan andra är gratis. Osäkerhet om på vilka grunder prioriteringar sker gäller inte bara för patienter utan även sjukvårdspersonal. Erfarenheter från flera olika håll i Sverige pekar på att de etiska riktlinjer som utgör kärnan i riksdagens prioriteringsprinciper är svåra att använda i praktiken. Det är därför angeläget att få mer kunskap om hur prioriteringsprinciper och begrepp uppfattas av sjukvårdspersonalen för att utveckla arbetsformer som är begripliga och förenliga med rådande rutiner.
Distriktsläkare, mottagningssköterskor och distriktssköterskor vid fyra vårdcentraler som tidigare deltagit i en prioriteringsstudie har inbjudits att diskutera prioriteringar utifrån ett antal frågeställningar. Resultaten från dessa diskussioner visar bland att olika begrepp tolkas på många olika sätt. En framgångsrik implementering av den etiska plattformen kräver antagligen betydligt mer av öppna diskussioner om prioriteringar och principer i det dagliga vårdarbetet.
Två allmänläkare Eva Arvidsson från Kalmar och Malin André från Falun har bidragit med den största insatsen i projektet som för övrigt inbegriper Lars Borgquist från Avdelningen för allmänmedicin vid Linköpings universitet och Kjell Lindström från Primärvårdens utvecklingsenhet i Jönköping. Studien har finansierats av Forskningsrådet för sydöstra sjukvårdsregionen (FORSS).
Jag vill på projektgruppens vägnar tacka alla medverkande från vårdcentralerna Lindsdal och Borgholm i Kalmar läns landsting, Öxnehaga i Jönköpings läns landsting och Ryds vårdcentral i Landstinget i Östergötland.
Linköping 2007-07-24
Per Carlsson
The aim of this study was to investigate how a screening program interacts with the dynamic natural history of cervical neoplasia in order to learn how screening for cervical cancer should be carried out most cost-effectively. For the purpose of optimization, the fundamental quantities of the natural history are the shape of the curve of age-specific prevalence rates of cancer in situ, and the duration of this stage before progression to invasive cancer. Since these quantities seem similar in different populations, the results probably can be generalized. Simulation studies revealed that optimal screening implies a nonperiodic schedule, and that this schedule is dependent not only on the number of screenings, but also on the efficiency of the screening rounds. With lower efficiency, the schedule should be concentrated into a shorter period. The effect of screening is also especially sensitive to the choice of age at the first and--to a smaller extent--last screening. The results concerning three different objectives also were compared, namely reduction of the cumulative number of invasive cancers, reduction of deaths due to cervical cancer, and reduction of years-of-life lost. The choice of objective also plays a role in the design of an optimal screening program. The theoretical approach in this analysis easily can be developed and accommodated to more complex individual situations such as prior screening histories and differing screening schedules in high- and low-risk women.
Cervical cancer incidence and mortality can be reduced by removal of precursor lesions detected at cytological screening. Organised screening, i.e. regular invitation of defined target groups, is generally considered more effective than opportunistic screening. The latter method however, is predominant in most settings. There is no scientific basis for advocating one type of screening or the other. Our aim was to compare the two types and to analyse their efficiency. We analysed 466,275 smears taken in an open cohort of 118,890 women during 1969-88. A computerised database permitted standardised classification of all smears and complete ascertainment of cancer in situ through record linkage. The number of in situ cancers detected per 1000 smears, the detection ratio, was used as an outcome measure both in univariate analyses and in multivariate logistic regression models. Cancer in situ was detected in 1076 women in the study cohort, with a detection ratio of 3.0 at organised and 2.1 at opportunistic screening, yielding an unadjusted odds ratio of 0.69 (95% CI 0.61-0.79). After adjustment for age and time period, the probability of detecting cancer in situ was around 25% higher with opportunistic than with organised screening (OR = 1.26; 95% CI 1.09-1.46). This difference in favour of opportunistic screening was most pronounced in the first 10 year period and disappeared during the last decade. The difference in efficiency between organised and opportunistic screening in the detection of cancer in situ was slight, if any. The dogma that organised screening is significantly more efficient than the opportunistic type needs reconsideration.
Human papillomavirus (HPV) is the main risk factor for invasive cervical cancer. High risk ratios are found in cross-sectional data on HPV prevalence. The question raised is whether this present evidence is sufficient for making firm recommendations on HPV screening. A validated cervical cancer screening model was extended by adding HPV infection as a possible precursor of cervical intraepithelial neoplasia (CIN). Two widely different model quantifications were constructed so that both were compatible with the observed HPV risk ratios. One model assumed a much longer duration of HPV infection before progressing to CIN and a higher sensitivity of the HPV test than the other. In one version of the model, the calculated mortality reduction from HPV screening was higher and the (cost-)effectiveness was much better than for Pap smear screening. In the other version, outcomes were the opposite, although the cost-effectiveness of the combined HPV + cytology test was close to that of Pap smear screening. Although small follow-up studies and studies with limited strength of design suggest that HPV testing may well improve cervical cancer screening, only large longitudinal screening studies on the association between HPV infection and the development of neoplasias can give outcomes that would enable a firm conclusion to be made on the (cost-)effectiveness of HPV screening. Prospective studies should address women aged 30-60 years.
Cost-effectiveness analyses are an important source of information for the design and evaluation of policies to reduce cervical cancer. This paper describes the recommendations of a panel on cost-effectiveness studies convened as part of the International Consensus Conference on the Fight Against Cervical Cancer. Recommendations for cost-effectiveness studies include: (1) the use of reference case methods to support comparisons across studies, (2) the use of a consistent standard of evidence on the clinical effectiveness of different screening strategies, (3)further research into the costs and effectiveness of different screening and treatment strategies for cervical cancer, (4) further research into screening and treatment strategies in a wide range of countries, (5) easily accessible and detailed descriptions of the methods and supplementary analyses underlying published studies, (6) greater use of newly developed models of cervical cancer, and (7) greater revelation of potential conflict of interest by researchers.
Despite quality assurance standards, Papanicolaou (Pap) test characteristics remain less than optimal.
To compare the societal costs and benefits of human papillomavirus (HPV) testing, Pap testing, and their combination to screen for cervical cancer.
