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Background: Eczema (atopic dermatitis) is the most burdensome skin condition worldwide and cannot currently be prevented or cured. Topical anti-inflammatory treatments are used to control eczema symptoms, but there is uncertainty about the relative effectiveness and safety of different topical anti-inflammatory treatments., Objectives: To compare and rank the efficacy and safety of topical anti-inflammatory treatments for people with eczema using a network meta-analysis., Search Methods: We searched the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase and trial registries on 29 June 2023, and checked the reference lists of included studies., Selection Criteria: We included within-participant or between-participant randomised controlled trials (RCTs) in people of any age with eczema of any severity, but excluded trials in clinically infected eczema, seborrhoeic eczema, contact eczema, or hand eczema. We included topical anti-inflammatory treatments used for at least one week, compared with another anti-inflammatory treatment, no treatment, or vehicle/placebo. Vehicle is a 'carrier system' for an active pharmaceutical substance, which may also be used on its own as an emollient for dry skin. We excluded trials of topical antibiotics used alone, complementary therapies, emollients used alone, phototherapy, wet wraps, and systemic treatments., Data Collection and Analysis: We used standard Cochrane methods. Primary outcomes were patient-reported eczema symptoms, clinician-reported eczema signs and investigator global assessment. Secondary outcomes were health-related quality of life, long-term control of eczema, withdrawal from treatment/study, and local adverse effects (application-site reactions, pigmentation changes and skin thinning/atrophy were identified as important concerns through patient and public involvement). We used CINeMA to quantify our confidence in the evidence for each outcome., Main Results: We included 291 studies involving 45,846 participants with the full spectrum of eczema severity, mainly conducted in high-income countries in secondary care settings. Most studies included adults, with only 31 studies limited to children aged < 12 years. Studies usually included male and female participants, multiple ethnic groups but predominantly white populations. Most studies were industry-funded (68%) or did not report their funding sources/details. Treatment duration and trial participation were a median of 21 and 28 days (ranging from 7 days to 5 years), respectively. Interventions used were topical corticosteroids (TCS) (172), topical calcineurin inhibitors (TCI) (134), phosphodiesterase-4 (PDE-4) inhibitors (55), janus kinase (JAK) inhibitors (30), aryl hydrocarbon receptor activators (10), or other topical agents (21). Comparators included vehicle (170) or other anti-inflammatory treatments. The risk of bias was high in 242 of the 272 (89.0%) trials contributing to data analyses, most commonly due to concerns about selective reporting. Network meta-analysis (NMA) was only possible for short-term outcomes. Patient-reported symptoms NMA of 40 trials (6482 participants) reporting patient-reported symptoms as a binary outcome ranked tacrolimus 0.1% (OR 6.27, 95% CI 1.19 to 32.98), potent TCS (OR 5.99, 95% CI 2.83 to 12.69), and ruxolitinib 1.5% (OR 5.64, 95% CI 1.26 to 25.25) as the most effective, all with low confidence. Mild TCS, roflumilast 0.15%, and crisaborole 2% were the least effective. Class-level sensitivity analysis found potent/very potent TCS had similar effectiveness to potent TCI and was more effective than mild TCI and PDE-4 inhibitors. NMA of 29 trials (3839 participants) reporting patient-reported symptoms as a continuous outcome ranked very potent TCS (SMD -1.99, 95% CI -3.25 to -0.73; low confidence) and tacrolimus 0.03% (SMD -1.57, 95% CI -2.42 to -0.72; moderate confidence) the highest. Direct information for tacrolimus 0.03% was based on one trial of 60 participants at high risk of bias. Roflumilast 0.15%, delgocitinib 0.25% or 0.5%, and tapinarof 1% were the least effective. Class-level sensitivity analysis found potent/very potent TCS had similar effectiveness to potent TCI and JAK inhibitors and mild/moderate TCS was less effective than mild TCI. A further 50 trials (9636 participants) reported patient-reported symptoms as a continuous outcome but could not be included in NMA. Clinician-reported signs NMA of 32 trials (4121 participants) reported clinician signs as a binary