Risk Factor For Squamous Cell Carcinoma Research Articles

Skin Cancer Risk, Sun-Protection Knowledge and Behavior in Athletes—A Narrative Review

Outdoor sports are associated with increased exposure to ultraviolet radiation, which may result in sunburn, solar damage, and skin cancers. Water and winter sports create additional adverse conditions, such as washing away sunscreen by water and reflection of UV rays by the water and snow. Sweating-increased skin photosensitivity and activity-induced immunosuppression are associated with a greater risk of developing skin cancers. In this review, we focus on a group of athletes and sports participants and analyze 62 articles concerning sun exposure during outdoor sports, the risk of developing skin cancer, and knowledge and behavior regarding photoprotection methods. Various practices have been linked to an increased risk of developing basal cell carcinoma (BCC), squamous cell carcinoma (SCC), malignant melanoma (MM), or UV-induced skin damage. Water sports and mountaineering increase the risk of BCC. Surfing and swimming are risk factors for SCC. Melanoma is more common in swimmers, surfers, and marathon runners. Photoprotection behaviors can reduce potential skin damage and skin cancers. Athletes’ knowledge about the risk of malignant lesions was satisfactory, but despite the risks, outdoor sports participants seem not to protect themselves from the sun adequately.

Oral Cavity Squamous Cell Carcinoma Risk Factors: State of the Art.

Head and neck (HN) squamous cell carcinomas (SCCs) originate from the epithelial cells of the mucosal linings of the upper aerodigestive tract, which includes the oral cavity, the pharynx, the larynx, and the sinonasal cavities. There are many associated risk factors, including alcohol drinking coupled with tobacco use, which accounts for 70% to 80% of HNSCCs. Human papilloma virus (HPV) is another independent risk factor for oropharyngeal SCC, but it is only a minor contributor to oral cavity SCC (OSCC). Betel quid chewing is also an established risk factor in southeast Asian countries. However, OSCC, and especially oral tongue cancer, incidence has been reported to be increasing in several countries, suggesting risk factors that have not been identified yet. This review summarizes the established risk factors for oral cavity squamous cell carcinomas and examines other undemonstrated risk factors for HNSCC.

Active search screening for oral potentially malignant disorders and oral cancer in the city of Piracicaba.

Oral cancer is a public health problem worldwide with approximately 300,000 new cases diagnosed every year and more than 170,000 deaths annually. Squamous cell carcinoma (SCC) accounts for approximately 90% of all oral malignancies and it is frequently preceded by lesions known as oral potentially malignant disorders (OPMDs). Screening programs for early detection of oral lesions have been conducted. Therefore, the objective of this research was to carry out an active search in a screening program in the city of Piracicaba, Brazil. High-risk patients were identified at the city's health center through their medical records and referred for dental consultation. Other patients who opportunistically sought dental care were also seen and if they did not present risk factors for SCC, they were considered low-risk. A total of 756 patients were examined, and 445 met the criteria for the high-risk group and 311 for the low-risk group. It was possible to diagnose 27 OPMDs and six SCCs - 21 OPMDs and six SCCs occurred in high-risk patients and six OPMDs in low-risk patients. A chi-square test was applied and a statistically significant value (p = 0.006) was obtained for the detection of OPMD and SCC in patients of the high-risk group. Screening of high-risk patients through active search proved to be an effective program for diagnosing OPMD and SCC. Therefore, we encourage its implementation on a large scale to reduce the current scenario of this disease.

Assessment of High-Risk Human Papillomavirus Infection Characteristics in Cervical Squamous Cell Carcinoma and Adenocarcinoma in China.

