RESUMO
BACKGROUND: Sun exposure causes cutaneous squamous (SCC) and basal cell (BCC) carcinomas. Human papillomavirus (HPV) infection might cause SCC. METHODS: We examined associations of ß and γ HPV infection in skin-swab DNA and serum antibodies with skin cancer risk, and modification of the carcinogenic effects of sun exposure by them, in case-control studies of 385 SCC cases, 832 BCC cases, and 1,100 controls nested in an Australian prospective cohort study (enrolled 2006-2009). RESULTS: Presence of ß-1 and ß-3 HPV DNA appeared to increase risks for SCC and BCC by 30% to 40% (P adjusted <0.01). BCC was also associated with genus ß DNA, OR = 1.48; 95% confidence interval (CI), 1.10 to 2.00 (P adjusted <0.01). Associations were strengthened with each additional positive ß HPV DNA type: SCC (OR = 1.07; 95% CI, 1.02-1.12) and BCC (OR = 1.06; 95% CI, 1.03-1.10), Ptrend<0.01. Positivity to genus ß or γ in serology, and genus γ in DNA, was not associated with either cancer. There was little evidence that any ß HPV type was more strongly associated than others with either cancer. A weaker association of sun exposure with SCC and BCC in the presence of ß-3 HPVs than in their absence suggests that ß-3 HPVs modify sun exposure's effect. CONCLUSIONS: Our substantive findings are at the level of genus ß HPV. Like SCC, BCC risk may increase with increasing numbers of ß HPV types on skin. IMPACT: The consistency in our findings that HPV infection may moderate the effects of sun exposure, the main environmental cause of SCC and BCC, merits further investigation.
Assuntos
Carcinoma Basocelular , Carcinoma de Células Escamosas , Infecções por Papillomavirus , Neoplasias Cutâneas , Austrália/epidemiologia , Carcinoma Basocelular/epidemiologia , Carcinoma Basocelular/etiologia , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/etiologia , Humanos , Papillomaviridae/genética , Estudos Prospectivos , Fatores de Risco , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/etiologia , Luz Solar/efeitos adversosRESUMO
IMPORTANCE: Patient-led surveillance is a promising new model of follow-up care following excision of localized melanoma. OBJECTIVE: To determine whether patient-led surveillance in patients with prior localized primary cutaneous melanoma is as safe, feasible, and acceptable as clinician-led surveillance. DESIGN, SETTING, AND PARTICIPANTS: This was a pilot for a randomized clinical trial at 2 specialist-led clinics in metropolitan Sydney, Australia, and a primary care skin cancer clinic managed by general practitioners in metropolitan Newcastle, Australia. The participants were 100 patients who had been treated for localized melanoma, owned a smartphone, had a partner to assist with skin self-examination (SSE), and had been routinely attending scheduled follow-up visits. The study was conducted from November 1, 2018, to January 17, 2020, with analysis performed from September 1, 2020, to November 15, 2020. INTERVENTION: Participants were randomized (1:1) to 6 months of patient-led surveillance (the intervention comprised usual care plus reminders to perform SSE, patient-performed dermoscopy, teledermatologist assessment, and fast-tracked unscheduled clinic visits) or clinician-led surveillance (the control was usual care). MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion of eligible and contacted patients who were randomized. Secondary outcomes included patient-reported outcomes (eg, SSE knowledge, attitudes, and practices, psychological outcomes, other health care use) and clinical outcomes (eg, clinic visits, skin surgeries, subsequent new primary or recurrent melanoma). RESULTS: Of 326 patients who were eligible and contacted, 100 (31%) patients (mean [SD] age, 58.7 [12.0] years; 53 [53%] men) were randomized to patient-led (n = 49) or clinician-led (n = 51) surveillance. Data were available on patient-reported outcomes for 66 participants and on clinical outcomes for 100 participants. Compared with clinician-led surveillance, patient-led surveillance was associated with increased SSE frequency (odds ratio [OR], 3.5; 95% CI, 0.9 to 14.0) and thoroughness (OR, 2.2; 95% CI, 0.8 to 5.7), had no detectable adverse effect on psychological outcomes (fear of cancer recurrence subscale score; mean difference, -1.3; 95% CI, -3.1 to 0.5), and increased clinic visits (risk ratio [RR], 1.5; 95% CI, 1.1 to 2.1), skin lesion excisions (RR, 1.1; 95% CI, 0.6 to 2.0), and subsequent melanoma diagnoses and subsequent melanoma diagnoses (risk difference, 10%; 95% CI, -2% to 23%). New primary melanomas and 1 local recurrence were diagnosed in 8 (16%) of the participants in the intervention group, including 5 (10%) ahead of routinely scheduled visits; and in 3 (6%) of the participants in the control group, with none (0%) ahead of routinely scheduled visits (risk difference, 10%; 95% CI, 2% to 19%). CONCLUSIONS AND RELEVANCE: This pilot of a randomized clinical trial found that patient-led surveillance after treatment of localized melanoma appears to be safe, feasible, and acceptable. Experiences from this pilot study have prompted improvements to the trial processes for the larger trial of the same intervention. TRIAL REGISTRATION: http://anzctr.org.au Identifier: ACTRN12616001716459.
