The Risk of Developing Kaposi Sarcoma After a Primary Malignancy: A SEER-Based Analysis

Summary: Kaposi sarcoma (KS) is a rare human herpesvirus-8 (HHV-8)-driven lymphatic hyperplasia arising in skin and rarely the internal organs. KS is associated with several different states of immunosuppression, such as HIV or an acquired immune deficiency syndrome. There is a growing body of evidence to suggest that having a separate primary malignancy may be associated with KS. Our cohort of patients that developed a second primary KS after an initial primary malignancy was generated using the SEER-17 cancer registries with data from 2000–2020. Our initial cohort of patients were those that developed any primary malignancy with a chosen second event of KS limited to the skin. Patients were excluded if they developed KS within two months of initial primary or if the report was obtained solely from death certificate. Using this data the Standard Incidence Ratio was calculated with 95% confidence intervals. Results A cohort of 6,096,737 individuals developed a primary malignancy in the period from 2000- 2020. Of those, 312 persons developed a second primary Kaposi sarcoma (SIR, 1.06). The majority, 275 (88%), were male. 39% were non-White (n=122). Non-Hispanic Black and Hispanic individuals had the highest risk of developing KS (SIR, 1.72 and SIR, 2.31). Males had the highest risk of developing a KS within a year of their malignancy (SIR, 3.04). Males younger than 40 had the highest risk of developing a secondary KS (SIR, 3.56). Patients had the highest risk of developing cancers of the anorectum (SIR, 12.86), lymphoma (SIR, 4.11), and leukemia (SIR, 2.08). This study was the first to examine the cancers that precede Kaposi sarcoma in a contemporary setting. The highest risk of KS occurred within one year of the original cancer, which could be due to increased diagnostic workup and close follow up after the discovery of an initial primary malignancy. Younger patients had the most increased risk of developing KS after separate initial cancer diagnosis. This could be attributed to iatrogenic causes related to chemotherapy. Consistent with previous studies, we that found anorectal cancer increased risk of KS. Other malignancies preceding KS were non-epithelial skin cancers, lymphoma, and leukemia. Anorectal cancer, NHL, and leukemias may arise from viral causes, such as human papillomavirus, Epstein Barr virus, and human T-cell leukemia virus, respectively. The interplay between genetics, low T-cell function, and viral infection could contribute to the development of KS after these first cancers. Further studies are needed to uncover the precise mechanisms behind the associations between the primary tumors associated with KS