Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 21
Filter
1.
BMC Cancer ; 23(1): 1084, 2023 Nov 09.
Article in English | MEDLINE | ID: mdl-37946198

ABSTRACT

BACKGROUND: Survival following melanoma and chronic lymphocytic leukemia (CLL) have both been individually associated with previous history of non-melanoma skin cancers (specifically keratinocyte carcinomas [KC]). Furthermore, melanoma and CLL have been reported to occur within the same patients. The survival experience of patients with both cancers is understudied, and the role of history of KC is unknown. Additional research is needed to tease apart the independent associations between KC and CLL survival, KC and melanoma survival, and the co-occurrence of all three cancers. METHODS: A retrospective cohort study was conducted among patients who were diagnosed with melanoma and/or CLL at a comprehensive cancer center between 2008 and 2020. Multivariable Cox regression models were used to examine the association between history of KC and survival following melanoma and/or CLL with careful consideration of calendar year of diagnosis, treatment regimens and other risk factors. A nested case-control study comparing patients with both CLL and melanoma to those with only CLL or only melanoma was conducted to compare blood parameters across the three groups. RESULTS: A time-dependent association was observed between history of KC and favorable melanoma survival within 4 years following diagnosis and poorer survival post 7 years after melanoma diagnosis. History of KC was not significantly associated with survival following the diagnosis of CLL, after adjustment for clinical factors including historical/concurrent melanoma. Patients with co-occurring melanoma and CLL tended to be diagnosed with melanoma first and had elevated blood parameters including white blood cell and lymphocyte counts as compared with patients who were diagnosed with only melanoma. CONCLUSIONS: History of KC was an independent predictor of survival following melanoma but not of CLL. Additional studies are needed to determine if blood parameters obtained at the time of melanoma diagnosis could be used as a cost-effective way to identify those at high risk of asymptomatic CLL for the promotion of earlier CLL diagnosis.


Subject(s)
Carcinoma , Leukemia, Lymphocytic, Chronic, B-Cell , Melanoma , Skin Neoplasms , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/complications , Leukemia, Lymphocytic, Chronic, B-Cell/epidemiology , Leukemia, Lymphocytic, Chronic, B-Cell/pathology , Skin Neoplasms/epidemiology , Retrospective Studies , Case-Control Studies , Melanoma/complications , Melanoma/epidemiology , Carcinoma/pathology , Keratinocytes/pathology
2.
Article in English | MEDLINE | ID: mdl-37917235

ABSTRACT

BACKGROUND: COVID-19 infection severity differs by race and ethnicity, but its long-term effect on cancer-related outcomes is unknown. Therefore, information on COVID-19 history is critical to ascertain among new cancer patients in order to advance research on its impact on cancer outcomes and potentially related health disparities. METHODS: A cross-sectional study was conducted among 16,025 new patients seeking care at Moffitt Cancer Center (MCC) between 2021 and 2022. Patient self-reported histories of COVID-19 infection and other pre-existing health conditions were obtained from electronic questionnaires administered to all new MCC patients. Associations between demographics and COVID-19 infection and hospitalization were examined. RESULTS: A total of 1,971 patients (12.3%) reported ever having COVID-19. Self-reported COVID-19 history was significantly more prevalent in Hispanic vs. non-Hispanic patients (OR = 1.24, 1.05-1.45) and less prevalent in Asian versus White patients (OR = 0.49, 95% 0.33-0.70). Among patients who ever had COVID-19, 10.6% reported a COVID-19-related hospitalization. Males had higher odds of a COVID-19 related hospitalization than females (OR = 1.50, 95% CI = 1.09-2.05), as did Black/African American patients (OR = 2.11, 95% CI = 1.18-3.60) and patients of races other than Black/African American and Asian (OR = 2.61, 95% CI = 1.43-4.54) compared to White patients. Hispanic patients also experienced higher odds of hospitalization (OR = 2.06, 95% CI-1.29- 3.23) compared with non-Hispanic patients of all races in a sensitivity analysis that combined race/ethnicity. Pre-existing lung and breathing problems were associated with higher odds of being hospitalized with COVID-19 (OR = 2.38, 95% CI = 1.61-3.48), but these and other health conditions did not explain the observed associations between race and COVID-19 hospitalization. CONCLUSIONS: Higher rates of COVID-19 hospitalization were observed among patients identifying as Black/African American or Hispanic independent of pre-existing health conditions. Future studies evaluating long-term effects of COVID-19 should carefully examine potential racial/ethnic disparities in cancer outcomes.

