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Biomedical subjects

David C Whiteman

Publications and source records attributed to David C Whiteman.

At least 19 recordsLinked to original sources

Phenotypic and genotypic risk factors for uveal melanoma in a high ambient UV radiation environment.

BACKGROUND: Most evidence regarding risk factors for uveal melanoma (UM) derives from case-control studies prone to recall bias, and its rarity has limited prospective research. To address these gaps, we applied a population-based case-control design incorporating polygenic risk scores and Mendelian randomization to explore genetic and phenotypic determinants of UM risk. METHODS: The study was conducted in Queensland, Australia. Incident UM cases diagnosed between 2011 and 2022 were recruited through specialist ocular oncology clinics. Controls were participants in the QSkin Sun and Health Study, a prospective cohort of 43,794 adults aged 40-69 at baseline (2010-2011). Demographic, phenotypic, and sun exposure factors were harmonized across studies. Polygenic risk scores were calculated for pigmentation traits and nevi characteristics using genome-wide association study datasets, and Mendelian randomization was used to assess potential causal relationships with UM risk. RESULTS: Among 485 UM cases and 43,724 controls, several phenotypic traits were strongly associated with UM risk: male sex, blue or light eye color, inability to tan, freckling, and high nevus density. A family history of cutaneous melanoma and a personal history of keratinocyte cancer were also associated with higher risk. Polygenic risk score analyses confirmed significant associations for eye color and freckling. Mendelian randomization analyses supported causal relationships between lighter eye color, freckling propensity, reduced tanning ability and UM risk. CONCLUSIONS: These findings provide genetic evidence supporting a causal role for pigmentation-related traits in UM susceptibility. IMPACT: This evidence may help refine risk assessment and inform counselling for individuals with suspicious ocular lesions.

Journal Article↗

GWAS meta-analysis provides new insights into uveal melanoma risk.

OBJECTIVE: The aim of this research is to identify germline genetic variants that predispose to uveal melanoma (UM) using data from nine studies involving 5839 individuals with UM (3853 novel) and 349,863 healthy controls. METHODS: Five novel UM genome-wide association studies (GWAS) were performed and included for meta-analysis with four previously published UM GWAS. A fixed-effects inverse-variance weighted (IVW) meta-analysis was performed by combining data from these nine UM case-control cohorts. A follow-up transcriptome-wide association study (TWAS) was conducted to identify candidate target genes at UM risk loci. Genetic correlations with melanoma-related phenotypes were measured to elucidate UM's genetic architecture. RESULTS: We identify nine linkage disequilibrium (LD)-independent loci (three novel) with an IVW P value of less than 5 × 10-8. TWAS analysis indicates five potential target genes, including MOB3B, RBAK, and MTSS1, which have established links to multiple cancer types. We note a significant genetic correlation (rg = 0.31, P = 0.01) between UM and cutaneous melanoma (CM), and a non-significant but consistent correlation with naevus count (rg = 0.25, P = 0.08). CONCLUSIONS: This meta-analysis offers new insights into the genetic architecture of UM, highlights potential therapeutic targets, and explores the genetic relationship with CM and skin pigmentation.

Humans↗

Unravelling sex differences in the genetic architecture of anxiety.

BACKGROUND: Anxiety disorders show striking sex differences in prevalence, symptoms, and clinical characteristics, shaping how they manifest and are experienced. METHODS: Here, we report the first sex-specific meta-analysis of genome-wide association studies (GWAS) of anxiety, leveraging two of the largest biobank datasets, UK Biobank and All of Us, comprising 85,042 female cases with 196,789 controls and 36,732 male cases with 136,924 controls. Functional annotation, sex-specific polygenic scores (PGS), and genetic correlations were performed to assess genetic differences and functional implications. RESULTS: In females, 21 lead SNPs were significantly associated with anxiety, compared to five in males. Although the genetic correlation between sexes was high, it was significantly different from one, indicating partially distinct genetic architectures. In addition, both the SNP-based observed and liability-scale heritabilities (assuming a 2:1 female-to-male prevalence ratio) were significantly higher in females. Gene-based tests and functional prioritization identified different genes associated with anxiety in females and males. Moreover, genetic correlation analyses revealed stronger associations of female anxiety with attention-deficit/hyperactivity disorder (ADHD) and body mass index (BMI), whereas male anxiety showed stronger correlations with waist-hip-ratio-adjusted BMI. CONCLUSIONS: While the overall genetic architecture of anxiety is largely shared, our findings reveal distinct sex-specific genetic associations and correlations, highlighting the value of analyzing the sexes separately to uncover genetic signals that may be masked in sex-combined samples.