The characteristics of high-risk human papillomavirus (HR-HPV) infection in different pathological types of cervical cancer in China are unclear. The aim of this study was to evaluate HR-HPV genotypes and age stratification with cervical squamous cell carcinoma (SCC) and adenocarcinoma (ADC) in China. Patients diagnosed with cervical cancer by histopathology in Fujian Maternity and Child Health Hospital from January 1, 2014, to December 31, 2017, were included in this study. The HR-HPV genotype was analyzed in cervical specimens. Logistic regression was used to calculate odds ratios (ORs). All tests of statistical significance were two-sided, and the P value<0.05. A total of 1,590,476 women were screened for cervical cancer, and 688 cervical cancers were detected, including 554 SCC and 93 ADC. The overall HR-HPV infection rate in SCC was higher than that in ADC (91.2% vs 81.7%, P=0.005). HPV-16 was the most prevalent genotype in SCC (70.0%) but was only 31.2% in ADC (P<0.001). However, the prevalence of HPV-18 in ADC was significantly higher than that in SCC (45.2% vs 7.0%; P<0.001). In SCC, the prevalence of HPV-16 was consistently much higher than that of HPV-18 regardless of age group. Among ADC, the prevalence of HPV-18 was higher than that of HPV-16 in women aged ≥45 years. Interestingly, in those aged <35 years, the highest prevalence was observed for HPV-16. HPV-18 infection has the highest risk of ADC (OR= 12.109; P< 0.001), and HPV-45 and HPV-51 were also found to be associated with the occurrence of ADC. However, HPV-16 infection greatly increased the risk of having histological SCC. HPV-16 and HPV-18 infections are key risk factors for SCC and ADC. The use of HR-HPV genotyping tests in cervical cancer screening and vaccination against major HPV genotypes could reduce the incidence of cervical cancer.

Comparison of Bayesian, Frequentist and Machine learning models for predicting the two-year mortality of patients diagnosed with squamous cell carcinoma of the oral cavity

BackgroundStatistical models developed in frequentist and Bayesian context along with machine learning algorithms can encompass the multifactorial effect of the prognostic factors in predicting the outcome. This paper is aimed to compare the effect estimates and predictive performance of Bayesian, frequentist and machine learning algorithm in predicting the two-year mortality of patients diagnosed with squamous cell carcinoma (SCC) of oral cavity. Materials and methodsLogistic regression (LR), Binary Discriminant analysis (BDA), Naïve Bayes (NB), Bayesian regression (BLR), K nearest neighbor (KNN), Artificial neural network (ANN) and Random Forest (RF) models were built. The effect estimate of each prognostic factor was estimated and compared by LR and BLR model. 10-fold cross-validation was performed for internal validation of the models. The predictive performance of the models was assessed and compared. ResultsBLR model had lower and narrower effect estimates in comparison to LR model. Age and smoking are the biggest prognostic risk factors for SCC whereas surgery had the best response amongst the mode of treatment. Random forest had an AUROC of 0.86 (0.82, 0.90) whereas it was estimated to be 0.77 (0.71, 0.82) for both BLR and LR models. ConclusionsBLR model had better precision in estimating the effect size of prognostic factors and can be an alternative for predicting mortality in patients with SCC of oral cavity. Machine learning classifiers had the best predictive ability as compared to statistical models.

ACTIVE SEARCH SCREENING FOR ORAL POTENTIALLY MALIGNANT DISORDERS AND ORAL CANCER AND IN THE CITY OF PIRACICABA

<h3>Objectives</h3> Oral cancer is a world public health problem. Squamous cell carcinoma (SCC) represents approximately 90% of all oral malignancies and is frequently preceded by oral potentially malignant disorders (OPMDs). Screening programs aimed at early detection of oral lesions have been conducted. Therefore, the objective of this research was to carry out an active search screening program in the city of Piracicaba. <h3>Study Design</h3> High-risk patients were identified at the city's health center through their medical records and invited for a dental consultation. Patients who opportunistically sought consultation also attended, and if they did not presented risk factors for SCC they were considered low risk. <h3>Results</h3> Seven hundred fifty-six patients were examined: 445 in the high-risk group and 311 in the low-risk group. Of 33 OPMD and SCC diagnosed, 27 occurred in high-risk patients and 6 in low-risk patients. After chi-square was applied, a statistically significant value (<i>P</i> = .006) for the detection of these diseases in high-risk patients was observed. <h3>Conclusions</h3> It was noted that active search screening focusing on high-risk patients was effective in diagnosing OPMD and SCC, and we encourage its implementation at large scales to reduce the current scenario of this disease.

Clinical practicality of reporting cutaneous squamous cell carcinoma risk factors at the time of Mohs surgery.