3.
JNCI Cancer Spectr ; 7(6)2023 Oct 31.
Article in English | MEDLINE | ID: mdl-37738580

ABSTRACT

BACKGROUND: Randomized clinical trials of novel treatments for solid tumors normally measure disease progression using the Response Evaluation Criteria in Solid Tumors. However, novel, scalable approaches to estimate disease progression using real-world data are needed to advance cancer outcomes research. The purpose of this narrative review is to summarize examples from the existing literature on approaches to estimate real-world disease progression and their relative strengths and limitations, using lung cancer as a case study. METHODS: A narrative literature review was conducted in PubMed to identify articles that used approaches to estimate real-world disease progression in lung cancer patients. Data abstracted included data source, approach used to estimate real-world progression, and comparison to a selected gold standard (if applicable). RESULTS: A total of 40 articles were identified from 2008 to 2022. Five approaches to estimate real-world disease progression were identified including manual abstraction of medical records, natural language processing of clinical notes and/or radiology reports, treatment-based algorithms, changes in tumor volume, and delta radiomics-based approaches. The accuracy of these progression approaches were assessed using different methods, including correlations between real-world endpoints and overall survival for manual abstraction (Spearman rank ρ = 0.61-0.84) and area under the curve for natural language processing approaches (area under the curve = 0.86-0.96). CONCLUSIONS: Real-world disease progression has been measured in several observational studies of lung cancer. However, comparing the accuracy of methods across studies is challenging, in part, because of the lack of a gold standard and the different methods used to evaluate accuracy. Concerted efforts are needed to define a gold standard and quality metrics for real-world data.


Subject(s)
Lung Neoplasms , Humans , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/therapy , Outcome Assessment, Health Care , Disease Progression
4.
Cancer Med ; 12(18): 19033-19046, 2023 09.
Article in English | MEDLINE | ID: mdl-37596773

ABSTRACT

BACKGROUND: Patient-reported data can improve quality of healthcare delivery and patient outcomes. Moffitt Cancer Center ("Moffitt") administers the Electronic Patient Questionnaire (EPQ) to collect data on demographics, including sexual orientation and gender identity (SOGI), medical history, cancer risk factors, and quality of life. Here we investigated differences in EPQ completion by demographic and cancer characteristics. METHODS: An analysis including 146,142 new adult patients at Moffitt in 2009-2020 was conducted using scheduling, EPQ and cancer registry data. EPQ completion was described by calendar year and demographics. Logistic regression was used to estimate associations between demographic/cancer characteristics and EPQ completion. More recently collected information on SOGI were described. RESULTS: Patient portal usage (81%) and EPQ completion rates (79%) were consistently high since 2014. Among patients in the cancer registry, females were more likely to complete the EPQ than males (odds ratio [OR] = 1.17, 95% confidence interval [CI] = 1.14-1.20). Patients ages 18-64 years were more likely to complete the EPQ than patients aged ≥65. Lower EPQ completion rates were observed among Black or African American patients (OR = 0.59, 95% CI = 0.56-0.63) as compared to Whites and among patients whose preferred language was Spanish (OR = 0.40, 95% CI = 0.36-0.44) or another language as compared to English. Furthermore, patients with localized (OR = 1.16, 95% CI = 1.12-1.19) or regional (OR = 1.16, 95% CI = 1.12-1.20) cancer were more likely to complete the EPQ compared to those with metastatic disease. Less than 3% of patients self-identified as being lesbian, gay, or bisexual and <0.1% self-identified as transgender, genderqueer, or other. CONCLUSIONS: EPQ completion rates differed across demographics highlighting opportunities for targeted process improvement. Healthcare organizations should evaluate data acquisition methods to identify potential disparities in data completeness that can impact quality of clinical care and generalizability of self-reported data.


Subject(s)
Gender Identity , Neoplasms , Adult , Humans , Male , Female , Quality of Life , Sexual Behavior , Neoplasms/epidemiology , Neoplasms/therapy , Patient Reported Outcome Measures
5.
Cancer Med ; 12(12): 13687-13700, 2023 06.
Article in English | MEDLINE | ID: mdl-37114585

ABSTRACT

BACKGROUND: National Cancer Institute cancer centers (NCICCs) provide specialized cancer care including precision oncology and clinical treatment trials. While these centers can offer novel therapeutic options, less is known about when patients access these centers or at what timepoint in their disease course they receive specialized care. This is especially important since precision diagnostics and receipt of the optimal therapy upfront can impact patient outcomes and previous research suggests that access to these centers may vary by demographic characteristics. Here, we examine the timing of patients' presentation at Moffitt Cancer Center (MCC) relative to their initial diagnosis across several demographic characteristics. METHODS: A retrospective cohort study was conducted among patients who presented to MCC with breast, colon, lung, melanoma, and prostate cancers between December 2008 and April 2020. Patient demographic and clinical characteristics were obtained from the Moffitt Cancer Registry. The association between patient characteristics and the timing of patient presentation to MCC relative to the patient's cancer diagnosis was examined using logistic regression. RESULTS: Black patients (median days = 510) had a longer time between diagnosis and presentation to MCC compared to Whites (median days = 368). Black patients were also more likely to have received their initial cancer care outside of MCC compared to White patients (odds ratio [OR] and 95% confidence interval [CI] = 1.45 [1.32-1.60]). Furthermore, Hispanics were more likely to present to MCC at an advanced stage compared to non-Hispanic patients (OR [95% CI] = 1.28 [1.05-1.55]). CONCLUSIONS: We observed racial and ethnic differences in timing of receipt of care at MCC. Future studies should aim to identify contributing factors for the development of novel mitigation strategies and assess whether timing differences in referral to an NCICC correlate with long-term patient outcomes.


