Food intake and risk of squamous cell carcinoma of the skin in a community: the Nambour skin cancer cohort study

There is some evidence that dietary factors may modify the risk of squamous cell carcinoma (SCC) of the skin, but the association between food intake and SCC has not been evaluated prospectively. We examined the association between food intake and SCC incidence among 1,056 randomly selected adults living in an Australian sub-tropical community. Measurement-error corrected estimates of intake in 15 food groups were defined from a validated food frequency questionnaire in 1992. Associations with SCC risk were assessed using Poisson and negative binomial regression to the persons affected and tumour counts, respectively, based on incident, histologically confirmed tumours occurring between 1992 and 2002. After multivariable adjustment, none of the food groups was significantly associated with SCC risk. Stratified analysis in participants with a past history of skin cancer showed a decreased risk of SCC tumours for high intakes of green leafy vegetables (RR = 0.45, 95% CI = 0.22-0.91; p for trend = 0.02) and an increased risk for high intake of unmodified dairy products (RR = 2.53, 95% CI: 1.15-5.54; p for trend = 0.03). Food intake was not associated with SCC risk in persons who had no past history of skin cancer. These findings suggest that consumption of green leafy vegetables may help prevent development of subsequent SCCs of the skin among people with previous skin cancer and that consumption of unmodified dairy products, such as whole milk, cheese and yoghurt, may increase SCC risk in susceptible persons.     

Management of high-risk squamous cell carcinoma of the skin

Cutaneous squamous cell cancer (SCC) is the second most common skin cancer, accounting for one-fifth of all cutaneous malignancies. The majority arise on the head and neck skin, and cumulative UV exposure is thought to be the most likely etiological factor. The majority of deaths from SCC occur in a high-risk subgroup of patients. This high-risk subgroup of patients can be identified as those with tumors greater than 2 cm in diameter; tumor thickness over 4 mm; moderately/poorly differentiated or desmoplastic histological SCC subtype; ear, lip, hand, feet or genital tumor site; presence of perineural or lymphovascular invasion; nodal metastasis at presentation; recurrent SCC; SCC arising from scars or chronic skin disease, for example, chronic ulcers; and SCC arising in immunosuppressed patients. It is important to identify and aggressively treat these patients, as high-risk SCC are associated with a greater mortality and morbidity. This article reviews the diagnosis and management of such high-risk SCC.     

Niacin intake and risk of skin cancer in US women and men

A recent clinical trial found a protective role of niacinamide, a derivative of niacin, against skin cancer recurrence. However, there is no epidemiologic study to assess the association between niacin intake and risk of skin cancer [basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and melanoma]. We prospectively evaluated whether total, dietary and supplemental niacin intake was associated with skin cancer risk based on 72,308 women in the Nurses' Health Study (1984–2010) and 41,808 men in the Health Professionals Follow‐up Study (1986–2010). Niacin intake was assessed every 2 to 4 years during follow‐up and cumulative averaged intake. Cox proportional hazard models were used to compute the hazard ratios (HR) and 95% confidence intervals (CI) and cohort‐specific results were pooled using a random‐effects model. During the follow‐up, we documented 23,256 BCC, 2,530 SCC and 887 melanoma cases. Total niacin intake was inversely associated with SCC risk; the pooled HR for top vs. bottom quintiles was 0.84 (95% CI = 0.74–0.95; p_trend = 0.08). However, there were a marginally positive association between total niacin intake and BCC risk; the pooled HR for top versus bottom quintiles was 1.05 (95% CI = 1.01–1.10; p_trend < 0.01). Higher total niacin intake was also marginally positively associated with melanoma risk in men, but not in women. The results were similar in stratified analyses according to sun exposure related factors and by body location of melanoma and SCC. Our study supports a potential beneficial role of niacin intake in relation to SCC but not of BCC or melanoma.     