A simulation model of neoplasia natural history was used to estimate the societal costs and quality-adjusted life expectancy associated with 18 different general population screening strategies: Pap plus HPV testing, Pap testing alone, and HPV testing alone every 2 or 3 years among hypothetical longitudinal cohorts of US women beginning at age 20 years and continuing to 65 years, 75 years, or death.
Discounted costs per quality-adjusted life-year (QALY) saved of each screening strategy.
Maximal savings in lives were achieved by screening every 2 years until death with combined HPV and Pap testing at an incremental cost of 70 347 per QALY. Combined biennial HPV and Pap testing to age 65 years captures 86.6% of the benefits achievable by continuing to screen until age 75 years. Human papillomavirus screening alone was equally effective as Pap testing alone at any given screening interval or age of screening cessation but was more costly and therefore was dominated. In sensitivity analyses, HPV testing would be more effective and less costly than Pap testing at a cost threshold of $5 for an HPV test.
Screening with HPV plus Pap tests every 2 years appears to save additional years of life at reasonable costs compared with Pap testing alone. Applying age limits to screening is a viable option to maintain benefits while reducing costs.
To investigate the role of human papillomavirus (HPV) in the development of cervical neoplasia in women with no previous cervical cytological abnormalities; whether the presence of virus DNA predicts development of squamous intraepithelial lesion; and whether the risk of incident squamous intraepithelial lesions differs with repeated detection of the same HPV type versus repeated detection of different types.
Population based prospective cohort study.
General population in Copenhagen, Denmark.
10 758 women aged 20-29 years followed up for development of cervical cytological abnormalities; 370 incident cases were detected (40 with atypical squamous cells of undetermined significance, 165 with low grade squamous intraepithelial lesions, 165 with high grade squamous intraepithelial lesions).
Results of cervical smear tests and cervical swabs at enrollment and at the second examination about two years later. Results: Compared with women who were negative for human papillomavirus at enrollment, those with positive results had a significantly increased risk at follow up of having atypical cells (odds ratio 3.2, 95% confidence interval 1.3 to 7.9), low grade lesions (7.5, 4.8 to 11.7), or high grade lesions (25.8, 15.3 to 43.6). Similarly, women who were positive for HPV at the second examination had a strongly increased risk of low (34.3, 17.6 to 67.0) and high grade lesions (60.7, 25.5 to 144.0). For high grade lesions the risk was strongly increased if the same virus type was present at both examinations (813.0, 168.2 to 3229.2).
Infection with human papillomavirus precedes the development of low and high grade squamous intraepithelial lesions. For high grade lesions the risk is greatest in women positive for the same type of HPV on repeated testing.
The human papillomavirus test (HPV) test could improve the (cost-) effectiveness of cervical screening by selecting women with a very low risk for cervical cancer during a long period. An analysis of a longitudinal study suggests that women with a negative Pap smear and a negative HPV test have a strongly reduced risk of developing cervical abnormalities in the years following the test, and that HPV testing lengthens the detectable stage by 2-5 years, compared to Pap smear detection alone.
The aim of this study is to evaluate different options for introducing liquid-based cytology (LBC) and human papillomavirus (HPV) testing into the UK cervical cancer screening programme. These include options that incorporate HPV testing either as a triage for mild and borderline smear abnormalities or as a primary screening test. Outcomes include the predicted impact on resource use, total cost, life years and cost-effectiveness. Extensive sensitivity analysis has been carried out to explore the importance of the uncertainty associated with disease natural history and the impact of screening. Under baseline assumptions, the cost-effectiveness of different options for introducing LBC appears favourable, and these results are consistent under a range of assumptions for its impact on the diagnostic effectiveness of cytology. However, if we assume a higher marginal cost of LBC in comparison to conventional methods, primary smear testing options are predicted to be more cost-effective without LBC. Combined LBC primary smear and HPV testing with a 5-year interval is similar in both cost and effectiveness to the other 3-yearly options of primary smear testing or primary HPV testing alone. However, both primary HPV testing and combined options would give rise to a far greater risk of inappropriate colposcopy throughout a woman's lifetime. British Journal of Cancer (2004) 91, 84-91. doi:10.1038/sj.bjc.6601884 www.bjcancer.com Published online 25 May 2004
In a prospective cohort study 8466 women attending routine cervical cancer screening were recruited. Colposcopy was performed on women with any degree of atypia on cytology and/or a positive high-risk human papillomavirus (HPV)-DNA test (HC2; Hybrid Capture 2((c))), and for a randomly selected sample of 3.4% women with negative findings on both. Quality control included reviews of cytology, histology, colposcopy images and retesting of samples with polymerase chain reaction. Test diagnostic performances were based on 7908 women who had complete baseline and follow-up results. Routine histology identified 86 women with high-grade cervical intraepithelial neoplasia (CIN2+), which was confirmed by review histology in only 46 cases. Sensitivity of routine cytology for the detection of CIN2+ was 43.5%, with a specificity, positive predictive value (PPV), negative predictive value (NPV) of 98.0, 11.4 and 99.7%, respectively. Sensitivity of the HC2 test for the detection of CIN2+ was 97.8%, with a specificity, PPV and NPV, of 95.3, 10.9 and 100%, respectively. No high-grade neoplasia was detected in the randomly selected control group. A negative HPV-test result, even in combination with a positive Papanicolaou (Pap) result, virtually excluded any risk of underlying high-grade disease, but this was not the case for a negative Pap result. These data show that HPV testing is of value for the detection or exclusion of prevalent CIN in a routine cervical cancer-screening setting and could be used for further risk classification of women for follow-up management.
The use of modelling in economic evaluation is widespread, and it most often involves synthesising data from a number of sources. However, even when economic evaluations are conducted alongside clinical trials, some form of modelling is usually essential. The aim of this article is to review the handling of uncertainty in the cost-effectiveness results that are generated by the use of decision-analytic-type modelling. The modelling process is split into a number of stages: 1. a set of methods to be employed in a study are defined, which should include a `reference case' of agreed methods to enhance the comparability of results; 2. the clinical and demographic characteristics of the patients the model relates to should be specified as carefully as in any experimental study; and 3. the data requirements of the model should be estimated using the principles of Bayesian statistics, such that prior distributions are specified for unknown model parameters. Monte Carlo simulation can then be employed to sample from these prior distributions to obtain a distribution of the cost effectiveness of the intervention. Such probabilistic analyses are related to parameter uncertainty. In addition, modelling uncertainty is likely to add a further layer of uncertainty to the results of particular analyses.
