tacrolimus and Papillomavirus-Infections

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

Immunomodulators include both immunostimulatory and immunosuppressive agents. Obligate contact sensitizers such as diphencyprone or dinitrochlorobenzene have been used against viral and autoimmune diseases. Newer agents such as the toll-like receptor agonists imiquimod and resiquimod have been clinically used to treat viral infections and skin cancers in immunocompetent and immunosuppressed patients. On the other hand, the topical immunosuppressive agents tacrolimus and pimecrolimus have been used with great success in the treatment of chronic inflammatory diseases in children and adults. The introduction of this new class of drugs (i.e. Calcineurin inhibitors) marked the beginning of the post-cortisone era in clinical dermatology. Toll-like receptor agonists and calcineurin antagonists will supplement corticosteroids to improve specific dermatological therapy. Topical immunotherapy with both immunostimulatory and immunosuppressive agents show potential for effective and patient-friendly treatment of inflammatory, infectious and neoplastic skin diseases. Long-term evaluation will define the tolerability and the safety profile.

Topics: Adjuvants, Immunologic; Administration, Topical; Adult; Aged; Aged, 80 and over; Aminoquinolines; Asthma; Autoimmune Diseases; Bowen's Disease; Child; Cyclopropanes; Dermatitis, Atopic; Dinitrochlorobenzene; Female; Follow-Up Studies; Herpes Simplex; Humans; Imidazoles; Imiquimod; Immunity, Cellular; Immunocompromised Host; Immunoglobulin A; Immunosuppressive Agents; Lichen Sclerosus et Atrophicus; Male; Molluscum Contagiosum; Papillomavirus Infections; Precancerous Conditions; Skin Diseases; Skin Diseases, Viral; Skin Neoplasms; Tacrolimus; Time Factors; Warts

Polyoma virus infection is characterized by lymphocytic interstitial infiltrate in the kidney, and it mimics acute rejection. The purpose of this study is to estimate renal allograft outcome with this infection and characterize the lymphocytic infiltrates in polyoma virus-infected renal allografts.. Patients who had polyoma virus inclusions in renal allograft biopsies were identified. Other viral inclusions were excluded by immunohistochemistry. The lymphocytic infiltrates of six cases of polyoma virus infection were compared with six cases of definite acute rejection by immunostaining for T and B cells.. There were 10 cases of polyoma virus infections in renal transplant recipients. Immunosuppressants consisted of mycophenolate mofetil with tacrolimus in eight cases and mycophenolate mofetil with cyclosporine in two. The median time of diagnosis of polyoma virus infection after transplantation was 9.5 months, and the time to graft failure after the diagnosis was 4 months. Reduced allograft survival was seen in patients who had polyoma virus infection. Immunostaining for T and B cells revealed marked increase in the B cells (CD20) in renal allografts with polyoma virus infection of 21% (range, 5-40%) compared with 6% (range, 0-10%) in those with acute rejection (P=0.039). Reduced cytotoxic T cells (TIA-1: median, 7%; range, 2-15%) were seen in polyoma virus-infected allografts compared with 24% (range, 15-30%) in those patients who had acute rejection (P=0.0159).. Irreversible graft failure is more prevalent with polyoma virus infection. Enhanced immunosuppressants with mycophenolate mofetil with tacrolimus may play a role in the development of this infection. An increase in CD20 and a decrease in cytotoxic T cells in allografts is characteristic of polyoma virus infection.

Topics: Acute Disease; Adult; Antigens, CD20; B-Lymphocytes; Female; Graft Rejection; Graft Survival; Humans; Immunohistochemistry; Immunosuppressive Agents; Kidney; Kidney Transplantation; Lymphocyte Count; Male; Middle Aged; Mycophenolic Acid; Papillomavirus Infections; Polyomavirus; Staining and Labeling; T-Lymphocytes, Cytotoxic; Tacrolimus; Tumor Virus Infections