[Less pap-2 results ('minor abnormalities') in the population screening for cervical cancer since the introduction of new guidelines in 1996]. / Minder Pap-2-uitslagen ('lichte afwijkingen') in het bevolkingsonderzoek naar baarmoederhalskanker sinds de invoering van nieuwe richtlijnen in 1996.

OBJECTIVE: To determine whether the 1996 implementation of new guidelines for the classification and management of cervical smears in the Dutch population screening programme for cervical cancer (i.e. inflammatory symptoms are no longer classified as moderate dysplasia and women with two smears with moderate dysplasia are referred directly to the gynaecologist) was followed by a reduction in both the number of women with repeat smears and the length of follow-up. METHODS: The results of all smears of women aged 35-54 years from 1990 onwards, were retrieved from the Dutch Network and National Database for Pathology (PALGA). The percentage of smears with moderate dysplasia was analysed with respect to time. The percentage of women with a histological examination during the follow-up phase of the population screening programme (1990 and 1991) was compared with that for the new screening programme (1996). RESULTS: Following the implementation of the new guidelines, the percentage of smears with moderate dysplasia was reduced from 10% to 2%. The percentage of women with a histological examination during the follow up of two smears with moderate dysplasia remained the same. The new recommendations for additional smears were not followed: for 28% no repeat smear was available after 2.25 years versus 10% in 1992. There were indications that the referral of women with two cases of moderate dysplasia to a gynaecologist was not strictly adhered to either. Since the introduction of the new guidelines, the estimated percentage of women that should be referred to the gynaecologist following smears with moderate dysplasia has not changed. CONCLUSION: The new recommendations have lead to fewer smears being classified as moderate dysplasia. The long-term effects, such as a reduction in the length of the follow-up period, can only be analysed in a few years time.

Women who participate in spontaneous screening are not at higher risk for cervical cancer than women who attend programme screening.

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.

Endocervical status is not predictive of the incidence of cervical cancer in the years after negative smears.

The clinical relevance of the lack of endocervical cells was never well established in a longitudinal study with histologically proven cervical cancer as an end point. From the Dutch Network and National Database for Pathology, results for all negative smears obtained in 1990 and 1991 in the Netherlands were retrieved, as were data for all cytologic and histologic examinations performed after the negative smears before April 1998. There were no significant differences between the proportion of preinvasive lesions (cervical intraepithelial neoplasia 1, 2, and 3) detected after negative smears without endocervical cells compared with negative smears with endocervical cells. The proportion of women in whom invasive cancer developed was the same in both groups. These data suggest there is no reason to advise women with negative smears without endocervical cells to undergo an additional smear.

The diagnostic value of computer-assisted primary cervical smear screening: a longitudinal cohort study.

OBJECTIVES: To assess computer-assisted (neural network based) cervical smear screening as a primary tool for the early detection of cervical dysplasia. DESIGN: Longitudinal cohort study. SETTING: Cytology laboratory reviewing cervical smears taken by general practitioners in a mass screening program in the Netherlands. SUBJECTS: 846 women who developed (pre-)neoplasia of the cervix in the seven years after the baseline smear, and 5217 controls. INTERVENTIONS: Cervical smears were evaluated both by conventional light microscopy and with use of the PAPNET Testing System by the same cytotechnologists. MAIN OUTCOME MEASURES: Seven year histological and cytological follow-up results were obtained for all women from a nation-wide pathology database. RESULTS: Conventional screening diagnosed dysplasia or carcinoma in the baseline smears of 458 (54.1%) of the 846 women who were diagnosed with (pre-)neoplasia during follow-up, whereas computer-assisted PAPNET analysis detected such lesions in 462 (54.6%) of these women. In the control population of 5217 (86.0%) women, in whom follow-up revealed no cervical dysplasia, conventional screening gave false positive results in 210 (4.0%) and computer-assisted PAPNET analysis gave false positive results in 207 (4.0%) smears. The areas under the receiver operation curves (AUC) were 80% (95% confidence interval, 78 to 82%) and 79% (95% confidence interval, 77 to 81%) for conventional and PAPNET-assisted screening, respectively. CONCLUSIONS: The PAPNET Testing System has similar diagnostic value as the conventional screening of Pap smears when used for primary screening.

Observer variation in cytologic grading for cervical dysplasia of Papanicolaou smears with the PAPNET testing system.

