Non-melanoma Skin Cancer Patients Research Articles

Seroreactivity to Cutaneous Human Papillomaviruses among Patients with Nonmelanoma Skin Cancer or Benign Skin Lesions

Cutaneous human papillomaviruses (HPV) are common in nonmelanoma skin cancers, benign skin lesions, and healthy skin. Increased seroprevalences for cutaneous HPV among nonmelanoma skin cancer patients have been described. To determine whether antibodies to cutaneous HPV are related to presence of the virus and/or to skin disease, we collected serum and biopsies from both lesions and healthy skin from 434 nonimmunosuppressed patients (72 squamous cell carcinomas, 160 basal cell carcinomas, 81 actinic keratoses, and 121 benign lesions). Biopsies were analyzed for HPV DNA by PCR, cloning, and sequencing. Serum antibodies to the major capsid protein L1 of HPV 1, 5, 6, 8, 9, 10, 15, 16, 20, 24, 32, 36, 38, and 57 as well as to the oncoproteins E6 and E7 of HPV 8 and 38 were detected using a multiplexed fluorescent bead-based assay. Type-specific seroprevalence among patients with the same type of HPV DNA (sensitivity of serology) varied from 0% to at most 28%. Presence of HPV DNA and antibodies to the same HPV type was not significantly correlated. However, seropositivity to any HPV type was significantly more common among patients positive for HPV DNA of any HPV type (odds ratio, 1.90; 95% confidence interval, 1.55-2.34). Seroprevalences were similar among the different patient groups but was, for most HPV types, somewhat higher among squamous cell carcinoma patients than among basal cell carcinoma patients (P < 0.01). In conclusion, additional studies are required to clarify the biological meaning of seropositivity as a marker of cutaneous HPV infection and skin disease.

Repair Capacity for UV Light–Induced DNA Damage Associated with Risk of Nonmelanoma Skin Cancer and Tumor Progression

To examine the role of suboptimal DNA repair capacity (DRC) for UV light-induced DNA damage in the development of nonmelanoma skin cancer (NMSC) and tumor progression. We conducted a hospital-based case-control study of 255 patients with newly diagnosed NMSC [146 with basal cell carcinoma (BCC) and 109 with squamous cell carcinoma (SCC)] and 333 cancer-free controls. We collected information on demographic variables and risk factors from questionnaires, tumor characteristics from medical records, and lymphocytic DRC phenotype by the host-cell reactivation assay. Multivariable logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (95% CI). Overall, there was a relative 16% reduction in DRC in NMSC patients compared with controls (P < 0.001 for BCC and for SCC, respectively). DRC below the controls' median value was associated with increased risk significantly for BCC (OR, 1.62; 95% CI, 1.07-2.45) but borderline for SCC (OR, 1.63; 95% CI, 0.95-2.79) after adjustment for age, sex, and other assay-related covariates. When the highest tertile of controls' DRC was used as the reference, the intermediate and low DRC were associated with a statistically significant trend for increasing risk for both BCC (P(trend) = 0.007) and SCC (P(trend) = 0.020). However, patients with aggressive or multiple SCC tended to have a higher DRC than those with nonaggressive or single SCC. Reduced DRC is an independent risk factor for BCC and single or nonaggressive SCC but not for multiple primaries, local aggressiveness, or recurrence of NMSC.

Photodynamic therapy in dermatooncology

Non-melanoma skin cancers are the most common skin tumors. Because of their frequent localization on the face and hand, aesthetic aspects of the therapeutic procedures should also be considered. Surgical excision still remains the first choice, but recently several new alternative therapies have emerged, especially for the treatment of superficial skin cancer. Photodynamic therapy has become a widely accepted therapeutic method for certain non-melanoma skin tumors. Photodynamic therapy involves the use of light to activate a photosensitizer, localized in diseased tissues. Photosensitizers are tumor-selective: their accumulation in rapidly proliferating cells and newly formed blood vessels is significantly higher than in the surrounding healthy tissues. During photodynamic therapy, cytotoxic reactive oxygen species are formed from the photosensitizer, leading to changes in subcellular pathways or apoptosis of the cells. Efficacy of the photodynamic therapy has been proven in solar keratosis, superficial basal cell carcinoma and morbus Bowen, with significantly better cosmetic outcome than that of the conventional therapeutic methods. Side effects, like erythema, crusting, serous discharge, or oedema, are usually moderate, and dissolve rapidly. The present article summarizes the authors' experiences with photodynamic treatment (212 non-melanoma skin cancer patients were treated with PDT between December 2003 and January 2006), at the Department of Dermatology and Allergology, University of Szeged, Hungary, and reviews the literature of photodynamic therapy in dermatooncology.

