Maryam M. Asgari

Detection of Human Papillomavirus DNA in Cutaneous Squamous Cell Carcinoma among Immunocompetent Individuals

The presence of certain types of human papillomavirus (HPV) is a known risk factor for the development of anogenital squamous cell carcinomas (SCCs). A similar association has been hypothesized for cutaneous SCCs, although, to our knowledge, no studies to date have combined sensitive HPV DNA detection techniques with epidemiologic data controlling for known risk factors to explore the association. We designed a case-control study examining HPV prevalence using highly sensitive PCR-detection assays in tissue samples from 85 immunocompetent patients with histologically confirmed SCCs and 95 age-matched individuals without a prior history of skin cancer. A standardized interview was administered to all study subjects to collect information pertaining to potential confounding variables. The overall detection rate of HPV DNA was high in case lesions (54%) and perilesions (50%) and in both sun-exposed normal tissue (59%) and non-sun-exposed normal tissue (49%) from controls. In comparing case tissue to control tissue, there was no differential detection of HPV DNA across various HPV species. However, HPV DNA from beta-papillomavirus species 2 was more likely to be identified in tumors than in adjacent healthy tissue among cases (paired analysis, odds ratio=4.0, confidence interval=1.3-12.0). The high prevalence of HPV DNA detected among controls suggests that HPV DNA is widely distributed among the general population. However, the differential detection of HPV beta-papillomavirus species in tumors among cases suggests that certain HPV types may be involved in the progression of cutaneous SCCs.

HIV Infection Status, Immunodeficiency, and the Incidence of Non-Melanoma Skin Cancer

Background The incidence of non-melanoma skin cancers (NMSCs), including basal cell (BCC) or squamous cell carcinoma (SCC), is not well documented among HIV-positive (HIV(+)) individuals. Methods We identified 6560 HIV(+) and 36 821 HIV-negative (HIV(-)) non-Hispanic white adults who were enrolled and followed up in Kaiser Permanente Northern California from 1996 to 2008. The first biopsy-proven NMSCs diagnosed during follow-up were identified from pathology records. Poisson models estimated rate ratios that compared HIV(+) (overall and stratified by recent CD4 T-cell counts and serum HIV RNA levels) with HIV(-) subjects and were adjusted for age, sex, smoking history, obesity diagnosis history, and census-based household income. Sensitivity analyses were adjusted for outpatient visits (ie, a proxy for screening). All statistical tests were two-sided. Results The NMSC incidence rate was 1426 and 766 per 100 000 person-years for HIV(+) and HIV(-) individuals, respectively, which corresponds with an adjusted rate ratio of 2.1 (95% confidence interval [CI] = 1.9 to 2.3). Similarly, the adjusted rate ratio for HIV(+) vs HIV(-) subjects was 2.6 (95% CI = 2.1 to 3.2) for SCCs, and it was 2.1 (95% CI = 1.8 to 2.3) for BCCs. There was a statistically significant trend of higher rate ratios with lower recent CD4 counts among HIV(+) subjects compared with HIV(-) subjects for SCCs (P trend < .001). Adjustment for number of outpatient visits did not affect the results. Conclusion HIV(+) subjects had a twofold higher incidence rate of NMSCs compared with HIV(-) subjects. SCCs but not BCCs were associated with immunodeficiency.

Systemic Immune Suppression Predicts Diminished Merkel Cell Carcinoma–Specific Survival Independent of Stage

Merkel cell carcinoma (MCC) is an aggressive cutaneous malignancy linked to a contributory virus (Merkel cell polyomavirus/MCPyV). Multiple epidemiologic studies have established an increased incidence of MCC among persons with systemic immune suppression. Several forms of immune suppression are associated with increased MCC incidence, including hematologic malignancies, HIV/AIDS, and immunosuppressive medications for autoimmune disease or transplant. Indeed, immune suppressed persons represent approximately 10% of the MCC patients, a significant over-representation relative to the general population. We hypothesized that immune suppressed patients may have a poorer MCC-specific prognosis and examined a cohort of 471 patients with a combined follow-up of 1427 years (median 2.1 years). Immune suppressed persons (n=41) demonstrated reduced MCC-specific survival (40% at 3 years) compared to persons with no known systemic immune suppression (n=430; 74% MCC-specific survival at 3 years). By competing risk regression analysis, immune suppression was a stage-independent predictor of worsened MCC-specific survival (hazard ratio 3.8, p < 0.01). Immune-suppressed persons thus have both an increased chance of developing MCC and poorer MCC-specific survival. It may be appropriate to follow these higher-risk individuals more closely, and, when clinically feasible, there may be benefit of diminishing iatrogenic systemic immune suppression.Merkel cell carcinoma (MCC) is an aggressive cutaneous malignancy linked to a contributory virus (Merkel cell polyomavirus). Multiple epidemiologic studies have established an increased incidence of MCC among persons with systemic immune suppression. Several forms of immune suppression are associated with increased MCC incidence, including hematologic malignancies, HIV/AIDS, and immunosuppressive medications for autoimmune disease or transplant. Indeed, immune-suppressed individuals represent ∼10% of MCC patients, a significant overrepresentation relative to the general population. We hypothesized that immune-suppressed patients may have a poorer MCC-specific prognosis and examined a cohort of 471 patients with a combined follow-up of 1,427 years (median 2.1 years). Immune-suppressed patients (n=41) demonstrated reduced MCC-specific survival (40% at 3 years) compared with patients with no known systemic immune suppression (n=430; 74% MCC-specific survival at 3 years). By competing risk regression analysis, immune suppression was a stage-independent predictor of worsened MCC-specific survival (hazard ratio 3.8, P<0.01). Thus, immune-suppressed individuals have both an increased chance of developing MCC and poorer MCC-specific survival. It may be appropriate to follow these higher-risk individuals more closely, and, when clinically feasible, there may be a benefit of diminishing iatrogenic systemic immune suppression.

