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Basal cell and squamous cell carcinomas of the skin are the commonest cancers in humans, yet no validated tools exist to estimate future risks of developing keratinocyte carcinomas. To develop a prediction tool, we used baseline data from a prospective cohort study (n = 38,726) in Queensland, Australia, and used data linkage to capture all surgically excised keratinocyte carcinomas arising within the cohort. Predictive factors were identified through stepwise logistic regression models. In secondary analyses, we derived separate models within strata of prior skin cancer history, age, and sex. The primary model included terms for 10 items. Factors with the strongest effects were >20 prior skin cancers excised (odds ratio 8.57, 95% confidence interval [95% CI] 6.73–10.91), >50 skin lesions destroyed (odds ratio 3.37, 95% CI 2.85–3.99), age ≥ 70 years (odds ratio 3.47, 95% CI 2.53–4.77), and fair skin color (odds ratio 1.75, 95% CI 1.42–2.15). Discrimination in the validation dataset was high (area under the receiver operator characteristic curve 0.80, 95% CI 0.79–0.81) and the model appeared well calibrated. Among those reporting no prior history of skin cancer, a similar model with 10 factors predicted keratinocyte carcinoma events with reasonable discrimination (area under the receiver operator characteristic curve 0.72, 95% CI 0.70–0.75). Algorithms using self-reported patient data have high accuracy for predicting risks of keratinocyte carcinomas.

Globally, 39% of the world's adult population is overweight or obese and 23% is insufficiently active. These percentages are even larger in high-income countries with 58% overweight/obese and 33% insufficiently active. Fourteen cancer types have been declared by the World Cancer Research Fund to be causally associated with being overweight or obese: oesophageal adenocarcinoma, stomach cardia, colon, rectum, liver, gallbladder, pancreas, breast, endometrium, ovary, advanced/fatal prostate, kidney, thyroid and multiple myeloma. Colon, postmenopausal breast and endometrial cancers have also been judged causally associated with physical inactivity. We aimed to quantify the proportion of cancer cases that would be potentially avoidable in Australia if the prevalence of overweight/obesity and physical inactivity in the population could be reduced. We used the simulation modelling software PREVENT 3.01 to calculate the proportion of avoidable cancers over a 25-year period under different theoretical intervention scenarios that change the prevalence of overweight/obesity and physical inactivity in the population. Between 2013 and 2037, 10-13% of overweight/obesity-related cancers in men and 7-11% in women could be avoided if overweight and obesity were eliminated in the Australian population. If everyone in the population met the Australian physical activity guidelines for cancer prevention (i.e. engaged in at least 300 min of moderate-intensity physical activity per week), an estimated 2-3% of physical inactivity-related cancers could be prevented in men (colon cancer) and 1-2% in women (colon, breast and endometrial cancers). This would translate to the prevention of up to 190,500 overweight/obesity-related cancers and 19,200 inactivity-related cancers over 25 years.

Cancer is a leading cause of disease burden in Australia, particularly fatal burden, accounting for an estimated thirty percent of deaths. Many cancers develop because of exposure to lifestyle and environmental factors that are potentially modifiable. We aimed to quantify the proportions and numbers of cancer deaths and cases in Australia in 2013 attributable to 20 modifiable factors in eight broad groupings that are established causes of cancer, namely: tobacco smoke (smoking and second-hand), dietary factors (low intake of fruit, non-starchy vegetables and dietary fibre; and high intake of red and processed meat), overweight/obesity, alcohol, physical inactivity, solar ultraviolet radiation, infections (seven agents), and reproductive factors (lack of breastfeeding, menopausal hormone therapy use, combined oral contraceptive use). We estimated population attributable fractions (PAF) using standard formulae incorporating exposure prevalence and relative risk data. Of all cancer deaths in Australia in 2013, approximately 38% overall (males 41%, females 34%) could be attributed to the factors assessed; the corresponding PAF for cancer cases was 33% (males 34%, females 32%). Tobacco smoke was the leading cause of cancer deaths and cases, with PAFs of 23 and 13%, respectively, followed by dietary factors (5% deaths/5% cases), overweight/obesity (5%/4%) and infections (5%/3%). Cancer sites with the highest numbers of potentially preventable deaths/cases were lung (n = 6,776/9,272), colorectum (n = 1,974/7,380) and cutaneous melanoma (n = 1,390/7,918). We estimate that about 16,700 cancer deaths and 41,200 cancer cases could be prevented in Australia each year if people's exposures to 20 causal factors were aligned with levels recommended to minimise cancer risk.

