Heterogeneous relationships of squamous and basal cell carcinomas of the skin with smoking: the UK Million Women Study and meta-analysis of prospective studies.

INTRODUCTION: Published findings on the associations between smoking and the incidence of cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) are inconsistent. We aimed to generate prospective evidence on these relationships overall and by anatomical site. METHODS: We followed 1,223,626 women without prior cancer by electronic linkage to national cancer registration data. Questionnaire information about smoking and other factors was recorded at recruitment (1996-2001) and every 3-5 years subsequently. Cox regression yielded adjusted relative risks (RRs) comparing smokers versus never-smokers. RESULTS: After 14 (SD4) years follow-up per woman, 6699 had a first registered cutaneous SCC and 48,666 a first BCC. In current versus never-smokers, SCC incidence was increased (RR = 1.22, 95% CI 1.15-1.31) but BCC incidence was decreased (RR = 0.80, 0.78-0.82). RRs varied substantially by anatomical site; for the limbs, current smoking was associated with an increased incidence of SCC (1.55, 1.41-1.71) and a decreased incidence of BCC (0.72, 0.66-0.79), but for facial lesions there was little association of current smoking with either SCC (0.93, 0.82-1.06) or BCC (0.92, 0.88-0.96). Findings in meta-analyses of results from this and seven other prospective studies were largely dominated by the findings in this study. CONCLUSIONS: Smoking-associated risks for cutaneous SCC and BCC are in the opposite direction to each other and appear to vary by anatomical site.

Plantar verrucous carcinoma masquerading as toe web intertrigo.

A 77-year-old man presented with a 6-month history of intractable toe web intertrigo located in the third and fourth web spaces of his left foot. Biopsy and histological examination confirmed the presence of a verrucous carcinoma. Verrucous carcinoma of the foot has been called epithelioma cuniculatum, a case arising in the intertriginous area of the foot is presented.

Sun-related factors, betapapillomavirus, and actinic keratoses: a prospective study.

OBJECTIVE: To examine prospectively the relationship among sun exposure, Betapapillomavirus, and development of actinic keratoses. DESIGN: Prospective, community-based cohort study. SETTING: Township of Nambour in Southeast Queensland, Australia. PARTICIPANTS: A total of 291 randomly selected adults aged 36 to 86 years with the presence or absence of Betapapillomavirus DNA in eyebrow hair follicle cells known at baseline in August 1996 and with subsequently documented sun exposure histories. MAIN OUTCOME MEASURES: Prevalence of actinic keratoses in March 2003 after 7 years of follow-up. RESULTS: Beyond the known determinants of multiple actinic keratoses, namely, advanced age, male sex, fair skin, and lifetime occupational sun exposure, Betapapillomavirus infection was associated with having more than 10 actinic keratoses (odds ratio, 1.8; 95% confidence interval, 0.7-4.4). However, Betapapillomavirus positivity led to a significant 13-fold increase in the risk of actinic keratoses among those 60 years or older, a nearly 6-fold increase in risk when combined with fair skin color, and a doubling in risk of actinic keratoses when combined with high sun exposure, recent or cumulative, compared with those who had neither Betapapillomavirus infection nor the respective risk factor of interest. CONCLUSIONS: Although the presence of Betapapillomavirus DNA in eyebrow hair follicle cells had only a small independent association with actinic keratoses, Betapapillomavirus infection in combination with key risk factors increased the risk of actinic keratoses, which is consistent with a potentiation by Betapapillomavirus of the effect of established causal factors.

Squamous cell carcinoma of the skin (non-metastatic).

INTRODUCTION: Cutaneous squamous cell carcinoma is a malignant tumour of keratinocytes arising in the epidermis, with histological evidence of dermal invasion. Incidence varies by country, skin colour, and outdoor behaviour, and is as high as 400/100,000 in Australia. People with fair skin colour who have high sun exposure and sunburn easily with little or no tanning, people with xeroderma pigmentosum, and people who are immunosuppressed are most susceptible to squamous cell carcinoma. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: Does the use of sunscreen help prevent cutaneous squamous cell carcinoma and actinic (solar) keratosis? What is the optimal margin for primary excision of cutaneous squamous cell carcinoma (non-metastatic)? Does radiotherapy after surgery affect local recurrence of cutaneous squamous cell carcinoma in people with squamous cell carcinoma of the skin (non-metastatic)? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2013 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found five studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review, we present information relating to the effectiveness and safety of the following interventions: sunscreens, primary excision, and radiotherapy after surgery.

Childhood exposure to ultraviolet radiation and harmful skin effects: epidemiological evidence.

We review the general amount and patterns of exposure to solar ultraviolet (UV) radiation that children and teenagers experience and the spectrum of UV-related skin damage that can occur as a result. Data about the amount of solar UV received by children and teenagers are relatively few but suggest that around 40-50% of total UV to age 60 occurs before age 20. Among white children, those with the palest complexions suffer the most damage. Comparisons of prevalence and incidence of outcomes in children and teenagers sharing common ancestry, but living at different latitudes, show that prevalence rates of photoaging and melanocytic naevi are higher in Australian compared with British children, and similarly for melanoma. Genetic risk for the majority of the melanomas in teens is a function of genes controlling naevus propensity and pigmentation in the skin. High numbers of naevi and freckles, red hair, blue eyes, inability to tan, as well as a family history are the primary determinants of melanoma among adolescents. Beyond the signs of skin damage seen in children are the latent effects observed later in adulthood. Childhood is believed to be a susceptible window for long-term harmful effects of UV, as evidenced by clear differences in skin cancer risk between child and adult migrants from high to low latitudes. Effective UV radiation protection from childhood is necessary to control both immediate and long-term harmful effects on children's skin.

