Management of skin cancer in solid organ transplant recipients

The incidence of catastrophic skin cancer in the solid organ transplant population continues to rise. As transplant patients are living longer, it is likely that dermatologists will be looking after an increasing number of organ transplant recipients. The key to managing this patient population lies in a multidisciplinary approach encompassing patient education, skin screening in the immediate post-transplant period, regular follow-up, and rapid referral to a dermatologist once skin lesions suspicious for skin cancer are diagnosed. Of paramount importance is discussion with transplant physicians to negotiate reduction of immunosuppression in the setting of catastrophic skin cancer. This article defines the scope of the problem of skin cancer in the solid organ transplant population, defines the nature of the lesions commonly presented, and reinforces the benefit of a multidisciplinary approach in the management of these patients.     

人乳头瘤病毒感染与非黑素瘤皮肤癌研究进展

人乳头瘤病毒通过侵犯皮肤和黏膜上皮细胞导致皮肤黏膜的各种良恶性病变.非黑素瘤皮肤癌包括皮肤鳞状细胞癌、基底细胞癌、光线性角化病等,在白种人中发病率极高,且全球发病率显著增加.仅在美国,每年约有超过200万的新发病例被确诊为皮肤鳞状细胞癌.除了已知的危险因素,如年龄、紫外线、皮肤的光敏感性以及免疫抑制以外,已有大量流行病学证据显示,人乳头瘤病毒与非黑素瘤皮肤癌的发生发展有关,尤其是皮肤型人乳头瘤病毒感染.     

Current approaches to skin cancer management in organ transplant recipients

Approximately 225,000 people are living with organ transplants in the United States. Organ transplant recipients have a greater risk of developing skin cancer, including basal cell carcinoma, squamous cell carcinoma, and malignant melanoma, with an approximately 250 times greater incidence of squamous cell carcinoma in certain transplant recipients, compared with the general population. Because skin cancers are the most common posttransplant malignancy, the resultant morbidity and mortality in these high-risk patients is quite significant.     

Human papillomavirus heterogeneity in 36 renal transplant recipients

Immunosuppressed patients such as renal transplant recipients are prone to increased incidence of wart disease. We examined 48 tissue specimens from 36 renal transplant recipients using human papillomaviruses (HPVs) 1, 2, 3, 4, 5, and 6 in filter hybridization under stringent conditions. The results showed that 90% of the samples contained HPV DNA. Of these 43 positive samples, we found HPV-1 in 2%, HPV-2 in 56%, HPV-3 in 19%, HPV-4 in 47%, HPV-5 in 9%, and HPV-6 in 5%. In several cases, more than one type of HPV DNA was observed. In a few of these cases, the clinical appearance of the lesions differed from what might have been expected, such as those lesions containing HPV-3- or HPV-5-related DNAs.     

Human papillomavirus and skin cancer

Human papillomavirus (HPV) appears to be the most ubiquitous of the human viruses. Over 100 HPV types have been identified. A minority of HPV cause cutaneous warts and mucosal condylomata. The HPV that cause mucosal condylomata put the patient at various degrees of risk for developing cancers, particularly cervical cancer. The majority of HPV infect the skin of normal and immunocompromised individuals. In normal people, most of these HPV appear to establish a latent infection of the skin, most likely as normal flora residing in hair follicles; however, in patients with various systemic and localized depressions of cell-mediated immunity, some HPV infections appear to be involved in the development of nonmelanotic skin cancer and its precursor lesions in skin, usually in sunlight-exposed areas. Circumstantial evidence suggests that these HPV may have a role in promoting proliferative lesions of the skin, although their sites of active infection and mode of transmission to susceptible individuals remain unknown.     

Human papillomavirus infections in a group of renal transplant recipients

One hundred and twenty renal transplant recipients were investigated. Fifty-eight (48%) were found to have warts, 13 (11%) keratoses and six (5%) to have, or recently to have had cancers. The longer the time of immunosuppression, the greater the prevalence of warts; of those patients who had had their transplant for at least 5 years, 87% had warts. Those with a graft survival time of 10 years or more are at special risk of warts, keratoses and malignancy. Five (10%) of 50 women had genital warts, four of whom had internal lesions (vaginal, cervical or anal) and one developed a carcinoma of the vulva. These findings indicate the advisability of colposcopy for all female renal transplant recipients, a high risk group. Eighty-eight specimens from 42 patients were examined by DNA restriction enzyme analysis and cross hybridization for the presence and type of human papillomavirus (HPV). HPV DNA was detected in 66% of the warts examined, HPV2 and HPV4 occurring most often and HPV1 and HPV3 only infrequently. In sequential specimens from common hand warts of one individual, an HPV was found which could not be precisely identified but was related to HPV4. HPV16 was detected in a vaginal wart from one patient and an HPV6-related virus in a vulval wart of another. HPV DNA of an unknown type was demonstrated in one of 11 keratoses examined. With the probes used to examine the few samples of skin cancers available, HPV16 was found in a squamous cell carcinoma of the vulva, and faint bands from an unidentified type of HPV were detected in two squamous cell carcinomata from a patient's hand. One woman had plaque lesions morphologically and histologically resembling those found in epidermodysplasia verruciformis (EV). HPV5 was identified in these lesions. This is only the third reported case of HPV5, previously thought to be unique to EV, in a renal transplant recipient.     