Female↗

Genome-wide association meta-regression identifies stem cell lineage orchestration as a key driver of acne risk.

Over 85% of the population experience acne at some point in their lives, with its severity spanning a quantitative spectrum, from mild, transient outbreaks to more persistent, severe forms of the condition. Moderate to severe disease poses a substantial global burden arising from both the physical and psychological impacts of this highly visible condition. The analytical approach taken in this study aimed to address the impact of variation in the dichotomisation of acne case control status, driven by ascertainment and study design, on effect size estimates across independent genetic association studies of acne. Through a fixed intercept meta-regression framework, we combined evidence genome-wide for association with acne across studies in which case-control status had been ascertained in different settings, allowing for different severity threshold definitions. Across a combined sample of 73,997 cases and 1,103,940 controls of European, South Asian and African American ancestry we identify genetic variation at 165 genomic loci that influence acne risk. There is evidence for both shared and ancestry specific components to the genetic susceptibility to acne and for sex differences in the magnitude of effect of risk alleles at three loci. We observe that common genetic variation explains 13.4% of acne heritability on the liability scale. Consistent with the hypothesis that genetic risk primarily operates at the level of individual pilosebaceous units, a polygenic score derived from this case-control study of acne susceptibility is associated with both self-reported and clinically assessed acne severity in adolescence, further strengthening the link between genetic risk and disease severity. Prioritisation of causal genes at the identified acne risk loci, provides genetic validation of the targets of established and emerging acne therapies, including retinoid treatments. The identified acne risk loci are enriched for genes encoding downstream effectors of RXRA signalling, including SOX9 and components of the WNT and p53 pathways. Illustrating that the control of stem cell lineage plasticity and cellular fate are important mechanisms through which genetic variation influences acne susceptibility within the pilosebaceous unit.

Journal Article↗

Cost-Effectiveness Analysis of 3D Total-Body Photography for People at High Risk of Melanoma.

IMPORTANCE: Greater use of novel digital technologies could be associated with improved health outcomes and save health care costs by detecting smaller melanomas earlier (needing less treatment) or benign tumors (needing no treatment). OBJECTIVE: To compare costs and health effects of 3-dimensional (3D) total-body photography (TBP) and sequential digital dermoscopy imaging (SDDI) vs usual care for early detection of melanoma. DESIGN, SETTING, AND PARTICIPANTS: This prespecified cost-effectiveness analysis using randomized clinical trial (n = 309) data with 2 years of follow-up was conducted at a research hospital in Brisbane, Australia, and took a health system perspective. It included adults 18 years or older at high risk of developing a primary or subsequent melanoma. INTERVENTION: The intervention group received usual care plus clinical skin examinations by junior clinicians at baseline and 6, 12, 18, and 24 months with 3D TBP-SDDI reviewed by a teledermatologist. The control group continued to receive usual care and completed online surveys every 6 months. MAIN OUTCOMES AND MEASURES: Government health care costs, patient out-of-pocket costs, numbers of benign and malignant skin tumor excisions, and quality-adjusted life-years. Skin biopsy, excisions, pathology, and their costs were collected using administrative claims data. Quality of life was collected using the EuroQol-5D-5L. RESULTS: The trial included 314 participants (mean [SD] age, 51.6 [12.8] years; 194 female individuals [62%]) who completed all of the study procedures (158 in the intervention and 156 in the control groups). Compared with controls, intervention group participants had fewer melanoma excisions, more keratinocyte carcinomas and benign excisions, and more biopsy specimens. Over 24 months, mean per-person costs (analyzed in Australian dollars and converted to US$) for the intervention group were $1708 (95% CI, $1455-$1961) vs $763 (95% CI, $655-$870) for controls, an incremental cost of $945 (95% CI, $738-$1157) to provide the intervention. Total quality-adjusted life-years per person were similar for the intervention (1.84; 95% CI, 1.82-1.86) and control groups (1.84; 95% CI, 1.83-1.86). The incremental cost per additional malignant skin tumor excised was $40 (95% CI, $34-$48). CONCLUSIONS AND RELEVANCE: Over 2 years of the trial, the 3D TBP-SDDI model by junior clinicians and teledermatologist review generated higher costs and detected similar numbers of malignant tumors than usual care in a high-risk melanoma cohort. Cost-effectiveness is a necessary but not sufficient consideration for implementation. Other benefits of 3D TBP-SDDI may arise once artificial intelligence clinician support systems are integrated, and more research is needed to understand factors associated with costs and whether there are other benefits of 3D TBP-SDDI.