Although most women diagnosed with ovarian cancer initially respond to first-line chemotherapy, the vast majority eventually relapses and requires retreatment with second-line chemotherapy. Patient response is classified as either platinum sensitive or platinum resistant on the basis of the time of relapse after first-line treatment. A cancer with a progression-free interval of more than 6 months after completion of first-line chemotherapy is classified as “platinum-sensitive disease” and responds well to retreatment. A cancer with a progression-free interval of less than 6 months after completion of first-line chemotherapy is classified as “platinum-resistant disease” and responds poorly to second-line retreatment. Cure is not possible in patients with platinum-resistant recurrent ovarian cancer, and long-term progression-free survival is rare. The goal of care in these patients should be to maximize their quality of life. The aim of this population-based longitudinal study was to determine whether quality of life improves after second-line chemotherapy among women with platinum-resistant recurrent ovarian cancer. A secondary aim was to evaluate treatment response. Data for 172 women from 2 studies were combined. All participants were treated with chemotherapy for recurrent ovarian cancer and completed a validated quality of life questionnaire every 3 months. Change in quality of life during the first 6 months after second-line chemotherapy was analyzed using mixed effect models. A comparison group was composed of women with platinum-sensitive disease. Among the 172 patients, 44 (25%) were classified as having platinum-resistant disease. After the start of second-line chemotherapy, there was no significant increase or decrease in quality of life of women with platinum-resistant disease (least square mean scores at chemotherapy start, 3 months later, and 6 months later: 107, 105, and 103, respectively), although 26% reported a meaningful increase and 31% reported a meaningful decline. One third of the women with platinum-resistant cancer responded (11% complete and 21% partial response) to second-line chemotherapy; the response rate increased to 54% among the subset retreated with platinum-based agents with or without other agents. Preliminary subgroup analysis suggested that quality of life in women whose disease responded may be higher at the start of chemotherapy (median score, 121 vs 110). These findings show that the overall quality of life is maintained among women with recurrent platinum-resistant disease after retreatment with chemotherapy; however, some patients showed a meaningful increase whereas some showed a decline.

The vitamin D endocrine system is implicated in skin carcinogenesis and polymorphisms in genes associated with the vitamin D receptor (VDR) gene may alter the risk of keratinocyte cancers (basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)).In a nested case-control study of 1,124 adults, we investigated associations between polymorphisms in VDR-related pathways and incident keratinocyte cancers during 11 years of follow-up using adjusted multivariate regression analysis. We also performed a meta-analysis of rs2228570, rs7975232, rs1544410 and rs739837 polymorphisms.A total of 286 BCCs and 161 SCCs were newly-diagnosed during follow-up. Participants with rs2228570 and rs927650 recessive genotypes had a decreased risk of SCC (odds ratio (OR)=0.34, 95% confidence interval (CI)=0.17-0.68; OR=0.48, CI=0.27-0.84, respectively). Meta-analysis showed a lower SCC risk in rs1544410 recessive genotypes (summary OR (SOR)=0.74, CI=0.53-0.94), while rs7975232 and rs739837 recessive genotypes were associated with a decreased BCC risk (SOR=0.74, CI=0.56-0.98; SOR=0.65, CI=0.43-0.88).Our meta-analysis indicated that vitamin D receptor polymorphisms may be associated with the risk of keratinocyte cancers.