Outcomes after radiotherapy for squamous cell carcinoma of the eyelid

BACKGROUND: Squamous cell carcinoma (SCC) of the eyelid is a rare malignancy with metastatic potential. In the current study, the outcomes of patients with SCC of the eyelid were evaluated after definitive and postoperative radiation therapy. METHODS: The medical records of all patients treated with radiotherapy for SCC of the eyelid at 1 institution between 1950 and 2005 were reviewed. Patient records were analyzed for clinical characteristics, pathologic features, radiation techniques, and outcomes. Survival rates were calculated using the Kaplan-Meier method; factors affecting survival were assessed using the log-rank test. RESULTS: During the study period, 39 patients with 42 eyelid SCCs were treated with radiotherapy. Thirty-two tumors were treated with primary radiotherapy and 10 were treated with postoperative radiotherapy after wide local excision. Surviving patients were followed for a median of 76 months. The 5-year disease-specific and overall survival rates for all patients were 86% and 71%, respectively. At 5 years, local, regional, and distant disease control rates for all tumors were 88%, 95%, and 97%, respectively. There were no significant differences in the 5-year local, regional, and distant control rates between tumors treated with definitive and those treated with postoperative radiotherapy. There were no grade 3 or 4 complications. CONCLUSIONS: Primary radiotherapy for SCC of the eyelid provides excellent locoregional control with reasonable complication rates and should be considered an alternative to surgery in selected patients.     

Cytoskeletal protein flightless I inhibits apoptosis,enhances tumor cell invasion and promotes cutaneous squamous cell carcinoma progression

Flightless I (Flii) is an actin remodeling protein that affects cellular processes including adhesion, proliferation and migration. In order to determine the role of Flii during carcinogenesis, squamous cell carcinomas (SCCs) were induced in Flii heterozygous (Flii^+/−), wild-type and Flii overexpressing (Flii^Tg/Tg) mice by intradermal injection of 3-methylcholanthrene (MCA). Flii levels were further assessed in biopsies from human SCCs and the human SCC cell line (MET-1) was used to determine the effect of Flii on cellular invasion. Flii was highly expressed in human SCC biopsies particularly by the invading cells at the tumor edge. Flii^Tg/Tg mice developed large, aggressive SCCs in response to MCA. In contrast Flii^+/− mice had significantly smaller tumors that were less invasive. Intradermal injection of Flii neutralizing antibodies during SCC initiation and progression significantly reduced the size of the tumors and, in vitro, decreased cellular sphere formation and invasion. Analysis of the tumors from the Flii overexpressing mice showed reduced caspase I and annexin V expression suggesting Flii may negatively regulate apoptosis within these tumors. These studies therefore suggest that Flii enhances SCC tumor progression by decreasing apoptosis and enhancing tumor cell invasion. Targeting Flii may be a potential strategy for reducing the severity of SCCs.     

Survival after squamous cell and basal cell carcinoma of the skin: A retrospective cohort analysis

A retrospective cohort analysis of survival after keratinocyte cancer (KC) was conducted using data from a large, population‐based case–control study of KC in New Hampshire. The original study collected detailed information during personal interviews between 1993 and 2002 from individuals with squamous (SCC) and basal (BCC) cell carcinoma, and controls identified through the Department of Transportation, frequency‐matched on age and sex. Participants without a history of non‐skin cancer at enrolment were followed as a retrospective cohort to assess survival after either SCC or BCC, or a reference date for controls. Through 2009, cancers were identified from the New Hampshire State Cancer Registry and self‐report; death information was obtained from state death certificate files and the National Death Index. There were significant differences in survival between those with SCC, BCC and controls (p = 0.040), with significantly greater risk of mortality after SCC compared to controls (adjusted hazard ratio [HR] 1.25; 95% confidence interval 1.01–1.54). Mortality after BCC was not significantly altered (HR 0.96; 95% CI 0.77–1.19). The excess mortality after SCC persisted after adjustment for numerous personal risk factors including time‐varying non‐skin cancer occurrence, age, sex and smoking. Survival from the date of the intervening cancer, however, did not vary (HR for SCC 0.98; 95% CI 0.70–1.38). Mortality also remained elevated when individuals with subsequent melanoma were excluded (HR for SCC 1.30; 95% CI 1.05–1.61). Increased mortality after SCC cannot be explained by the occurrence of intervening cancers, but may reflect a more general predisposition to life threatening illness that merits further investigation.     