Multiple high-risk factors have been associated with poor outcomes in cutaneous squamous cell carcinoma, including immunosuppression, poor differentiation, depth, diameter, and perineural invasion. While many of these are included in major staging systems, their measurement and reporting vary considerably in clinical practice. We performed a survey study of fellowship-trained Mohs surgeons to explore their attitudes and practices related to recording squamous cell carcinoma high-risk factors and staging information at the time of Mohs. An anonymous Qualtrics survey of 25 questions was distributed to the American College of Mohs Surgery membership listserv. There were 107 complete surveys (response rate 7.1%), with over 95% of subjects from the United States. Fifty-five percent had been practicing 10years or less, 28% between 11 and 20years, and the remainder greater than 20years. Fifty-seven percent were in private or group practices, and 43% were in academia. Nearly all respondents consistently report tumor recurrence (100%), location (100%), immunosuppression (94%), and diameter (93%). Only 70% grade differentiation for every squamous cell carcinoma case. Sixty-six percent of participants consistently record anatomic depth, while only 2% always or almost always record Breslow depth. Although 96% of respondents almost always or always record perineural invasion, only 34% consistently record nerve diameter. Forty-three percent reported that they never or rarely stage cutaneous squamous cell carcinomas, whereas 43% often, almost always, or always stage. In conclusion, certain high-risk factors, such as differentiation, Breslow depth, and stage, are recorded inconsistently by Mohs surgeons. Several participants commented that they prefer to send a central debulk to dermatopathology to assess staging parameters in all tumors with high-risk features. While this strategy may be useful in some practice settings, Mohs surgeons possess the skills necessary to perform a central debulk analysis themselves at the time of Mohs. Whether performed at the time of Mohs or by dermatopathology, assessing high-risk features and accurately staging cutaneous squamous cell carcinoma is paramount to detecting tumors at higher risk of poor outcomes.

INCIDENCE OF PREMALIGNANT CHANGES IN ORAL CHRONIC HYPERPLASTIC CANDIDOSIS (CHC)

<h3>Background</h3> There has been an ongoing debate on the correlation between fungal infection and oral squamous cell carcinoma (SCC). Some argue that chronic hyperplastic candidosis (CHC) is a premalignant condition. However, the risk of malignant change in these lesions remains controversial, with limited evidence to support this. <h3>Objective</h3> To assess if there is any correlation between CHC and the possibility of it developing into epithelial dysplasia or malignancy and determine if other known SCC risk factors play a role. <h3>Methods</h3> Retrospective evaluation of a cohort of 105 patients diagnosed with CHC over a 2-year period (2011-2012) were undertaken using the histopathology reports and tissue slides. Five-year clinical follow-up information was obtained to determine if any of the cases developed dysplastic or malignant changes over the years. Information about risk factors and habits was also acquired. <h3>Results</h3> There were 5 cases where initially biopsied CHC lesions were suggested to have progressed to epithelial dysplasia and SCC. Review of these "progressed" cases did not show typical CHC features with evidence of atypia and/or dysplasia in the first instance (with overlying fungal infection). None of the typical CHC cases developed dysplasia/malignancy over the follow-up period. <h3>Conclusions</h3> This project has demonstrated that the risk of CHC being a premalignant condition is minimal compared to what has been reported in the literature. Although this might only represent a local population and small cohort, a multicenter investigation would be beneficial to establish the significance of findings from this work.

Lipid droplet biogenesis and COX-2 pathway activation are triggered by Barrett\u2019s esophagus and adenocarcinoma, but not esophageal squamous cell carcinoma risk factors

Esophageal cancer (EC) is an aggressive disease, presenting two main histological subtypes: adenocarcinoma (EAC) and squamous cell carcinoma (ESCC). The two EC subtypes widely differ concerning virtually all factors. ESCC development is mainly associated with tobacco and alcohol abuse, whereas obesity and chronic gastroesophageal reflux disease (GERD) are important risk factors not only for EAC, but also for for Barrett’s esophagus (BE), an intestinal metaplasia that precedes EAC. Obesity triggers ectopic lipid droplets (LD) accumulation in non-adipose tissues. LD are organelles involved in cell metabolism, signaling, proliferation and production of inflammatory mediators. Therefore, the aim of this work was to investigate LD occurrence and role in EC. This study shows progressive LD levels increase along EAC development, in esophageal samples from non-obese through obese individuals, as well as BE, and EAC patients, whereas no significant changes were observed in ESCC samples, when compared to non-tumor samples. Additionally, in order to mimic BE and EAC risk factors exposure, a non-tumor esophageal cell line was incubated with oleic acid (OA) and acidified medium and/or deoxycholic acid (DCA), revealing a significant increment in LD amount as well as in COX-2 and CXCL-8 expression, and in IL-8 secretion. Further, COX-2 expression and LD amount presented a significant positive correlation and were detected co-localized in EAC, but not in ESCC, suggesting that LD may be the site for eicosanoid production in EAC. In conclusion, this study shows that obesity, and BE- and EAC-associated inflammatory stimuli result in a gradual increase of LD, that may be responsible for orchestrating inflammatory mediators’ production and/or action, thus contributing to BE and EAC genesis and progression.