outcome and ranked potent TCS (OR 8.15, 95% CI 4.99, 13.57), tacrolimus 0.1% (OR 8.06, 95% CI 3.30, 19.67), ruxolitinib 1.5% (OR 7.72, 95% CI 4.92, 12.10), and delgocitinib 0.5% (OR 7.61, 95% CI 3.72, 15.58) as most effective, all with moderate confidence. Mild TCS, roflumilast 0.15%, crisaborole 2%, and tapinarof 1% were the least effective. Class-level sensitivity analysis found potent/very potent TCS more effective than potent TCI, mild TCI, JAK inhibitors, PDE-4 inhibitors; and mild TCS and PDE-4 inhibitors had similar effectiveness. NMA of 49 trials (5261 participants) reported clinician signs as a continuous outcome and ranked tacrolimus 0.03% (SMD -2.69, 95% CI -3.36, -2.02) and very potent TCS (SMD -1.87, 95% CI -2.69, -1.05) as most effective, both with moderate confidence; roflumilast 0.15%, difamilast 0.3% and tapinarof 1% were ranked as least effective. Direct information for tacrolimus 0.03% was based on one trial in 60 participants with a high risk of bias. For some sensitivity analyses, potent TCS, tacrolimus 0.1%, ruxolitinib 1.5%, delgocitinib 0.5% and delgocitinib 0.25% became some of the most effective treatments. Class-level analysis found potent/very potent TCS had similar effectiveness to potent TCI and JAK inhibitors, and moderate/mild TCS was more effective than mild TCI. A further 100 trials (22,814 participants) reported clinician signs as a continuous outcome but could not be included in NMA. Investigator Global Assessment NMA of 140 trials (23,383 participants) reported IGA as a binary outcome and ranked ruxolitinib 1.5% (OR 9.34, 95% CI 4.8, 18.18), delgocitinib 0.5% (OR 10.08, 95% CI 2.65, 38.37), delgocitinib 0.25% (OR 6.87, 95% CI 1.79, 26.33), very potent TCS (OR 8.34, 95% CI 4.73, 14.67), potent TCS (OR 5.00, 95% CI 3.80, 6.58), and tacrolimus 0.1% (OR 5.06, 95% CI 3.59, 7.13) as most effective, all with moderate confidence. Mild TCS, crisaborole 2%, pimecrolimus 1%, roflumilast 0.15%, difamilast 0.3% and 1%, and tacrolimus 0.03% were the least effective. In a sensitivity analysis of low risk of bias information (12 trials, 1639 participants), potent TCS, delgocitinib 0.5% and delgocitinib 0.25% were most effective, and pimecrolimus 1%, roflumilast 0.15%, difamilast 1% and difamilast 0.3% least effective. Class-level sensitivity analysis found potent/very potent TCS had similar effectiveness to potent TCI and JAK inhibitors and were more effective than PDE-4 inhibitors; mild/moderate TCS were less effective than potent TCI and had similar effectiveness to mild TCI. Longer-term outcomes over 6 to 12 months showed a possible increase in effectiveness for pimecrolimus 1% versus vehicle (4 trials, 2218 participants) in a pairwise meta-analysis, and greater treatment success with mild/moderate TCS than pimecrolimus 1% (based on 1 trial of 2045 participants). Local adverse effects NMA of 83 trials (18,992 participants, 2424 events) reporting application-site reactions ranked tacrolimus 0.1% (OR 2.2, 95% CI 1.53, 3.17; moderate confidence), crisaborole 2% (OR 2.12, 95% CI 1.18, 3.81; high confidence), tacrolimus 0.03% (OR 1.51, 95%CI 1.10, 2.09; low confidence), and pimecrolimus 1% (OR 1.44, 95% CI 1.01, 2.04; low confidence) as most likely to cause site reactions. Very potent, potent, moderate, and mild TCS were least likely to cause site reactions. NMA of eight trials (1786 participants, 3 events) reporting pigmentation changes found no evidence for increased pigmentation changes with TCS and crisaborole 2%, with low confidence for mild, moderate or potent TCS and moderate confidence for crisaborole 2%. NMA of 25 trials (3691 participants, 36 events) reporting skin thinning found no evidence for increased skin thinning with short-term (median 3 weeks, range 1-16 weeks) use of mild TCS (OR 0.72, 95% CI 0.12, 4.31), moderate TCS (OR 0.91, 95% CI 0.16, 5.33), potent TCS (OR 0.96, 95% CI 0.21, 4.43) or very potent TCS (OR 0.88, 95% CI 0.31, 2.49), all with low confidence. Longer-term outcomes over 6 to 60 months showed increased skin thinning with mild to potent TCS versus TCI (3 trials, 4069 participants, 6 events with TCS)., Authors' Conclusions: Potent TCS, JAK inhibitors and tacrolimus 0.1% were consistently ranked as amongst the most effective topical anti-inflammatory treatments for eczema and PDE-4 inhibitors as amongst the least effective. Mild TCS and tapinarof 1% were ranked amongst the least effective treatments in three of five efficacy networks. TCI and crisaborole 2% were ranked most likely to cause local application-site reactions and TCS least likely. We found no evidence for increased skin thinning with short-term TCS but an increase with longer-term TCS., (Copyright © 2024 The Authors. Cochrane Database of Systematic Reviews published by John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration.)

