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 randomised phase III trial was conducted to assess the role of interferon-alpha (INFa) 2a as maintenance therapy following surgery and/or chemotherapy in patients with epithelial ovarian carcinoma. Patients were randomised following initial surgery/chemotherapy to interferon-alpha 2a as 4.5 mega-units subcutaneously 3 days per week or to no further treatment. A total of 300 patients were randomised within the study between February 1990 and July 1997. No benefit for interferon maintenance was seen in terms of either overall or clinical event-free survival. We conclude that INF-a is not effective as a maintenance therapy in the management of women with ovarian cancer. The need for novel therapeutics or strategies to prevent the almost inevitable relapse of patients despite increasingly effective surgery and chemotherapy remains.

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