The Influence of Immune Modifier Therapy on the Development of Non-Melanoma Skin Cancer in Patients with Crohnʼs Disease under Age Fifty

Purpose: A few case reports have identified the use of immune suppressive drugs for treatment of inflammatory bowel disease as a risk for the development of skin cancer. Non-melanoma skin cancer (NMSC) is more common in men and usually occurs in those older than age 50. The aim of this study was to investigate the relationship of NMSC to immune suppression therapy among patients with Crohn's disease less than age 50. Methods: With IRB approval, a retrospective chart review of patients at Mayo Clinic, Rochester, MN, who had documented CD diagnosed between 1975 and 2004 and who were subsequently diagnosed with NMSC. Inclusion criteria were: age less than 50 at the time of skin cancer diagnosis; diagnosis of skin cancer at least 2 years after CD diagnosis; no prior history of skin cancer or pre-malignant skin disease; and residence in Minnesota, Iowa, Illinois, Wisconsin, N. Dakota, or South Dakota. Results: 15 patients (7 Caucasian males, 8 Caucasian females), who met the inclusion criteria were identified: 7 received either no medical therapy or only mesalamine for CD prior to developing NMSC while 8 received immune suppressive drugs (steroids only = 2, Azathioprine/6-MP = 6). None of the patients had received infliximab or other biologic therapies. The median ages for those who did not and those who did receive immune suppression were 43 years and 46 years, respectively, P= 0.327. The median time from diagnosis of CD to diagnosis of NMSC was 14.1 years in the group receiving no immune suppressives and 15.5 years in the immune suppressive group, P= 0.921. All 7 patients (4 males, 3 females) who did not take immune suppressives developed basal cell carcinomas (BCCs), and 2 also developed squamous cell cancers (SCC). Among the 8 patients (3 males, 5 females) who took immune suppressives, 6 developed SCCs (2 also had BCCs), and 2 other patients had BCCs only. No patient developed more than 2 NMSCs over the study period. Conclusion: Among patients with Crohn's disease who developed non-melanoma skin cancer before age 50, there was no gender predominance, and treatment with immune suppression was not associated with an increased risk of skin cancer.

Teledermatology-Based Presurgical Management for Nonmelanoma Skin Cancer

BACKGROUND To date, no previous experiences of teledermatology (TD) as a preoperative management facility have been published. OBJECTIVE The objective was to evaluate a store-and-forward TD (SFTD) system aimed at the presurgical management of nonmelanoma skin cancer patients. METHODS AND MATERIALS This was a multicenter, longitudinal, descriptive, and evaluative pilot study. Patients included in the TD-based surgical referral system presented with a nonmelanoma skin cancer or a fast-growth vascular tumor suitable for surgery under local anesthesia. Waiting intervals and on-the-day cancellation rates were evaluated and compared with a sample of patients managed through the conventional system. The accuracy of the diagnoses yielded and of the surgical techniques planned through teleconsultation was also calculated. RESULTS A total of 134 patients were enrolled in the study. The mean waiting interval was 26.10 days [95% confidence interval (CI), 24.51–27.70] in patients managed through TD and 60.57 days (95% CI, 56.20–64.93 days; n=92; p < .001) in the conventional system. On-the-day surgery cancellation was 2.99% (95% CI, 1.52%–4.46%) for the TD series and 8.85% (95% CI, 5.62%–11.81%; p<.005) in the conventional system. The accuracy of the telediagnoses was κ=0.86 (95% CI, 0.83–0.89). The agreement rate between the surgical technique planned through teleconsultation and the technique finally performed was κ=0.75 (95% CI, 0.04–0.79). CONCLUSION SFTD has been demonstrated to be effective and accurate as a preoperative tool for nonmelanoma skin cancer, avoiding unnecessary visits to the hospital and shortening the waiting intervals to the surgical treatment.