Background: Melanoma is one of the most aggressive forms of skin cancer, with the potential to metastasise to other parts of the body via the lymphatic system and the bloodstream. Melanoma accounts for a small percentage of skin cancer cases but is responsible for the majority of skin cancer deaths. Various imaging tests can be used with the aim of detecting metastatic spread of disease following a primary diagnosis of melanoma (primary staging) or on clinical suspicion of disease recurrence (re-staging). Accurate staging is crucial to ensuring that patients are directed to the most appropriate and effective treatment at different points on the clinical pathway. Establishing the comparative accuracy of ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET)-CT imaging for detection of nodal or distant metastases, or both, is critical to understanding if, how, and where on the pathway these tests might be used., Objectives: Primary objectivesWe estimated accuracy separately according to the point in the clinical pathway at which imaging tests were used. Our objectives were:• to determine the diagnostic accuracy of ultrasound or PET-CT for detection of nodal metastases before sentinel lymph node biopsy in adults with confirmed cutaneous invasive melanoma; and• to determine the diagnostic accuracy of ultrasound, CT, MRI, or PET-CT for whole body imaging in adults with cutaneous invasive melanoma:○ for detection of any metastasis in adults with a primary diagnosis of melanoma (i.e. primary staging at presentation); and○ for detection of any metastasis in adults undergoing staging of recurrence of melanoma (i.e. re-staging prompted by findings on routine follow-up).We undertook separate analyses according to whether accuracy data were reported per patient or per lesion.Secondary objectivesWe sought to determine the diagnostic accuracy of ultrasound, CT, MRI, or PET-CT for whole body imaging (detection of any metastasis) in mixed or not clearly described populations of adults with cutaneous invasive melanoma.For study participants undergoing primary staging or re-staging (for possible recurrence), and for mixed or unclear populations, our objectives were:• to determine the diagnostic accuracy of ultrasound, CT, MRI, or PET-CT for detection of nodal metastases;• to determine the diagnostic accuracy of ultrasound, CT, MRI, or PET-CT for detection of distant metastases; and• to determine the diagnostic accuracy of ultrasound, CT, MRI, or PET-CT for detection of distant metastases according to metastatic site., Search Methods: We undertook a comprehensive search of the following databases from inception up to August 2016: Cochrane Central Register of Controlled Trials; MEDLINE; Embase; CINAHL; CPCI; Zetoc; Science Citation Index; US National Institutes of Health Ongoing Trials Register; NIHR Clinical Research Network Portfolio Database; and the World Health Organization International Clinical Trials Registry Platform. We studied reference lists as well as published systematic review articles., Selection Criteria: We included studies of any design that evaluated ultrasound (with or without the use of fine needle aspiration cytology (FNAC)), CT, MRI, or PET-CT for staging of cutaneous melanoma in adults, compared with a reference standard of histological confirmation or imaging with clinical follow-up of at least three months' duration. We excluded studies reporting multiple applications of the same test in more than 10% of study participants., Data Collection and Analysis: Two review authors independently extracted all data using a standardised data extraction and quality assessment form (based on the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2)). We estimated accuracy using the bivariate hierarchical method to produce summary sensitivities and specificities with 95% confidence and prediction regions. We undertook analysis of studies allowing direct and indirect comparison between tests. We examined heterogeneity between studies by visually inspecting the forest plots of sensitivity and specificity and summary receiver operating characteristic (ROC) plots. Numbers of identified studies were insufficient to allow formal investigation of potential sources of heterogeneity., Main Results: