[Health technology assessment report: Computer-assisted Pap test for cervical cancer screening]

HEALTH PROBLEM: Cervical cancer is a disease which is highly preventable by means of Pap test screening for the precancerous lesions, which can be easily treated. Furthermore, in the near future, control of the disease will be enhanced by the vaccination which prevents the infection of those human papillomavirus types that cause the vast majority of cervical cancers. The effectiveness of screening in drastically reducing cervical cancer incidence has been clearly demonstrated. The epidemiology of cervical cancer in industrialised countries is now determined mostly by the Pap test coverage of the female population and by the ability of health systems to assure appropriate follow up after an abnormal Pap test.

Today there are two fully automated systems for computer-assisted Pap test: the BD FocalPoint and the Hologic Imager. Recently, the Hologic Integrated Imager, a semi-automated system, was launched. The two fully automated systems are composed of a central scanner, where the machine examines the cytologic slide, and of one or more review stations, where the cytologists analyze the slides previously centrally scanned. The softwares used by the two systems identify the fields of interest so that the cytologists can look only at those points, automatically pointed out by the review station. Furthermore, the FocalPoint system classifies the slides according to their level of risk of containing signs of relevant lesions. Those in the upper classes--about one fifth of the slides--are labelled as « further review », while those in the lower level of risk, i.e. slides that have such a low level of risk that they can be considered as negative with no human review, are labelled as « no further review ». The aim of computer-assisted Pap test is to reduce the time of slide examination and to increase productivity. Furthermore, the number of errors due to lack of attention may decrease. Both the systems can be applied to liquidbased cytology, while only the BD Focal Point can be used on conventional smears.

Cytology screening has some critical points: there is a shortage of cytologists/cytotechnicians; the quality strongly depends on the experience and ability of the cytologist; there is a subjective component in the cytological diagnosis; in highly screened populations, the prevalence of lesions is very low and the activity of cytologists is very monotonous. On the other hand, a progressive shift to molecular screening using HPV-DNA test as primary screening test is very likely in the near future; cytology will be used as triage test, dramatically reducing the number of slides to process and increasing the prevalence of lesions in those Pap tests.

In this Report we assume that the diagnostic accuracy of computer-assisted Pap test is equal to the accuracy of manual Pap test and, consequently, that screening using computer-assisted Pap test has the same efficacy in reducing cervical cancer incidence and mortality. Under this assumption, the effectiveness/ benefit/utility is the same for the two screening modes, i.e. the economic analysis will be a cost minimization study. Furthermore, the screening process is identical for the two modalities in all the phases except for slide interpretation. The cost minimization analysis will be limited to the only phase differing between the two modes, i.e. the study will be a differential cost analysis between a labour-intensive strategy (traditional Pap test) and a technology-intensive strategy (the computer-assisted Pap test). Briefly, the objectives of this HTA Report are: to determine the break even point of computer-assisted Pap test systems, i.e. the volume of slides processed per year at which putting in place a computer-assisted Pap test system becomes economically convenient; to quantify the cost per Pap test in different scenarios according to screening centre activity volume, productivity of cytologist, type of cytology (conventional smear or liquid-based, fully automated or semi-automated computer-assisted); to analyse the computer-assisted Pap test in the Italian context, through a survey of the centres using the technology, collecting data useful for the sensitivity analysis of the economic evaluation; to evaluate the acceptability of the technology in the screening services; to evaluate the organizational and financial impact of the computer-assisted Pap test in different scenarios; to illustrate the ideal organization to implement computer-assisted Pap test in terms of volume of activity, productivity, and human and technological resources.

to produce this Report, the following process was adopted: application to the Ministry of health for a grant « Analysis of the impact of professional involvement in evidence generation for the HTA process »; within this project, the sub-project « Cost effectiveness evaluation of the computer-assisted Pap test in the Italian screening programmes » was financed; constitution of the Working Group, which included the project coordinator, the principal investigator, and the health economist; identification of the centres using the computer-assisted Pap test and which had published scientific reports on the subject; identification of the Consulting Committee (stakeholder), which included screening programmes managers, pathologists, economists, health policy-makers, citizen organizations, and manufacturers. Once the evaluation was concluded, a plenary meeting with Working Group and Consulting Committee was held. The working group drafted the final version of this Report, which took into account the comments received.

the fully automated computer-assisted Pap test has an important financial and organizational impact on screening programmes. The assessment of this health technology reached the following conclusions: according to the survey results, after some distrust, cytologists accepted the use of the machine and appreciated the reduction in interpretation time and the reliability in identifying the fields of interest; from an economic point of view, the automated computer-assisted Pap test can be convenient only with conventional smears if the screening centre has a volume of more than 49,000 slides/year and the cytologist productivity increases about threefold. It must be highlighted that it is not sufficient to adopt the automated Pap test to reach such an increase in productivity; the laboratory must be organised or re-organised to optimise the use of the review stations and the person time. In the case of liquid-based cytology, the adoption of automated computer- assisted Pap test can only increase the costs. In fact, liquid-based cytology increases the cost of consumable materials but reduces the interpretation time, even in manual screening. Consequently, the reduction of human costs is smaller in the case of computer-assisted screening. Liquid-based cytology has other implications and advantages not linked to the use of computer-assisted Pap test that should be taken into account and are beyond the scope of this Report; given that the computer-assisted Pap test reduces human costs, it may be more advantageous where the cost of cytologists is higher; given the relatively small volume of activity of screening centres in Italy, computer-assisted Pap test may be reasonable for a network using only one central scanner and several remote review stations; the use of automated computer-assisted Pap test only for quality control in a single centre is not economically sustainable. In this case as well, several centres, for example at the regional level, may form a consortium to reach a reasonable number of slides to achieve the break even point. Regarding the use of a machine rather than human intelligence to interpret the slides, some ethical issues were initially raised, but both the scientific community and healthcare professionals have accepted this technology. The identification of fields of interest by the machine is highly reproducible, reducing subjectivity in the diagnostic process. The Hologic system always includes a check by the human eye, while the FocalPoint system identifies about one fifth of the slides as No Further Review. Several studies, some of which conducted in Italy, confirmed the reliability of this classification. There is still some resistance to accept the practice of No Further Review. A check of previous slides and clinical data can be useful to make the cytologist and the clinician more confident.

Computer-assisted automated Pap test may be introduced only if there is a need to increase the volume of slides screened to cover the screening target population and sufficient human resources are not available. Switching a programme using conventional slides to automatic scanning can only lead to a reduction in costs if the volume of slides per year exceeds 49,000 slides/annum and cytologist productivity is optimised to more than 20,000 slides per year. At a productivity of 15,000 or fewer, the automated computer-assisted Pap test cannot be convenient. Switching from manual screening with conventional slides to automatic scanning with liquid-based cytology cannot generate any economic saving, but the system could increase output with a given number of staff. The transition from manual to computer assisted automated screening of liquid based cytology will not generate savings and the increase in productivity will be lower than that of the switch from manual/conventional to automated/conventional. The use of biologists or pathologists as cytologists is more costly than the use of cytoscreeners. Given that the automated computer-assisted Pap test reduces human resource costs, its adoption in a model using only biologists and pathologists for screening is more economically advantageous. (ABSTRACT TRUNCATED)