Effects and Costs of Cervical Cancer Screening

The objective of this thesis is to evaluate cervical eaueer screening by assessing its various effects and costs. Questions to be addressed concern the rednetion in incidence and mortality, the unfavourablc effects and the cost-effectiveness of different screening polides (age range and interval combinations). To this end, we used acervical eaueer version of MISCAN, a simulation model that was designed and programmed to evaluate cancer screening. This cervical eaueer screening model. had already been tested against screening data sets from British Columbia (Canada) and from Dutch pilot screeningprojectsin 1976- 1985. The potential impact of new developments in cervical eaueer screening, such as auto~1ated cytological evaluation and HPV-testing, has been investigated. The ultimate questions are: should ccrvical caoeer screening be conti. nued, and what changes should be recommended in order to iinprove its efficiency? The relationship between benefits and unfavourable effects was stuclied for three efficient cervical cancer screening strategies incorporating 5, 10 and 25 smears per woman (Chapter 2). It was concluded that wlien the screening frequency was increased, the ratio of favourable to unfavourable effects became worse

The management of cervical intra-epithelial neoplasia (CIN): Extensiveness and costs in The Netherlands

In order to provide greater insight into both the extensiveness and the medical costs of the diagnosis and treatment of screen-detected cervical intra-epithelial neoplasia (CIN) in general medical practice in The Netherlands, data from national registries and gynaecology departments were retrieved, and experts were interviewed. Of the 5060 women diagnosed with CIN in 1988, more than 50% were treated in hospital with conisation or hysterectomy, which on average took 5.5 days stay per admission. The assessed average duration of the total pre- and post-treatment period is 4.6 years. The average total medical costs in women with detected CIN III are Dfl 3700 per woman. The diagnosis of CIN I and II involves more medical procedures and time than CIN III, but fewer women have conisation or hysterectomy, resulting in lower total medical costs (Dfl 2572). The overall extent and costs of the management of CIN should be accounted for when balancing the benefits, unfavourable effects and costs of cervical cancer screening

Positive diagnostic values and histological detection ratios from the Rotterdam cervical cancer screening programme

BACKGROUND: In organized screening programmes for cervical cancer, pre-cancerous lesions are detected by cervical smears. However, during follow-up after a positive smear these pre-cancerous lesions are not always found. The purpose of the study is to analyse positive diagnostic values of smears of at least mild dysplasia, made under the organized screening programmes in the Rotterdam area (1979-1991), and detection ratios of histologically confirmed CIN > or =3, among women participating in these screening programmes. METHODS: Positive diagnostic values and histological detection ratios, by age and history of previous smears, recorded during the national screening programme (1989-1991), were compared with those of the experimental cervical cancer screening project (1976-1984). RESULTS: The positive diagnostic value of a smear with at least severe dysplasia (histologically confirmed CIN > or =3) remains approximately 78%. For smears with mild and moderate dysplasia only lower limits of the diagnostic value could be determined. This was 9% for a smear with mild dysplasia obtained during the national screening programme and 25% and 35% for smears with moderate dysplasia taken during the experimental and national screening programmes respectively. Histological detection ratios for CIN > or =3 in the three rounds of the experimental screening project were 4.7, 2.9 and 1.9. In the first round of the national screening programme the ratio was 4.7, and about three times higher in younger compared to older women. CONCLUSION: Immediate referral for colposcopy after a smear showing moderate dysplasia seems questionable. Whether the increased detection ratio among young women indicates a rise in the risk of cervical cancer is unclear

The potential harms of primary human papillomavirus screening in over-screened women: a microsimulation study

Background: It is well acknowledged that HPV testing should not be performed at young age and at short intervals. Cytological screening practices have shown that over-screening, i.e., from a younger age and at shorter intervals than recommended, is hard to avoid. We quantified the consequences of a switch to primary HPV screening for over-screened women, taking into account its higher sensitivity but lower specificity than cytology. Methods: The health effects of using the HPV test instead of cytology as the primary screening method were determined with the MISCAN-Cervix model. We varied the age women start screening and the interval between screens. In the sensitivity analyses, we varied the background risk of cervical cancer, the HPV prevalence, the discount rate, the triage strategy after cytology, and the test characteristics of both cytology and the HPV test. Results: For women screened 5 yearly from age 30, 32 extra deaths per 100,000 simulated women were prevented when switching from primary cytology to primary HPV testing. For annual screening from age 20, such a switch resulted in 6 extra deaths prevented. It was associated with 9,044 more positive primary screens in the former scenario versus 76,480 in the latter. Under all conditions, for women screened annually, switching to HPV screening resulted in a net loss of quality-adjusted life years. Conclusion: For over-screened women, the harms associated with a lower test specificity outweigh the life years gained when switching from primary cytology to primary HPV testing. The extent of over-screening should be considered when deciding on inclusion of primary HPV screening in cervical cancer screening guidelines

Vitamin K status and physical decline in older adults—The Longitudinal Aging Study Amsterdam

