tacrolimus and Oropharyngeal-Neoplasms

Transplant recipients have elevated cancer risk including risk of human papillomavirus (HPV)-associated cancers of the cervix, anus, penis, vagina, vulva and oropharynx. We examined the incidence of HPV-related cancers in 187 649 US recipients in the Transplant Cancer Match Study. Standardized incidence ratios (SIRs) compared incidence rates to the general population, and incidence rate ratios (IRRs) compared rates across transplant subgroups. We observed elevated incidence of HPV-related cancers (SIRs: in situ 3.3-20.3, invasive 2.2-7.3), except for invasive cervical cancer (SIR 1.0). Incidence increased with time since transplant for vulvar, anal and penile cancers (IRRs 2.1-4.6 for 5+ vs. <2 years). Immunophenotype, characterized by decreased incidence with HLA DRB1:13 and increased incidence with B:44, contributed to susceptibility at several sites. Use of specific immunosuppressive medications was variably associated with incidence; for example, tacrolimus, was associated with reduced incidence for some anogenital cancers (IRRs 0.4-0.7) but increased incidence of oropharyngeal cancer (IRR 2.1). Thus, specific features associated with recipient characteristics, transplanted organs and medications are associated with incidence of HPV-related cancers after transplant. The absence of increased incidence of invasive cervical cancer highlights the success of cervical screening in this population and suggests a need for screening for other HPV-related cancers.

Topics: Adolescent; Adult; Anus Neoplasms; Cohort Studies; Female; Humans; Immunosuppression Therapy; Incidence; Male; Middle Aged; Organ Transplantation; Oropharyngeal Neoplasms; Papillomavirus Infections; Penile Neoplasms; Registries; Tacrolimus; United States; Uterine Cervical Neoplasms; Vulvar Neoplasms; Young Adult

An increased incidence of de novo nonlymphoid malignancies has been shown in immunocompromised patients. However, the true risk over time compared to the general population has not been determined.. One thousand consecutive patients were carefully followed for an average of 77.8+/-11.1 (range, 56.3-96.3) months after primary liver transplantation at a single center. All de novo nonlymphoid malignancies were recorded. Each malignancy was compared with a standard Occupational Cohort Mortality Analysis Program population matched for age, sex, and length of follow-up using modified life table technique and surveillance epidemiology end result (SEER) data.. Fifty-seven patients accounted for de novo malignancies and contributed 4795.3 total person years, a mean+/-SD of 36+/-21 (median, 36; range, 6-74) months after liver transplantation. Twenty-two of these malignancies were skin malignancies including two melanomas. Oropharyngeal cancers (n=7) were found to be 7.6 times higher (P<0.05) and respiratory malignancies (n=8) were 1.7 times higher (P>0.05) compared to the SEER incidence rate. Female reproductive system malignancies including breast cancer (n=3) were 1.9 times lower (P>0.05) and genitourinary malignancies were (n=5) 1.5 times lower (P>0.05) than their matched cohorts. No differences was observed in gastrointestinal malignancies (n=5). There was a significant difference in survival of the patients after diagnosis of malignancy depending on the type of cancer. There were two Kaposi's sarcomas, two metastatic unknown primaries, one thyroid, one brain, and one ophthalmic malignancies in the series. Mortality for Kaposi's and metastatic disease of unknown primary was 100% within 5 months, while the 1-year mortality for oropharyngeal cancer was 57.1% and that for lung cancers was 62.5%. Long-term survival for skin cancer was highest: 86.4% at 3 years (P=0.015 by log-rank test).. An increased incidence of de novo cancers in the chronically immunocompromised patient demands careful long-term screening protocols which will help to facilitate the diagnosis at an early stage of the disease. This is particularly true for oropharyngeal cancers where the risk is more than 7 times higher compared to SEER incidence data matched for age, sex, and length of follow-up.

Topics: Adult; Aged; Female; Gastrointestinal Neoplasms; Graft Rejection; Humans; Immunosuppressive Agents; Incidence; Liver Transplantation; Male; Middle Aged; Neoplasms; Oropharyngeal Neoplasms; Respiratory Tract Neoplasms; Skin Neoplasms; Tacrolimus; Urogenital Neoplasms