Psoriasis is a chronic autoimmune skin condition characterized by an accelerated life cycle of skin cells, causing them to build up rapidly on the skin’s surface. This rapid turnover leads to the formation of thick, scaly, and often itchy patches, most commonly on the elbows, knees, and scalp. The disorder affects an estimated 2% to 3% of the world’s population. Whether this long-term inflammatory state poses an increased risk for other serious illnesses, specifically cancer, is a complex public health concern.
Defining the Relationship Between Psoriasis and Cancer
The connection between psoriasis and cancer is a correlation rather than a direct cause-and-effect relationship. Psoriasis does not directly initiate malignant cell transformation. Instead, the persistent systemic inflammation characterizing moderate to severe disease may promote oncogenesis. Individuals with mild or well-controlled psoriasis maintain a cancer risk profile comparable to the general population.
For patients with severe, long-standing psoriasis, data suggests a slightly elevated risk for certain types of malignancy. The overall lifetime risk increase is modest, highlighting the importance of managing the underlying chronic disease effectively. This association stems from the disease’s biological mechanisms and, in some cases, the long-term effects of therapeutic interventions. Researchers continue to distinguish the risks driven by the disease from those introduced by its treatment.
The Role of Chronic Inflammation
The primary biological mechanism linking psoriasis to malignancy is chronic, systemic inflammation. Psoriasis is an immune-mediated disease that generates high levels of inflammatory molecules throughout the body. This continuous immune activation is a known risk factor for tumor development, as sustained inflammation can lead to DNA damage and genetic instability in various tissues.
In psoriatic skin lesions, there is uncontrolled proliferation of keratinocytes, the primary skin cells, which multiply at an abnormal rate. This unregulated cellular turnover increases the chances of a replication error that could lead to a malignant mutation. Immune dysregulation also involves the overproduction of specific pro-inflammatory cytokines, which act as potent signaling molecules.
Tumor necrosis factor-alpha (TNF-alpha) and interleukins, particularly those in the IL-23/Th17 axis, are implicated in both psoriasis pathology and the promotion of oncogenesis. IL-23 drives the expansion of Th17 T cells, which secrete IL-17. This cytokine exacerbates skin cell proliferation and exhibits complex regulatory effects in the tumor microenvironment. The sustained presence of these inflammatory mediators can suppress immune surveillance, making it more difficult for the body to eliminate newly formed cancerous cells.
Identifying Associated Malignancies
The increased incidence in psoriasis patients is concentrated in specific cancer categories. Non-melanoma skin cancers (NMSCs), particularly squamous cell carcinoma (SCC), show the strongest association, attributed to the rapid skin cell turnover inherent in the disease. Studies report a risk ratio for keratinocyte cancer as high as 2.28, emphasizing the need for regular dermatologic screening.
Psoriasis is also associated with an elevated risk of certain hematological malignancies, most notably lymphoma. A meta-analysis found the risk ratio for lymphomas to be around 1.56, encompassing both Hodgkin and non-Hodgkin subtypes. This elevated risk results from the chronic immune system stimulation and dysregulation that defines the disease.
Beyond skin and blood cancers, there are less strong associations with certain internal solid tumors. These include malignancies of the lung, bladder, liver, and larynx. These internal cancers are often tied to shared risk factors, such as smoking and obesity, which are more prevalent in patients with severe psoriasis.
Treatment Induced Cancer Risk
A distinction exists between the cancer risk driven by the disease and the risk introduced by its long-term treatment. Phototherapy, specifically Psoralen plus Ultraviolet A (PUVA) therapy, carries a dose-dependent risk of non-melanoma skin cancer. The cumulative number of PUVA treatments is a predictor for developing squamous cell carcinoma, with some studies reporting an incidence up to 32 times higher than expected.
Traditional systemic agents, which are often immunosuppressive, also present specific risks. Cyclosporine is strongly associated with a heightened risk of developing non-melanoma skin cancers and lymphoproliferative disorders, especially when used for prolonged periods. Methotrexate has been associated with a slightly increased risk of melanoma and lymphoproliferative disorders, though the absolute increase is minimal.
The newer class of biologic agents, including TNF inhibitors and IL-12/23 or IL-17 inhibitors, have been subject to extensive safety monitoring regarding malignancy. While initial concerns existed due to their immunosuppressive nature, large-scale, long-term registry studies have largely been reassuring. These studies indicate that cumulative exposure to biologics is not associated with a statistically significant increase in the overall risk of cancer compared to the risk already inherent to the disease.