Subject(s)
Cancer Care Facilities , Healthcare Disparities , Precision Medicine , Humans , Demography , Healthcare Disparities/ethnology , Healthcare Disparities/statistics & numerical data , Hispanic or Latino/statistics & numerical data , Precision Medicine/statistics & numerical data , Prostatic Neoplasms/epidemiology , Prostatic Neoplasms/therapy , Retrospective Studies , United States/epidemiology , Cancer Care Facilities/statistics & numerical data , White/statistics & numerical data , Black or African American/statistics & numerical data , Time-to-Treatment/statistics & numerical data , National Cancer Institute (U.S.)/statistics & numerical data
6.
JCO Clin Cancer Inform ; 7: e2200118, 2023 02.
Article in English | MEDLINE | ID: mdl-36791386

ABSTRACT

PURPOSE: Electronic health record (EHR) data are widely used in precision medicine, quality improvement, disease surveillance, and population health management. However, a significant amount of EHR data are stored in unstructured formats including scanned documents external to the treatment facility presenting an informatics challenge for secondary use. Studies are needed to characterize the clinical information uniquely available in scanned outside documents (SODs) to understand to what extent the availability of such information affects the use of these real-world data for cancer research. MATERIALS AND METHODS: Two independent EHR data abstractions capturing 30 variables commonly used in oncology research were conducted for 125 patients treated for advanced non-small-cell lung cancer at a comprehensive cancer center, with and without consideration of SODs. Completeness and concordance were compared between the two abstractions, overall, and by patient groups and variable types. RESULTS: The overall completeness of the data with SODs was 77.6% as compared with 54.3% for the abstraction without SODs. The differences in completeness were driven by data related to biomarker tests, which were more likely to be uniquely available in SODs. Such data were prone to missingness among patients who were diagnosed externally. CONCLUSION: There were no major differences in completeness between the two abstractions by demographics, diagnosis, disease progression, performance status, or oral therapy use. However, biomarker data were more likely to be uniquely contained in the SODs. Our findings may help cancer centers prioritize the types of SOD data being abstracted for research or other secondary purposes.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/epidemiology , Electronic Health Records , Lung Neoplasms/diagnosis , Lung Neoplasms/epidemiology , Medical Oncology , Disease Progression
7.
J Cancer Res Clin Oncol ; 149(7): 3607-3621, 2023 Jul.
Article in English | MEDLINE | ID: mdl-35962814

ABSTRACT

PURPOSE: History of keratinocyte carcinoma (KC) has been associated with survival following the diagnosis of a second primary malignancy (SPM), with the direction of the association varying by cancer type. Research is needed to elucidate the role of other key factors in this association. METHODS: A retrospective cohort study was conducted among patients newly diagnosed and/or treated at Moffitt Cancer Center in December 2008-April 2020 with breast cancer, lung cancer, melanoma, colon cancer, prostate cancer, and non-Hodgkin lymphoma/chronic lymphocytic leukemia (NHL/CLL) (n = 29,156). History of KC was obtained from new patient intake questionnaires. Age- and stage-adjusted hazard ratios (HR) and 95% confidence intervals (CI) were calculated to estimate the association between history of KC and survival following each cancer, stratified by demographic/clinical characteristics. RESULTS: KC history was most prevalent in patients with melanoma (28.7%), CLL (19.8%) and lung cancer (16.1%). KC history was associated with better overall survival following prostate cancer (HR = 0.74, 95% CI = 0.55-0.99) and poorer overall survival following CLL (HR = 1.73, 95% CI = 1.10-2.71). Patients with a history of KC experienced better survival within the first four years of a melanoma diagnosis (HR = 0.79, 95% CI = 0.67-0.92); whereas poorer survival was observed for patients who survived 7 + years after a melanoma diagnosis (HR = 2.18, 95% CI = 1.17-4.05). Stratification by treatment and stage revealed directional differences in the associations between KC history and survival among patients with breast cancer and melanoma. CONCLUSIONS: KC history may be a predictor of survival following an SPM, possibly serving as a marker of immune function and/or DNA damage repair capacity.


Subject(s)
Breast Neoplasms , Carcinoma , Leukemia, Lymphocytic, Chronic, B-Cell , Lung Neoplasms , Melanoma , Neoplasms, Second Primary , Skin Neoplasms , Male , Humans , Skin Neoplasms/pathology , Leukemia, Lymphocytic, Chronic, B-Cell/pathology , Neoplasms, Second Primary/diagnosis , Retrospective Studies , Melanoma/pathology , Carcinoma/pathology , Breast Neoplasms/pathology , Lung Neoplasms/pathology , Keratinocytes/pathology , Patient Outcome Assessment
8.
J Infect Dis ; 226(7): 1162-1174, 2022 09 28.
Article in English | MEDLINE | ID: mdl-35022780

ABSTRACT

BACKGROUND: Cutaneous human papillomaviruses (cuHPV) and polyomaviruses (HPyV) have been implicated in skin cancers; however, interpretation of findings across studies is complicated by limited understanding of the natural history of these infections across normal tissue types. METHODS: In total, 675 eyebrow hair (EBH) and skin swab (SSW) samples were collected from 71 skin cancer screening patients every 6 months over 2 years and measured for presence of ß-HPV, γ-HPV, and HPyV. Incidence, persistence, and clearance of cuHPV/HPyV were estimated, and risk factors associated with infection were examined. RESULTS: Prevalence, incidence, and persistence of ß-HPV, γ-HPV, and HPyV were consistently higher in SSW than in EBH, with types 5, 24, 49, 76 and Merkel cell polyomavirus (MCPyV) having incidence rates greater than 20 per 1000 person-months. Prevalent γ-HPV EBH infections persisted more often in women (P = .024), incident ß-HPV EBH infections persisted less often among individuals with history of blistering sunburn (P = .019), and prevalent MCPyV SSW infections persisted more often in those with a history of skin cancer (P = .033). CONCLUSIONS: Incidence and persistence of cuHPV/HPyV were observed in SSW and EBH; however, none of the risk factors examined were commonly associated with cuHPV/HPyV infections across normal tissue types.