We included a total of 39 publications reporting on 5204 study participants; 34 studies reporting data per patient included 4980 study participants with 1265 cases of metastatic disease, and seven studies reporting data per lesion included 417 study participants with 1846 potentially metastatic lesions, 1061 of which were confirmed metastases. The risk of bias was low or unclear for all domains apart from participant flow. Concerns regarding applicability of the evidence were high or unclear for almost all domains. Participant selection from mixed or not clearly defined populations and poorly described application and interpretation of index tests were particularly problematic.The accuracy of imaging for detection of regional nodal metastases before sentinel lymph node biopsy (SLNB) was evaluated in 18 studies. In 11 studies (2614 participants; 542 cases), the summary sensitivity of ultrasound alone was 35.4% (95% confidence interval (CI) 17.0% to 59.4%) and specificity was 93.9% (95% CI 86.1% to 97.5%). Combining pre-SLNB ultrasound with FNAC revealed summary sensitivity of 18.0% (95% CI 3.58% to 56.5%) and specificity of 99.8% (95% CI 99.1% to 99.9%) (1164 participants; 259 cases). Four studies demonstrated lower sensitivity (10.2%, 95% CI 4.31% to 22.3%) and specificity (96.5%,95% CI 87.1% to 99.1%) for PET-CT before SLNB (170 participants, 49 cases). When these data are translated to a hypothetical cohort of 1000 people eligible for SLNB, 237 of whom have nodal metastases (median prevalence), the combination of ultrasound with FNAC potentially allows 43 people with nodal metastases to be triaged directly to adjuvant therapy rather than having SLNB first, at a cost of two people with false positive results (who are incorrectly managed). Those with a false negative ultrasound will be identified on subsequent SLNB.Limited test accuracy data were available for whole body imaging via PET-CT for primary staging or re-staging for disease recurrence, and none evaluated MRI. Twenty-four studies evaluated whole body imaging. Six of these studies explored primary staging following a confirmed diagnosis of melanoma (492 participants), three evaluated re-staging of disease following some clinical indication of recurrence (589 participants), and 15 included mixed or not clearly described population groups comprising participants at a number of different points on the clinical pathway and at varying stages of disease (1265 participants). Results for whole body imaging could not be translated to a hypothetical cohort of people due to paucity of data.Most of the studies (6/9) of primary disease or re-staging of disease considered PET-CT, two in comparison to CT alone, and three studies examined the use of ultrasound. No eligible evaluations of MRI in these groups were identified. All studies used histological reference standards combined with follow-up, and two included FNAC for some participants. Observed accuracy for detection of any metastases for PET-CT was higher for re-staging of disease (summary sensitivity from two studies: 92.6%, 95% CI 85.3% to 96.4%; specificity: 89.7%, 95% CI 78.8% to 95.3%; 153 participants; 95 cases) compared to primary staging (sensitivities from individual studies ranged from 30% to 47% and specificities from 73% to 88%), and was more sensitive than CT alone in both population groups, but participant numbers were very small.No conclusions can be drawn regarding routine imaging of the brain via MRI or CT., Authors' Conclusions: Review authors found a disappointing lack of evidence on the accuracy of imaging in people with a diagnosis of melanoma at different points on the clinical pathway. Studies were small and often reported data according to the number of lesions rather than the number of study participants. Imaging with ultrasound combined with FNAC before SLNB may identify around one-fifth of those with nodal disease, but confidence intervals are wide and further work is needed to establish cost-effectiveness. Much of the evidence for whole body imaging for primary staging or re-staging of disease is focused on PET-CT, and comparative data with CT or MRI are lacking. Future studies should go beyond diagnostic accuracy and consider the effects of different imaging tests on disease management. The increasing availability of adjuvant therapies for people with melanoma at high risk of disease spread at presentation will have a considerable impact on imaging services, yet evidence for the relative diagnostic accuracy of available tests is limited.