Tobacco smoking and cutaneous squamous cell carcinoma: a 16-year longitudinal population-based study.

BACKGROUND: Although tobacco smoking is commonly cited as a risk factor for cutaneous squamous cell carcinoma (SCC), the evidence from previous clinical and case-control studies is conflicting. We therefore aimed to prospectively examine the role of tobacco smoking in the development of SCC of the skin in a population-based study. METHODS: Study participants were 1,287 adults aged 25 to 75 years in 1992, randomly selected from the Nambour community, with no previous history of SCC. Standard skin pigment and sun-sensitivity profiles were obtained at baseline. Detailed prospective information on sun exposure, smoking, and skin cancer occurrence (histologically confirmed) was collected over a 16-year period, 1992 to 2007. RESULTS: Of 1,287 participants, 43% were male and average age was 48 years. A total of 188 first cutaneous SCCs were identified during the study period. After adjustment for other known risk factors, neither former nor current smokers were at raised risk of SCC: relative risk (RR) = 1.1, 95% CI: 0.8-1.5 and RR = 1.1, 95% CI: 0.7-1.5, respectively, compared with lifelong nonsmokers, nor were there any dose-response relationships with amount smoked or duration of smoking and risk of SCC. CONCLUSIONS: In this Australian follow-up study, tobacco smoking did not increase the risk of SCC of the skin. IMPACT: These prospective adjusted data provide strong evidence which suggests that cutaneous SCC should not be on the list of tobacco-related cancers.

Squamous cell carcinoma of the skin (non-metastatic).

INTRODUCTION: Cutaneous squamous cell carcinoma is a malignant tumour of keratinocytes arising in the epidermis, with histological evidence of dermal invasion. Incidence varies by country and skin colour, and is as high as 400/100,000 in Australia. People with fair skin colour who sunburn easily without tanning, people with xeroderma pigmentosum, and people who are immunosuppressed are most susceptible to squamous cell carcinoma. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: Does the use of sunscreen help prevent cutaneous squamous cell carcinoma and solar keratosis? What is the optimal margin for primary excision of cutaneous squamous cell carcinoma (non-metastatic)? Does micrographically controlled surgery result in lower rates of local recurrence than standard primary excision in people with squamous cell carcinoma of the skin (non-metastatic)? Does radiotherapy after surgery affect local recurrence of cutaneous squamous cell carcinoma in people with squamous cell carcinoma of the skin (non-metastatic)? We searched: Medline, Embase, The Cochrane Library, and other important databases up to October 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 11 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: micrographically controlled surgery, primary excision, radiotherapy after surgery, and sunscreens.

Regular sunscreen use is a cost-effective approach to skin cancer prevention in subtropical settings.

In many developed countries, total costs to health systems for cutaneous basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) are among the highest of all cancers, yet the investment value of preventive measures remains unknown. Using primary data from a randomized controlled trial, we estimated the cost-effectiveness of a skin cancer prevention initiative based on regular sunscreen use. Compared with usual practice (discretionary use), the sunscreen intervention cost an additional USD 106,449 (2007) to prevent 11 BCCs, 24 SCCs, and 838 actinic keratoses among 812 residents over 5 years. These health outcomes required an annual average investment of USD 0.74 per person and saved the Australian government a total of USD 88,203 in health-care costs over the same period. Such community-based interventions promoting regular sunscreen use among Caucasians in subtropical settings can prevent skin cancer and related skin tumors in practical ways and with great cost efficiency.

Persistence of betapapillomavirus infections as a risk factor for actinic keratoses, precursor to cutaneous squamous cell carcinoma.

Human papillomaviruses from the beta genus (betaPV) are a possible cause of cutaneous squamous cell carcinoma (SCC). We assessed the extent to which betaPV infections persisted long-term in a subtropical Australian community and whether betaPV persistence is positively associated with actinic keratoses, precursor for SCC. Eyebrow hairs were collected from 171 participants of the community-based Nambour Skin Cancer Study in 1996 and 2003. Hair samples were tested for the presence of DNA from 25 different betaPV types and assessed in relation to actinic keratosis presence in 2007. In 1996, a total of 413 betaPV infections were found in 73% of participants, increasing to 490 infections among 85% in 2003. Of the total betaPV infections detected, 211 (30%) were found to persist. Age was significantly associated with betaPV persistence: those ages >60 years had 1.5-fold (95% confidence interval, 1.1-1.9) increased risk of type-specific viral persistence than those ages <40 years. After accounting for actinic keratoses at baseline, persistence of betaPV DNA resulted in a 1.4-fold (95% confidence interval, 1.0-1.9) increase in risk of having actinic keratoses on the face in 2007. In conclusion, persistent betaPV infections in this population were associated with an increased occurrence of actinic keratosis. Additional studies are needed to determine the possible association of betaPV persistence with SCC.