Indirect evidence indicates that cervical cancer screening should reduce the incidence and mortality of invasive cervical cancer by about 90%. In the absence of screening, a 20-year-old average-risk woman has about a 250 in 10,000 chance of developing invasive cervical cancer during the rest of her life, and about a 118 in 10,000 chance of dying from it. Screening at least every 3 years from 20 to 75 years of age will decrease these probabilities by about 215 in 10,000 and 107 in 10,000, respectively, and will increase a 20-year-old woman's life expectancy by about 96 days. The particular age at which screening is begun (for example, 17 or 20 years), the requirement of several initial annual examinations before reducing the frequency, and screening every 1 or 2 years compared with every 3 years improves the effectiveness by less than 5%. Screening is recommended at least every 3 years from about age 20 to about age 65 years.
56117 women registered in the Swedish National Cancer Registry with the diagnosis carcinoma in situ of the uterine cervix were followed up and the risk for developing an invasive carcinoma of the uterine cervix was studied. The studied cohort provided 453 362 women years at risk. The primary treatment for carcinoma in situ in Sweden is generally conization. Hysterectomy is carried out in relatively few cases and intracavitary radium treatment was given to a limited number during the period studied. Cryosurgery and laser conization were of less quantitative importance during this period. The incidence rates of invasive carcinoma of the uterine cervix were compared with expected rates calculated from the National Cancer Registry. The ratio between observed and expected number of cases of invasive carcinomas of the uterine cervix is roughly 2.5 from the first year of observation after treatment of the in situ carcinoma until 20 years. There seems to be a distinct difference in risk for development of an invasive carcinoma of the uterine cervix for different age groups. In age group 50 years and older at time for treatment of the in situ lesion, 66 cases of invasive cancer were observed against 10.7 expected - O/E = 6.2. In ages 49 years or less, 145 cases were observed compared with 77.4 expected - O/E = 1.9. The conclusion from this study is that women treated for an in situ lesion are at a higher risk for an invasive carcinoma than the common female population and should be carefully followed up for a long time after treatment of the in situ lesion.
More than 90% of the total female population of three Swedish counties between the ages of 30 and 59 years, 53% of women between 60 and 69 years, and 25% of women older than 70 years were screened for cervical cancer with the Papanicolaou smear over a ten-year period. The uniqueness of the study is that in Sweden it is possible to follow up the entire population during their lifetimes via a population register, which has its roots in the 17th century, natural to Swedes but almost incomprehensible in the United States or United Kingdom. Every Papanicolaou smear taken was computer recorded and linked on an individual level to the cancer registry. There were 207,455 women followed up for ten years. No women were lost to follow-up. There was a 75% decrease in invasive cervical cancer incidence among women who had smears taken at least once during the ten-year period. Among those women who had never had smears taken, the incidence of invasive cervical cancer was four times as great as among those women who had been examined at least once. We estimate that the system proposed by Swedish Medical Board (at least one smear every three years) for cervical cancer screening can reduce the incidence of invasive cervical cancer to a level between one and five cases per 100,000 women per year in a completely screened population.
(JAMA 1984;252:1423-1426)
The aim of this study was to evaluate the effects of screening for cancer in the Nordic countries. There is sufficient scientific evidence to conclude that screening for cervical cancer, breast cancer and colorectal cancer will result in a reduction in mortality. The effects on mortality were predicted for the future up to the year 2017 assuming that the Nordic countries are covered by screening as a nation-wide population-based public health policy and comparing the predicted mortality trends with those assuming no screening programmes. For cervical cancer the programme as practised in Finland was used as a point of reference. For breast cancer and for colorectal cancer the results of randomized preventive trials were assumed in the absence of detailed results based on any public health policy, i.e., a reduction of 30% in mortality from breast cancer and 20% in mortality from colorectal cancer. The assumed ages and frequencies of screening ranged from 25 to 59 years at 5-year intervals for cervical cancer, from 50 to 69 at 2-year intervals for breast cancer and annual screening from 50 to 74 years for colorectal cancer. Data on incidence and incidence predicted up to the year 2012, mortality, survival and size of the general population were employed in the estimation. Age-cohort and age-period-cohort log-linear models were applied in predicting future mortality rates with and without screening. The choice of the models depended on the age distribution of deaths from each particular site of cancer, on changes in public health policy, such as establishment of mass-screening, and on the goodness of fit of the model. The screening policy assumed would result in 1600 annual deaths prevented out of the potential 13,600 deaths in the Nordic countries in 1995, corresponding to 11% of the deaths from the three primary sites. Only after the year 2010 will the ultimate effect of such a screening policy have as full an effect and in 2013-2017 the annual number of cancer deaths prevented will be 3900 out of 15,000 potential deaths, i.e., a 26% reduction. This is equal to 5.7% of all cancer deaths in the Nordic countries in 2013-2017 (2.0% for males and 9.7% for females). The predicted numbers of annual deaths prevented in 2013-2017 are 1500 for cervical cancer, 1000 for breast cancer and 1500 for colorectal cancer. Most (91%) of the cervical cancers can be prevented, whereas the proportion of breast cancer deaths (18%) and colorectal cancer deaths (18%) prevented will be much smaller. Costs of the screening programmes were estimated taking into consideration the direct costs of screening and savings from advanced disease treatment and terminal care. The total cost of screening for cervical, breast and colorectal cancer in the Nordic countries in the year 2010 is estimated to be 17 m yearly in the period 2008-2012. Screening for cervical cancer is approaching a phase when both the effect and costs are relatively stable and it was estimated to be cost-saving. The effect of screening for breast and colorectal cancers is expected to become apparent gradually during the predicted period due to the increasing number (and percentage) of patients diagnosed by screening. When the screening programmes are assumed to achieve the optimal effect, the reduction in mortality will increase and treatment costs fall, resulting in a substantial decrease in the cost-effectiveness ratio. In the last considered period (2008-2012) the costs per life year gained (breast cancer 5700) are approximately one half of those at the onset of screening. The differences in the costs per LYG were relatively small between the Nordic countries and mainly dependent on the differences in baseline risk of cancer. The total cost of the three screening programmes was estimated at $4400 per life years gained in the year 2010.(ABSTRACT TRUNCATED)
Screening programmes for cervical cancer have been credited with reducing the incidence of and mortality from cervical cancer. The main components of these screening programmes are: (i) their level of organisation; (ii) the age at which women begin screening; (iii) the age at which women discontinue screening; (iv) the interval between repeat screens; (v) the frequency at which the programmes provide screening; and (vi) the response to an abnormal screening test. However, not all screening programmes are equally efficient and differences in programme components can result in big differences in their cost effectiveness.
