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Long term risk of invasive cancer after treatment for cervical intraepithelial neoplasia grade 3: population based cohort study

BMJ 2007; 335 doi: (Published 22 November 2007) Cite this as: BMJ 2007;335:1077

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  1. Björn Strander, senior consultant1,
  2. Agneta Andersson-Ellström, senior consultant1,
  3. Ian Milsom, professor1,
  4. Pär Sparén, professor of medical epidemiology2
  1. 1Department of Obstetrics and Gynecology, Sahlgren's Academy, University of Gothenburg, SU/Östra sjukhuset, SE-416 85, Sweden
  2. 2Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
  1. Correspondence to: B Strander, Oncology Center, Sahlgren's University Hospital, SE-413 45 Gothenburg, Sweden bjorn.strander{at}
  • Accepted 9 September 2007


Objective To study the long term risk of invasive cancer of the cervix or vagina after treatment for cervical intraepithelial neoplasia grade 3.

Design Prospective cohort study.

Setting Swedish cancer registry.

Participants All women in Sweden with severe dysplasia or cervical carcinoma in situ (equivalent to cervical intraepithelial neoplasia grade 3) treated during 1958-2002 (n=132 493) contributing 2 315 724 woman years.

Main outcome measures Standardised incidence ratios with risk of cancer in the Swedish general female population as reference, and relative risks in multivariable log-linear regression model, with internal references.

Results Women with previous cervical intraepithelial neoplasia grade 3 had an increased risk of invasive cervical cancer compared with the general female population (standardised incidence ratio 2.34, 95% confidence interval 2.18 to 2.50). The increased risk showed a decreasing trend with time since diagnosis for women treated later than 1970 but the risk was still increased after 25 years. An effect of age was found, with an accentuated increase in risk for women aged more than 50. The excess risk for cervical cancer associated with previous cervical intraepithelial neoplasia grade 3 has steadily increased since 1958. For vaginal cancer the standardised incidence ratio was 6.82 (5.61 to 8.21) but this decreased to 2.65 after 25 years. Adjustments in the multivariable log-linear regression model did not substantially alter these results.

Conclusions Women previously treated for cervical intraepithelial neoplasia grade 3 are at an increased risk of developing invasive cervical cancer and vaginal cancer. This risk has increased since the 1960s and is accentuated in women aged more than 50. The risk is still increased 25 years after treatment.


  • Contributors: BS and IM conceived the study. BS, AAE, and PS designed the study. BS and PS analysed the data. All authors drafted and revised the manuscript. PS is guarantor.

  • Funding: This study was partially financed with a grant from the county of Halland, Sweden and the Gothenburg Medical Society.

  • Competing interests: None declared.

  • Ethical approval: Data retrieval was approved by the ethics committee of the Karolinska University Hospital (No 02-556).

  • Accepted 9 September 2007
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