Subject(s)
Alphapapillomavirus , Papillomavirus Infections , Polyomavirus Infections , Polyomavirus , Skin Neoplasms , DNA, Viral/genetics , Female , Humans , Papillomaviridae/genetics , Polyomavirus/genetics , Polyomavirus Infections/epidemiology , Skin Neoplasms/epidemiology
9.
Front Med (Lausanne) ; 8: 735585, 2021.
Article in English | MEDLINE | ID: mdl-34796183

ABSTRACT

Ultraviolet radiation exposure (UVR) is a risk factor for cutaneous squamous cell carcinoma (cuSCC) and has been shown to be positively associated with circulating immunosuppressive regulatory T cells ("Tregs"). However, the risk of cuSCC in association with circulating Tregs has not been studied. The aim of this study was to determine whether circulating Treg levels are associated with cuSCC development, particularly in the context of high UVR. Blood and spectrophotometer-based UVR measurements were obtained on 327 immunocompetent individuals undergoing routine skin cancer screenings at baseline and followed for up to 4 years for incident cuSCC development within a prospective cohort study. Proportions of phenotypically distinct Tregs, especially CCR4hi and CLA+ cells which are associated with activation and homing, respectively, were measured by flow cytometry. Tregs in cuSCC tumors were assessed using immunohistochemistry and graded for solar elastosis, a measure of cumulative UVR damage. Of several Treg phenotypes examined, higher levels of circulating CCR4hi Tregs at baseline were significantly associated with increased risk of subsequent cuSCC; those with higher levels of both CCR4hi and UVR were four times more likely to develop cuSCC compared to those with lower levels of both (Hazard Ratio = 4.11, 95% CI = 1.22-13.90). Within cuSCC tumors, CCR4hi Tregs were positively associated with solar elastosis. Results show that a higher proportion of CCR4hi peripheral Tregs predicts incident cuSCC up to 4 years, especially among highly UV-exposed individuals. Research of the underpinning biology of Tregs in UVR-associated skin damage may possibly reveal novel opportunities for screening, prevention, and treatment.

10.
Contemp Clin Trials ; 109: 106519, 2021 10.
Article in English | MEDLINE | ID: mdl-34333138

ABSTRACT

While extensive literature exists on barriers and strategies to increase minority participation in clinical trials, progress is limited. Few strategies were evaluated in randomized trials. We studied the impact of RECRUIT, a trust-based, cluster randomized minority recruitment trial layered on top of four traditional NIH-funded parent trials (BMT CTN, CABANA, PACES, STEADY-PD III; fifty specialty sites). RECRUIT was conducted from July 2013 through April 2017. Intervention sites implemented trust-based approaches customized to individual sites, promoting relationships between physician-investigators and minority-serving physicians and their minority patients. Control sites implemented only parent trials' recruitment procedures. Adjusting for within-site clustering, we detected no overall intervention effect, odds ratio 1.3 (95% confidence limits 0.7,2.4). Heterogeneity among parent trials may have obscured the effect. Of the four parent trials, three enrolled more minorities in intervention versus control sites. CABANA odds ratio = 4.2 (adjusted 95%CL 1.5,11.3). PACES intervention sites enrolled 63% (10/16) minorities; control sites enrolled one participant in total, a minority, yielding an incalculable odds ratio. STEADY-PD III odds ratio = 2.2 (adjusted 95%CL 0.6,8.5). BMT CTN odds ratio < 1, 0.8 (adjusted 95%CL 0.4,1.8). In conclusion, RECRUIT findings suggest the unique trust-based intervention increased minority recruitment to intervention trials in ¾ of studied trials. Physician-investigators' participation was critical to recruitment success. Lack of commitment to minority recruitment remained a barrier for some physician-investigators, especially in control sites. We recommend prospective physician investigators commit to minority recruitment activities prior to selection as site investigators and trial funding include some compensation for minority recruitment efforts. TRIAL REGISTRATION ClinicalTrials.govNCT01911208.