Studies that employ cost-effectiveness analysis (CEA) to examine the efficiency of different programme components can inform the development of costeffective programmes. This article presents findings of an international review of cost-effectiveness studies of cervical cancer screening. These studies consistently find that certain types of programmes are more cost effective than others. Programmes that are centrally organised and implemented by the public sector are reported to be more cost effective than those that use public funds for screening at other medical visits (convenience screening), or those that provide guidelines for healthcare professionals and the public to promote spontaneous discretionary screening.
There is also substantial agreement about the cost effectiveness of other programme components. When multiple screenings are possible, studies report that they should generally begin at age 25 to 35 years and end at age 65 to 70 years, although it is important that older women have 3 normal Papanicolaou (Pap) smears before the discontinuation of screening. The interval for repeat screens that is reported to provide the best balance between cost and life-years saved is between 3 and 5 years. However, when a choice must be made between screening more women fewer times, or screening fewer women more times, most studies indicate that it is more cost effective to prioritise resources to obtain at least one screening for each woman. The screening of previously unscreened and high-risk populations has been shown to be especially cost effective.
Despite this agreement, many studies report that models of the cost effectiveness of screening for cervical cancer are sensitive to a number of parameters. Changes in the attendance rate of the programme, the quality of the Pap smear, and the cost of the Pap smear can markedly change the cost effectiveness of a screening programme.
Finally, this review discusses different perspectives of social choice analysis (e.g. CEA and cost-benefit analysis), when the objective is to prevent cervical cancer and the options are to screen, detect and treat, to reduce behavioural risk factors, and/or to pursue promising biological research.
Screening by cytology is a potentially highly effective procedure for preventing carcinoma of the uterine cervix. To elucidate any weaknesses in the screening procedure in a Swedish county where screening started many years ago, the detection of invasive cervical squamous cell carcinoma was compared to the prior cytological screening.
On the basis of the complete Pathology data files, including cytology and histology, all 112 women with invasive cervical squamous carcinoma were compared to 112 matched controls from the Swedish Population Register, regarding attendance rate and results of Pap-smears prior to the date of discovery of an invasive carcinoma in the case.
Almost as many cases as controls had a history of pap-smear testing, but the cases had significantly more prior atypias registered. Only 16% of women with cervical carcinoma and younger than 60 years were lacking Pap-smear tests prior to the carcinoma diagnosis, but 46% had former atypias registered. More than half of them presented, however, a negative Pap-smear test less than three years before the diagnosis. Among the controls, 10% were lacking prior Pap-smears and only 9% had former atypias registered.
The policy for follow-up and treatment of cervical dysplasias has to be improved in order to achieve a further reduction of the incidence of invasive carcinoma.
To evaluate the accuracy of conventional and new methods of Papanicolaou (Pap) testing when used to detect cervical cancer and its precursors.
Systematic search of English-language literature through October 1999 using MEDLINE, EMBASE, other computerized databases, and hand searching.
All studies that compared Pap testing (conventional methods, computer screening or rescreening, or monolayer cytology) with a concurrent reference standard (histologic examination, colposcopy, or cytology).
Two reviewers independently reviewed selection criteria and completed 2 x 2 tables for each study.
94 studies of the conventional Pap test and three studies of monolayer cytology met inclusion criteria. No studies of computerized screening were included. Data were organized by cytologic and histologic thresholds used to define disease. For conventional Pap tests, estimates of sensitivity and specificity varied greatly in individual studies. Methodologic quality and frequency of histologic abnormalities also varied greatly between studies. In the 12 studies with the least biased estimates, sensitivity ranged from 30% to 87% and specificity ranged from 86% to 100%.
Insufficient high-quality data exist to estimate test operating characteristics of new cytologic methods for cervical screening. Future studies of these technologies should apply adequate reference standards. Most studies of the conventional Pap test are severely biased: The best estimates suggest that it is only moderately accurate and does not achieve concurrently high sensitivity and specificity. Cost-effectiveness models of cervical cancer screening should use more conservative estimates of Pap test sensitivity.
To determine the potential effects on costs and outcomes of changes in sensitivity and specificity with new screening methods for cervical cancer.
Using a Markov model of the natural history of cervical cancer, we estimated the effects of sensitivity, specificity, and screening frequency on cost-effectiveness. Our estimates of conventional Papanicolaou test sensitivity of 51% and specificity of 97% were obtained from a meta-analysis. We estimated the effect of reducing false-negative rates from 40-90% and increasing false-positive rates by up to 20%, independently and jointly. We varied the marginal cost of improving sensitivity from 15.
When specificity was held constant, increasing sensitivity of the Papanicolaou test increased life expectancy and costs. When sensitivity was held constant, decreasing specificity of the Papanicolaou test increased costs, an effect that was more dramatic at more frequent intervals. Decreased specificity had a substantial effect on cost-effectiveness estimates of improved Papanicolaou test sensitivity. Most of those effects are related to the cost of evaluation and treatment of low-grade lesions.
Policies or technologies that increased sensitivity of cervical cytologic screening increased overall costs, even if the cost of the technology was identical to that of conventional Papanicolaou smears. These effects appear to be caused by relatively high prevalence of low-grade lesions and are magnified at frequent screening intervals. Efficient cervical cancer screening requires methods with greater ability to detect lesions that are most likely to become cancerous.