Risk Prediction Model for Cutaneous SCC in Cardiac Allograft Recipients

Post-transplant patients are at increased risk for squamous cell carcinoma (SCC) of the skin, secondary to long-term immunosuppression. This study was undertaken to identify risk factors using the UNOS database population. The study population of 1766 patients derived from the UNOS database (2000-2015) was divided into two equal groups. One group was used for testing and the other for validation. Descriptive statistics were used to characterize the study cohort. Cox's proportional hazards regression was used to investigate the effect of different risk factors for SCC post-heart transplantation. Multivariate analysis was used to test the correlation between SCC and potential risk factors. Hazard ratio (OR) and the 95% confidence interval (CI) were calculated for each risk factor. Statistical significance was set at p< 0.05. Forward sequential feature selection was done to select significant risk factors for multivariate modeling. The multivariate model was used to predict the risk of SCC at 5, 8 and 10 years post-transplant. Analyses were performed using MATLAB software from The Math Works, Inc. Receiver Operating Curves (ROCs) were generated to derive Area Under the Curve (AUC) to assess the quality of the prediction model. Multivariate analysis showed that Black, Hispanic and other races as compared to whites had an OR of 0.07,0.35, 0.17 (p=0.0000). Recipient PRAs had an OR of 0.97 (p=<0.0001). Age >60 years had an OR of 2.5 (p=0.0000). Males had an OR of 2.05 (p=0.000). The ROC curves generated showed AUC at 5, 8 and 10 years post-transplant of 0.76, 0.76, 0.76 respectively in the testing set and 0.79, 0.77, 0.78 respectively in the validation set (figure 1). Male sex, white race, age >60 years higher PRAs are major risk factors for SCC. The risk prediction model generated for the first time for SCC in post-cardiac transplant patients has a robust c-statistic of >0.75. This is important for risk stratification as SCC is the most common skin cancer seen in the post-cardiac transplant population.

Ongoing cancer burden after a diagnosis of cutaneous squamous cell carcinoma.

Squamous cell carcinoma (SCC) is the second most commonly diagnosed type of skin cancer after basal cell carcinoma.1 Cumulative exposure to ultraviolet radiation has long been established as the strongest risk factor for SCC.2 Family history of any skin cancer also has an independent role in the development of SCC, associated with a fourfold higher risk3 after adjusting for other factors (including self‐reported sun exposure).

EPIDEMIOLOGIC SURVEY OF SQUAMOUS CELL CARCINOMA IN A STOMATOLOGY CLINIC—A 7-YEAR STUDY

Objective To accomplish a retrospective statistical survey on cases of squamous cell carcinoma (SCC) in a stomatology clinic, from March 2011 to February 2018, given the importance of this type of cancer, which represents 94% of all oral malignant neoplasms. Study Design Retrospective cross-sectional study of issued reports and medical records of patients diagnosed as having SCC. Results This study had 94 analyzed patients: 51.6% of them were white, 61.78% were male, 58.51% were regular smokers, and 45.74% were alcoholics. The average age was 64.2 years. The more common locations were tongue (43.61%), mouth floor (29.78%), alveolar ridge (12.76%), hard palate (10.63%), and lower lip (8.51%). It can be suggested that 36.77% were referred from the public service. The diagnosis is usually obtained late, considerably affecting the prognosis. Factors such as lack of information from patients and lack of training of health professionals are the main responsible for the delay in the diagnosis of oral cancer. Conclusion We would like to emphasize the importance of a critical clinical examination, the accomplishment of an early diagnosis, and the orientation regarding the risk factors of SCC. To accomplish a retrospective statistical survey on cases of squamous cell carcinoma (SCC) in a stomatology clinic, from March 2011 to February 2018, given the importance of this type of cancer, which represents 94% of all oral malignant neoplasms. Retrospective cross-sectional study of issued reports and medical records of patients diagnosed as having SCC. This study had 94 analyzed patients: 51.6% of them were white, 61.78% were male, 58.51% were regular smokers, and 45.74% were alcoholics. The average age was 64.2 years. The more common locations were tongue (43.61%), mouth floor (29.78%), alveolar ridge (12.76%), hard palate (10.63%), and lower lip (8.51%). It can be suggested that 36.77% were referred from the public service. The diagnosis is usually obtained late, considerably affecting the prognosis. Factors such as lack of information from patients and lack of training of health professionals are the main responsible for the delay in the diagnosis of oral cancer. We would like to emphasize the importance of a critical clinical examination, the accomplishment of an early diagnosis, and the orientation regarding the risk factors of SCC.

