Azathioprine Has No Role in Treating Uterine Cancer But Increases Cervical Cancer Risk in Patients Taking It for Other Conditions
Azathioprine is not a therapeutic agent for uterine cancer and should not be used for this indication. The drug is an immunosuppressant used for autoimmune diseases and transplant recipients, not an oncologic treatment for gynecologic malignancies 1.
Critical Safety Concern: Increased Cervical and Uterine Malignancy Risk
Patients receiving azathioprine have significantly elevated risks of cervical intraepithelial neoplasia (CIN) with higher progression rates to invasive cervical cancer and lower treatment success rates 2.
Quantified Risk Data
Cervical cancer risk increases substantially with cumulative azathioprine exposure: patients receiving high cumulative doses show a hazard ratio of 2.2 (95% CI: 1.2-3.9) for developing cervical cancer, with the risk appearing highest when considering a 5-year lag time between drug exposure and cancer development 3.
Renal transplant recipients on multiple immunosuppressants (including azathioprine) demonstrate a fivefold increase in abnormal cervical cytology prevalence (15%) compared to the general population 2.
The risk of progression from CIN to invasive disease is higher in immunosuppressed patients, and treatment success rates are lower 2.
Mandatory Screening Protocol for Women on Azathioprine
Before initiating azathioprine therapy in women, ensure concordance with national cervical screening programs, and request pretreatment gynecological review in those with previous CIN 2.
Annual cytology combined with colposcopy is recommended in some European centers (Manchester Royal Infirmary) for immunosuppressed patients 2.
Patients taking substantial amounts of azathioprine require more stringent cervical screening measures beyond standard population-based protocols 3.
Clinical Context: When Azathioprine Cannot Be Avoided
Autoimmune Disease or Transplant Recipients with Concurrent Gynecologic Concerns
If a patient requires azathioprine for life-threatening autoimmune disease or transplant maintenance and develops uterine cancer:
Discontinue azathioprine immediately upon uterine cancer diagnosis, as immunosuppression may increase risk of disease progression 4.
Known malignancy is an absolute contraindication to azathioprine therapy 4.
Pregnancy Considerations in Patients on Azathioprine
If a patient on azathioprine for autoimmune hepatitis becomes pregnant, continuation of azathioprine is acceptable and likely beneficial for maintaining disease control, despite FDA Category D classification 5.
The European Association for the Study of the Liver recommends continuing immunosuppressive therapy throughout pregnancy with prednisolone as the preferred agent, with azathioprine continuation being acceptable 5.
Large observational studies show 73% live birth rates with no increase in congenital abnormalities beyond baseline population rates 5.
The most dangerous error is discontinuing immunosuppression during pregnancy based on outdated teratogenicity concerns, as disease flares pose greater maternal and fetal risks than continued medication 5.
Genotoxic Mechanisms Underlying Cancer Risk
Azathioprine induces significant genotoxicity through homologous recombination as the predominant genotoxic event, which may explain the high rate of neoplasms in patients with long-term use 6.
The drug demonstrates recombinogenic, genotoxic, and cytotoxic effects in multiple in vivo assays, with genotoxic effects associated with increased cancer development risk 6.
Common Pitfall to Avoid
Do not assume that azathioprine has any anti-neoplastic properties for uterine malignancies—it is purely immunosuppressive and paradoxically increases cancer risk through immune surveillance impairment and direct genotoxic mechanisms 2, 6, 3.
Strict photoprotection is essential for all patients on azathioprine, as photocarcinogenesis risk escalates with increasing treatment duration 4.