Organised cervical cancer screening was implemented in Sweden in the mid-1960s. A marked decline in cervical cancer incidence could be attributed to the time-point of start of screening. Squamous cell carcinoma has declined by 60%, whereas adenocarcinoma has increased. About 950000 papanicolaou (Pap) smears are taken annually. Only 31% of the smears taken in the organised screening programme. As of 1998, the screening guidelines are 3-yearly tests between 23 and 50 years of age and 5-yearly tests between 50 and 60 years of age. The article reviews the screening practise in Sweden, the current efforts to improve the quality of the screening programme, as well as the ongoing randomised evaluations of organised primary screening for cervical human papilloma virus (HPV) infection.
Age-incidence relationships are informative of carcinogenic mechanisms. These have been previously assessed for cervical squamous cell carcinoma (SCC) but not for adenocarcinoma. The aim was to assess by means of age-, period- and cohort-specific analyses and Poisson regression modelling whether the two types of cervical cancer show an age-incidence maximum at a relatively young age, as shown in cross-sectional analyses. The Swedish Family-Cancer Database was used to analyse age-incidence relationships in cervical SCC and adenocarcinoma diagnosed in years 1958-1996, including a total of 15,118 and 1866 cases, respectively. Area of residence and socio-economic status were included in analyses because they were risk factors of cervical cancer. The analysis of cervical SCC confirmed an incidence maximum at ages 35-39 years. The data for adenocarcinoma also suggested a similar early age maximum but the curves differed extensively by birth cohort. The incidence of adenocarcinoma increased substantially at young age groups towards the end of follow-up. Endometrial adenocarcinoma and vaginal and vulvar SCC, which share some risk factors with cervical cancer, did not show an early age incidence maximum. The results also showed that there was a decrease in the incidence of cervical SCC around year 1960, almost 10 years before the organized population screening, probably due to introduced opportunistic pap testing. The benefits of the organized screening were observed as a further decline in the incidence rates. The unique age-incidence relationships in cervical cancer call for biological explanations.
Human papillomavirus (HPV) DNA testing can be used to identify women at risk of the development of cervical cancer. The cost-effectiveness of HPV screening is dependent on the type-specific HPV prevalence in the general population. The present study describes the prevalence and spectrum of high-risk HPV types found in a large real-life population-based HPV screening trial undertaken entirely within the cervical screening program offered to middle-aged Swedish women. Cervical brush samples from 6,123 women aged 32-38 years were analyzed using a general HPV primer (GP5+/6+) polymerase chain reaction-enzyme immunoassay (PCR-EIA) combined with reverse dot-blot hybridization for confirmation and HPV typing by a single assay. In this study, 6.8% (95% CI 6.2-7.5) (417/6,123) were confirmed as high-risk HPV positive. Infections with 13 different high-risk HPV types were detected, of which HPV 16 was the most prevalent type (2.1%; 128/6,123), followed by HPV 31 (1.1%; 67/6,123). Any one of the HPV types 18, 33, 35, 39, 45, 51, 52, 56, 58, 59, or 66 was detected in 3.6% (223/6,123) of the women. Infection with two, three, and five types simultaneously was identified in 32, 5, and 1 women, respectively. The combination of PCR-EIA as a screening test and reverse dot-blot hybridization as a confirmatory test, was found to be readily applicable to a real-life population-based cervical screening. The type-specific HPV prevalence found support in previous modeling studies suggesting that HPV screening may be a favorable cervical screening strategy.
Up to 1995, programme screening for cervical cancer in The Netherlands was targeted at women between 35 and 54 years of age at 3-yearly intervals. Spontaneous screening in addition to programme screening was common practice. Our aim was to compare the underlying risk for cervical neoplasia for women involved in both types of screening. From the national pathological database, we retrieved all primary smears (n=693318) taken in 1994 in The Netherlands. Among the smears registered for screening purposes (39%), 79% was taken within the mass screening programme and 21% was taken for spontaneous screening. The underlying risk was studied from the detection rates of histologically confirmed severe dysplasia or worse, using a multivariate loglinear model, including age and screening history. The detection rate of at least severe dysplasia, adjusted for age and screening history, was equal for women who had a spontaneous smear and for those who had a programme smear (odds ratio (OR): 0.97; 95% Confidence Interval (CI): 0.84-1.14). In our data, women participating in spontaneous screening were not at a higher risk for cervical cancer than women who used programme screening. Therefore, all asymptomatic women in the Netherlands should follow the general guidelines for age-range and screening-interval.
To estimate the potential effects, on costs and outcomes, of changes in sensitivity and specificity associated with new screening methods for cervical cancer in the military.
A Markov model of the natural history of cervical cancer was created to simulate a cohort of 100,000 military beneficiaries aged 18-85. Probability estimates for various outcomes and the accuracy of screening tests were obtained from the literature. Cost estimates were obtained from military sources where available; otherwise, civilian costs were used. The outcomes and costs of conventional cytology, liquid-based cytology, and liquid-based cytology with human papillomavirus (HPV) triage were compared at 1-, 2-, and 3-year screening frequencies.
Marginal reductions in the incidence of cervical cancer from increasing screening sensitivity are greater than reductions in cancer mortality at every screening interval. Incremental improvements in both cancer incidence and mortality are higher at less frequent screening intervals. Increases in the ratio of low- to high-grade lesions result from increasing the sensitivity of the screening test or shortening the screening interval. Both liquid-based cytology and liquid-based cytology with HPV testing are cost effective (less than $50,000 per life-year saved) when performed at 3-year screening intervals. However, neither strategy is cost-effective when performed more frequently than every 3 years.
Use of a more sensitive cervical cancer screening test increases costs. However, a more sensitive test performed less frequently may be more effective and less expensive than conventional cytology done annually. In the military setting, this has significant implications for both expense reduction and readiness enhancement.