507 The Acute Development of Donor Site Squamous Cell Carcinoma: A Case Report and Review of the Literature

The mainstay of burn reconstruction remains autografting. Donor site management centers on pain control, infection prevention, and scarring mitigation. Here we report a rare case of rapidly developing squamous cell carcinoma (SCC) at a split-thickness skin graft donor site. A 49-year-old man with no significant medical history sustained a 5% total body surface area (TBSA) full-thickness burn to the right upper arm, axilla, and trunk when his shirt sleeve caught fire at work. He underwent tangential excision and split-thickness skin grafting with VAC placement on post-burn day two. His right thigh donor site was dressed with an iodine-impregnated adhesive dressing. Graft loss necessitated return to the operating room on post-operative day 17 for re-excision and split-thickness skin grafting, again harvested from the right thigh. The donor site was dressed with a collagen-bound silicone dressing. On post-operative day 58/41 a lesion was noted on his right thigh donor site, presumed to be a cyst. On post-operative day 86/69, the lesion had grown to 7 millimeters. Excisional biopsy on post-operative day 129/112 revealed the lesion to be a well-differentiated squamous cell carcinoma with positive deep and peripheral margins. The patient returned for excision to negative margins 24 days later. Since 1948, seventeen prior cases of split-thickness skin graft donor site lesions have been reported in the literature. Fourteen of these (82%) were squamous cell carcinomas, with the remainder diagnosed as keratoacanthomas (KA) - a spontaneously regressing form of SCC, which rarely becomes invasive. Of the fourteen cases of SCC, thirteen (93%) were diagnosed within one year of graft harvest, and eleven (79%) were diagnosed within 6 months. Including our case, five of the cases involved burn patients. The acute development of SCC at skin graft donor sites is a rare but serious phenomenon. Marjolin’s ulcers - the development of malignancies, commonly SCC, within chronic wounds - typically develop decades after injury. Trauma, including skin graft harvest, has been associated with the development of KAs, but, is not a typical risk factor for SCC. Given the diversity of autograft indications in reviewed literature, it seems unlikely that the burn itself contributed to the development of SCC. Rather, suspected contributing factors include an increased population of dividing cells provided by re-epithelialization in combination with decreased immune surveillance provided by the lack of lymphatic regeneration. The rapid development of squamous cell carcinoma at a skin graft donor site represents a rare but serious possibility. Donor site diligence must be maintained post-operatively.

SQUAMOUS CELL CARCINOMA IN THE FOOT: CASE SERIES AND LITERATURE REVIEW.

ABSTRACTObjectives:To report a case series of squamous cell carcinoma (SCC) in the foot, describing previous risk factors, surgical treatment, histopathological findings, and functional and oncological results. Methods:Nine consecutive patients diagnosed with SCC of the foot were treated at a single institution and prospectively analyzed for risk factors related to the disease, surgical outcome, and histopathological, functional and oncological results. All patients had identifiable risk factors for SCC. Results:Definitive treatment consisted of partial (6 patients) or total (3 patients) amputation of the foot. The functional score was good or excellent in the surviving patients. Early identifiable risk factors are present in most patients. Biopsy when this diagnosis is suspected, in association with oncological principles, avoids diagnostic and treatment errors. Conclusion:Despite delayed diagnosis and surgical treatment with partial and total amputations of the foot in our series, we observed good oncological outcomes that avoided systemic spread of the disease and achieved expected functional results. Level of Evidence V; Case series.