The Skin Cancer Index: Clinical Responsiveness and Predictors of Quality of Life

To establish the clinical responsiveness of the Skin Cancer Index (SCI), a new disease-specific quality of life (QOL) instrument, and to assess demographic and clinical factors which impact QOL in patients with nonmelanoma skin cancer (NMSC). Prospective study of 183 patients with NMSC of the face and neck referred to a tertiary care Mohs surgery clinic. The SCI is a 15 item, validated, disease-specific QOL instrument with 3 distinct subscales, Emotion, Social, and Appearance. Higher scores reflect better QOL. The SCI and the Dermatology Life Quality Index (DLQI), a general dermatology instrument, was administered at initial consultation and 4 months after surgical treatment. Multivariate analysis was conducted to assess demographic and clinical factors predictive of QOL for both instruments. The SCI total score and all three subscale scores increased with treatment, demonstrating strong evidence of responsiveness over time (P < .001) in contrast with the DLQI (P = .46). Predictors of poorer QOL for the SCI included female sex and cancers located on the lip. Patients who demonstrated greatest improvement in QOL with treatment included those who were younger (<50 yr) and had lower reported household income. Also, first time NMSC patients and those patients who underwent less extensive reconstructions demonstrated greater improvements in QOL. The SCI is a sensitive and responsive QOL instrument for patients with NMSC. Distinct demographic and clinical variables that impact QOL have been demonstrated using this multidimensional, disease-specific instrument.

The association between non‐melanoma skin cancer and a young dimorphic Alu element within the major histocompatibility complex class I genomic region

A non-melanoma skin cancer (NMSC) susceptibility locus within the major histocompatibility complex (MHC) class I region was previously identified telomeric of the HLA-C gene using high-density microsatellite markers. Here, we have extended the previous microsatellite study by using the same DNA samples obtained from 154 NMSC patients and 213 normal controls from the town of Busselton in Western Australia and examined the relationship between five polymorphic Alu insertions (POALINs) within the MHC class I region and their association with NMSC. The genotype distribution of the AluyTF insertion that is located within the NMSC susceptibility region telomeric of the HLA-C gene was significantly increased according to the Fisher's exact test in the NMSC patients, and it was not in Hardy-Weinberg equilibrium in the control group. There was no difference between the cancer patients and controls for the genotypes of the AluyMICB locus within intron 1 of the MICB gene and the other three POALINs (AluyHJ, AluyHG and AluyHF) that are located within the genomic region of the HLA-A, -G and -F gene cluster. The test for significant linkage disequilibrium for 10 pairs of POALIN loci and estimations of two locus POALIN haplotype frequencies also revealed AluyTF differences between the cases and controls. In conclusion, the MHC class I POALIN, AluyTF, that is located within the NMSC susceptibility locus and near the HLA-C gene was strongly associated with NMSC. This finding, using five different polymorphic Alu insertion markers, supports the previous microsatellite association study that one or more genes located in close proximity to the AluyTF insertion has a potential role in NMSC.