Association of prediagnostic serum vitamin D levels with the development of basal cell carcinoma.

We investigated the association between serum 25-hydroxyvitamin D (25(OH)D) levels and basal cell carcinoma (BCC) risk in a nested case-control study at Kaiser Permanente Northern California (KPNC). A total of 220 case patients with BCC diagnosed after serum collection were matched to 220 control subjects. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using conditional logistic regression. Fully adjusted models included body mass index (BMI), smoking, education, sun-exposure variables, X-ray exposure, and personal history of cancer. For each measure of serum 25(OH)D (continuous, clinically relevant tertiles, quintiles), we found an increased risk of BCC in unadjusted models (OR=1.03, 95% CI 1.00-1.05, P<0.05; OR=3.98, 95% CI: 1.31-12.31, deficient vs. sufficient, test for trend P-value <0.01; OR=2.32, 95% CI: 1.20-4.50, 1st vs. 5th quintile, test for trend P-value 0.03). In fully adjusted models, the values attenuated slightly (OR=1.02, 95% CI 1.00-1.05, P<0.05; OR=3.61, 95% CI: 1.00-13.10, deficient vs. sufficient, t-trend P=0.03; OR=2.09 1st vs. 5th quintile, 95% CI: 0.95-4.58, t-trend P=0.11). Our findings suggest that higher prediagnostic serum 25(OH)D levels may be associated with increased risk of subsequent BCC. Further studies to evaluate the effect of sun exposure on BCC and serum 25(OH)D levels may be warranted.

A cohort study of vitamin D intake and melanoma risk.

Data suggest that vitamin D intake may have chemopreventive efficacy against melanoma, but there have been no published epidemiologic studies examining the association between vitamin D intake and melanoma risk in a large prospective cohort. We examined whether dietary and supplemental vitamin D intake was associated with melanoma risk among 68,611 men and women who were participants of the Vitamins and Lifestyle cohort study. Participants reported dietary vitamin D intake over the past year and 10-year use of multivitamin and individual vitamin D supplements on a baseline questionnaire. After follow-up through 2006, 455 incident melanomas were identified through linkage to the Surveillance, Epidemiology, and End Results cancer registry. Cox proportional hazards regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for vitamin D intake after adjustment for melanoma risk factors. Compared with the lowest quartile, we did not detect a risk reduction of melanoma in the highest quartiles of dietary vitamin D intake (RR=1.31, CI=0.94-1.82), 10-year average supplemental vitamin D intake (RR=1.13, CI=0.89-1.43), or combined dietary and supplemental intake (1.05, CI=0.79-1.40). In this large prospective cohort, we did not find an association between vitamin D intake and melanoma risk.

Skin Cancer Education for Primary Care Physicians: A Systematic Review of Published Evaluated Interventions

ABSTRACTBACKGROUNDEarly detection of melanoma may provide an opportunity to positively impact melanoma mortality. Numerous skin cancer educational interventions have been developed for primary care physicians (PCPs) to improve diagnostic accuracy. Standardized training is also a prerequisite for formal testing of melanoma screening in the primary care setting.OBJECTIVEWe conducted a systematic review to determine the extent of evaluated interventions designed to educate PCPs about skin cancer, including melanoma.DESIGNRelevant studies in the English language were identified through systemic searches performed in MEDLINE, EMBASE, BIOSIS, and Cochrane through December 2010. Supplementary information was obtained from corresponding authors of the included studies when necessary.APPROACHStudies eligible for inclusion formally evaluated skin cancer education interventions and were designed primarily for PCPs. Excluded studies lacked a specified training intervention, used decision-making software, focused solely on risk factor identification, or did not directly educate or assess participants. Twenty studies met the selection criteria. Data were extracted according to intervention content and delivery format, and study outcomes.KEY RESULTSAll interventions included instructions about skin cancer diagnosis, but otherwise varied in content. Curricula utilized six distinct educational techniques, usually incorporating more than one. Intervention duration varied from 12 min to over 6 h. Eight of the 20 studies were randomized trials. Most studies (18/20, 90%) found a significant improvement in at least one of the following five outcome categories: knowledge, competence, confidence, diagnostic performance, or systems outcomes. Competence was most commonly measured; no study evaluated all categories. Variability in study design, interventions, and outcome measures prevented correlation of outcomes with intervention characteristics.CONCLUSIONSDespite the development of many isolated educational interventions, few have been tested rigorously or evaluated under sufficient standardized conditions to allow for quantitative comparison. Improved and rigorously tested skin cancer educational interventions for PCPs with outcome measures focusing on changes in performance are needed.