Squamous Cell Carcinoma of the Tongue in a Crohnʼs Disease Patient

Case: A 36 year-old woman with CD ileocolitis presents with a new left-sided tongue lesion of 4 month's duration. There was no pain and no change in taste. She was able to scrape off the lesion but it returned. The lesion would not bleed and was not enlarging. There was no other neck swelling. Her CD had required hospitalization and small bowel resection, and has been maintained on infliximab 5 mg/kg IV every 8 weeks, azathioprine (AZA) 100 mg daily and mesalamine 2.5 g/d. Her CD has been in clinical remission for >5 years. She is a lifetime non-smoker, and does not drink alcohol. On exam, there was no submandibular, cervical or supraclavicular lymphadenopathy. There was no oral thrush, the tongue appears symmetric, and on the left lateral side is a 3 mm x 7 mm flat lesion with irregular borders (image). There were no skin lesions. Biopsy revealed superficially invasive squamous cell carcinoma (SCC), keratinizing type. The AZA was discontinued; infliximab and mesalamine continued. She underwent local excision with healing by secondary intent. Pathology confirmed a non-invasive 1.3 mm cancer, and she is thought to be cured. Discussion: The differential diagnosis of a tongue lesion in an IBD patient on immune suppression includes infectious (viral or fungal), inflammatory (lichen planus or IBD-related) and neoplastic (SCC or other) lesions. Evaluation requires careful examination and early diagnosis. IBD itself does not confer an increased risk of SCC, but exposure to AZA is a known risk factor for dermatologic and other malignancies. Tobacco and alcohol are other risk factors for SCC, but are not present in this case. Human Papilloma Virus (HPV) is another risk for SCC, but HPV-related cancers are usually more posterior in the oropharynx so that seems less likely a contributor in this case. Studies of anti-TNF have found no increased risk for SCC. Management includes discontinuation of the AZA, appropriate staging and in early stage lesions (< 3 mm deep), such as this one, surgical resection without adjuvant therapy is often curative. Clinical monitoring and close follow-up is important. Conclusions: Clinicians managing IBD should be aware of the differential diagnosis of tongue lesions and in at-risk patients, perform careful examinations and refer for early tissue diagnosis.Figure: Tongue lesion before resection.

Voriconazole increases the risk for cutaneous squamous cell carcinoma after lung transplantation

Lung transplant recipients (LTR) are at high risk of cutaneous squamous cell carcinoma (SCC). Voriconazole exposure after lung transplant has recently been reported as a risk factor for SCC. We sought to study the relationship between fungal prophylaxis with voriconazole and the risk of SCC in sequential cohorts from a single center. We evaluated 400 adult LTR at UCLA between 7/1/2005 and 12/22/2012. On 7/1/2009, our center instituted a protocol switch from targeted to universal antifungal prophylaxis for at least 6 months post-transplant. Using Cox proportional hazards models, time to SCC was compared between targeted (N = 199) and universal (N = 201) prophylaxis cohorts. Cox models were also used to assess SCC risk as a function of time-dependent cumulative exposure to voriconazole and other antifungal agents. The risk of SCC was greater in the universal prophylaxis cohort (HR 2.02, P < 0.01). Voriconazole exposure was greater in the universal prophylaxis cohort, and the cumulative exposure to voriconazole was associated with SCC (HR 1.75, P < 0.01), even after adjustment for other important SCC risk factors. Voriconazole did not increase the risk of advanced tumors. Exposure to other antifungal agents was not associated with SCC. Voriconazole should be used cautiously in this population.

Sirolimus use and risk of cutaneous squamous cell carcinoma (SCC) in solid organ transplant recipients (SOTRs)

Little is known about the use of sirolimus for primary prevention of cutaneous squamous cell carcinoma (SCC) among solid organ transplant recipients (SOTRs). We examined the association between sirolimus exposure and incident SCC risk among SOTRs within Kaiser Permanente Northern California. Using a retrospective cohort of all Kaiser Permanente Northern California members given a diagnosis of SOTR from 2000 through 2010, we evaluated incident posttransplantation SCC risk in relation to sirolimus exposure. Sirolimus use was determined from electronic pharmacy records, and incident posttransplantation SCCs were identified from health plan electronic pathology records. We used extended Cox regression to examine the independent association between receipt of sirolimus and risk of SCC. Among 3539 SOTRs, 488 were exposed to sirolimus and 47 developed an incident SCC. SCC riskwas not associated with ever use of sirolimus (adjusted hazard ratio 1.18, 95% confidence interval 0.84-1.16) or cumulative duration of sirolimus exposure (adjusted hazard ratio 2.75, 95% confidence interval 0.84-9.04, comparing long-term users with nonusers). No information was available for some known SCC risk factors, such as skin type and sun exposure. Among a large cohort of SOTRs, sirolimus exposure was not associated with a reduction in incident posttransplantation SCC risk.