During the past 50 years, the histologic classification of cervical intraepithelial neoplasia (CIN) has evolved to incorporate the entire spectrum of genital papillomavirus infections, segregating those lesions with the higher risk of containing prototypic high-risk human papillomavirus types, and recently has meshed with treatment algorithms that include loop electrical excision procedures and follow-up alone. This review describes a classification system that divides CIN into categories of low-grade (CIN 1) and high-grade (CIN 2 and CIN 3). To successfully apply this system, the practitioner must efficiently exclude nonneoplastic entities and base the distinction of CIN 1 from CIN 2/3 on criteria that recognize the effects of viral oncogenes on replicating cells. This is achieved by basing the diagnosis of CIN 1 on uniform polarized epithelial growth, low mitotic index, low mitotic counts, and minimal parabasal cell anisokaryosis and coarse chromatin and CIN 2 on the presence of these features or abnormal mitoses. Simply put, the definition of CIN 2 (or higher) is the presence of atypical immature cells in the biopsy that if seen in a cytologic smear would merit a diagnosis of high-grade squamous intraepithelial lesion. In essence, a successful two-grade system requires careful application of cytologic criteria in a histologic milieu. This model is illustrated in a set of 25 images that underscore the importance of excluding benign changes (with the appropriate use of biomarkers), segregating unusual variants of low-grade squamous intraepithelial lesions, and identifying the morphologic transition to high-grade squamous intraepithelial lesions (CIN 2 or CIN 3) with an acceptable level of reproducibility.
To determine the frequency of different outcomes in women participating in cervical screening.
Analysis of screening records from 348 419 women, and modelling of cases of cervical cancer and deaths with and without screening.
Cervical screening programme in Bristol.
For every 10 000 women screened from 1976 to 1996, 1564 had abnormal cytology, 818 were investigated, and 543 had abnormal histology. One hundred and seventy six had persistent abnormality for two years or more. In the absence of screening 80 women would be expected to develop cancer of the cervix by 2011, of whom 25 would die. With screening 10 of these deaths would be avoided. Comparison of cumulative abnormality rates with numbers expected to develop cancer in the absence of screening suggests that at least 80% of high grade dyskaryosis and of high grade dysplasia would not progress to cancer. The lifetime risk of having abnormal cytology detected could be as high as 40% for women born since 1960.
Screening is labour and resource intensive. It involves treatment for many women not destined to develop invasive cancer. The increased intervention rate for cervical abnormality in England is due to change in practice, not a cohort effect, and is probably the reason for the marked fall in incidence and mortality during the 1990s. For other cancers there is scope for major iatrogenic harm from screening because of invasive tests and treatments.
The need for consistency and standardization of methods for economic appraisals has been recognized for some time and has led to the development of several sets of guidelines for economic evaluations and for costs. Despite this, considerable diversity is still apparent in applied studies. Some of these diversities might be defensible, and some might not. The objectives of this study are to explore sources of variations in the methods used in applied studies and to discuss the nature of these variations and the possibility of reducing some of them.
We first use a systematic approach to identify the major sources of variation in costing methods used in applied economic evaluations. We then compare the methods used with the recommendations made in available guidelines.
Four possible sources of variation are identified. The first is where guidelines do not agree in their recommendations; therefore, it is not surprising that applied studies use different methods. The second is where guidelines agree in principle but provide little detail on how to comply with their recommendations; and the third is where a particular methodological issue is not discussed in guidelines. The fourth reason is simply lack of compliance with accepted guidelines.
Variability in costing methods used in applied studies raises questions about the validity of their results and makes it difficult to compare the results of different studies. We discuss the implications for the transferability and generalizability of results and suggest ways to minimize the variability in the methods so that the results of costing studies and economic evaluations can be of more value to policy-makers.
Our objective was to review current large studies of human papillomavirus (HPV) DNA testing as an adjunct to the Papanicolaou test for cervical cancer screening programs. We analyzed 10 large screening studies that used the Hybrid Capture 2 test and 3 studies that used the polymerase chain reaction test in a manner that enabled reliable estimates of accuracy for detecting or predicting high-grade cervical intraepithelial neoplasia (CIN). Most studies allowed comparison of HPV DNA and Papanicolaou testing and estimates of the performance of Papanicolaou and HPV DNA as combined tests. The studies were selected on the basis of a sufficient number of cases of high-grade CIN and cancer to provide meaningful statistical values. Investigators had to demonstrate the ability to generate reasonably reliable Hybrid Capture 2 or polymerase chain reaction data that were either minimally biased by nature of study design or that permitted analytical techniques for addressing issues of study bias to be applied. Studies had to provide data for the calculation of test sensitivity, specificity, predictive values, odds ratios, relative risks, confidence intervals, and other relevant measures. Final data were abstracted directly from published articles or estimated from descriptive statistics presented in the articles. In some studies, new analyses were performed from raw data supplied by the principal investigators. We concluded that HPV DNA testing was a more sensitive indicator for prevalent high-grade CIN than either conventional or liquid cytology. A combination of HPV DNA and Papanicolaou testing had almost 100% sensitivity and negative predictive value. The specificity of the combined tests was slightly lower than the specificity of the Papanicolaou test alone, but this decrease could potentially be offset by greater protection from neoplastic progression and cost savings available from extended screening intervals. One "double-negative" HPV DNA and Papanicolaou test indicated better prognostic assurance against risk of future CIN 3 than 3 subsequent negative conventional Papanicolaou tests and may safely allow 3-year screening intervals for such low-risk women.
Cervical cancer is caused by infection with a range of high risk “oncogenic” human papillomavirus (HPV) types, and it is now accepted that >99% of cervical cancer is initiated by HPV infection. The estimated lifetime risk of cervical cancer is nevertheless relatively low (less than 1 in 20 for most community based studies). Although sensitivity and specificity of the available diagnostic techniques are suboptimal, screening for persistent HPV infection is effective in reducing the incidence of cervical cancer. Infection can be detected by molecular techniques or by cytological examination of exfoliated cervical cells. Persistent infection is the single best predictor of risk of cervical cancer.1
The latest findings of HPV and cervical cancer research need to be widely disseminated to the scientific and medical societies that are updating screening and management protocols, public health professionals, and to women and clinicians. This report reviews current evidence, clinical implications and directions for further research in the prevention, control and management of cervical cancer. We report the conclusions of the Experts' Meeting at the EUROGIN 2003 conference.
Certain types of human papillomavirus (HPV) are the primary cause of almost all cervical cancers. HPV testing of cervical smears is more sensitive but less specific than cytology for detecting high-grade cervical intraepithelial neoplasia (CIN2+). HPV testing as a primary screening approach requires efficient management of HPV-positive women with negative or borderline cytology. We aimed to compare the detection rate and positive predictive values of HPV assay with cytology and to determine the best management strategy for HPV-positive women.