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Melanoma , Neoplasias Cutâneas , Humanos , Masculino , Melanoma/diagnóstico , Melanoma/cirurgia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Projetos Piloto , Autoexame , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgiaRESUMO
IMPORTANCE: Early melanoma diagnosis is associated with better health outcomes, but there is insufficient evidence that screening, such as having routine skin checks, reduces mortality. OBJECTIVE: To assess melanoma-specific and all-cause mortality associated with melanomas detected through routine skin checks, incidentally or patient detected. A secondary aim was to examine patient, sociodemographic, and clinicopathologic factors associated with different modes of melanoma detection. DESIGN, SETTING, AND PARTICIPANTS: This prospective, population-based, cohort study included patients in New South Wales, Australia, who were diagnosed with melanoma over 1 year from October 23, 2006, to October 22, 2007, in the Melanoma Patterns of Care Study and followed up until 2018 (mean [SD] length of follow-up, 11.9 [0.3] years) by using linked mortality and cancer registry data. All patients who had invasive melanomas recorded at the cancer registry were eligible for the study, but the number of in situ melanomas was capped. The treating doctors recorded details of melanoma detection and patient and clinical characteristics in a baseline questionnaire. Histopathologic variables were obtained from pathology reports. Of 3932 recorded melanomas, data were available and analyzed for 2452 (62%; 1 per patient) with primary in situ (n = 291) or invasive (n = 2161) cutaneous melanoma. Data were analyzed from March 2020 to January 2021. MAIN OUTCOMES AND MEASURES: Melanoma-specific mortality and all-cause mortality. RESULTS: A total of 2452 patients were included in the analyses. The median age at diagnosis was 65 years (range, 16-98 years), and 1502 patients (61%) were men. A total of 858 patients (35%) had their melanoma detected during a routine skin check, 1148 (47%) self-detected their melanoma, 293 (12%) had their melanoma discovered incidentally when checking another skin lesion, and 153 (6%) reported "other" presentation. Routine skin-check detection of invasive melanomas was associated with 59% lower melanoma-specific mortality (subhazard ratio, 0.41; 95% CI, 0.28-0.60; P < .001) and 36% lower all-cause mortality (hazard ratio, 0.64; 95% CI, 0.54-0.76; P < .001), adjusted for age and sex, compared with patient-detected melanomas. After adjusting for prognostic factors including ulceration and mitotic rate, the associations were 0.68 (95% CI, 0.44-1.03; P = .13), and 0.75 (95% CI, 0.63-0.90; P = .006), respectively. Factors associated with higher odds of routine skin-check melanoma detection included being male (female vs male, odds ratio [OR], 0.73; 95% CI, 0.60-0.89; P = .003), having previous melanoma (vs none, OR, 2.36; 95% CI, 1.77-3.15; P < .001), having many moles (vs not, OR, 1.39; 95% CI, 1.10-1.77; P = .02), being 50 years or older (eg, 50-59 years vs <40 years, OR, 2.89; 95% CI, 1.92-4.34; P < .001), and living in nonremote areas (eg, remote or very remote vs major cities, OR, 0.23; 95% CI, 0.05-1.04; P = .003). CONCLUSIONS AND RELEVANCE: In this cohort study, melanomas diagnosed through routine skin checks were associated with significantly lower all-cause mortality, but not melanoma-specific mortality, after adjustment for patient, sociodemographic, and clinicopathologic factors.