Objective: We examined the association between vitamin K status and physical functioning over 13 years in the Longitudinal Aging Study Amsterdam. Study design: Longitudinal cohort study of 633 community-dwelling adults from the Longitudinal Aging Study Amsterdam (LASA) aged 55–65 years (54% women). Main outcome measures: At baseline (2002–2003), plasma desphospho-uncarboxylated matrix Gla protein (dp-ucMGP) was measured with a sandwich ELISA as a marker of vitamin K status. The outcome measures handgrip strength, calf circumference, self-reported functional limitations and functional performance were obtained at baseline and four follow-up examinations. We used generalized estimating equations to determine the relationship between dp-ucMGP tertiles and the various outcome measurements after adjusting for potential confounders. The lowest dp-ucMGP tertile reflects a high vitamin K status and was the reference. Results: Mean dp-ucMGP was 376 ± 233 pmol/L and mean follow-up was 11.1 years. Participants showed a decline in the outcome measures over time. Compared with the lowest tertile, the highest dp-ucMGP tertile had: lower handgrip strength, 1.1 kg (95% confidence interval (−2.1, −0.1; P-trend <0.001); smaller calf circumference, −0.5 cm (−0.9 −0.1; P-trend = 0.018); and, only among women, a 0.7-point poorer functional performance score (−1.1, −0.3; P-interaction = 0.002). Dp-ucMGP was not related to self-reported functional limitations. No interaction effects between time and dp-ucMGP were observed. Conclusions: Low vitamin K status was associated with lower handgrip strength, smaller calf circumference, and, in women only, with poorer functional performance score. A low vitamin K status was however not related to the 13-year decline in these measures

Geen basis voor verlaging onderste leeftijdsgrens van bevolkingsonderzoek op baarmoederhalskanker

Doel:\ud Nagaan of de onderste leeftijdsgrens van het bevolkingsonderzoek op baarmoederhalskanker verlaagd moet worden.\ud \ud Opzet:\ud Retrospectieve data-analyse.\ud \ud Methode:\ud Uit de Nederlandse Kankerregistratie werden alle gevallen geselecteerd van invasieve baarmoederhalskanker, gediagnosticeerd in de periode 1989-2003. Voor de leeftijdsgroep van 25-39 jaar waren ook gegevens beschikbaar over 2004 en 2005. Gegevens over sterfte werden verkregen via het Centraal Bureau voor de Statistiek. Trends werden beschreven met behulp van de geschatte jaarlijkse procentuele verandering en ‘joinpoint’-analyse.\ud \ud Resultaten:\ud Bij de 25-29-jarigen varieerde het aantal gevallen van baarmoederhalskanker van 0 tot 9 per jaar. De incidentie van baarmoederhalskanker daalde in de leeftijdsgroepen van 35-39 en 45-49 jaar (respectievelijk p < 0,001 en p = 0,012). Het aantal vrouwen dat stierf aan baarmoederhalskanker fluctueerde per jaar en daalde in de leeftijdsgroepen van 30-34 en 35-39 jaar (respectievelijk p = 0,01 en p = 0,03).\ud \ud Conclusie:\ud De incidentie- en sterftecijfers van baarmoederhalskanker onder vrouwen jonger dan 30 jaar zijn heel laag en stijgen niet. Met het verlagen van de onderste leeftijdsgrens van het bevolkingsonderzoek zouden veel afwijkingen worden opgespoord die normaliter in regressie zouden gaan. Omdat de voordelen van het verlagen van de leeftijdsgrens niet opwegen tegen de nadelen in termen van overbehandeling en angst heeft deze verlaging volgens ons op dit moment geen zin

Cost-effectiveness of cervical cancer screening: comparison of screening policies

BACKGROUND: Recommended screening policies for cervical cancer differ widely among countries with respect to targeted age range, screening interval, and total number of scheduled screening examinations (i.e., Pap smears). We compared the efficiency of cervical cancer-screening programs by performing a cost-effectiveness analysis of cervical cancer-screening policies from high-income countries. METHODS: We used the microsimulation screening analysis (MISCAN) program to model and determine the costs and effects of almost 500 screening policies, some fictitious and some actual (i.e., recommended by national guidelines). The costs (in U.S. dollars) and effects (in years of life gained) were compared for each policy to identify the most efficient policies. RESULTS: There were 15 efficient screening policies (i.e., no alternative policy exists that results in more life-years gained for lower costs). For these policies, which considered two to 40 total scheduled examinations, the age range expanded gradually from 40-52 years to 20-80 years as the screening interval decreased from 12 to 1.5 years. For the efficient policies, the predicted gain in life expectancy ranged from 11.6 to 32.4 days, compared with a gain of 46 days if cervical cancer mortality were eliminated entirely. The average cost-effectiveness ratios increased from $6700 (for the longest screening interval) to$23 900 per life-year gained. For some countries, the recommended screening policies were close to efficient, but the cost-effectiveness could be improved by reducing the number of scheduled examinations, starting them at later ages, or lengthening the screening interval. CONCLUSIONS: The basis for the diversity in the screening policies among high-income countries does not appear to relate to the screening policies' cost-effectiveness ratios, which are highly sensitive to the number of Pap smears offered during a lifetime