Subject(s)
Minority Groups , Trust , Humans , Patient Selection , Pilot Projects , Prospective Studies
11.
Cancer Res ; 81(17): 4628-4638, 2021 09 01.
Article in English | MEDLINE | ID: mdl-34266893

ABSTRACT

Cutaneous human papillomavirus (cuHPV) infections may be novel targets for skin cancer prevention and treatment, but critical information regarding the development of virus-positive skin cancers following cuHPV infection has been lacking. In this study, baseline cuHPV infection was measured by serology and viral DNA detection in eyebrow hairs (EBH) and forearm skin swabs (SSW) among 1,008 individuals undergoing routine skin cancer screening exams and followed for incidence of basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cuSCC). Baseline ß-HPV detection, particularly in SSW, significantly predicted cuSCC (HR = 4.32; 95% confidence interval, 1.00-18.66), whereas serologic evidence of past ß-HPV infection was not associated with cuSCC. Less than 5% of baseline ß-HPV types detected in SSW were present in subsequent cuSCC tumors, and cuHPV detected in SSW with higher mean fluorescence intensity values were more likely to be present in cuSCC compared with those with lower levels (P < 0.001). ß-HPV-positive cuSCC occurred more often in areas of highly sun-damaged skin than did ß-HPV-negative cuSCC. Overall, no clear patterns were observed between baseline ß-HPV detection and subsequent development of BCC, or between baseline γ-HPV detection and either cuSCC or BCC. Collectively, these results demonstrate that ß-HPV detection in SSW is a significant predictor of cuSCC risk, although evidence suggests only a small subset of cuSCC is etiologically linked to ß-HPV infection. SIGNIFICANCE: ß-HPV positivity may be a useful biomarker for identifying individuals who could benefit from increased screening or novel cutaneous squamous cell carcinoma prevention strategies.


Subject(s)
Alphapapillomavirus , Carcinoma, Squamous Cell/diagnosis , Keratinocytes/cytology , Skin Neoplasms/diagnosis , Aged , Aged, 80 and over , Biomarkers, Tumor/metabolism , Carcinoma, Basal Cell/diagnosis , Carcinoma, Basal Cell/metabolism , Carcinoma, Basal Cell/virology , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/virology , DNA, Viral , Early Detection of Cancer , Female , Follow-Up Studies , Hair/metabolism , Humans , Male , Middle Aged , Neoplasms, Basal Cell/diagnosis , Neoplasms, Basal Cell/metabolism , Neoplasms, Basal Cell/virology , Papillomavirus Infections/diagnosis , Papillomavirus Infections/metabolism , Prospective Studies , Risk Factors , Skin Neoplasms/metabolism , Skin Neoplasms/virology , Specimen Handling , Surveys and Questionnaires
12.
Cancer Epidemiol Biomarkers Prev ; 30(9): 1761-1764, 2021 09.
Article in English | MEDLINE | ID: mdl-34187857

ABSTRACT

BACKGROUND: A positive association between Merkel cell polyomavirus (MCPyV) infection and cutaneous squamous cell carcinoma (cuSCC) has been observed in at least one previous case-control study. To evaluate this association in a prospective context, we investigated infections with human polyomaviruses (HPyV), including MCPyV, as predictors of keratinocyte carcinomas, including cuSCC and basal cell carcinoma (BCC), among a cohort of immunocompetent individuals enrolled in the Viruses in Skin Cancer (VIRUSCAN) Study. METHODS: Associations between markers of baseline HPyV infection (serum antibodies and viral DNA in eyebrow hairs and skin swabs) and incident keratinocyte carcinomas were modeled using Cox proportional hazards regression. Proportions of baseline HPyV infections that were concordant with a subsequent tumor positive for the same HPyV type were assessed. RESULTS: No significant associations were observed between baseline markers of MCPyV or other HPyV infections and cuSCC or BCC. Less than 4.5% of baseline MCPyV infections were also detected in subsequently developed keratinocyte carcinoma tumors. CONCLUSIONS: HPyV infection was not a predictor of keratinocyte carcinoma risk in this prospective cohort. IMPACT: Cancer-associated infections represent attractive targets for cancer prevention; however, HPyV infections have limited potential as novel targets for cuSCC prevention.


Subject(s)
Carcinoma, Basal Cell/virology , Carcinoma, Squamous Cell/virology , Polyomavirus Infections/virology , Skin Neoplasms/virology , Aged , Biomarkers, Tumor/blood , DNA, Viral/isolation & purification , Female , Humans , Keratinocytes/pathology , Male , Middle Aged , Negative Results , Polyomavirus Infections/complications , Surveys and Questionnaires
13.
Int J Cancer ; 148(2): 448-458, 2021 01 15.
Article in English | MEDLINE | ID: mdl-32818302

ABSTRACT

The complex interplay between ultraviolet radiation (UVR) and cutaneous viral infections in the context of cancer etiology is challenging to unravel, given the limited information on the independent association between UVR and cutaneous viral infections. Using multiple biomarkers of infection with 24 types of cutaneous human papillomavirus (HPV) and 4 types of polyomaviruses (HPyV), we investigated cross-sectional associations with recent UVR exposure, using skin pigmentation measured by spectrophotometer. Age- and sex-adjusted associations between UVR and viral seropositivity, viral DNA present in eyebrow hairs (EBH) and skin swabs (SSW) were estimated using logistic regression. Beta-HPV seropositivity was associated with viral DNA positivity in EBH (OR = 1.40, 95% CI = 1.05-1.88) and SSW (OR = 1.86, 95% CI = 1.25-2.74). Similar associations were observed for Merkel cell polyomavirus. Participants in the highest tertile of UVR exposure were more likely to be seropositive for beta-HPV (OR = 1.81, 95% CI = 1.16-2.38), and have beta-HPV DNA in EBH (OR = 1.57, 95% CI = 1.06-2.33) and SSW (OR = 2.22, 95% CI = 1.25-3.96), compared to participants with the lowest tertile of UVR exposure. UVR exposure was positively associated with three different markers of beta-HPV infection. Therefore, future studies of HPV associated KC development should address more directly the role of HPV and UVR exposure as potential co-carcinogens.