Adult↗

Obesity and the risk of epithelial ovarian cancer: a systematic review and meta-analysis.

Obesity is a risk factor for several hormone-related cancers but evidence for an effect on risk of epithelial ovarian cancer remains inconclusive. Many studies evaluating this association have had insufficient statistical power to detect modest effects, particularly for histological subtypes of ovarian cancer. We have therefore assembled the published evidence on obesity and ovarian cancer in a systematic literature review and meta-analysis. We identified eligible studies using Medline and manual review of retrieved references, and included all population-based studies that assessed the association between overweight, body mass index (BMI25-29.9) and obesity (BMI30) and histologically confirmed ovarian cancer. Meta-analysis was restricted to those studies that expressed effect as an odds ratio (OR), risk ratio, or standardised incidence ratio and 95% confidence interval (CI). We identified 28 eligible studies, of which 16 on adult obesity and 9 on obesity in early adulthood were suitable for meta-analysis. Overall, 24 of 28 studies reported a positive association between obesity and ovarian cancer, and in 10 this reached statistical significance. The pooled effect estimate for adult obesity was 1.3 (95%CI1.1-1.5) with a smaller increased risk for overweight (OR1.2;95%CI1.0-1.3). The pooled OR was stronger among case-control studies (OR=1.5) than cohort studies (OR=1.1). Overweight/obesity in early adulthood was also associated with an increased risk of ovarian cancer. There was no evidence that the association varied for the different histological subtypes of ovarian cancer. Ovarian cancer should be added to the list of cancers likely to be related to obesity.

Adolescent↗

Basal cell carcinoma on the trunk is associated with excessive sun exposure.

BACKGROUND AND OBJECTIVE: Basal cell carcinoma (BCC) is the most common of all cancers. Ultraviolet radiation is the major etiologic agent in the pathogenesis of BCC, but there is not a straightforward relationship between cumulative exposure and risk. A high proportion of lesions arise on the trunk, which is generally much less exposed to the sun than the head, the major site affected. We tested the hypothesis that the phenotypic determinants and patterns of sun exposure that give rise to BCC on the head and trunk vary in a way that explains the anomalous site distribution. METHODS: The study was set in the context of the Nambour Skin Cancer Study, a community-based follow-up study among 1621 participants with virtually complete ascertainment of BCCs between 1992 and 2004. We compared phenotypic and sun exposure characteristics of participants who developed a first BCC of the head or trunk with those of participants who had no diagnosis of BCC. RESULTS: BCCs of the trunk were more likely to occur in men; they also occurred at a younger age than BCCs of the head. There was a positive association between sun sensitivity and BCC of the head that was absent for BCC of the trunk. A high number of solar keratoses conferred a greater than 3-fold risk for BCCs of both the head and the trunk. BCCs of the trunk had a particularly strong association with the number of reported sunburns and solar lentigines on the trunk, whereas many lentigines conferred a greater than 3-fold risk of truncal BCC compared with a 50% increased risk of BCC of the head. LIMITATIONS: The relatively small numbers of tumors may have limited our ability to detect statistically significant differences. CONCLUSIONS: BCCs of the trunk are the result of overexposure of the sensitive basal cells of the epidermis to ultraviolet radiation. This may result from acute intense exposures sufficient to cause sunburn among people whose ability to tan makes the skin of their face generally less susceptible to the carcinogenic effects of ultraviolet radiation.

Age Distribution↗

Does smoking increase risk of ovarian cancer? A systematic review.