Real-time PCR analysis of a 3895 bp mitochondrial DNA deletion in nonmelanoma skin cancer and its use as a quantitative marker for sunlight exposure in human skin

Previous findings from our own laboratory have shown that the frequency of occurrence (i.e. the simple presence or absence) of the 3895 bp mitochondrial DNA deletion is increased with increasing sun exposure. The present study has significantly extended this work by developing, validating and then using a quantitative real-time PCR assay to investigate for the first time the actual level (as opposed to the frequency of occurrence) of the 3895 bp deletion in human skin from different sun-exposed body sites and tumours from nonmelanoma skin cancer patients. We investigated the 3895 bp deletion in 104 age-matched split human skin samples taken from various sun-exposed sites defined as usually exposed (n=60) and occasionally exposed (n=44) when outdoors. The results clearly show an increased level of the 3895 bp deletion with increasing sun exposure. Specifically, there was a significantly higher level of the deletion in the usually sun-exposed compared to the occasionally sun-exposed skin (P=0.0009 for dermis, P=0.008 for epidermis; two-tailed t-test). Our study has also extended previous findings by showing that the level of the 3895 bp deletion is significantly higher in the dermis compared with the epidermis both in the occasionally sun-exposed samples (P=0.0143) and in the usually sun-exposed skin. (P=0.0007).

DNA damage, oxidative mutagen sensitivity, and repair of oxidative DNA damage in nonmelanoma skin cancer patients

Nonmelanoma skin cancer (NMSC) is the most frequent type of cancer in humans. Exposure to UV radiation is a major risk factor for NMSC, and oxidative DNA damage, caused either by UV radiation itself or by other agents, may be involved in its induction. Increased sensitivity to oxidative damage and an altered DNA repair capacity (DRC) increase the risk of many types of cancer; however, sensitivity to oxidizing agents has not been evaluated for NMSC, and results regarding DRC in NMSC are inconclusive. In the present study, we evaluated DNA damage and repair in leukocytes from 41 NMSC patients and 45 controls. The Comet assay was used to measure basal and H(2)O(2)-induced DNA damage, as well as the DRC, while the cytokinesis-block micronucleus assay was used to measure the basal level of chromosome damage. Although basal DNA damage was higher for the controls than for the patients, this finding was mainly due to sampling more controls in the summer, which was associated with longer comet tails. In contrast, H(2)O(2)-induced DNA damage was significantly higher in cases than in controls, and this parameter was not influenced by the season of the year. The DRC for the H(2)O(2)-induced damage was similar for cases and controls and unrelated to seasonality. Finally, the frequency of binucleated lymphocytes with micronuclei was similar for cases and controls. The results of this study indicate that NMSC patients are distinguished from controls by an increased sensitivity to oxidative DNA damage.

Mitochondrial DNA Deletions Serve as Biomarkers of Aging in the Skin, but Are Typically Absent in Nonmelanoma Skin Cancers

The potential role of mitochondrial DNA (mtDNA) deletions in nonmelanoma skin cancer (NMSC) and in cutaneous photoaging was explored using a genetic approach. Tumors and photodamaged tumor-free "margin" skin were obtained from NMSC patients undergoing excision and the mtDNA from these specimens was screened for the presence of deletions using long extension PCR. mtDNA deletions were abundant in margin tissue specimens from older patients and their number correlated with the patient age. There was a statistically significant difference between the number of mtDNA deletions in tumors and margins. Fewer deletions were detected in the tumors than the margins and the tumors often had no deletions, implying a potential selection for full-length mtDNA or perhaps a protective role for mtDNA deletions in the process of tumorigenesis. The observed mtDNA deletions from skin were often unreported (19 of 21 deletions), but typically shared structural features with mtDNA deletions reported in other tissues. Some mtDNA deletions were detected from the skin of multiple individuals, including 3,715 and 6,278-base pair (bp) deletions, whose frequencies approached that of the previously well-characterized 4977-bp "common" deletion. These data support the use of mtDNA mutations as biomarkers of photoaging in the skin.

Medical Student Exposure to Drug Company Interactions

1. de Gruijl FR, van Kranen HJ, Mullenders LH. UV-induced DNA damage, repair, mutations and oncogenic pathways in skin cancer. J Photochem Photobiol B. 2001; 63:19-27. 2. Dennis LK, Beane Freeman LE, VanBeek MJ. Sunscreen use and the risk for melanoma: a quantitative review. Ann Intern Med. 2003;139:966-978. 3. Marks R, Staples M, Giles GG. Trends in non-melanocytic skin cancer treated in Australia: the second national survey. Int J Cancer. 1993;53:585-590. 4. Marcil I, Stern RS. Risk of developing a subsequent nonmelanoma skin cancer in patients with a history of nonmelanoma skin cancer: a critical review of the literature and meta-analysis. Arch Dermatol. 2000;136:1524-1530.

