Cervical intraepithelial neoplasia outcomes after treatment: long-term follow-up from the British Columbia Cohort Study

Abstract

Background: Information on the long-term risk of cervical intraepithelial neoplasia (CIN) recurrence among women treated for CIN is limited yet critical for evidence-based surveillance recommendations.

Methods: We retrospectively identified 37,142 women treated for CIN 1, 2, or 3 from January 1, 1986, through December 31, 2000 (CIN cohort), from the British Columbia Cancer Agency cytology database and linked their records with cancer registry and vital statistics data. Treatment included cryotherapy, loop electrosurgical excision procedure, cone biopsy, and laser vaporization or excision. A comparison cohort contained 71,213 women with normal cytology and no previous CIN diagnosis. Follow-up continued through December 31, 2004. Among women in both cohorts under active surveillance, we compared rates of CIN 2 or 3 (CIN 2/3) and cervical cancer. Cumulative incidence rates of CIN 2/3 and 95% confidence intervals (CIs) were estimated by a life table approach by using annual rates. Cumulative rates of invasive cancer were examined by the person-years method.

Results: Overall observed cumulative rates of CIN 2/3 in the first 6 years after treatment were 14.0% (95% CI = 13.84% to 14.15%) for women originally treated for CIN 3, 9.3% (95% CI = 9.09% to 9.42%) for CIN 2, and 5.6% (95% CI = 4.91% to 5.21%) for CIN 1. Annual rates of CIN 2/3 were less than 1% after 6 years. Initial diagnosis, age, and treatment type were associated with a diagnosis of CIN 2/3 after treatment, with 6-year adjusted rates for women aged 40-49 years ranging from 2.6% (95% CI = 1.9% to 3.4%) for treatment of CIN 1 with the loop electrosurgical excision procedure to 34.0% (95% CI = 30.9% to 37.1%) for treatment of CIN 3 with cryotherapy. Overall incidence of invasive cancer (per 100,000 woman-years) was higher in the CIN cohort (37 invasive cancers, 95% CI = 30.6 to 42.5 cancers) than in the comparison cohort (six cancers, 95% CI = 4.3 to 7.7 cancers). Cryotherapy, compared with other treatments, was associated with the highest rate of subsequent disease (adjusted odds ratio for invasive cancer = 2.98, 95% CI = 2.09 to 4.60).

Conclusion: Risk of CIN 2/3 after treatment was associated with initial CIN grade, treatment type, and age. Long-term risk of invasive cancer remained higher among women treated for CIN, particularly those treated with cryotherapy.

Figure 1

Incidence rates of cervical intraepithelial neoplasia 2 or 3 (CIN 2/3) per 1000 women by index diagnosis among women under active surveillance in the CIN and comparison (COMP) cohorts. The index event was treatment for the CIN cohort and normal cytology result at entry for the comparison cohort. Error bars = 95% confidence intervals.

Figure 2

Cumulative rates of invasive cervical cancer over the follow-up period for all women in the cervical intraepithelial neoplasia (CIN) cohort, for women in the CIN cohort under active surveillance, for the comparison cohort (COMP), and for the comparison cohort under surveillance (COMP—under surveillance). We used the same definition as in the CIN cohort (ie, must have had a cervical cytology within the previous 2 years to be included for that year). Error bars = 95% confidence intervals.