OBJECTIVES: Although early reports suggested that smoking was not associated with ovarian cancer risk, recent studies have reported positive associations for cancers of the mucinous subtype. We sought to clarify the relationship between smoking and ovarian cancer by histological subtype. METHODS: We conducted a systematic literature review and meta-analysis of studies investigating the association between smoking and risk of the different histological subtypes of epithelial ovarian cancer. Eight population-based case-control studies, one pooled analysis of case-control studies, and one cohort study met the inclusion criteria. Summary relative risks (RR), 95% confidence intervals (CI), and tests for heterogeneity were generated from random effects models. RESULTS: Combined, these studies included a total of 910 women with mucinous and 5564 with non-mucinous ovarian cancers. There was a significant doubling of risk of mucinous ovarian cancer in current smokers compared to never smokers (summary RR 2.1, 95% CI 1.7-2.7), but no increased risk of serous (1.0, 95% CI 0.8-1.2) or endometrioid (0.8, 95% CI 0.6-1.1) cancers and a significant risk reduction for clear cell cancers (0.6, 95% CI 0.3-0.9). The risk of mucinous cancer increased with increasing amount smoked but returned to that of never smokers within 20-30 years of stopping smoking. CONCLUSIONS: Meta-analysis suggests that current smoking doubles a woman's risk of developing mucinous ovarian cancer. Stopping smoking returns the risk to normal in the long term. Smoking may thus be one of the few modifiable factors offering potential for primary prevention of mucinous ovarian cancer.

Adenocarcinoma, Clear Cell↗

Novel variants in growth differentiation factor 9 in mothers of dizygotic twins.

CONTEXT: Genes from the ovarian bone morphogenetic signaling pathway (GDF9 and BMP15) are critical for normal human fertility. We previously identified a deletion mutation in GDF9 in sisters with spontaneous dizygotic (DZ) twins, but the prevalence of rare GDF9 variants in twinning families is unknown. OBJECTIVE: The objective was to evaluate the frequency of rare variants in GDF9 in families with a history of DZ twinning. DESIGN AND SUBJECTS: We recruited 3450 individuals from 915 DZ twinning families (1693 mothers of twins) and 1512 controls of Caucasian origin. One mother of DZ twins was selected from 279 of the 915 families, and a DNA sample was screened for rare variants in GDF9 using denaturant HPLC. Variants were confirmed by DNA sequencing and genotyped in the entire sample by matrix-assisted laser desorption ionization time of flight (MALDI-TOF) mass spectrometry. RESULTS: We found two novel insertion/deletions (c.392-393insT, c.1268-1269delAA) and four missense alterations in the GDF9 sequence in mothers of twins. Two of the missense variants (c.307C > T, p.Pro103Ser and c.362C > T, p.Thr121Leu) were located in the pro-region of GDF9 and two (c.1121C > T, p.Pro374Leu and c.1360C > T, p.Arg454Cys) in the mature protein region. For each variant, the frequencies were higher in cases compared with controls. The proportion of mothers of DZ twins carrying any variant (4.12%) was significantly higher (P < 0.0001) than the proportion of carriers in controls (2.29%). CONCLUSION: We describe new variants in the GDF9 gene that are significantly more common in mothers of DZ twins than controls, suggesting that rare GDF9 variants contribute to the likelihood of DZ twinning.

Bone Morphogenetic Protein 15↗

Sun exposure and host phenotype as predictors of cutaneous melanoma associated with neval remnants or dermal elastosis.

Recent research suggests that cutaneous melanomas may arise through 2 distinct pathways, characterized by chronic sun exposure on one hand and nevus-prone phenotype of the host on the other. Two histological characteristics of melanoma consistent with these divergent origins are dermal elastosis in adjacent skin and neval remnants contiguous with the tumor, respectively. To further explore causal heterogeneity in melanoma, we compared sun exposure histories and phenotypic characteristics among a population-based sample of patients newly diagnosed with cutaneous melanoma with and without contiguous neval remnants or dermal elastosis. Tissue blocks were obtained for 141 patients: 53 with superficial spreading melanoma (SSM) of the back, 42 with SSM of head and neck (H & N), and 39 and 7 with lentigo maligna/lentigo maligna melanoma (LM/LMM) of the H & N and back, respectively. Melanomas of the H & N were less likely than those on back to have neval remnants (adjusted OR 0.6, 95% CI 0.3-1.4), but were significantly more likely to have dermal elastosis (adjusted OR 9.3, 95% CI 3.5-25). In site-specific analyses, we found that H & N melanomas with neval remnants were more likely than those without neval remnants to arise in people with more than 60 nevi (adjusted OR 2.1, 95% CI 0.3-14.3), but were less likely to arise in those with more than 20 actinic keratoses. Less marked associations were observed for melanomas of the back. High levels of sun exposure strongly predicted dermal elastosis for H & N melanomas (OR 22.5, 95% CI 2.1-245), but not for melanomas of the back (OR 2.1, 95% CI 0.4-11). We conclude that melanomas with different histologic characteristics have different risk factor profiles, particularly on the head and neck. These data accord with the hypothesis that melanomas arise through different causal pathways.