Site-Specific Occurrence of Nonmelanoma Skin Cancers in Patients With Cutaneous Melanoma

Site-Specific Occurrence of Nonmelanoma Skin Cancers in Patients With Cutaneous Melanoma

Risk of Second Primary Cancer and Death Following a Diagnosis of Nonmelanoma Skin Cancer

Cancer-free patients diagnosed with a first primary nonmelanoma skin cancer (NMSC) offer an opportunity for studying the risk of a second primary cancer without the confounding effect of systemic treatment. The objective of the study was to estimate the risk of second primary cancer in people with a history of basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) and the risk of dying in cancer patients with a NMSC history. BCC and SCC cases diagnosed between 1956 and 2000 in Manitoba, Canada were followed-up for second primaries (other than NMSC). Standardized incidence and mortality ratios (SIR and SMR) were calculated. Men [SIR, 1.06; 95% confidence interval (95% CI), 1.02-1.10] and women (SIR, 1.07; 95% CI, 1.02-1.12) with a BCC history as well as men (SIR, 1.15; 95% CI, 1.08-1.22) with a SCC history were at greater risk of a second primary cancer. Overall, the increased risk was observed only in the first 4 years following a NMSC, although it remained increased for specific cancer sites. The risk remained higher in all age groups up to 75 years of age. People with a history of BCC (males: SMR, 1.09; 95% CI, 1.04-1.14; females: SMR, 1.24; 95% CI, 1.16-1.32) or SCC (males: SMR, 1.18; 95% CI, 1.09-1.27; females: SMR, 1.55; 95% CI, 1.35-1.79) had a greater risk of death following their second primaries. Even if NMSC patients are at greater risk of a second cancer, it is not recommended to follow them up beyond the generally accepted periodic examination of the skin.

Site-specific occurrence of nonmelanoma skin cancers in patients with cutaneous melanoma

In a registry-based case–control study, we compared the site-specific occurrence of nonmelanoma (keratinocytic) skin cancers among patients with cutaneous melanoma cases (cases, n=3774) and solid tumours (controls, n=349 923), respectively. Overall, patients with melanoma were almost five-fold more likely to develop keratinocytic cancers compared with solid tumour controls (adjusted OR 4.7, 95% CI 4.1–5.3), but the risks varied depending upon the site of melanoma. Whereas patients with melanoma of the head and neck had similarly increased risks of keratinocytic cancers across all body sites, patients with melanoma of the trunk were significantly more likely to develop keratinocyte cancer diagnosed on the trunk (adjusted OR 12.5, 95% CI 7.2–20.2) than on the head and neck (adjusted OR 3.0, 95% CI 2.2–4.3). Similar colocalisation of skin tumours was observed for patients with melanomas of the lower limb. These findings provide support for the hypothesis that skin cancers at different anatomical sites may arise through different causal pathways.

Decreased incidence of nonmelanoma skin cancer in patients with type 2 diabetes mellitus using insulin: a pilot study

