Journal of the National Cancer Institute Advance Access originally published online on May 12, 2009
JNCI Journal of the National Cancer Institute 2009 101(10):721-728; doi:10.1093/jnci/djp089
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© The Author 2009. Published by Oxford University Press.
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Cervical Intraepithelial Neoplasia Outcomes After Treatment: Long-term Follow-up From the British Columbia Cohort Study
Affiliations of authors: Department of Family and Community Medicine, Center for Healthcare Policy and Research, University of California, Sacramento, CA (JM); Surveillance and Outcomes Unit (CM), Division of Gynecologic Oncology (TE), and Department of Population Oncology (AC), British Columbia Cancer Agency, Vancouver, BC, Canada; Department of Obstetrics, Gynecology and Reproductive Sciences, Department of Epidemiology and Biostatistics, University of California, San Francisco, CA (GFS)
Correspondence to: Joy Melnikow, MD, MPH, Department of Family and Community Medicine, Center for Healthcare Policy and Research, University of California, Davis, 4860 Y St, Ste 2300, Sacramento, CA 95817 (e-mail: jamelnikow{at}ucdavis.edu).
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.
| CONTEXT AND CAVEATS Prior knowledge Only limited information on the long-term risk of cervical intraepithelial neoplasia (CIN) recurrence among women treated for CIN is available. Study design A retrospective cohort of women who were treated for CIN 1, 2, or 3 and a comparison cohort of women with normal cytology and no previous CIN diagnosis. Contribution The risk of subsequent CIN 2 or 3 (CIN 2/3) was associated with initial CIN grade, treatment type, and age. Two years after treatment for CIN, there was a rapid decline in the rate of subsequent diagnoses of CIN 2/3. However, 6 years after treatment the risk of invasive cancer continued to be higher among women treated for CIN than among those with no CIN diagnosis, although the risk of CIN 2/3 remained low. Risk was highest for women treated for CIN with cryotherapy. Implications Findings of this study support the shift in recommendations for screening of women with CIN from indefinite annual screening to an initial period of 6–18 months of more intensive annual examination, followed by a return to routine screening. Limitations Data were observational. Treatment patterns shifted during the study period. Among women treated with cryotherapy or laser ablation, neither satisfactory colposcopy results nor treatment according to guidelines could be documented. From the Editors
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The authors had full responsibility for the design of the study, the collection of the data, the analysis and interpretation of the data, the decision to submit the manuscript for publication, and the writing of the manuscript The authors thank Catarina Kiefe, MD, PhD, for critical review of the manuscript and Mairin Rooney and Galen Sanderlin for assistance with the figures and tables.
Manuscript received July 17, 2008; revised March 3, 2009; accepted March 12, 2009.
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J Natl Cancer Inst 2009 101: 695.
J Natl Cancer Inst 2009 101: 695.
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