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Melanoma , Neoplasias Cutâneas , Estudos de Coortes , Feminino , Humanos , Masculino , Melanoma/diagnóstico , Melanoma/patologia , Estudos Prospectivos , Pele/patologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologiaRESUMO
BACKGROUND: Most subsequent new primary or recurrent melanomas might be self-detected if patients are trained to systematically self-examine their skin and have access to timely medical review (patient-led surveillance). Routinely scheduled clinic visits (clinician-led surveillance) is resource-intensive and has not been shown to improve health outcomes; fewer visits may be possible if patient-led surveillance is shown to be safe and effective. The MEL-SELF trial is a randomised controlled trial comparing patient-led surveillance with clinician-led surveillance in people who have been previously treated for localised melanoma. METHODS: Stage 0/I/II melanoma patients (n = 600) from dermatology, surgical, or general practice clinics in NSW Australia, will be randomised (1:1) to the intervention (patient-led surveillance, n = 300) or control (usual care, n = 300). Patients in the intervention will undergo a second randomisation 1:1 to polarised (n = 150) or non-polarised (n = 150) dermatoscope. Patient-led surveillance comprises an educational booklet, skin self-examination (SSE) instructional videos; 3-monthly email/SMS reminders to perform SSE; patient-performed dermoscopy with teledermatologist feedback; clinical review of positive teledermoscopy through fast-tracked unscheduled clinic visits; and routinely scheduled clinic visits following each clinician's usual practice. Clinician-led surveillance comprises an educational booklet and routinely scheduled clinic visits following each clinician's usual practice. The primary outcome, measured at 12 months, is the proportion of participants diagnosed with a subsequent new primary or recurrent melanoma at an unscheduled clinic visit. Secondary outcomes include time from randomisation to diagnosis (of a subsequent new primary or recurrent melanoma and of a new keratinocyte cancer), clinicopathological characteristics of subsequent new primary or recurrent melanomas (including AJCC stage), psychological outcomes, and healthcare use. A nested qualitative study will include interviews with patients and clinicians, and a costing study we will compare costs from a societal perspective. We will compare the technical performance of two different models of dermatoscope (polarised vs non-polarised). DISCUSSION: The findings from this study may inform guidance on evidence-based follow-up care, that maximises early detection of subsequent new primary or recurrent melanoma and patient wellbeing, while minimising costs to patients, health systems, and society. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12621000176864 . Registered on 18 February 2021.
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Melanoma , Neoplasias Cutâneas , Austrália , Seguimentos , Humanos , Melanoma/diagnóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Autoexame , Neoplasias Cutâneas/diagnósticoRESUMO
BACKGROUND: Human papillomavirus (HPV) infection is highly prevalent worldwide and may have a role, with sun exposure, in causing cutaneous squamous cell carcinoma. Little is known about the relationship of UV exposure and seroprevalence of cutaneous HPVs in the general population. METHODS: Using multiplex serology, we estimated the seroprevalence of 23 beta and 7 gamma HPVs and 7 other antigens (mu HPV1, HPV63, nu HPV41, alpha HPV16; polyomaviruses HPyV7 and MCV; p53) in a population-based sample of 1,161 Australian 45 and Up Study participants with valid data from blood specimens collected from 2010 to 2012. We calculated prevalence ratios (PR) for the association of each antigen with residential ambient solar UV and other UV-related variables. RESULTS: Seropositivity for at least one beta or gamma HPV was high at 88% (beta HPVs 74%, gamma HPVs 70%), and less in women than men [e.g., PR beta-2 HPV38 = 0.70; 95% confidence interval (CI), 0.56-0.87; any gamma = 0.90; 95% CI, 0.84-0.97]. A high ambient UV level in the 10 years before study enrollment was associated with elevated seroprevalence for genus beta (PRtertile3vs1 any beta = 1.17; 95% CI, 1.07-1.28), and beta-1 to beta-3 species, but not for gamma HPVs. Other UV-related measures had less or no evidence of an association. CONCLUSIONS: Seroprevalence of cutaneous beta HPVs is higher with higher ambient UV exposure in the past 10 years. IMPACT: The observed association between ambient UV in the past 10 years and cutaneous HPVs supports further study of the possible joint role of solar UV and HPV in causing skin cancer.
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Betapapillomavirus/isolamento & purificação , Carcinoma Basocelular/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Neoplasias Cutâneas/epidemiologia , Luz Solar/efeitos adversos , Verrugas/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Antígenos Virais/sangue , Antígenos Virais/imunologia , Betapapillomavirus/patogenicidade , Carcinoma Basocelular/etiologia , Carcinoma Basocelular/patologia , Carcinoma de Células Escamosas/etiologia , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , New South Wales/epidemiologia , Prevalência , Fatores de Risco , Estudos Soroepidemiológicos , Fatores Sexuais , Pele/patologia , Pele/efeitos da radiação , Pele/virologia , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/patologia , Verrugas/sangue , Verrugas/virologiaRESUMO
Sun exposure is the main cause of squamous (SCC) and basal cell carcinoma (BCC) although pattern and amount differ by cancer type, and sun sensitivity is the major host risk factor. Our study investigated risk factors and residential ambient UV in a population-based sample of Australian 45 and Up Study participants: 916 BCC cases, 433 SCC cases, 1224 controls. Unconditional logistic regression models adjusting for key covariates demonstrated 60% increased BCC risk and two-fold increased SCC risk with sun sensitivity, and three- and four-fold increased risk, respectively, with solar keratoses. BCC but not SCC risk increased with higher early-life residential UV in all participants (odds ratio (OR) = 1.54; 95% CI 1.22-1.96 for intermediate; OR = 1.31; 95% CI 1.03-1.68 for high UV at birthplace) and similarly in Australian-born participants (P-values < 0.05). Risk of SCC but not BCC increased with long-term cumulative sun exposure assessed by self-reported outdoor work (OR 1.74, 95% CI 1.21-2.49). In conclusion, sun sensitivity is important for both cancers, early-life UV but not cumulative UV appears to increase BCC risk, the former an apparently novel finding, and SCC risk appears only to be related to long-term cumulative sun exposure.
