Human papillomaviruses in transplant-associated skin cancers.

BACKGROUND: Human papillomavirus (HPV) infection has been suggested to be involved in the development of nonmelanoma skin cancer, the most common malignancy after solid-organ transplantation. OBJECTIVE: The objective of this study was to analyze the prevalence of different HPV types in squamous cell carcinomas (SCC) and basal cell carcinomas (BCC) of transplant recipients and nonimmunosuppressed patients. METHODS: To include the complete spectrum of HPV types in skin lesions, a comprehensive polymerase chain reaction assay with five different primer combinations was used. RESULTS: For SCC, HPV DNA was detected more frequently in tumors of transplant recipients (12/16, 75%) than of nonimmunosuppressed patients (7/19, 37%). In contrast, the HPV detection rate was similar in BCC specimens (4/8 or 50% in transplanted patients; 27/56 or 48% in nonimmunosupressed patients). Overall, 22 different HPV types were identified. HPV types 5 and 8 were detected predominately in SCC from transplant recipients. The amount of viral DNA was slightly higher in SCC of transplanted than in nonimmunosuppressed patients, but much lower than in both cutaneous and genital warts. CONCLUSIONS: Cutaneous infections with HPV5 and HPV8 may represent an increased risk for SCC development in transplant recipients. The mechanisms by which these viruses may contribute to skin cancer development still remain unclear.

Comparative epidemiology and pathogenic factors for nonmelanoma skin cancer in organ transplant patients.

BACKGROUND: Organ transplantation has been performed for almost 40 years with steadily increasing success regarding long-time survival of the graft as well as quality of life for the patient. An increase of skin cancers as a consequence of the lowered cellular immune response seems to parallel the overall increased survival rate of organ transplant recipients. Against the background of chronic immunosuppression, known risk factors like the amount of sun exposure before and after transplantation and oncogenic viruses as well as the genetic background and place of residence (latitude) are strongly related with the increased skin cancer incidence. The goal of this review is to compare the epidemiologic prevalence of nonmelanoma skin cancer between various geographic locations and to highlight pathogenesis factors. METHODS: This study was based on a review of the current literature. RESULTS: The increasing incidence of nonmelanoma skin cancer paralleling a prolonged survival of patients after organ transplantation represents a significant reason for morbidity and long-term mortality in organ transplant recipients worldwide. The incidence of nonmelanoma skin cancer in liver, kidney, and heart transplant recipients varies from 1.5% to 22%, 2% to 24%, and 6% to 34%, respectively, within 5 years of transplantation depending on geographic location and other pathogenesis factors. Ultraviolet radiation (UVR) as well as immunosuppressant therapy are crucial risk factors regarding the induction and progression of skin cancer. UVR is related to the induction of DNA damage as well as interference with Langerhans cell antigen presentation and a TH1-TH2 shift induced via release of IL-10. Whereas the overall duration of immunosuppression and the accumulative dosage applied are relevant measures in the pathogenesis of an increased tumor risk, individual differences between specific immunosuppressive agents are more difficult to assess. CONCLUSIONS: Multiple international studies assess risk factors and pathophysiology of skin cancer in organ transplant patients, with variable results in the literature. Large multicenter studies with thorough multivariant analysis may provide useful information for center-independent analysis of pathogenesis factors for transplant-related skin cancer.

Human papillomavirus and overexpression of P16INK4a in nonmelanoma skin cancer.

BACKGROUND: P16INK4a overexpression has been identified as a specific biomarker in high-risk human papillomavirus (HPV)-infected cervical (pre)cancer lesions. OBJECTIVE: To evaluate the overexpression of this cyclin-dependent kinase inhibitor in skin tumors depending on HPV infections, we analyzed normal skin, benign skin disease, and skin cancer specimens. METHODS: Biopsies of 23 patients with normal histology (3), psoriasis (2), verrucae vulgaris (2), actinic keratoses (5), squamous cell carcinoma (SCC) in situ (3), Bowen's carcinoma (1), and SCC (7) were analyzed. Specimens of 23 patients were immunostained using the monoclonal antibody E6H4 specific for p16INK4a. HPV status was assessed by a polymerase chain reaction (PCR) system to detect all currently known HPV types. MY (MY09/MY11 and MYN9/MYN10)-, CP (CP65/CP70 and CP66/CP69)-nested PCR, and three single PCR methods CN1, CN3, and CN4 were used in a first step, and HPV typing was performed by restriction fragment length polymorphism analysis. Only beta-globin-positive patients were included in this study. RESULTS: HPV DNA was detected in all actinic keratoses, SCC in situ, Bowen's carcinoma, and SCC, in 50% (one of two) of verrucae vulgaris, in 66% (two of three) of normal skin, and in none of two psoriasis. P16INK4a expression was not detected in normal skin, psoriasis, and verrucae vulgares. Overexpression of p16INK4a was detected in a subset of dysplastic cells (10% to 80%) of all skin (pre)cancer lesions such as actinic keratoses, SCC in situ, Bowen's carcinoma, and SCC infected with HPV independent of sun exposure. CONCLUSION: P16INK4a appears to be overexpressed in a portion of dysplastic cells from actinic keratoses and SCC. Further studies to examine the association of HPV infection and the overexpression of p16INK4a are warranted.

[Successful treatment of Stewart-Treves syndrome with liposomal doxorubicin]. / Erfolgreiche Therapie eines Stewart-Treves-Syndroms mit liposomal verkapseltem Doxorubicin.

The Stewart-Treves syndrome (STS) is a lymphedema-associated angiosarcoma which usually develops in female patients after mastectomy and axillary lymph node dissection. A 55-year old woman developed STS in her lymphedematous left arm seven years after breast-preserving surgery with axillary lymph node dissection and radiotherapy. Various therapies which have been employed are radiotherapy and isolated limb perfusion with cytostatic agents. Since our patient had a huge lesion with additional chest wall involvement, neither approach represented a good option. Radiological staging showed no evidence of further lesions or metastases. We started infusion therapy with liposomal doxorubicin (20 mg/m2 body surface) fort six cycles at regular intervals of 14 days. The patient tolerated the therapy well. Palmar-plantar erythrodysesthesia, a well-known side effect of doxorubicin, did develop. Because the disease was stable, the therapy interval was increased to six weeks after the 6th cycle. The patient has shown no recurrence for eight months. STS is a very rare variant of an angiosarcoma with poor prognosis. The case report shows that liposomal doxorubicin provides an effective therapeutic option.