Aggressive squamous cell carcinoma of the skin after chronic lymphocytic leukemia

We report two cases of squamous cell carcinoma (SCC) of the skin subsequent to chronic lymphocytic leukemia (CLL). Both cases had an unusually aggressive course for a nonmelanoma skin malignancy with extensive metastases in both, resulting in death in one patient. A literature review supports the likelihood of an increased incidence of SCC in patients with CLL. Though the mechanism is unknown, immunosuppression may play a central role. We urge patients with CLL to avoid exposure to direct sun. Any questionable skin lesion should be biopsied early, and completely excised if it is a tumor. The patient should also be examined thoroughly for metastatic disease via subsequent follow-up visits.     

宫颈鳞状细胞癌患者血清鳞状细胞癌抗原变化的临床意义

目的　研究子宫颈鳞状细胞癌患者血清中鳞状细胞癌抗原水平与病理分级、临床分期及对治疗反应之间的关系。方法　利用雅培公司提供的 IMX全自动快速粒子酶免疫分析系统 ,对 2 5例正常献血员和 83例经病理学诊断的宫颈鳞状细胞癌患者 ,进行了血清中鳞状细胞癌抗原血清检测并分析其与病理分级、临床分期之间关系。其中 80例患者放射治疗前后血清鳞状细胞癌抗原水平变化情况进行了自身比较。结果　中晚期宫颈鳞状细胞癌患者血清鳞状细胞癌抗原水平与病理分级、临床分期之间无相关性。放射治疗前后患者血清鳞状细胞癌抗原水平有明显变化。结论　对子宫颈鳞状细胞癌患者 ,在治疗前后检测血清鳞状细胞癌抗原水平 ,可以作为对放射治疗疗效判断的参考指标之一。     

Second primary cancers in patients with squamous cell carcinoma of the skin

The occurrence of second primary cancers was explored in patients with squamous cell cancer of the skin (SCC). The excess incidence subsequent to SCC was mainly in cancers related to sunlight and smoking, and in lymphoproliferative malignancies, it was largest (10-fold) in salivary gland cancer.     

A case of adenoid squamous cell carcinoma of the breast skin

We report a case of a 45-year-old Japanese woman with adenoid squamous cell carcinoma (ASCC) of the left breast skin. The patient had showed a large mass in the left breast region with axillary swelling about 1 year before admission. Grossly, the tumor was an extensively ulcerated and elevated lesion measuring 15X16X5 cm. Based on the tumor biopsy and cytologic examination of the axillary lymph nodes, squamous cell carcinoma (SCC) was diagnosed. No evidence of distant metastasis was identified. A modified radical mastectomy with left axillary node dissection was performed. Microscopically, the resected tumor showed an invasive proliferation of atypical squamous cells with marked keratinization. At the periphery of the tumor, an adenoid growth pattern was frequently seen with a transitional area showing squamous cell carcinoma and adenoid growth components. ASCC was diagnosed. A transition between the overlying squamous cell epithelium and squamous cell carcinoma component was also seen, thus the tumor was thought to have originated from the breast skin. The patient died of respiratory failure due to multiple lung metastasis about 1 month after the mastectomy. Tumor rarely originates at the breast region to include both the mammary glands and breast skin. The pathogenesis and management of ASCC are discussed following the presentation of this case.     

Comparison of risk factors for invasive squamous cell carcinoma and adenocarcinoma of the cervix: collaborative reanalysis of individual data on 8,097 women with squamous cell carcinoma and 1,374 women with adenocarcinoma from 12 epidemiological studies

Squamous cell carcinomas account for about 80% of cancers of the uterine cervix, and the majority of the remainder are adenocarcinomas. There is limited evidence on the extent to which these histological types share a common etiology. The International Collaboration of Epidemiological Studies of Cervical Cancer has brought together and combined individual data on 8,097 women with invasive squamous cell carcinoma, 1,374 women with invasive adenocarcinoma and 26,445 women without cervical cancer (controls) from 12 epidemiological studies. Compared to controls, the relative risk of each histological type of invasive cervical cancer was increased with increasing number of sexual partners, younger age at first intercourse, increasing parity, younger age at first full-term pregnancy and increasing duration of oral contraceptive use. Current smoking was associated with a significantly increased risk of squamous cell carcinoma (RR = 1.50, 95% CI: 1.35-1.66) but not of adenocarcinoma (RR = 0.86 (0.70-1.05)), and the difference between the two histological types was statistically significant (case-case comparison p < 0.001). A history of screening (assessed as having had at least one previous nondiagnostic cervical smear) was associated with a reduced risk of both histological types, but the reduction was significantly greater for squamous cell carcinoma than for adenocarcinoma (RR = 0.46 (0.42-0.50) and 0.68 (0.56-0.82), respectively; case-case comparison, p = 0.002). A positive test for cervical high-risk HPV-DNA was a strong risk factor for each histological type, with 74% of squamous cell carcinomas and 78% of adenocarcinomas testing positive for HPV types 16 or 18. Squamous cell and adenocarcinoma of the cervix share most risk factors, with the exception of smoking.     