We did a multicentre screening study of 11085 women aged 30-60 years. Women with borderline cytology and women positive for high-risk HPV with negative cytology were randomised to immediate colposcopy or to surveillance by repeat HPV testing, cytology, and colposcopy at 12 months.
HPV testing was more sensitive than borderline or worse cytology (97.1% vs 76.6%, p=0.002) but less specific (93.3% vs 95.8%, p<0.0001) for detecting CIN2+. Of 825 randomised women, surveillance at 12 months was as effective as immediate colposcopy. In women positive for HPV at baseline, who had surveillance, 73 (45%) of 164 women with negative cytology and eight (35%) of 23 women with borderline cytology were HPV negative at 6-12 months. No CIN2+ was found in these women, nor in women with an initial negative HPV test with borderline (n=211) or mild (32) cytology.
HPV testing could be used for primary screening in women older than 30 years, with cytology used to triage HPV-positive women. HPV-positive women with normal or borderline cytology (about 6% of screened women) could be managed by repeat testing after 12 months. This approach could potentially improve detection rates of CIN2+ without increasing the colposcopy referral rate.
Human papillomavirus (HPV) DNA testing was recently approved by the Food and Drug Administration for use as an adjunct to cytology for cervical cancer screening. To help provide guidance to clinicians and patients when using HPV DNA testing as an adjunct to cervical cytology for screening, a workshop was cosponsored by the National Institutes of Health-National Cancer Institute, American Society of Colposcopy and Cervical Pathology (ASCCP), and American Cancer Society. Consensus was reached based on a literature review, expert opinion, and unpublished results from large ongoing screening studies. The conclusions of the workshop were that HPV DNA testing may be added to cervical cytology for screening in women aged 30 years or more. Women whose results are negative by both HPV DNA testing and cytology should not be rescreened before 3 years. Women whose results are negative by cytology, but are high-risk HPV DNA positive, are at a relatively low risk of having high-grade cervical neoplasia, and colposcopy should not be performed routinely in this setting. Instead, HPV DNA testing along with cervical cytology should be repeated in these women at 6 to 12 months. If test results of either are abnormal, colposcopy should then be performed. This guidance should assist clinicians in utilizing HPV DNA testing in an effective manner, while minimizing unnecessary evaluations and treatments.
To evaluate the cost-effectiveness of human papillomavirus (HPV) DNA testing as a primary screening test in combination with cervical cytology in women aged 30 years or more.
A state-transition mathematical model was used to simulate the natural history of HPV and cervical cancer in a cohort of U.S. women. Strategies included no screening and screening at different frequencies with conventional cytology, liquid-based cytology with HPV testing used for triage of equivocal results, and HPV DNA testing and cytology in combination after women had reached the age of 30. Outcomes measured included cancer incidence, life expectancy, lifetime costs, and incremental cost-effectiveness ratios.
The estimated reduction in lifetime risk of cervical cancer varies from 81% to 93% depending on the screening frequency, type of cytology, and test strategy. Every 3-year screening with liquid-based cytology administered to women at all ages and every 3-year screening using HPV DNA testing and cytology in combination administered to women aged 30 years or more provide equivalent or greater benefits than those provided by annual conventional cytology and have incremental cost-effectiveness ratios of US dollars 95300 and US dollars 228700 per year of life gained, respectively. In comparison, annual screening with HPV DNA testing and cytology in combination provides only a few hours of additional life expectancy and has a cost-effectiveness ratio of more than Us dollars 2000000 per year of life gained.
For women aged 30 years and more, every 2- or 3-year screening strategy that uses either HPV DNA testing in combination with cytology for primary screening or cytology with reflex HPV DNA testing for equivocal results will provide a greater reduction in cancer and be less costly than annual conventional cytology.
We evaluated the interlaboratory reproducibility of the Hybrid Capture 2 (HC2; Digene, Gaithersburg, MD), a test for oncogenic human papillomavirus (HPV) DNA, using data from 4 clinical center (CC) laboratories and the quality control (QC) laboratory participating in the ASCUS (atypical squamous cells of undetermined significance) and LSIL (low-grade squamous intraepithelial lesion) Triage Study (ALTS). Residual liquid cytology specimens were tested routinely throughout the duration of ALTS at CC laboratories, and a stratified (by time in the study) random sample of specimens was retested by the HPV QC laboratory using equivalent protocols. Of the specimens selected (N = 1,175, 5.50% of all specimens obtained), 1,072 (91.23%) had sufficient specimen volume for retesting. The kappa value between all CC laboratories and the HPV QC laboratory was 0.84 (95% confidence interval, 0.78-0.89), with kappa values for individual CCs and the HPV QC laboratory ranging from 0.79 to 0.89. Agreement between test results was lowest among results for women with negative cytologic findings (0.73); among those with equivocal or abnormal cytologic findings, kappa values were 0.80 or more. These data show that HC2 is a reliable test for detecting clinically relevant oncogenic HPV DNA.
Evaluation of colposcopic and histopathological findings in women screened for cervical human papillomavirus deoxyribonucleic acid persistence.
A total of 12 527 women, aged 32 to 38 years old, attending the population-based cervical cancer screening program in Sweden were randomized 1:1 to mock testing or human papillomavirus deoxyribonucleic acid testing by general primer 5+/6+ polymerase chain reaction and subsequent typing. Human papillomavirus deoxyribonucleic acid-positive women with a normal Papanicolaou smear (n=341) and an equal number from the control group were human papillomavirus tested on average 19 months later. One hundred nineteen women with type-specific human papillomavirus persistence and 111 controls were referred to colposcopy, and 84.8% attended.
Histopathology from colposcopically directed biopsies confirmed cervical intraepithelial neoplasia grade 2 or 3 in 28 of 100 of the women with human papillomavirus deoxyribonucleic acid persistence and in 2 of 95 among controls.
Among women with normal Papanicolaou smear attending population-based screening, the positive predictive value of human papillomavirus deoxyribonucleic acid persistence for detection of biopsy-confirmed cervical intraepithelial neoplasia 2 or 3 was 29%.
More than ever, clinicians need regularly updated reviews given the continuously increasing amount of new information regarding innovative cervical cancer prevention methods.