Background: Melanoma accounts for a small proportion of all skin cancer cases but is responsible for most skin cancer-related deaths. Early detection and treatment can improve survival. Smartphone applications are readily accessible and potentially offer an instant risk assessment of the likelihood of malignancy so that the right people seek further medical attention from a clinician for more detailed assessment of the lesion. There is, however, a risk that melanomas will be missed and treatment delayed if the application reassures the user that their lesion is low risk., Objectives: To assess the diagnostic accuracy of smartphone applications to rule out cutaneous invasive melanoma and atypical intraepidermal melanocytic variants in adults with concerns about suspicious skin lesions., Search Methods: We undertook a comprehensive search of the following databases from inception to August 2016: Cochrane Central Register of Controlled Trials; MEDLINE; Embase; CINAHL; CPCI; Zetoc; Science Citation Index; US National Institutes of Health Ongoing Trials Register; NIHR Clinical Research Network Portfolio Database; and the World Health Organization International Clinical Trials Registry Platform. We studied reference lists and published systematic review articles., Selection Criteria: Studies of any design evaluating smartphone applications intended for use by individuals in a community setting who have lesions that might be suspicious for melanoma or atypical intraepidermal melanocytic variants versus a reference standard of histological confirmation or clinical follow-up and expert opinion., Data Collection and Analysis: Two review authors independently extracted all data using a standardised data extraction and quality assessment form (based on QUADAS-2). Due to scarcity of data and poor quality of studies, we did not perform a meta-analysis for this review. For illustrative purposes, we plotted estimates of sensitivity and specificity on coupled forest plots for each application under consideration., Main Results: This review reports on two cohorts of lesions published in two studies. Both studies were at high risk of bias from selective participant recruitment and high rates of non-evaluable images. Concerns about applicability of findings were high due to inclusion only of lesions already selected for excision in a dermatology clinic setting, and image acquisition by clinicians rather than by smartphone app users.We report data for five mobile phone applications and 332 suspicious skin lesions with 86 melanomas across the two studies. Across the four artificial intelligence-based applications that classified lesion images (photographs) as melanomas (one application) or as high risk or 'problematic' lesions (three applications) using a pre-programmed algorithm, sensitivities ranged from 7% (95% CI 2% to 16%) to 73% (95% CI 52% to 88%) and specificities from 37% (95% CI 29% to 46%) to 94% (95% CI 87% to 97%). The single application using store-and-forward review of lesion images by a dermatologist had a sensitivity of 98% (95% CI 90% to 100%) and specificity of 30% (95% CI 22% to 40%).The number of test failures (lesion images analysed by the applications but classed as 'unevaluable' and excluded by the study authors) ranged from 3 to 31 (or 2% to 18% of lesions analysed). The store-and-forward application had one of the highest rates of test failure (15%). At least one melanoma was classed as unevaluable in three of the four application evaluations., Authors' Conclusions: Smartphone applications using artificial intelligence-based analysis have not yet demonstrated sufficient promise in terms of accuracy, and they are associated with a high likelihood of missing melanomas. Applications based on store-and-forward images could have a potential role in the timely presentation of people with potentially malignant lesions by facilitating active self-management health practices and early engagement of those with suspicious skin lesions; however, they may incur a significant increase in resource and workload. Given the paucity of evidence and low methodological quality of existing studies, it is not possible to draw any implications for practice. Nevertheless, this is a rapidly advancing field, and new and better applications with robust reporting of studies could change these conclusions substantially.