Loss of heterozygosity in actinic keratosis, squamous cell carcinoma and sun-exposed normal-appearing skin in Japanese: difference between Japanese and Caucasians

Actinic keratosis (AK) has been considered to be a precursor of squamous cell carcinoma (SCC). However, based on epidemiological and molecular studies, it has become questionable to regard AK as a precancerous lesion. We analyzed 37 AKs and 14 sporadic SCCs using six microsatellite markers in order to elucidate if any genetic instability or loss of heterozygosity (LOH) was implicated in tumorigenesis and progression of non-melanocytic skin tumor. Microsatellite instability (MSI) was not found in any of the AKs or SCCs indicating that genetic instability has little implication in the tumorigenesis of sporadic non-melanocytic skin tumor. LOH was found in seven of 37 lesions of AK, but in only one of 14 lesions of SCC. The significantly lower frequency of LOH than that previously reported in Caucasians suggested that the molecular pathogenesis of AKs and SCCs might be different between Japanese and Caucasians. The higher frequency of LOH in AKs than in SCCs in the present study supported the previous epidemiological and molecular studies that AK was not likely to proceed to SCC. LOH was also demonstrated in histologically normal-appearing skin in three cases suggesting that genetic alteration occurs before histological change appears in the sun-exposed skin.     

空洞型肺鳞癌与非空洞型肺鳞癌的临床特征分析

Objective： To identify the differences between cavitating squamous cell lung carcinoma （cSLC） and non-cavitating squamous cell lung carcinoma （ncSLC）. Methods： Fifty-one patients with cSLC and 281 with ncSLC confirmed by surgery in our hospital between 1999 to 2000 were collected and their clinical, histological and survival features were retrospectively ana（yzed. Results： Patients with cSLC had more frequent manifestation of infection and weight loss. They usually experienced longer duration of pre-diagnosis and showed bigger tumor mass, larger primary tumor invasion with worse differentiated than ncSLC patients. There was no significant difference in age, sex, smoking history, family tumor history, personal tuberculosis history, disease location, TNM stage, lymph node invasion, and metastasis between the two groups. Median survival time was 29 months for cSLC and 35 months for ncSLC. One- and 3- year survival rates were 86.3% and 43.1% for cSLC vs. 91.1% and 47,0% for ncSLC respectively （P〉0.05）. Conclusion： Patients with cSLC presented with a bigger mass, a larger extent of primary tumor invasion, worse differentiated, more obstructed pneumonia that might result in longer duration of pre-diagnosis and more weight loss. As lack of differences in disease stages, lymph node invasion, metastasis and especially survival time with ncSLC, cSLC couldn＇t be classified as a special type of squamous cell carcinoma by present evidences.     

Primary squamous cell carcinoma of the colorectum: case report and literature review of a rare entity

A case of primary squamous cell carcinoma of the rectum is presented. Although it is a rare condition, the diagnosis, treatment, and natural history of the disease are similar to that of adenocarcinoma of the colorectum. The patient in this report has done well to date with an abdominal perineal resection and early post-operative radiation. A review of the literature reveals that the precise etiology of this entity remains unknown.     

Expression of nuclear survivin in normal skin and squamous cell carcinoma: a possible role in tumour invasion

Background:

Survivin is detected in few adult normal cells and it is highly expressed in cancer. Nuclear survivin facilitates cell cycle entry, whereas the mitochondrial pool protects cells from apoptosis. Survivin is overexpressed in keratinocyte stem cells (KSCs) and protects them from apoptosis.

Methods:

As KSCs are at the origin of squamous cell carcinoma (SCC), we evaluated survivin expression in normal and cancerous skin in vivo by immunohistochemistry and western blotting. HaCaT cells overexpressing survivin and wound-healing assay are used. Analysis of variance and Student''s T-tests are used for statistical analysis.