In order to prevent the propagation of genetic mutations, human keratinocytes irradiated with ultraviolet (UV) B light in vitro undergo premature stress-induced senescence or apoptosis. This response to UVB irradiation is dependent on the functional activation of the insulin-like growth factor-1 receptor (IGF-1R). Based on this in vitro functional data, we hypothesized that the increased serum levels of insulin in patients with type 2 diabetes may activate the IGF-1R in skin and lead to a decreased frequency of skin cancer in these patients. To determine whether the use of insulin by patients with type 2 diabetes correlated with a change in the incidence in nonmelanoma skin cancer (NMSC). A historical cohort study identifying the incidence of NMSC following the use of two different pharmacological therapies. The patient population was restricted to caucasians who were at least 50 years old when they began the indicated pharmacological therapy. The first group consisted of 1440 patients who used insulin therapy to treat type 2 diabetes and the second group comprised 4135 patients who used cimetidine to treat their gastrointestinal ailments. An additional group of 6131 patients with diabetes who used noninsulin antidiabetics was added to examine the effect of noninsulin therapies. All patients had regular follow-up visits at the Regenstrief Clinics during the study period between 1980 and 1999. The Regenstrief Clinics is an outpatient facility which serves the general population in Metro-Indianapolis, Indiana, U.S.A. The incidence of NMSC in patients using insulin was significantly lower than in patients using cimetidine (1.25% vs. 2.35%, P < 0.02). The decrease in NMSC in patients with type 2 diabetes correlated specifically with the use of insulin (NMSC incidence insulin-only patients with diabetes: 1.40% vs. those with diabetes using noninsulin therapies: 2.35%, P = 0.11). Patients using exogenous insulin had a lower risk of developing NMSC and the protective effect of insulin use becomes more distinct with increasing age.

Creation of a Quality of Life Instrument for Nonmelanoma Skin Cancer Patients

Malignancies of the skin are the most common cancers among humans. The cervicofacial region is most affected by cutaneous malignancies, with approximately 80% of nonmelanoma skin cancers (NMSC) occurring in the head and neck. Treatment of cervicofacial skin cancers also is more likely to result in significant patient morbidity, because of the functional and cosmetic importance of this region. Unlike other malignancies, skin cancer has not been well investigated in terms of patient quality of life (QOL) assessment. Furthermore, no validated disease-specific QOL instrument currently exists for skin cancer. The aim of this study was to construct a new QOL instrument, The Facial Skin Cancer Index (FSCI), that captures the relevant QOL issues for NMSC patients. Cross-sectional study of patients presenting to a dermatologic surgery clinic with NMSC of the head and neck. For stage I, item generation, a sample of 20 patients with cervicofacial NMSC and six health care providers specializing in the care of NMSC patients completed semistructured interviews. For stage II, item reduction, a second sample (n = 52) of NMSC patients rated the items in terms of their importance for QOL among skin cancer patients. Domains of the FSCI were evaluated in terms of data quality, item variability, internal consistency, and range and skewness of scale score on aggregation and floor and ceiling effects. A total of 71 distinct items were generated in stage I. After using the outlined item reduction techniques in stage II, the FSCI was reduced from 71 to 36 items, representing 6 domains. With the exception of Physical Functioning (alpha = 0.63) that suggested adequate reliability, all subscale scores showed excellent reliability coefficients, with Cronbach's alpha ranging from 0.78 (Lifestyle) to 0.87 (Social/Family). A new disease-specific QOL instrument for patients with NMSC of the head and neck has been created. Validation studies are currently underway. Future directions will include sensitivity analysis to determine whether the FSCI is sensitive to change over time among patients undergoing treatment for NMSC.

Nonmelanoma Skin Cancer in Survivors of Childhood and Adolescent Cancer: A Report From the Childhood Cancer Survivor Study

Nonmelanoma skin cancer (NMSC) has become the most common type of cancer in many populations throughout the world. Ultraviolet and ionizing radiation are known risk factors. Because NMSCs are rarely lethal and most cancer registries do not routinely report data regarding these cancers, they have received little attention in studies evaluating long-term effects of cancer therapy. This article reports on the occurrence of secondary NMSC as a long-term effect of cancer therapy in survivors of childhood cancer. The Childhood Cancer Survivor Study (CCSS) is a cohort study of 5-year survivors of childhood and adolescent cancer from 25 participating institutions in North America. NMSC patients were defined by a history of basal cell or squamous cell carcinoma of the skin after primary malignancy treatment. Demographic and treatment data were collected and analyzed. Among the 13,132 eligible CCSS participants, 213 have reported NMSC; 99 patients (46%) have had multiple occurrences. Median age of occurrence was 31 years (range, 7 to 46 years). Location of NMSC included head and neck (43%), back (24%), chest (22%), abdomen and pelvis (5%), extremity (3%), and unknown (4%). Ninety percent of patients had previously received radiation therapy (RT); 90% of tumors occurred within the RT field. RT was associated with a 6.3-fold increase in risk (95% CI, 3.5- to 11.3-fold). Long-term survivors of childhood and adolescent cancer who were treated with RT are at highest risk for developing NMSC. Educational efforts need to be directed to this population to facilitate early diagnosis of NMSC and reduction in sun exposure.