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Carcinoma Basocelular/etiologia , Carcinoma de Células Escamosas/etiologia , Neoplasias Cutâneas/etiologia , Raios Ultravioleta , Adolescente , Fatores Etários , Austrália , Criança , Feminino , Humanos , Masculino , Melanoma/patologia , New South Wales , Padrões de Referência , Fatores de Risco , Sistema Solar , Luz Solar/efeitos adversos , Inquéritos e Questionários , Raios Ultravioleta/efeitos adversosRESUMO
OBJECTIVE: To determine whether there is an excess risk of breast cancer among female employees of the Australian Broadcasting Corporation (ABC), especially outside Queensland, compared with women in the general populations of the states and territories. DESIGN, SETTING AND PARTICIPANTS: We used an occupational cohort design. Information from ABC staff records was linked with data from state and territory cancer registries to identify female employees of the ABC with an incident, histologically confirmed breast cancer. Data linkage was complemented by a self-report method. We included a cohort of ABC female employees who had developed breast cancer at any time between 1994 and 2005, during their employment or after cessation of employment with the ABC. The standardised incidence ratio (SIR) was calculated as the number of women at the ABC observed with breast cancer divided by the expected number based on population rates in each state and territory. Tests for heterogeneity were performed to examine the variation of breast cancer risk between states and territories. RESULTS: Out of 5969 women who were permanently employed either part-time or full-time at the ABC between 1994 and 2005, 48 eligible women with breast cancer were identified. An excess risk of breast cancer among ABC female employees in Queensland (identified in an earlier study) was reconfirmed. No excess risk of breast cancer was observed among ABC staff diagnosed in states outside Queensland (SIR, 1.01 [95% CI, 0.72-1.38]), or in Australia as a whole (including Queensland) (SIR, 1.12 [95% CI, 0.83-1.49]). There was no significant heterogeneity in breast cancer risk among states and territories once Queensland was excluded from the analysis (P = 0.39). CONCLUSION: No statistically significant excess risk of breast cancer in ABC female employees was found across the Australian states and territories as a whole compared with their respective population incidences. A statistically significant increased risk of breast cancer was found among ABC female employees in Queensland, consistent with the findings in an earlier report.
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Neoplasias da Mama/epidemiologia , Ocupações , Adolescente , Adulto , Austrália/epidemiologia , Neoplasias da Mama/etiologia , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Queensland/epidemiologia , Fatores de Risco , Televisão , Adulto JovemRESUMO
PURPOSE: This study investigated cardiovascular and hemodynamic responses during the transition from rest to electrical stimulation-induced leg cycling exercise (ES-LCE) in individuals with chronic paraplegia (PARA). METHODS: Ten PARA (T(4)-T(9); ASIA A) participated in this study. Heart rate (HR), mean arterial pressure (MAP), stroke volume (SV), and cardiac output (Q) were measured on a beat-to-beat basis at rest and during the first 60 s of ES-LCE. RESULTS: PARA exhibited two discrete MAP responses during ES-LCE. Those with high thoracic lesions (HIGH: T(4) -T(6), = 5) responded to ES-LCE with a significant rise in MAP (maxdelta 8.3 +/- 3.6 mm Hg), whereas MAP did not exhibit any sustained change from resting values during ES-LCE in those subjects with lower lesions (LOW: T -T, = 5). In HIGH PARA, the immediate increase in MAP corresponded to a decrease in HR (maxdelta 6.8 +/- 3.1 b x min(-1)), which returned toward resting levels by the end of 60 s. In contrast, for LOW PARA there was no change in HR from resting levels during transition to ES-LCE. In both subgroups, SV and Q were not significantly increased during ES-LCE. CONCLUSION: These results suggest that the on-transient responses of MAP during ES-LCE in HIGH PARA elicited reflex changes in HR via the arterial baroreflex, whereas in LOW PARA, an unchanged HR from rest was likely due to a constant MAP during ES-LCE.