Original article
The risk of squamous cell and basal cell cancer associated with psoralen and ultraviolet A therapy: A 30-year prospective study

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Background

By 1977, psoralen and ultraviolet A (PUVA) was established as a highly effective therapy for psoriasis. Because of concerns about potential long-term adverse effects, particularly cancer, the PUVA Follow-Up Study was established to assess long-term risk and benefits of PUVA.

Objective

We sought to determine the association of certain squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) risk with exposure to PUVA.

Methods

For nearly 30 years, this prospective cohort study of 1380 patients with psoriasis first treated with PUVA in 1975 to 1976 documented exposures and incident events including biopsy-proven skin cancers.

Results

From 1975 to 2005, 351 of 1380 (25%) cohort patients developed 2973 biopsy-proven SCC and 330 (24%) developed 1729 BCCs. After adjusting for age, gender, and significant confounders, the risk of developing one or more SCC in a year was strongly associated with total number of PUVA treatments (350-450 vs <50 treatments, incidence rate ratio [IRR] = 6.01, 95% confidence interval [CI] = 4.41-8.20). When all tumors are included this risk is significantly higher (IRR = 20.92, 95% CI = 14.08-31.08). Corresponding risks for BCC were much lower (person counts IRR = 3.09, 95% CI = 2.36-4.06; tumor counts IRR = 2.12, 95% CI = 1.47-3.05).

Limitations

This was an observational prospective study of a cohort with severe psoriasis. An unknown factor associated with higher dose exposure to PUVA in our cohort that was not included in our analysis could account for the observed associations.

Conclusion

Exposure to more than 350 PUVA treatments greatly increases the risk of SCC. Exposure to fewer than 150 PUVA treatments has, at most, modest effects on SCC risk. Even high-dose exposure to PUVA does not greatly increase BCC risk. The risks of SCC in long-term PUVA-treated patients should be considered in determining the risk of this therapy relative to other treatments for severe psoriasis.

Section snippets

Study population

The PUVA Follow-Up Study has prospectively studied 1380 of 1450 patients with psoriasis first treated with PUVA in 1975 to 1976 in 16 university centers.3, 4 At entry to the clinical trial, all patients completed a detailed health history that included past exposures to other psoriasis therapy, risk factors for NMSC, and general health. Before first treatment, laboratory studies were done and dermatologists examined all patients to assess skin cancers, photodamage, extent of psoriasis, and

Follow-up

From enrollment (1975-1976) to the final cycle of interviews (2003-2005), the potential maximum duration of a prospective follow-up was 30 years with a mean interval from entry to last interview for those completing the final cycle duration of 28 years. Table I provides patient demographic characteristics and exposures to selected psoriasis therapies. Of the 759 patients who survived to the end of the study, 283 (37%) had one or more NMSCs documented.17 The mean duration of follow-up was 27

Discussion

In 1975 and 1976 the PUVA Clinical Cooperative Study enrolled 1450 patients with psoriasis at 16 university centers who were among the first treated with oral psoralen photochemotherapy (PUVA).3 In early 1977, 1380 of these 1450 consented to enroll in a long-term prospective safety study: the PUVA Follow-Up Study. This study spanned nearly 30 years and included 22 cycles of patient interviews that documented health events, treatments for psoriasis, medications, hospitalization, and cancer,

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  • Cited by (0)

    Supported in part by National Institutes of Health Contract No. NO1-AR-0-2246.

    Conflicts of interest: None declared.

    Reprints not available from the authors.

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