Family history of skin cancer is associated with increased risk of cutaneous squamous cell carcinoma.

The contribution of family history to cutaneous squamous cell carcinoma (SCC) risk has not been systematically quantified. To examine the association between self-reported family history of skin cancer and SCC risk. Cases (n = 415) with a pathology-verified SCC and 415 age-, gender-, and race-matched controls were identified within a large integrated health care delivery system. Family history and skin cancer risk factors were ascertained by survey. Odds ratios (ORs) for associations of SCC with family history of skin cancer were estimated using conditional logistic regression adjusted for environmental and innate SCC risk factors. Any known family history of skin cancer was associated with a four-fold higher risk of SCC, adjusting for known environmental and innate SCC risk factors (OR, 4.0; confidence interval [CI]: 2.5-6.5). An unknown family history of skin cancer showed similar risk for SCC (OR, 3.9; CI: 2.4-6.5). In models including skin cancer type, the strongest association was for family history of basal cell carcinoma (OR, 9.8; CI: 2.6-36.8) and for multiple skin cancer types (OR, 10.5; CI: 3.7-29.6). Family history of skin cancer is an important independent risk factor for cutaneous SCCs.

Voriconazole exposure and the risk of cutaneous squamous cell carcinoma in allogeneic hematopoietic stem cell transplant patients.

Voriconazole is a commonly used antifungal medication in allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients. In solid organ transplantation, voriconazole use has been associated with the development of cutaneous squamous cell carcinoma (SCC). We sought to determine if voriconazole use was associated with SCC in patients undergoing allo-HSCT. We retrospectively reviewed consecutive adult patients who underwent allo-HSCT at Mayo Clinic from January 2007 through July 2012. Multivariable Cox models were created to assess the relationship of SCC with two time-dependent voriconazole exposure variables: (i) history of voriconazole exposure (yes/no), and (ii) cumulative days of voriconazole use. In our cohort of 381 allo-HSCT patients, SCC developed in 26 of 312 patients exposed to voriconazole (25 post-voriconazole) and in 1 of 69 patients who received alternative antifungal agent(s). Cumulative incidence of SCC was estimated to be 19% at 5years post allo-transplant. Cumulative days of voriconazole use was found to be a risk factor for SCC, and this relationship persisted in a multivariable model using previously identified risk factors as covariates (hazard ratio 1.859 for each 180days of use, P<0.001). This is the first study, to our knowledge, to identify cumulative days of voriconazole use as a risk factor for SCC development following allo-HSCT, and may help guide appropriate antifungal use in this patient population.

Prevention of occupational solar UV radiation-induced epithelial skin cancer

Malignancies of the skin, with an incidence of more than 200,000 newly registered cases/year, are the most frequently notified malignances in Germany. In Europe, squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) account for about 30cases/100,000persons and 50-100 cases/100,000 persons, respectively. Ultraviolet (UV) exposure is the main risk factor to induce these cancers. Increased incidence rates were shown for persons having red/blonde hair as well as light eye colour, acquire sun burns easily, hardly tan and develop freckles. The majority of the malignancies and precursor lesions are acquired by UV exposure in leisure time. However, in highly occupationally UV-exposed outdoor workers, UV monitoring revealed that exposure levels are 2-3times higher compared to the general population. Occupations likely to be highly exposed are farmers, forestry workers, gardeners, landscapers, fishermen and seafarers, construction workers, builders, tin smiths, sport teachers, mountain guides, etc. Recent metaanalyses showed that occupational UV exposure is a relevant and independent risk factor for SCC and to a lesser extent also for BCC. To prevent occupationally caused malignancies of the skin a significant reduction of occupationally acquired UV dosages in outdoor workers is mandatory. Relevant factors influencing the cumulative sun exposure in outdoor workers are the amount of UV exposure, the specific tasks to be performed in the sun as well as the UV protection habits of the workers. Besides adequate behavior, textile protection by headgear and clothing as well as the regular use of sunscreens and sun glasses are important.