Age Factors↗

Anatomic site, sun exposure, and risk of cutaneous melanoma.

PURPOSE: Sunlight is the principal environmental risk factor for cutaneous melanoma. A current hypothesis postulates that the role of sunlight in causing melanoma differs according to anatomic site. We tested this hypothesis in a population-based case-case comparative study of melanoma patients. METHODS: Patients were sampled from the Queensland cancer registry in three groups: superficial spreading or nodular melanomas of the trunk (n = 154), of the head and neck (HN; n = 76), and lentigo maligna (LM) and lentigo maligna melanoma (LMM; for both LM and LMM, n = 76). Data were collected on school-age sun exposure and occupational and recreational sun exposure in adulthood. Odds ratios (OR) and 95% CIs were calculated using polytomous logistic regression. RESULTS: HN melanoma patients were substantially more likely than trunk patients to have higher levels of sun exposure in adulthood (OR, 2.43; 95% CI, 0.98 to 5.99) and specifically, higher levels of occupational exposure (OR, 3.25; 95% CI, 1.32 to 8.00), but lower levels of recreational sun exposure (OR, 0.50; 95% CI, 0.21 to 1.19). LM and LMM patients reported higher occupational exposure and lower recreational sun exposure than trunk melanoma patients, although this was not significant. We found no significant differences between the groups for school-age sun exposures. CONCLUSION: Melanomas developing at different body sites are associated with distinct patterns of sun exposure. Melanomas of the head and neck are associated with chronic patterns of sun exposure whereas trunk melanomas are associated with intermittent patterns of sun exposure, supporting the hypothesis that melanomas may arise through divergent causal pathways.

Case-Control Studies↗

Anatomical distribution of solar ultraviolet exposures among cyclists.

Exposure to solar ultraviolet (UV) radiation is the major environmental factor implicated in the development of melanoma and other skin cancers, as well as eye damage and skin photoaging. Outdoor recreational activities such as cycling are increasingly pursued for health benefits, however little information is available regarding potential adverse effects of excessive sun exposure in this setting, nor about the anatomical distribution of solar dose. Polysulphone badges (UV dosimeters) were attached to the head, backs of hands and ankles of 22 cyclists during a seven-day charity bicycle ride in Queensland, Australia. Average daily exposures exceeded one minimal erythemal dose (MED) at all body sites except the ankle. Significant differences in UV dose among the various body sites were noted, with highest exposures recorded on the top of the head. Mean doses received at the ankle (0.94 MED), back of the hand (1.28 MED) and side of the head (1.14 MED) were 51%, 71% and 63% of those received at the top of the head (1.80 MED), respectively. These data indicate that cycling exposes adherents to substantial doses of UV radiation. Moreover, our observations suggest that even vertically-oriented, potentially shaded sites such as the lower leg typically receive doses of solar radiation no less than half of maximally exposed sites.

Analysis of Variance↗

Expression of p53 tumor suppressor protein in sun-exposed skin and associations with sunscreen use and time spent outdoors: a community-based study.

The p53 gene is a tumor suppressor gene that is commonly mutated in skin cancer and sun-exposed skin, and this can be detected through immunohistochemical expression of the p53 protein. The authors hypothesized that time spent outdoors is associated with p53 protein expression in human skin and that sunscreen use counteracts the association. In 1996, they investigated this in a community-based cross-sectional study in Australia. Detailed information about skin type, time spent outdoors, and sunscreen use was collected from 139 residents of a subtropical township who also provided a skin biopsy from the back of the hand for measurement of p53 expression. Increasing time spent outdoors was positively associated with immunoreactivity in the whole epidermis and in the basal layer of the epidermis. After adjustment for confounders, p53 immunoreactivity was twice as high for people who used sunscreen 1 or 2 days per week as for those who used sunscreen daily (whole epidermis: ratio estimate=2.0, 95% confidence interval: 1.1, 3.6; basal layer: ratio estimate=1.7, 95% confidence interval: 0.9, 3.1). The authors conclude that p53 immunoreactivity in the skin is a marker of exposure to ultraviolet light in the past 6 months, but this may be mitigated by regular application of sunscreen.

