Azathioprine Use Linked to Increased Squamous Cell Carcinoma Risk in Organ Transplant Recipients

Organ transplant recipients (OTRs) treated with azathioprine (AZA) face an increased risk for nonmelanoma skin cancer (NMSC), particularly squamous cell carcinoma (SCC), according to an updated meta-analysis published in Cancer Reports.¹

Skin Cancer Risk After Organ Transplantation

The researchers noted that immunosuppressants are essential treatments in OTRs. For example, AZA, a purine antimetabolite immunosuppressant, prevents the body from rejecting a transplanted organ. It is typically used in combination with other drugs after a kidney transplant, but it can also be used to treat severe rheumatoid arthritis and ulcerative colitis.

Skin cancer is the most common cancer type in OTRs of Caucasian descent, with its incidence steadily increasing worldwide. However, only 2 meta-analyses have examined the association between AZA and the risk of skin cancer in OTRs. They showed that AZA was a risk factor for SCC, but no significant associations between the treatment and either basal cell carcinoma (BCC) or NMSC were observed.² In addition, these analyses only included studies up to 2026 and did not cover the Web of Science database.

As a result, the researchers of this updated meta-analysis aimed to determine whether AZA usage is associated with an increased risk of skin cancer in OTRs.¹ To fill any knowledge gaps, they incorporated studies published up to November 2025 and included additional databases.

The meta-analysis pooled the relative risks (RR), ORs, and HRs from each analyzed study. The researchers also conducted additional analyses, including across cancer types, to identify significant variations among subgroups and explore the reliability of the correlation between AZA use and skin cancer risk in OTRs. Together, the study provided novel clinical insights into the risks of different NMSC types, including SCC and BCC, in OTRs treated with AZA.

Increased Risk for SCC but Not BCC

The investigators searched PubMed, Web of Science, Scopus, and ScienceDirect for eligible studies through November 30, 2025. Eligible studies included those that examined the risk of skin cancer development in OTRs treated with AZA. They considered any studies that mentioned the use of AZA in any treatment combination, as well as studies that reported ORs, RRs, or HR estimates with 95% CIs.

Of 738 records identified, 27 studies met the inclusion criteria, including 20 cohort studies, 6 case-control studies, and 1 cross-sectional study. Their study populations ranged from 116 to 3393 participants.

For NMSC overall, pooled analyses demonstrated increased risk associated with AZA exposure in OTRs. Specifically, the pooled OR was 1.83 (95% CI, 1.22-2.75), the pooled RR was 2.09 (95% CI, 1.41-3.10), and the pooled HR was 1.12 (95% CI, 0.93-1.34).

When stratified by cancer subtype, AZA use was consistently associated with SCC, with a pooled OR of 2.67 (95% CI, 1.72-4.14), a pooled RR of 2.59 (95% CI, 1.46-4.59), and a pooled HR of 1.26 (95% CI, 1.01-1.57). In contrast, none of the pooled estimates demonstrated a statistically significant association between AZA exposure and BCC.

Clinical Implications and Limitations

The researchers acknowledged several limitations to their results, including that they did not fully search all electronic databases, which may have potentially excluded relevant studies. As a result, the studies analyzed may not fully represent all the available research. Nonetheless, they expressed confidence in their findings and suggested ways to navigate posttransplant patient management.

“Our findings indicate that OTRs treated with AZA are at an increased risk for SCC and NMSC,” the authors concluded. “Therefore, it is recommended to prioritize monitoring for skin cancer in OTRs treated with AZA.”

References

1. Salehi AM, Rezaei R, Sadeghi A, Omidi S, Khazaei S, Ebrahimi B. Azathioprine increases the risk of non-melanoma skin cancer among organ transplant recipients; an updated systematic review and meta-analysis. Cancer Rep (Hoboken). 2026;9(2):e70473. doi:10.1002/cnr2.70473
2. Jiyad Z, Olsen CM, Burke MT, Isbel NM, Green AC. Azathioprine and risk of skin cancer in organ transplant recipients: systematic review and meta-analysis. Am J Transplant. 2016;16(12):3490-3503. doi:10.1111/ajt.13863