Results:

Survivin is localised in both the cytoplasm and nucleus of normal adult and young keratinocytes. Nuclear survivin is detected in one every 10 of 11 basal keratinocytes. When present in suprabasal cells, nuclear survivin is coexpressed with K10 but not with K15 or p75-neurotrophin receptor (p75NTR), a transit amplifying cell marker. Nuclear, but not cytoplasmic, survivin expression markedly increases in actinic keratosis and in SCC in situ, as compared with normal epidermis, and it is highest in poorly differentiated SCC. In SCC tumours, nuclear survivin-positive cells are mainly K10/p75NTR-negative and K15-positive. In poorly differentiated tumours, survivin mostly localises in the deep infiltrating areas. When overexpressed in keratinocytes, survivin increases cell migration.

Conclusion:

High survivin expression and the subcellular localisation of survivin correlate with keratinocyte differentiation and are associated with undifferentiated and more invasive SCC phenotype.     

Host characteristics,sun exposure,indoor tanning and risk of squamous cell carcinoma of the skin

Use of indoor tanning devices increases risk of cutaneous malignant melanoma, but the association with risk of squamous cell carcinoma (SCC) of the skin is unclear. Cohort studies of SCC risk are rare and we aimed to assess the association between SCC risk and host characteristics, sun exposure, and indoor tanning in a population‐based cohort of Norwegian and Swedish women conjunctly with SCC incidence data from national cancer registries. Host characteristics and exposure to sun and indoor tanning devices before 50‐years old were recorded by questionnaire at inclusion (30–50 years) in 1991/92. Multivariable relative risks (RRs) and 95% confidence intervals (CIs) were estimated by Poisson regression. During follow‐up of 106,548 women through December 2009, SCC was diagnosed in 141 women. Skin sensitivity to acute sun exposure was the most important pigmentation characteristic (RR = 2.73, 95% CI 1.47–5.05, for red with pain/red with pain and blisters versus brown). We found no consistent associations with sunburns and bathing vacations in the first five age decades, but a significant positive trend for bathing vacations summarized over ages 10–49 years (P_trend = 0.02). We also found significantly increased risks of SCC following indoor tanning at age 40–49 years (RR = 2.17, 95% CI 1.29–3.67, for ≥ 1 time/month versus never) and indoor tanning summarized over ages 10–49 years (P_trend = 0.001). RR for ever versus never use of indoor tanning over ages 10–49 years was 1.93 (95% CI 1.27–2.95). Propensity to burn was an important host characteristic, and bathing vacations and indoor tanning summarized over ages 10–49 years increased SCC risk.     

Differences in site-specific incidence and relative survival of cutaneous and mucocutaneous genital squamous cell carcinoma in Germany, 2007-2015

Direct comparisons of the incidence and survival of cutaneous vs mucocutaneous genital squamous cell carcinomas (SCCs) are lacking even though they may bring important insights. We aimed to compare incidence rates and survival of cutaneous and mucocutaneous genital SCCs head-to-head, using the same source population, cancer registry methodology and statistical methods in a population of predominantly white Caucasian descent. Using data (2007-2015) from the population-based cancer registry of North Rhine-Westphalia, (population of 18 million people), we estimated age-specific and age-standardized (old European standard) incidence rates and age-standardized relative 5-year survival of SCC with the period approach for the period 2012 to 2015. Overall, 83 650 SCC cases were registered. The age-standardized incidence rates (per 100 000 person-years) of cutaneous SCCs were 36.5 (SE 0.17) and 17.0 (SE 0.11) among men and women, respectively, with corresponding rates for mucocutaneous genital skin, 1.3 (SE 0.03) and 4.5 (SE 0.06) for men and women, respectively. In all age groups, incidence rates of mucocutaneous genital SCCs were higher in women than men. Men had higher cutaneous SCC incidence at all nongenital subsites than women, with the exception of the lower extremities. Five-year relative survival was considerably lower for mucocutaneous genital SCCs (men: 71%, women: 75%), especially of the scrotal skin (67%) and labia majora (62%) than for SCC of nongenital skin (men: 93%, women: 97%). Given their relatively high incidence together with a lower survival probability, future studies are warranted to establish therapies for advanced mucocutaneous genital SCC, such as immune checkpoint inhibition.