Effect of Host, Tumor, Diagnostic, and Treatment Variables on Outcomes in a Large Cohort With Merkel Cell Carcinoma

IMPORTANCE Merkel cell carcinoma (MCC) is a rare, aggressive, neuroendocrine-derived skin cancer with high rates of recurrence and associated mortality. Few published studies have used comprehensive patient data and long-term follow-up to examine factors that predict MCC outcomes. OBJECTIVE To characterize MCC in a large defined-population cohort and analyze predictors of disease recurrence and survival. SETTING, DESIGN, AND PARTICIPANTS Retrospective cohort study of 218 patients with MCC from the cancer registry of Kaiser Permanente Northern California, a large integrated health care delivery system. Patients were diagnosed as having MCC and followed up from January 1, 1995, through December 31, 2009. We examined host (age, sex, race, and immunosuppression), tumor (anatomic site, size, and extent), diagnostic (results of imaging and pathologic nodal evaluation), and treatment (surgery, radiation therapy, and chemotherapy) variables for their association with MCC outcomes. EXPOSURE Host, tumor, diagnostic, and treatment factors. MAIN OUTCOMES AND MEASURES Recurrence (locoregional and distant) of MCC and patient survival (overall and MCC specific). RESULTS We estimated adjusted hazard ratios (AHRs) and 95% CIs for outcomes using Cox proportional hazards regression models. After adjustment for host, tumor, diagnostic, and treatment variables, tumor extent (categorized as local, regional, and distant) remained significantly associated with all outcomes. Immunosuppression was associated with higher MCC-specific mortality (AHR, 4.9 [95% CI, 1.7-14.4]), and an unknown primary site was associated with a lower risk for distant metastasis (0.1 [0.0-0.7]) and improved survival (0.4 [0.2-0.9]). Pathological nodal evaluation was associated with a lower risk for metastasis (AHR, 0.2 [95% CI, 0.0-1.0]) and improved survival. Radiation treatment was associated with a decreased risk for locoregional recurrence (AHR, 0.3 [95% CI, 0.1-0.6]), whereas chemotherapy was not associated with any alteration in outcomes. CONCLUSIONS AND RELEVANCE Tumor site and extent, results of pathologic nodal evaluation, and the presence of radiation treatment were associated with MCC recurrence. Immunosuppression, tumor extent, and results of pathologic nodal evaluation were associated with MCC-specific survival, whereas chemotherapy was not associated with any outcomes. Our findings may help to inform diagnostic and therapeutic management of MCCs.

Aspirin is associated with lower melanoma risk among postmenopausal Caucasian women: the Women's Health Initiative.

Nonsteroidal anti‐inflammatory drugs (NSAIDs) have been associated with decreased risk of gastric, colorectal, and breast cancer. However, the impact of NSAIDs on the risk of melanoma has been inconsistent. The authors evaluated the association between NSAID use and cutaneous melanoma risk in the Womens Health Initiative (WHI) Observational Study (OS).

Patient Satisfaction after Treatment of Nonmelanoma Skin Cancer

BACKGROUND Patient satisfaction is an important aspect of patient‐centered care but has not been systematically studied after treatment of nonmelanoma skin cancer (NMSC), the most prevalent cancer. OBJECTIVE To compare patient satisfaction after treatment for NMSC and to determine factors associated with better satisfaction. METHODS We prospectively measured patient, tumor, and care characteristics in 834 consecutive patients at two centers before and after destruction, excision, and Mohs surgery. We evaluated factors associated with short‐term and long‐term satisfaction. RESULTS In all treatment groups, patients were more satisfied with the interpersonal manners of the staff, communication, and financial aspects of their care than with the technical quality, time with the clinician, and accessibility of their care (p<.05). Short‐term satisfaction did not differ across treatment groups. In multivariable regression models adjusting for patient, tumor, and care characteristics, higher long‐term satisfaction was independently associated with younger age, better pretreatment mental health and skin‐related quality of life, and treatment with Mohs surgery (p<.05). CONCLUSIONS Long‐term patient satisfaction after treatment of NMSC is related to pretreatment patient characteristics (mental health, skin‐related quality of life) and treatment type (Mohs) but not tumor characteristics. These results can guide informed decision‐making for treatment of NMSC. The authors have indicated no significant interest with commercial supporters.

Validity of diagnostic codes and prevalence of psoriasis and psoriatic arthritis in a managed care population, 1996-2009

Few population‐based studies have reported the prevalence of psoriatic disease.