BACKGROUND: To assess the interobserver and intraobserver variation of Papanicolaou (Pap) smear screening with the computer-assisted (neural network based) PAPNET Testing System in diagnosing cervical smear abnormalities, results of agreement were compared with the interobserver and intraobserver variation of conventional smear analysis. METHODS: Cervical smears obtained from women in 1996 were reevaluated both by conventional light microscopy and with use of the PAPNET Testing System by the same four investigators, and results were compared with the original screening diagnoses obtained by both methods. RESULTS: The interobserver results for epithelial abnormalities (the degree of agreement between the cytologists), characterized by weighted kappa statistics, were 0.71 (95% CI: 0. 68-0.73) for PAPNET screening and 0.69 (95% CI: 0.66-0.72) for conventional screening. No significant differences were found among the individual results obtained by the four cytotechnologists (intraobserver variation) with conventional screening versus PAPNET reviewing. CONCLUSIONS: Pap smear grading with the PAPNET Testing System has interobserver and intraobserver variation similar to that of conventional screening of Pap smears in routine use. Cancer (Cancer Cytopathol)

Organised cervical cancer screening still leads to higher coverage than spontaneous screening in The Netherlands.

In The Netherlands, early detection of cervical cancer by programme and spontaneous screening has been common practice for more than two decades. Both types of screening are mainly performed by general practitioners. Therefore, the question is raised of whether programme screening still enhances screening uptake. To answer this question, we analysed the national health interview survey in the years 1992-1996. The coverage rate, defined as the percentage of women with at least one smear taken in the previous 5 years, was 91% for women invited for programme screening compared with 68% for women not invited. The performance of the organised programme in reducing excessive screening, i.e. smears taken in excess of the recommended age and interval range, was not clear and the effect seemed small. Furthermore, we found that half the non-attenders were 'protected' by a recent smear or a hysterectomy, and of the unprotected women, 72% showed a positive attitude towards the programme. We conclude that even after a long history of cervical cancer screening, an organised programme is still required to ensure a high coverage.

Non-progression of cervical intraepithelial neoplasia estimated from population-screening data.

Non-progression and duration of preclinical neoplastic lesions of the cervix uteri were studied using screening data from a previously unscreened population, Maribo County, Denmark (1966-82). To estimate regression rates, the incidence of clinical cancer before the screening programme was related to the prevalence and incidence of preclinical lesions estimated from the detection rates of first smear and third and subsequent smears respectively. Duration was estimated from the time lag between the cumulative incidence of preclinical lesions and the combined cumulative incidence of clinical cancer and the estimated 'incidence of regression'. Of all preclinical lesions in women aged 25-50, 24% progressed, 39% regressed and 38% remained. Even if we assume no onset of preclinical lesions above age 50, we estimated that 48% of the preclinical lesions would not progress to clinical cancer in the women's lifetime. The estimated mean duration of preclinical lesions was 16 years. In Maribo County during the 1970s, the positive rate (1.6%) was low compared with current rates in several countries. We conclude that the detection of non-progressive lesions was outweighed by the prevention of clinical cancer.

Effect of a single dose of inhaled salmeterol on baseline airway caliber and methacholine-induced airway obstruction in asthmatic children.

BACKGROUND: Salmeterol is a new inhaled selective beta 2-adrenergic receptor agonist with a long duration of action. We studied the duration of the bronchodilation and the protective effect against methacholine-induced airway obstruction of a single dose of salmeterol in a double-blind, randomized, placebo-controlled, crossover design. METHODS: Seventeen boys and three girls with mild-to-moderate asthma participated in the study. On two separate days either 50 micrograms salmeterol or placebo was inhaled. FEV1 and PD20 methacholine were determined before and 1, 4, 8, 12, and 24 hours after inhalation. RESULTS: Salmeterol resulted in a significant bronchodilation compared with placebo, up to 12 hours (p = 0.0001). At 24 hours there was a residual effect that approached significance; mean FEV1 being 8.3% +/- 2.4% above baseline (p = 0.06). Significant protection against airway sensitivity to methacholine after salmeterol inhalation was found at all time points (p < 0.005). Twenty-four hours after administration mean PD20 was still 1.22 +/- 0.29 doubling dose above baseline. No important adverse effects were noted. CONCLUSION: We conclude that a single dose of 50 micrograms salmeterol in children with asthma gives a long-lasting bronchodilation, exceeding 12 hours, which is comparable to the results in adult studies. The duration of the protection against airway sensitivity to methacholine exceeds 24 hours.