Consequences in women of participating in a study of the natural history of cervical intraepithelial neoplasia 3.

BACKGROUND: A retrospective cohort study was performed in 1063 women diagnosed with cervical intraepithelial neoplasia grade 3 (CIN3) (previously termed carcinoma in situ- CIS) in the National Women's Hospital, Auckland, New Zealand. The study describes the clinical management and outcomes for women with CIN3 diagnosed in the decade of 1965-1974, when treatment with curative intent was withheld in an unethical clinical study of the natural history of CIS. A comparison is made with women who were diagnosed earlier (1955-1964) and later (1975-1976). AIMS: The aim of the study is to record the medical encounters, frequency and management of cytological abnormalities and the occurrence of invasive cancers. The medical records, cytology and histopathology were reviewed and data linked with cancer and death registers.
RESULTS: Women diagnosed with CIN3 in 1965-1974 (n = 422), compared with those diagnosed earlier (n = 385) or later (n = 256): (i) were less likely to have initial treatment with curative intent (51% vs 95 and 85%, respectively); (ii) had more follow-up biopsies (P < 0.0005); (iii) were more likely to have positive cytology during follow-up (P < 0.005) and positive smears that were not followed within six months by a treatment with curative intent (P < 0.005); and (iv) experienced a higher risk of cancer of the cervix or vaginal vault (RR = 3.3 compared with the first period, 95% CI: 1.7-5.3). Among women diagnosed in 1965-1974, those initially managed by punch or wedge biopsy alone had a cancer risk ten times (95% CI: 3.9-25.7) higher than women initially treated with curative intent.
CONCLUSIONS: During the 'clinical study' (1965-1974), women underwent numerous interventions that were aimed to observe rather than treat their condition, and their risk of cancer was substantially increased.