Subject(s)
Neoplasms, Radiation-Induced/etiology , Papillomavirus Infections/etiology , Polyomavirus Infections/etiology , Skin Diseases, Viral/etiology , Skin Neoplasms/etiology , Cohort Studies , DNA, Viral , Eyebrows/virology , Female , Humans , Keratinocytes/pathology , Male , Middle Aged , Neoplasms, Radiation-Induced/pathology , Neoplasms, Radiation-Induced/virology , Papillomaviridae/genetics , Papillomaviridae/isolation & purification , Papillomavirus Infections/pathology , Papillomavirus Infections/virology , Polyomavirus/genetics , Polyomavirus/isolation & purification , Polyomavirus Infections/pathology , Polyomavirus Infections/virology , Prospective Studies , Skin Diseases, Viral/pathology , Skin Diseases, Viral/virology , Skin Neoplasms/pathology , Skin Neoplasms/virology , Skin Pigmentation , Ultraviolet Rays
14.
Cancer Epidemiol Biomarkers Prev ; 29(1): 39-48, 2020 01.
Article in English | MEDLINE | ID: mdl-31427307

ABSTRACT

BACKGROUND: Accumulating evidence suggests that cutaneous viral infections are risk factors for the development of keratinocyte carcinomas. The Viruses in Skin Cancer (VIRUSCAN) Study, a prospective cohort study, was established in 2014 to investigate the risk of keratinocyte carcinoma associated with cutaneous human papillomavirus and polyomavirus infection and the possible interaction with ultraviolet radiation exposure (UVR). METHODS/RESULTS: VIRUSCAN incorporates repeated measures of viral infection using multiple markers of infection and quantitative measures of UVR using a spectrophotometer. Participants were recruited between July 14, 2014 and August 31, 2017 at the University of South Florida Dermatology Clinic in Tampa, FL. After excluding 124 individuals with prevalent keratinocyte carcinomas at baseline, 1,179 participants (53.2% women, 46.8% men, all ages 60 years and older) were followed for up to 4 years with routine skin exams occurring every 6 to 12 months. Here, we present the VIRUSCAN Study design, methods, and baseline characteristics, including demographics, sun exposure behavior, quantitative UVR exposure measurements, and cutaneous viral prevalence, for the full study cohort. CONCLUSIONS: The VIRUSCAN Study will provide critical temporal evidence needed to assess the causality of the role cutaneous viral infections play in the development of keratinocyte carcinomas, as well as the potential interaction between cutaneous viral infections and UVR exposure. IMPACT: Study findings will be valuable in future development of novel keratinocyte carcinoma prevention strategies.


Subject(s)
Carcinoma, Basal Cell/epidemiology , Carcinoma, Merkel Cell/epidemiology , Carcinoma, Squamous Cell/epidemiology , Skin Neoplasms/epidemiology , Warts/epidemiology , Aged , Carcinoma, Basal Cell/etiology , Carcinoma, Basal Cell/pathology , Carcinoma, Merkel Cell/diagnosis , Carcinoma, Merkel Cell/pathology , Carcinoma, Merkel Cell/virology , Carcinoma, Squamous Cell/etiology , Carcinoma, Squamous Cell/pathology , Female , Follow-Up Studies , Humans , Keratinocytes/pathology , Keratinocytes/radiation effects , Keratinocytes/virology , Male , Middle Aged , Prevalence , Prospective Studies , Research Design , Risk Factors , Skin/cytology , Skin/pathology , Skin/radiation effects , Skin/virology , Skin Neoplasms/diagnosis , Skin Neoplasms/etiology , Skin Neoplasms/pathology , Spectrophotometry, Ultraviolet , Ultraviolet Rays/adverse effects , Warts/diagnosis , Warts/pathology , Warts/virology
15.
J Virol ; 93(7)2019 04 01.
Article in English | MEDLINE | ID: mdl-30700603

ABSTRACT

Evidence suggests that beta human papillomaviruses (HPVs), together with ultraviolet radiation, contribute to the development of cutaneous squamous cell carcinoma. Beta HPVs appear to be not the main drivers of carcinogenesis but rather facilitators of the accumulation of ultraviolet-induced DNA mutations. Beta HPVs are promoters of skin carcinogenesis, although they are dispensable for the maintenance of the malignant phenotype. Therefore, beta HPV represents a target for skin cancer prevention, especially in high-risk populations.


