Squamous-cell cancer of the skin in patients given PUVA and ciclosporin: nested cohort crossover study

Lancet. 2001 Sep 29;358(9287):1042-5. doi: 10.1016/S0140-6736(01)06179-7.


Background: Immunosuppressive treatments have been associated with an increased risk of skin cancer, especially in patients who have had organ transplants. We aimed to assess the risk of skin cancer in patients taking the ciclosporin who had been exposed to psoralen and ultraviolet-A light (PUVA) and other treatments for severe psoriasis.

Methods: We did a nested cohort crossover study of 28 participants in the PUVA follow-up study who were on ciclosporin to compare the frequency of squamous-cell carcinoma before and after first use of ciclosporin. We also analysed the entire PUVA study cohort (1380) to assess the relation between use of this drug and frequency of squamous-cell carcinoma.

Findings: In the 5 years before first use, six of 28 (21%) ciclosporin users developed a total of 20 squamous cell cancers. After ciclosporin use (average follow-up 6 years), 13 (46%) developed a total of 169 squamous-cell carcinomas. In the nested cohort, after adjustment for amount of exposure to PUVA and methotrexate, incidence of tumours was seven times higher after first ciclosporin use than in the previous 5 years (incidence rate ratio 6.9 [95% CI 4.3-11]). Multivariate analysis of the entire cohort showed that risk of squamous-cell carcinoma after any use of ciclosporin is close to that recorded for at least 200 PUVA treatments (3.1 [2.6-3.7] and 2.8 [2.6-3.2], respectively).

Interpretation: The risk of squamous cell cancer of the skin is increased by ciclosporin in patients with psoriasis who have been exposed to PUVA. Such risks should be balanced against the effectiveness of the drug and possible newer immunosuppressive agents.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Carcinoma, Squamous Cell / chemically induced*
  • Cross-Over Studies
  • Cyclosporine / adverse effects*
  • Female
  • Humans
  • Immunosuppressive Agents / adverse effects*
  • Incidence
  • Male
  • Middle Aged
  • PUVA Therapy / adverse effects*
  • Prospective Studies
  • Psoriasis / drug therapy*
  • Risk Factors
  • Skin Neoplasms / chemically induced*


  • Immunosuppressive Agents
  • Cyclosporine