Management of organ transplant recipients attending a high-throughput skin cancer surgery and surveillance clinic in Queensland

People who undergo organ transplantation are more likely to develop skin cancers, due to long-term immunosuppressive therapy. This is especially concerning for organ transplant recipients (OTRs) living in Queensland, Australia, where skin cancer is more common than elsewhere. In an attempt to address the extreme skin cancer problem in OTRs living in Queensland, a dedicated Transplant Skin Clinic was established in Brisbane. This study aimed to describe the performance of this new clinic, the first of its kind in Queensland, Australia. Clinic attendees were invited to complete two surveys, supplied three months apart, about their health and personal characteristics, and permission was obtained to access participating attendees’ hospital records for details on detected and treated skin cancers over the same three-month period. In total, the authors recruited 101 clinic patients into the study. Over the three months, the authors found that 615 skin lesions were detected in the clinic. Of these, 55 were referred for treatment outside the clinic and 478 were treated in clinic, mostly (78%) with surgery. Of the lesions treated in clinic, 268 were confirmed to be skin cancers, equivalent to nearly 3 skin cancers per patient over the three months. On average, the clinic staff successfully treated one skin cancer for every 1.4 skin lesions they surgically removed. In conclusion, this study found that the clinic is detecting, and efficiently treating, a large number of skin cancers in OTRs and thus effectively contributing to the control of the skin cancer burden in OTRs living in Queensland.     

Treatment of nonmelanoma skin cancer in organ transplant recipients: review of responses to a survey

There are approximately 100,000 US organ transplant recipients, many with nonmelanoma skin cancers. To better understand how clinicians treat them, we e-mailed a survey to the International Transplant-Skin Cancer Collaborative and the Association of Academic Dermatologic Surgeons. Twenty-five physicians responded. The majority use topical 5-fluorouracil, cryosurgery, electrodesiccation and curettage, and surgery. We review when these modalities are used.     

Sunlight, keratotic skin lesions and skin cancer in renal transplant recipients

In a retrospective follow-up study, 36 renal transplant recipients with, and 101 without, skin cancer, who had received their first transplant before January 1981 and who were still alive with a functioning graft on 1 August 1989, were assessed to determine the risk of non-melanoma skin cancer in relation to exposure to sunlight during childhood and adolescence. The contribution of the number of keratotic skin lesions to the skin cancer risk was also assessed. The estimated relative risks (odds ratios) of skin cancer in relation to exposure to sunlight and the presence of keratotic skin lesions were calculated by maximum likelihood estimation in a logistic model. The majority of skin cancers and keratotic skin lesions were confined to sun-exposed skin. After adjustment for possible confounding variables, the odds ratios of skin cancer for moderate and high cumulative life-time exposure to sunlight, respectively, compared with low exposure, were 2·4 (95% confidence interval [CI] 0·64-9·3) and 47·6 (95% CI 5·4-418). Exposure to sunlight before the age of 30 contributed more to the risk of developing skin cancer later in life than exposure after the age of 30. No association was found between cumulative life-time exposure to sunlight and the number of keratotic skin lesions. Nevertheless, these lesions behaved as a strong independent risk factor in the development of skin cancer. The adjusted odds ratio of skin cancer for 50-99 lesions compared with >50 lesions was 4·5 (95% CI 1·1-18·2); the adjusted odds ratio for ≥100 lesions compared with >50 lesions was 20·8 (95% CI 5·3-81·7). We conclude that exposure to sunlight before the age of 30 contributes more to the risk of skin cancer in renal transplant recipients than exposure after the age of 30. Cumulative life-time exposure to sunlight does not appear to be associated with an increased number of keratotic skin lesions in these patients. The preferential localization of such lesions on sun-exposed skin suggests a possible role of recently received exposure to sunlight in the development of these lesions.     

Iatrogenic skin cancer: induction by psoralen/ultraviolet A and immunosuppression of organ transplant recipients

Photochemotherapy (psoralen/UVA (PUVA)) is an efficient therapeutic tool for a wide range of skin diseases. Concern, however, exists regarding the long-term carcinogenic effects of this treatment modality and, as a consequence, is being used less frequently. PUVA remains an important treatment in our therapeutic armamentarium but must be used with caution in those patients with risk factors and cumulative dose exposure must be limited. PUVA-induced cancers show features in common with skin cancers induced by immunosuppressed organ transplant recipients. Tumours in the latter group of individuals are, however, much more aggressive and difficult to manage.