Mortality Risk From Squamous Cell Skin Cancer

To identify nonmelanoma skin cancer patients with squamous cell carcinoma (SCC) who are at greatest risk of disease-specific mortality. Prospectively enrolled patients with a minimum of one pathologically confirmed skin SCC lesion, definitive treatment of the SCC lesion(s) resulting in no evidence of disease, and at least 2 months of follow-up after definitive treatment were eligible for the present longitudinal analysis. They received comprehensive clinical, pathologic evaluations and follow-up for patterns of failure and mortality. We enrolled 210 patients (187 men and 23 women) with a total of 277 skin SCC lesions and a median enrollment age of 68 years (range, 34 to 95 years). Median follow-up of surviving patients was 22 months. Three-year overall and disease-specific survival (DSS) rates were 70% and 85%, respectively. In univariate analyses, the clinical-pathologic factors associated with adverse DSS were local recurrence at presentation (P = .05), invasion beyond subcutaneous tissues (P = .009), perineural invasion (P = .002), lesion size (P = .0003), and depth of invasion (P = .05). Statistical models identified a homogeneous high-risk group of patients with lesions > or = 4 cm, perineural invasion, and deep invasion beyond subcutaneous structures. Three-year DSS was 100% for patients with no risk factors versus 70% for patients with at least one risk factor. Lesion size > or = 4 cm and histologic evidence of perineural invasion and deep invasion beyond subcutaneous structures were the clinical-pathologic factors most significantly associated with disease-specific mortality in skin SCC.

Non‐melanoma skin cancer in patients with atopic dermatitis treated with topical tacrolimus

Objective: To determine whether atopic dermatitis (AD) patients treated with tacrolimus ointment experienced an increased risk of non‐melanoma skin cancer (NMSC). Methods: Data were collected from 9813 adult and paediatric patients with AD who applied 0.03% or 0.1% tacrolimus ointment twice daily and were examined every 3 months during the tacrolimus ointment development programme. Results: Thirteen adult patients were diagnosed with NMSC during the follow‐up period. All patients with NMSC were white adults and 12 were over 40 years of age. Based on 1718 patient‐years of tacrolimus ointment exposure in patients⩾40 years of age, the calculated incidence of NMSC did not suggest an increased risk of first NMSC over that of a similarly aged US cohort. Conclusion: This study does not indicate an increased risk for the development of NMSC in patients with AD treated with tacrolimus ointment for a mean duration of 208 days with a maximum observation period of 1479 days.

UV-B irradiation stimulates the promoter activity of the high-risk, cutaneous human papillomavirus 5 and 8 in primary keratinocytes

Human papillomaviruses (HPV) have been implicated in the development of non-melanoma skin cancer (NMSC). HPV types 5 and 8 are strongly associated with NMSC in patients with the inherited disease Epidermodysplasia verruciformis (Ev). In these patients tumours arise predominantly on sun-exposed skin and consistently harbour HPV DNAs. To determine whether UV-B irradiation modulates the noncoding region (NCR) promoter activity of the Ev-HPV types 5, 8, 9, 14, 23, 24, and 25 we performed transient transfection assays with NCR luciferase reporter gene constructs in primary human epithelial keratinocytes (PHEKs) and in p53-null RTS3b cells. Each of the HPVs showed different basal NCR activity in both cell types and reacted differently upon UVB treatment and p53 cotransfection in RTS3b cells. The NCR of HPV5 and 8 were the only ones to be activated by UV-B in PHEKs. The stimulation of the NCR activity of the high-risk cutaneous HPV types 5 and 8 by UV-B irradiation may point to a role of this interaction in the development of NMSC.