Subject(s)
Carcinogenesis/genetics , Carcinoma, Squamous Cell/virology , Oncogenes/genetics , Papillomaviridae/genetics , Papillomavirus Infections/virology , Skin Neoplasms/virology , DNA/genetics , DNA/radiation effects , Humans , Mutation/genetics , Mutation/radiation effects , Ultraviolet Rays/adverse effects
16.
Acta Cytol ; 63(2): 100-108, 2019.
Article in English | MEDLINE | ID: mdl-30673666

ABSTRACT

The cutaneous human papillomavirus (HPV), mostly from ß- and γ-HPV genus, is ubiquitously distributed throughout the human body and may be part of the commensal flora. The association of ß-HPVs and cutaneous squamous cell carcinoma (cSCC) development was initially reported in patients with the rare genetic disorder Epidermodysplasia verruciformis. Likewise, immunosuppressed organ transplant recipients have an increased susceptibility to ß-HPV infections in the skin as well as to cSCC development. Although ultraviolet radiation (UVR) is the main risk factor of cSCC, experimental data points toward ß-HPVs as co-carcinogens, which appear to be required solely at early stages of skin carcinogenesis by facilitating the accumulation of UVR-induced DNA mutations. Several epidemiological studies relying on different biomarkers of ß-HPV infections have also been conducted in immunocompetent individuals to access their association with cSCC development. Additionally, in vivo and in vitro studies are presenting cumulative evidence that E6 and E7 proteins from specific ß-HPVs exhibit transforming activities and may collaborate with different environmental factors in promoting carcinogenesis. Nevertheless, further research is crucial to better understand the pathological implications of the broad distribution of these HPVs.


Subject(s)
Papillomaviridae/physiology , Papillomavirus Infections/virology , Humans , Papillomaviridae/classification , Papillomavirus Infections/epidemiology
17.
J Infect Dis ; 219(5): 711-722, 2019 02 15.
Article in English | MEDLINE | ID: mdl-30260406

ABSTRACT

BACKGROUND: Findings from previous studies of cutaneous human papillomavirus (cuHPV) infection and keratinocyte carcinomas have varied due to several factors, including use of different sample types for cuHPV DNA detection. Elucidating the relationship between cuHPV infection in eyebrow hairs (EBHs) and skin swabs (SSWs) is critical for advancing the design of future studies. METHODS: DNA corresponding to 46 ß-HPV and 52 γ-HPV types was measured in EBHs and SSWs obtained from 370 individuals undergoing routine skin cancer screening examinations. RESULTS: Prevalence of ß-HPV/γ-HPV was 92%/84% and 73%/43% in SSWs and EBHs, respectively, with 71%/39% of patients testing positive for ß-HPV/γ-HPV in both sample types. Number of cuHPV types detected and degree of infection were correlated across SSWs and EBHs. When the EBH was positive for a given ß-HPV/γ-HPV type, the SSW was positive for that same type 81%/72% of the time. CONCLUSIONS: Testing SSWs captures more cuHPV infection than EBHs, with EBH infections usually representing a subset of SSW infections. The importance of optimizing sensitivity of cuHPV infection detection using SSWs vs specificity using EBHs (or a combination of the 2) will be ascertained in an ongoing cohort study investigating cuHPV associations with subsequent keratinocyte carcinomas.


Subject(s)
Eyebrows/virology , Papillomaviridae/classification , Papillomaviridae/isolation & purification , Papillomavirus Infections/epidemiology , Papillomavirus Infections/virology , Skin/virology , Aged , Aged, 80 and over , Diagnostic Tests, Routine/methods , Female , Humans , Male , Middle Aged , Prevalence , Sensitivity and Specificity , Specimen Handling/methods
18.
J Immunol ; 201(11): 3269-3281, 2018 12 01.
Article in English | MEDLINE | ID: mdl-30389774

ABSTRACT

UV radiation (UVR) causing DNA damage is a well-documented risk factor for nonmelanoma skin cancer. Although poorly understood, UVR may also indirectly contribute to carcinogenesis by promoting immune evasion. To our knowledge, we report the first epidemiological study designed to investigate the association between quantitative measures of UVR, obtained using a spectrophotometer, and circulating T regulatory (Treg) cells. In addition to total Treg cells, the proportion of functionally distinct Treg cell subsets defined by CD45RA and CD27 phenotypic markers, graded expression of FOXP3 and CD25, and those expressing cutaneous lymphocyte-associated Ag and the chemokine receptor CCR4 were enumerated in 350 individuals undergoing routine skin cancer screening exams and determined not to have prevalent skin cancer. No associations were identified for UVR exposure or the overall proportion of circulating Treg cells; however, Treg cell subpopulations with an activation-associated phenotype, CD45RA-/CD27-, and those expressing cutaneous homing receptors were significantly positively associated with UVR. These subpopulations of Treg cells also differed by age, sex, and race. After stratification by natural skin tone, and adjusting for age and sex, we found that spectrophotometer-based measures of UVR exposure, but not self-reported measures of past sun exposure, were positively correlated with the highest levels of these Treg cell subpopulations, particularly among lighter-skinned individuals. Findings from this large epidemiologic study highlight the diversity of human Treg cell subpopulations associated with UVR, thus raising questions about the specific coordinated expression of CD45RA, CD27, CCR4, and cutaneous lymphocyte-associated Ag on Treg cells and the possibility that UVR contributes to nonmelanoma skin cancer carcinogenesis through Treg cell-mediated immune evasion.