Betapapillomavirus (betaPV) infections are often associated with squamous-cell carcinoma (SCC) and the prevalence of betaPV infections in (immunosuppressed) SCC patients is known to be high. The distribution and possible associated factors of betaPV infections in the general population, however, are largely unknown. To address this issue, betaPV infection was studied in 1405 SCC-free immunocompetent (n=845) and immunosuppressed (n=560) individuals from six countries of different latitudes. A standard study protocol was used to obtain information about age, sex, UV-irradiation and skin type, and from all participants eyebrow hairs were collected for detection and genotyping of 25 established betaPV types using the PM-PCR reverse hybridization assay (RHA) method. The frequency of betaPV-positive participants ranged from 84 to 91 % in the immunocompetent population with HPV23 as the most prevalent type, and from 81 to 98 % in the immunosuppressed population with HPV23 as the most or the second most prevalent type. The median number of infecting betaPV types ranged from four to six in the immunocompetent and from three to six in the immunosuppressed population. Increasing age in the immunocompetent participants and (duration of) immunosuppression in the immunosuppressed patients were associated with betaPV infection. In both groups, sex, skin phototype, sunburns and sun-exposure were not consistently associated with betaPV infection. This study demonstrates that betaPV infections are also highly prevalent in SCC-free individuals, with similar HPV types prevailing in both immunocompetent and immunosuppressed persons. Age and (duration of) immunosuppression were identified as betaPV infection-associated factors, whereas characteristics related to sun exposure and skin type were not.

There are significant disparities in cancer outcomes between Indigenous and non-Indigenous Australians. Identifying the unmet supportive care needs of Indigenous Australians with cancer is imperative to improve their cancer care. The purpose of the current study was to test the psychometric properties of a supportive cancer care needs assessment tool for Indigenous people (SCNAT-IP) with cancer.The SCNAT-IP was administered to 248 Indigenous Australians diagnosed with a range of cancer types and stages, and who received treatment in 1 of 4 Queensland hospitals. All 39 items were assessed for ceiling and floor effects and were analyzed using exploratory factor analysis to determine construct validity. Identified factors were assessed for internal consistency and convergent validity to validated psychosocial tools.Exploratory factor analysis revealed a 4-factor structure (physical and psychological, hospital care, information and communication, and practical and cultural needs) explaining 51% of the variance. Internal consistency of the 4 subscales was good, with Cronbach alpha reliability coefficients ranging from .70 to .89. Convergent validity was supported by significant correlations between the SCNAT-IP with the National Comprehensive Cancer Network Distress Thermometer (correlation coefficient [r] = 0.60; P.001) and the Cancer Worry Chart (r = 0.58; P.001) and a moderately strong negative correlation with the Assessment of Quality of Life questionnaire (r = -0.56; P.001).These data provide initial support for the SCNAT-IP, a measure of multiple supportive care needs domains specific to Indigenous Australian patients with cancer undergoing treatment.

The incidence of human papillomavirus (HPV)-associated tonsil cancer is increasing but the prevalence of HPV, and of premalignant precursors, in tonsil tissue is unknown. We aimed to assess prevalence of HPV infection in nonmalignant tonsillar crypt epithelia and to histopathologically characterise positive samples. Formalin-fixed paraffin-embedded (FFPE) tonsil tissue specimens were obtained from an age- and sex-stratified random sample of patients aged 0-69 years whose paired tonsils were archived following elective tonsillectomy at hospitals throughout England and Southern Scotland from 2004 to 2008. Homogenised fresh-frozen tonsil tissue was also obtained from archive for two random subsets of males aged 25-34 and over 44. HPV status was assessed in all samples for 20 mucosal HPV types by GP5+/6+ polymerase chain reaction (PCR) enzyme immunoassay and by HPV16 type-specific PCR targeting the E6 gene. In the homogenised material, HPV status was also assessed for 44 HPV types by SPF10-PCR enzyme immunoassay. Of 4,095 randomly sampled FFPE specimens, amplifiable DNA was extracted from 3,377 (82.5%) and from 511 of 524 (97.5%) homogenised tonsils. HPV DNA was identified in 0 of 3,377 (0%, 95% CI 0-0.089%) fixed samples and 0 of 511 (0%, 95% CI 0-0.58%) homogenised samples. This suggests HPV infection may be rare in tonsil reticulated crypt epithelia. Furthermore, we found no evidence of HPV-associated premalignant neoplasia. These data suggest that if HPV-associated premalignant lesions do occur, they are likely to be rare and may have a high risk of progression to carcinoma.