Adult↗

Hypothesis: hair cover can protect against invasive melanoma on the head and neck (Australia).

The anatomic distribution of cutaneous melanoma reflects people's levels and patterns of sun exposure. While examining trends of incident invasive melanomas by site in recent decades in Australia we noted significant increases in incidence on the ears but not the face or any other site in women younger than 40 years, by 6% (95% confidence interval [CI] 2-10%) per year, and 40-59 years by 7% (95% CI 4-10%) per year. Men of the same age showed no corresponding changes in ear melanoma. However incidence rates of ear melanoma in general were fourfold higher in males than females in Australia. Further, using data from the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) Program, rates of invasive melanoma on the ear were found to be sevenfold higher in males than females in the US population in the same period. Higher rates of scalp and neck melanomas were also seen in men and women in both populations. We therefore speculated that the isolated rises of ear melanoma in younger women in Australia, and the higher overall rates of ear, scalp and neck melanoma in men compared with women, reflect differences in hair coverage. We tested the specific hypothesis that hair cover reduces sun exposure of the ears using experimental manikins and found that hair cover of the ear reduced solar ultraviolet-B exposure by 81% [SE +/-8] compared with uncovered ears. We conclude that hair cover can protect against invasive melanoma on the ear and may similarly protect on the scalp and neck. When discretionary, hair may be an important additional factor to be considered for melanoma prevention.

Adult↗

Isoflavonoid photoprotection in mouse and human skin is dependent on metallothionein.

Previous studies report that selected topical isoflavonoids are immunoprotective in both mice and humans, when applied following UV irradiation. Isoflavonoids have documented antioxidant activity, but their mechanism of immunomodulation remains unclear. This study examines whether photoimmunoprotection by the isoflavonoids might result from their interaction with one cutaneous antioxidant known to modulate UV photodamage, metallothionein (MT). In mice bearing a null mutation for MT-I and -II, we found that immunoprotection by the isoflavonoid 4',7-dihydroxyisoflavane (equol) against solar-simulated UV radiation (SSUV) or exogenous cis-urocanic acid was abrogated. Topical equol did not activate MT expression in normal mouse skin, but markedly enhanced the increase in MT expression in murine epidermis following SSUV irradiation. Normal human skin, unlike murine, expressed MT in the basal epidermis. Following SSUV irradiation, topical application of the related synthetic isoflavonoid NV-07alpha to human skin also markedly enhanced epidermal MT expression. The NV-07alpha has been reported previously to protect humans against the UV suppression of Mantoux reactions. Thus, epidermal MT expression appears to protect against photoimmunosuppression in both human and mouse skin. We speculate that equol and its related derivative NV-07alpha may activate the MT gene synergistically with SSUV, to produce the enhanced immunoprotective effect.

Animals↗

Diagnostic accuracy in skin cancer clinics: the Australian experience.

BACKGROUND: Australia, with the world's highest incidence of skin cancer, has witnessed the emergence of "open access" skin cancer clinics during the past decade. These clinics are becoming increasingly popular destinations for the diagnosis and treatment of skin cancers, yet little is known about the diagnostic performance of practitioners in this setting. We sought to measure the accuracy of clinical diagnosis in this setting. METHODS: Clinical and histological data were obtained from 199 consecutive patients undergoing biopsy or excision for 287 skin lesions. We measured the sensitivity, specificity and predictive value of the clinical diagnoses compared with histological diagnoses. RESULTS: Of 287 biopsied or excised lesions, the most common were benign nevi (24%) and basal cell carcinomas (22%), followed by actinic keratoses (11%), dysplastic nevi (11%) and squamous cell carcinomas (7%). Sensitivity was highest for diagnosing BCC (0.89, 95%CI 0.78-0.95) and dysplastic nevi (0.80, 95%CI 0.61-0.93), and lowest for actinic keratoses and the group of benign lesions. Specificity was greater than 0.93 for all diagnoses except BCC (0.76, 95%CI 0.70-0.81). Treating clinicians perceived moderate to strong pressure to excise 49% of lesions overall, but in particular for benign nevi (73%). CONCLUSIONS: Australian family practitioners in open access skin cancer clinics diagnose a wide range of skin lesions with high specificity and moderate to high sensitivity. Benign nevi are accurately diagnosed and often excised because of patient pressure.

Australia↗