Subject(s)
Radiation Exposure/adverse effects , Skin Neoplasms/immunology , T-Lymphocyte Subsets/immunology , T-Lymphocytes, Regulatory/immunology , Ultraviolet Rays/adverse effects , Carcinogenesis/radiation effects , Cohort Studies , Early Detection of Cancer , Female , Forkhead Transcription Factors/metabolism , Humans , Immune Tolerance , Immunophenotyping , Leukocyte Common Antigens/metabolism , Male , Middle Aged , Receptors, CCR4/metabolism , Skin Neoplasms/epidemiology , Skin Physiological Phenomena , Skin Pigmentation , T-Lymphocyte Subsets/radiation effects , T-Lymphocytes, Regulatory/radiation effects , Tumor Escape , Tumor Necrosis Factor Receptor Superfamily, Member 7/metabolism , United States/epidemiology
19.
Trials ; 19(1): 115, 2018 Feb 17.
Article in English | MEDLINE | ID: mdl-29454389

ABSTRACT

BACKGROUND: Despite efforts to increase diversity in clinical trials, racial/ethnic minority groups generally remain underrepresented, limiting researchers' ability to test the efficacy and safety of new interventions across diverse populations. We describe the use of a systematic framework, intervention mapping (IM), to develop an intervention to modify recruitment behaviors of coordinators and specialist investigators with the goal of increasing diversity in trials conducted within specialty clinics. To our knowledge IM has not been used in this setting. METHODS: The IM framework was used to ensure that the intervention components were guided by health behavior theories and the evidence. The IM steps consisted of (1) conducting a needs assessment, (2) identification of determinants and objectives, (3) selection of theory-informed methods and practical applications, (4) development and creation of program components, (5) development of an adoption and implementation plan, and (6) creation of an evaluation plan. RESULTS: The intervention included five educational modules, one in-person and four web-based, plus technical assistance calls to coordinators. Modules addressed the intervention rationale, development of clinic-specific plans to obtain minority-serving physician referrals, physician-centered and patient-centered communication, and patient navigation. The evaluation, a randomized trial, was recently completed in 50 specialty clinics and is under analysis. CONCLUSIONS: Using IM we developed a recruitment intervention that focused on building relationships with minority-serving physicians to encourage minority patient referrals. IM enhanced our understanding of factors that may influence minority recruitment and helped us integrate strategies from multiple disciplines that were relevant for our audience.


Subject(s)
Clinical Trials as Topic/methods , Cultural Diversity , Ethnicity , Inservice Training , Minority Groups , Patient Selection , Racial Groups , Research Personnel/education , Research Subjects , Attitude of Health Personnel , Healthcare Disparities/ethnology , Humans , Interpersonal Relations , Referral and Consultation , Research Personnel/psychology , Stakeholder Participation , Trust
20.
Clin Trials ; 14(3): 286-298, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28545336

ABSTRACT

BACKGROUND: Racial/ethnic minority groups remain underrepresented in clinical trials. Many strategies to increase minority recruitment focus on minority communities and emphasize common diseases such as hypertension. Scant literature focuses on minority recruitment to trials of less common conditions, often conducted in specialty clinics and dependent on physician referrals. We identified trust/mistrust of specialist physician investigators and institutions conducting medical research and consequent participant reluctance to participate in clinical trials as key-shared barriers across racial/ethnic groups. We developed a trust-based continuous quality improvement intervention to build trust between specialist physician investigators and community minority-serving physicians and ultimately potential trial participants. To avoid the inherent biases of non-randomized studies, we evaluated the intervention in the national Randomized Recruitment Intervention Trial (RECRUIT). This report presents the design of RECRUIT. Specialty clinic follow-up continues through April 2017. METHODS: We hypothesized that specialist physician investigators and coordinators trained in the trust-based continuous quality improvement intervention would enroll a greater proportion of minority participants in their specialty clinics than specialist physician investigators in control specialty clinics. Specialty clinic was the unit of randomization. Using continuous quality improvement, the specialist physician investigators and coordinators tailored recruitment approaches to their specialty clinic characteristics and populations. Primary analyses were adjusted for clustering by specialty clinic within parent trial and matching covariates. RESULTS: RECRUIT was implemented in four multi-site clinical trials (parent trials) supported by three National Institutes of Health institutes and included 50 associated specialty clinics from these parent trials. Using current data, we have 88% power or greater to detect a 0.15 or greater difference from the currently observed control proportion adjusting for clustering. We detected no differences in baseline matching criteria between intervention and control specialty clinics (all p values > 0.17). CONCLUSION: RECRUIT was the first multi-site randomized control trial to examine the effectiveness of a trust-based continuous quality improvement intervention to increase minority recruitment into clinical trials. RECRUIT's innovations included its focus on building trust between specialist investigators and minority-serving physicians, the use of continuous quality improvement to tailor the intervention to each specialty clinic's specific racial/ethnic populations and barriers to minority recruitment, and the use of specialty clinics from more than one parent multi-site trial to increase generalizability. The effectiveness of the RECRUIT intervention will be determined after the completion of trial data collection and planned analyses.


Subject(s)
Biomedical Research/methods , Minority Groups , Patient Selection , Research Design , Healthcare Disparities/ethnology , Humans , Multicenter Studies as Topic , National Institutes of Health (U.S.) , Pilot Projects , Quality Improvement , Referral and Consultation , United States
SELECTION OF CITATIONS
SEARCH DETAIL
...