Human papillomavirus (HPV) infection is common worldwide and, in immunodeficient populations, may contribute to the pathogenesis of keratinocyte cancers, particularly squamous cell carcinomas (SCC). However, their role in SCC in the general population is less clear. We conducted a comprehensive analysis to investigate the independent effects of seropositivity for cutaneous alpha, beta and gamma HPV types on risk of SCC, and a meta-analysis of the available literature. In a population-based case-control study from New Hampshire, USA (n = 1,408), histologically confirmed SCC cases and controls were tested for L1 antibodies to alpha, beta and gamma cutaneous HPV types 2-5, 7-10, 15, 17, 20, 23, 24, 27b, 36, 38, 48-50, 57, 65, 75-77, 88, 92, 95, 96, 101, 103 and 107 using multiplex serology. An increasing risk of SCC with number of beta HPVs to which an individual tested positive was observed even among those seronegative for gamma types (p for trend = 0.016) with an odds ratio of 1.95 (95% confidence interval (CI) = 1.07-3.56) for four or more beta types positive. In a meta-analysis of six case-control studies, increased SCC risks in relation to beta HPV seropositivity were found across studies (meta odds ratio = 1.45, CI = 1.27-1.66). While the prevalence of gamma HPVs assayed was somewhat higher among SCC cases than controls, the association was only weakly evident among those seronegative for beta HPVs. Overall, the association between cutaneous HPVs and skin cancers appears to be specific to SCC and to genus beta HPVs in a general US population.

The outcome of patients with palpable melanoma metastases in lymph nodes in the presence (metastatic melanoma of known primary site, MKP) or absence (metastatic melanoma of unknown primary site, MUP) of an identifiable primary tumour remains controversial. Some of the previous studies contained large case series that included historical patients. We aimed to compare outcomes of those with MUPs versus MKPs with palpable lymph node invasion, after staging with modern imaging technology. Aprospective study of patients from a single tertiary institution who were undergoing lymph node dissection for palpable metastatic melanoma between 2000 and 2011 was conducted. All patients were ascertained by computerised tomography scanning and most diagnosed after 2004 had positron emission tomography scanning also. Clinicopathological details about the primary melanoma and lymph node dissections were gathered. Factors associated with recurrence and melanoma-specific mortality in those with MKP and with MUP were assessed using univariate and multivariate analyses. Out of 485 patients studied, 82 had MUP and 403 had MKP. Patients were followed up for a median of 17.4 and 19.0 months, for MKP and MUP, respectively. Five-year adjusted melanoma-specific survival was 58% for MUPs versus 49% for MKPs and was not significantly different between the two groups (adjusted Cox proportional Hazard ratio = 0.88 95% confidence interval [0.58, 1.33] p = 0.54). Previously established prognostic factors such as number of positive nodes and extracapsular extension were confirmed in both sets of patients. We conclude that among melanoma patients presenting with clinically detectable nodes, when accurately staged, those without an identifiable primary lesion have similar outcomes to patients with MKP.

We report cancer incidence and mortality among Indigenous children in Australia and compare the results with corresponding data for non-Indigenous children. This information is important in understanding the overall burden of cancer in this population, and where disparities exist, to plan what action is required. Age-standardized rates, and indirectly standardized incidence and mortality ratios (SIRs and SMRs) were calculated for the years 1997-2008. There were 224 cancers identified among Indigenous children (99.5 per million per year) and 52 Indigenous children died from cancer during the study period (22.9 per million per year). The SIR for all cancers was 0.64 (95% CI = 0.56-0.73; P0.001) while the SMR was 0.81 (95% CI = 0.61-1.07). These results provide a baseline with which to monitor cancer among Indigenous children over time.

