The smear histories of 312 women with cancer of the cervix have been determined. Eighty nine women had had at least one negative smear reported in the 10 years before a diagnosis of cancer and 14 had had more than one negative smear. Fifty six of the 89 women had had a negative smear in the three years preceding the diagnosis of cancer. The highest number of negative smears (61) reported was among the 115 women aged under 45. Fifty eight slides reported as negative were submitted to independent review; 13 were subsequently reported as negative, 11 as unsatisfactory, and 34 as abnormal.These findings may in part explain why in this region there has been a disappointing reduction in the incidence of clinically invasive cervix cancer, and our findings may also apply elsewhere. Nevertheless, the confirmed negative smears chiefly occurred within three years of clinical cancer, particularly in the younger women, and this finding suggests that these women may have a short preinvasive phase. IntroductionThe relation between cervical intraepithelial neoplasia and invasive cancer continues to cause controversy, although the bulk of cytological and epidemiological evidence suggests that progression from grade 3 cervical intraepithelial neoplasia (CIN III) to clinically invasive cancer takes over 10 years.' 2 The overall incidence of invasive cervical cancer in England and Wales has altered little between 1974 and 1980, although there has been some reduction in the number of deaths.3 In reviewing the results for Yorkshire from 1957 to 1982 we found that a change in the age distribution of cases had occurred (see figure). Women aged under 35 are now at greater risk of developing invasive cancer than ever before. Death rates also indicate a change in pattern, with more women dying in the younger age groups compared with women aged over 40 (table I).

A professionally applied two–stage chlorhexidine varnish, Chlorzoin^®, was developed to achieve sustained release and minimise the problems of staining and bad taste associated with chlorhexidine mouthrinses. The primary aim of this randomised controlled clinical trial was to assess the efficacy of Chlorzoin in reducing the caries increment in high–caries–risk adolescents. Secondary aims included investigating the effect of compliance upon caries increment, the effect of Chlorzoin upon salivary mutans streptococci levels and assessing the benefit of individual dental health advice by dental auxiliaries in a community setting. 1,240 children, initially aged 11–13 years, assessed to be at high caries risk were recruited into the trial. The trial design involved four arms: an observational group, a control group, an active (Chlorzoin) varnish group and a placebo varnish group. All subjects were examined annually by a calibrated examiner who was blind to the group allocation. Three–year caries increments were calculated using clinical, clinical and fibre–optic transillumination, and clinical and bitewing data sets. The results indicated that the use of Chlorzoin had an initial effect on mutans streptococci levels but that no long–term reduction in caries increment or mutans streptococci infection could be detected. One reason for this lack of efficacy may have been the regimen of reduced frequency of varnish applications after the initial period. Children who followed the protocol and, therefore, were seen regularly by dental auxiliaries had a lower caries increment than those who did not. This finding was independent of varnish allocation. In summary, under this regimen, Chlorzoin has been found to be effective in decreasing salivary mutans streptococci but ineffective as a caries–preventive agent in high–risk Scottish children when applied pragmatically in a community setting.

Summary and conclusionsVacuum curettage was performed on 348 women who had received various regimens of oestrogen treatment for an average of 9 7 months for climacteric symptoms. In 62 cases (18%) the specimens were unsatisfactory for histological assessment; among the remainder, however, they showed a normal endometrium in 257 cases (90%), cystic hyperplasia in 21 (7%), adenomatous hyperplasia in 7 (2%), and endometrial adenocarcinoma in one.Cyclical unopposed oral oestrogen treatment (98 cases) was associated with a 12% incidence of endometrial hyperplasia, but among those given an additional fiveday course of progestogen in each cycle (37 cases) the incidence was only 8%. No case of hyperplasia occurred among 102 women taking regimens including 10 or 13 days of progestogen. Among women treated with subcutaneous oestradiol implants and monthly five-day courses of oral progestogen (50 cases) there was a 28% incidence of hyperplasia including the one case of carcinoma, though some of those with hyperplasia may not have taken the full course of progestogen. Regular withdrawal bleeding during treatment was associated with a lower incidence of endometrial hyperplasia (6%) than unscheduled breakthrough bleeding (28%), but the one patient with carcinoma had experienced regular bleeding only.

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Summary and conclusionsA prospective study of 745 women receiving different regimens of hormone treatment for the cimacteric for a total of 21 736 months was performed. There was a lower incidence of endometrial hyperplasia in biopsy specimens in the women receiving cyclical low-dose oestrogen by mouth than in those receiving cyclical high-dose oestrogen by mouth. The incidence of abnormalities in the women receiving sequential oestrogen and progestogen was lower than in either of these two groups. Among the women receiving subcutaneous oestrogen implants the incidence was higher still, but over half of the abnormal specimens were from women who had not taken their progestogen. The incidence of hyperplasia fell with longer courses of progestogen, and no hyperplasia was found in patients taking progestogen for over 10 days each month.The incidence of adenomatous and atypical hyperplasia is significantly reduced by a progestogen when taken for 10 or more days monthly. The absence of vaginal bleeding or of a regular bleeding response does not guarantee histologically normal endometrium in patients taking oestrogens without progestogen.