A summary is given from recently published meta-analyses on three possible clinical applications of human papillomavirus (HPV)-DNA testing: triage of women with equivocal or low-grade cytological abnormalities; prediction of the therapeutic outcome after treatment of cervical intraepithelial neoplasia (CIN) lesions, and last not but not least, primary screening for cervical cancer and pre-cancer.
Consistent evidence is available indicating that HPV-triage with the Hybrid Capture-2 assay (HC2) is more accurate (significantly higher sensitivity, similar specificity) than repeat cytology to triage women with equivocal Pap smear results. When triaging women with low-grade squamous intraepithelial lesions (LSIL), a reflex HC2 test does not show a significantly higher sensitivity, but a significantly lower specificity compared to a repeat Pap smear. After treatment of cervical lesions, HPV testing easily detects (with higher sensitivity and not lower specificity) residual or recurrent CIN than follow-up cytology. Primary screening with HC2 generally detects 23% (95% confidence interval, CI: 13-23%) more CIN-2, CIN-3, or cancer compared to cytology at cut-off atypical squamous cells of undetermined significance (ASCUS) or LSIL, but is 6% (95% CI: 4-8%) less specific. By combined HPV and cytology screening, a further 4% (95% CI: 3-5%) more CIN-3 lesions can be identified but at the expense of a 7% (95% CI: 5-9%) loss in specificity, in comparison with isolated HC2 screening.
Sufficient evidence exists to recommend HPV testing in triage of women with atypical cytology and in surveillance after treatment of CIN lesions. In the United States, recently reviewed knowledge has resulted in the approval of combined cytology and HC2 primary screening in women older than 30 years. However, in Europe, cytology-based screening still remains the standard screening method. The European screening policy will be reviewed based on the longitudinal results of randomised population trials which are currently underway.
This chapter reviews the contribution of cervical cytology, what makes it successful, the management of screen positives and how technological advances may affect its use in the future. Cervical screening has saved hundreds of thousands of lives but has not been available to women in the poorest countries. In countries where wide coverage has been achieved and quality assurance is in place, incidence and death rates have fallen by over 50% even though cervical cytology is logistically complex. The management of high-grade cervical intraepithelial neoplasia (CIN) is very effective, but low-grade cytological abnormalities require care to avoid over-treatment. The increasing rate of human papillomavirus (HPV) testing and the prospect of prophylactic vaccination will change the way cervical cytology is used, possibly giving way to HPV testing as the primary test in secondary prevention.
The major steps in cervical carcinogenesis include infection of the metaplastic epithelium of the cervical transformation zone with one or more of the 12-18 carcinogenic types of human papillomavirus (HPV) infection, viral persistence, clonal progression of the persistently-infected epithelium to cervical precancer, and invasion. Although these fundamental steps are established, several new epidemiologic studies have shed light on the factors that influence each of these transitions. The importance of the transformation zone in cervical cancer has been extended to other HPV-induced cancers such as anal or tonsillar cancers. Natural history studies show that HPV with normal cervical cytology and cervical intraepithelial neoplasia (CIN) grade 1 behave similarly, with the majority of both showing regression. Although these studies have demonstrated the importance of HPV persistence in the development of precancer CIN-3, the timing from infection to evidence of CIN-3 varies from 1 to 10 years. Whether equivalent lesions diagnosed later differ in their natural history remains unknown. Several factors have been implicated in enhancing persistence and/or progression. However, none are consistently associated with both except age: young women are less likely to show persistence and older women with persistence are more likely to be at risk of invasive cancer. Recent studies have also underscored the importance of the host immune response in clearance of established infections. Finally, data on non-cervical HPV infections, such as penile infections are limited to date compared to cervical infections. Several ongoing cohort studies should give us further insight into male infections in the near future.
Geographical widespread data on human papillomavirus (HPV) type-distribution are essential for estimating the impact of HPV-16/18 vaccines on cervical cancer and cervical screening programmes. Epidemiological studies employing a variety of HPV typing protocols have been collated in meta-analyses. HPV-16/18 is estimated to account for 70% of all cervical cancers worldwide, although the estimated HPV-16/18 fraction is slightly higher in more developed (72-77%) than in less developed (65-72%) regions. About 41-67% of high-grade squamous intraepithelial lesion (HSIL), 16-32% of low-grade squamous intraepithelial lesion (LSIL) and 6-27% of atypical squamous cells of undetermined significance (ASCUS) are also estimated to be HPV-16/18-positive, thus highlighting the increasing relative frequency of HPV-16/18 with increasing lesion severity. After HPV-16/18, the six most common HPV types are the same in all world regions, namely 31, 33, 35, 45, 52 and 58; these account for an additional 20% of cervical cancers worldwide.
Bengt Andrae, överläkare, ordförande i Svensk förening för obstetrik och gynekologi arbets-och referensgrupp för cervixcancerprevention (C-ARG), kvinnokliniken, Gävle-Sandvikens sjukhus
- Agneta Andersson-Ellström
- Göteborg Mödrahälsovårdsöverläkare
Agneta Andersson-Ellström, mödrahälsovårdsöverläkare, Göteborg.
Bengt Andrae, överläkare, ordförande i Svensk förening för obstetrik och
gynekologi arbets-och referensgrupp för cervixcancerprevention (C-ARG),
kvinnokliniken, Gävle-Sandvikens sjukhus.
Björn Strander, överläkare, vårdcentralen Mölndal, sekreterare i Svensk förening för obstetrik och gynekologi arbets-och referensgrupp för cervixcancerprevention (C-ARG)
- Pär Sparen
- Karolinska Epidemiologi Och Biostatistik
- Institutet
Pär Sparen, professor, Institutionen för medicinsk epidemiologi och biostatistik,
Karolinska Institutet, Stockholm.
Björn Strander, överläkare, vårdcentralen Mölndal, sekreterare i Svensk
förening för obstetrik och gynekologi arbets-och referensgrupp för cervixcancerprevention (C-ARG), Onkologisk Centrum, Västra sjukvårdsregionen.
Clinical application of HPV testing: a summary of meta-analyses
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No comfirmed case of HPV DNA-negative CIN3 or invasive primary cancer of the uterine cervix among 511 patients
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