Dermoscopic understanding of naevus characteristics is essential baseline knowledge for identifying early malignant changes.This cross-sectional study includes 34 patients (56% female, mean age 48 years) at high risk of melanoma (personal or a first degree family member with history of melanoma) and 31 moderate/low melanoma risk volunteers (55% female, mean age 37 years) recruited at the Princess Alexandra Hospital, Brisbane, between October 2009 and March 2010. Participants received full body and individual dermoscopic imaging of clinically significant naevi (≥2 mm on the back of male/female and lower limbs of female and ≥5 mm at other body sites). Dermoscopic patterns of naevi were compared between people at high versus moderate/low melanoma risk according to age and body site.In both high and moderate/low risk groups, globular naevi predominated on the head/neck and abdomen/chest, reticular and non-specific naevi on the back, and non-specific pattern on the upper and lower limbs. Non-specific naevi were the most common in all age groups. In both risk groups, globular naevi were more frequent in the younger age bracket, and reticular naevi were more frequent in the older age bracket. Mixed naevus patterns were infrequent and were more common in the younger age brackets of both risk groups.Our preliminary data shows that dermoscopic naevus patterns were similar for age and body site in people at different levels of melanoma risk, suggesting high melanoma risk does not influence dermoscopic naevus patterns.

Background: Although most cases of esophageal squamous cell carcinoma (ESCC) in western populations have been attributed to high levels of exposure to tobacco and alcohol, infectious agents have been postulated as possible causes, particularly human papillomavirus (HPV). Methods: To explore this issue, we analyzed HPV DNA prevalence and HPV types together with lifestyle factors, in relation to tumor stage and survival in a low-incidence population. Archived tumor samples from a nationwide cohort of 222 ESCC patients were tested for the presence of HPV DNA by PCR; positive samples were sequenced to determine HPV type, and p16INK4a status was assessed by immunohistochemistry. Results: Of 222 ESCC patients, 8 tested HPV positive (prevalence, 3.6%; 95% confidence interval, 1.1-6.1%), of which 6 were HPV-16 positive and 2 were HPV-35 positive. Four of the eight HPV-positive tumors overexpressed p16INK4a. None of 55 normal esophageal tissue samples from healthy participants had any detectable HPV. Although the numbers were low, it seemed that patients with HPV-positive ESCC tumors were younger than those with HPV-negative tumors (mean age, 60.8 versus 65.3 years, P = 0.18) and had higher body mass index (BMI) throughout life (mean current BMI of 25.1 for HPV positive, 22.2 for HPV negative, P = 0.08; mean BMI at 20 years of 25.8 for HPV positive, 22.1 for HPV negative, P = 0.003). We found no difference between patients with HPV-positive and HPV-negative tumors with respect to other lifestyle factors. Conclusions: These findings suggest a very low prevalence of HPV DNA in human ESCC. Impact: HPV is very unlikely to be a common cause of ESCC in Australia. Cancer Epidemiol Biomarkers Prev; 19(8); 2080–7. ©2010 AACR.

Solar UV radiation is the main risk factor for cutaneous squamous cell carcinoma (SCC), but infections with skin human papillomavirus (HPV) types have also been linked to the development of SCC. Little is known about the natural history of these infections and whether the seroprevalence of skin HPV types is affected by ambient or individual levels of sun exposure. This study investigated this by analysing sera for antibodies to 26 skin HPV types from five phylogenetic genera obtained from 807 healthy individuals from the Netherlands, Italy and Australia, countries with strong differences in sunlight intensity. Overall HPV seroprevalence was similar across the three countries (50–57 % for β-HPV types, 40–48 % for γ-HPV types), and the most frequent β-HPV and γ-HPV types were the same in all countries. The highest seroprevalences for 24 of the 26 skin HPV types were observed in Italy (14 types) and Australia (ten types). Seroprevalence among men was generally higher than among women, and the male sex was significantly associated with both β-HPV [odds ratio (OR) 2.81, 95 % confidence interval (CI) 1.64–4.82] and γ-HPV (OR 2.42, 95 % CI 1.40–4.18) antibodies in Australia. The only measure of sun sensitivity or UV exposure significantly associated with skin HPV seroprevalence was found for weekend sun exposure in Australia and β-HPV antibodies. It was concluded that type spectra and HPV seroprevalence are similar in countries with different sunlight intensity, and that levels of UV exposure do not play a strong role in the development of skin HPV antibodies in this study population.