Affiliations of authors: P. Holowaty, Durham Region Health Department, Whitby, ON, Canada, and School of Public Health Sciences, University of Toronto, ON; A. B. Miller, International Agency for Research on Cancer, Lyon, France, and School of Public Health Sciences, University of Toronto; T. Rohan, School of Public Health Sciences, University of Toronto; T. To, Hospital for Sick Children, Toronto, and School of Public Health Sciences, University of Toronto.
Correspondence to: Philippa Holowaty, Ph.D., Durham Region Health Department, 1615 Dundas St. East, Suite 210, Whitby, ON, Canada L1N 2L1.
We are grateful for the opportunity to respond to Dr. Nyirjesy's comments on our report (1).
The study was based on a large cohort of women at a time (1962-1980) when a cytology smear interpreted as showing changes indicative of mild or moderate dysplasia (2,3) was commonly monitored by cytology alone. Such smears were usually repeated every 6 months unless there was cytologic evidence of progression, in which case the woman's practitioner was advised to refer her to a gynecologist.
There were two parts to our analysis. One part was based on the cytology data alone and enabled us to assess the probability of progression and regression of cytologically diagnosed mild and moderate dysplasia. This component was indeed based on cytologic diagnoses. The other part was based on linkage of the file to the Ontario Cancer Registry, which enabled us to determine the risk of progression to carcinoma in situ and invasive cervical cancer, as defined histologically. Women with smears classified as "minimal" dysplasia were not eligible for either analysis. The study was therefore designed to assess the utility of the cytologic classification of dysplasia in predicting subsequent outcomes, ranging over the whole spectrum of cervical lesions. In practice, our data show that the classification as applied in this large laboratory (which had considerable interest in and experience with cervical cytology) correlated remarkably well with subsequent outcomes, and thus, the study does indeed represent a study of the natural history of dysplasia.
Dr. Nyirjesy is concerned that somehow the exclusions that we had to make to ensure the effectiveness of the record linkage with the Ontario Cancer Registry may have biased our analyses. Full date of birth is a critical element in computerized record linkage; unfortunately, it was not always completed on requisition forms accompanying the smears, mostly (85% of missing values) before 1970. In case the exclusion of records without a full date of birth introduced a bias, we reanalyzed the data, restricting the analysis to women whose screening history began between 1970 and 1980. The results were the same as those reported with the use of the full (1964-1980) time window. We therefore feel confident that the exclusion of women without a full date of birth did not introduce a bias.
Dr. Nyirjesy was also concerned that biopsies of the lesion may have influenced the natural progression. We regarded a biopsy as an intervention that might alter the course of the natural history. For the progression and regression of dysplasia, records were censored when the woman received a biopsy, unless the biopsy showed a more severe dysplastic state.
We disagree that conservative management failed in this study. Indeed, the study confirms the validity of the recommendations made by a Canadian National Workshop on cervical screening that recommended conservative management for women with cytologically diagnosed mild dysplasia or CIN 1 (4). Of the12 058 women with mild dysplasia, only 14 died of cervical cancer (to the end of 1989). All 14 women had only one mild dysplasia cervical cytology result and nine had only a single cervical smear sent to the laboratory. It is vital that women with dysplasia are carefully monitored or are sent for treatment if loss to follow-up is likely (5).
We agree that practicing physicians are responsible to their patients for the detection and treatment of preventable and curable disease. But they are also responsible both to their patients, and to society as a whole to avoid overtreatment. Pending the development of other tests or procedures, we maintain that our study confirms the appropriateness of conservative management of women with low-grade cytology.
REFERENCES
1
Holowaty P, Miller AB, Rohan T, To T. The natural history of
dysplasia of the uterine cervix. J Natl Cancer Inst 1999;91:252-8.
2 Riotton G, Christopherson WM. Cytology of the female genital tract. In: World Health Organization, editor. International histological classification of tumors. Geneva (Switzerland): World Health Organization; 1973.
3 Task Force appointed by the Conference of Deputy Ministers of Health. Cervical cancer screening programmes. Can Med Assoc J 1976;114:1003-33.[Medline]
4 Miller AB, Anderson G, Brisson J, Laidlaw J, Le Pitre N, Malcolmson P, et al. Report of a National Workshop on Screening for Cancer of the Cervix. CMAJ 1991;145:1301-25.[Medline]
5 Miller AB. Failures of cervical cancer screening [editorial]. Am J Public Health 1995;85:761-2.[Medline]
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