Background: Early accurate detection of all skin cancer types is essential to guide appropriate management and to improve morbidity and survival. Melanoma and squamous cell carcinoma (SCC) are high-risk skin cancers which have the potential to metastasise and ultimately lead to death, whereas basal cell carcinoma (BCC) is usually localised with potential to infiltrate and damage surrounding tissue. Anxiety around missing early curable cases needs to be balanced against inappropriate referral and unnecessary excision of benign lesions. Teledermatology provides a way for generalist clinicians to access the opinion of a specialist dermatologist for skin lesions that they consider to be suspicious without referring the patients through the normal referral pathway. Teledermatology consultations can be 'store-and-forward' with electronic digital images of a lesion sent to a dermatologist for review at a later time, or can be live and interactive consultations using videoconferencing to connect the patient, referrer and dermatologist in real time., Objectives: To determine the diagnostic accuracy of teledermatology for the detection of any skin cancer (melanoma, BCC or cutaneous squamous cell carcinoma (cSCC)) in adults, and to compare its accuracy with that of in-person diagnosis., Search Methods: We undertook a comprehensive search of the following databases from inception up to August 2016: Cochrane Central Register of Controlled Trials, MEDLINE, Embase, CINAHL, CPCI, Zetoc, Science Citation Index, US National Institutes of Health Ongoing Trials Register, NIHR Clinical Research Network Portfolio Database and the World Health Organization International Clinical Trials Registry Platform. We studied reference lists and published systematic review articles., Selection Criteria: Studies evaluating skin cancer diagnosis for teledermatology alone, or in comparison with face-to-face diagnosis by a specialist clinician, compared with a reference standard of histological confirmation or clinical follow-up and expert opinion. We also included studies evaluating the referral accuracy of teledermatology compared with a reference standard of face-to-face diagnosis by a specialist clinician., Data Collection and Analysis: Two review authors independently extracted all data using a standardised data extraction and quality assessment form (based on QUADAS-2). We contacted authors of included studies where there were information related to the target condition of any skin cancer missing. Data permitting, we estimated summary sensitivities and specificities using the bivariate hierarchical model. Due to the scarcity of data, we undertook no covariate investigations for this review. For illustrative purposes, we plotted estimates of sensitivity and specificity on coupled forest plots for diagnostic threshold and target condition under consideration., Main Results: The review included 22 studies reporting diagnostic accuracy data for 4057 lesions and 879 malignant cases (16 studies) and referral accuracy data for reported data for 1449 lesions and 270 'positive' cases as determined by the reference standard face-to-face decision (six studies). Methodological quality was variable with poor reporting hindering assessment. The overall risk of bias was high or unclear for participant selection, reference standard, and participant flow and timing in at least half of all studies; the majority were at low risk of bias for the index test. The applicability of study findings were of high or unclear concern for most studies in all domains assessed due to the recruitment of participants from secondary care settings or specialist clinics rather than from primary or community-based settings in which teledermatology is more likely to be used and due to the acquisition of lesion images by dermatologists or in specialist imaging units rather than by primary care clinicians.Seven studies provided data for the primary target condition of any skin cancer (1588 lesions and 638 malignancies). For the correct diagnosis of lesions as malignant using photographic images, summary sensitivity was 94.9% (95% confidence interval (CI) 90.1% to 97.4%) and summary specificity was 84.3% (95% CI 48.5% to 96.8%) (from four studies). Individual study estimates using dermoscopic images or a combination of photographic and dermoscopic images generally suggested similarly high sensitivities with highly variable specificities. Limited comparative data suggested similar diagnostic accuracy between teledermatology assessment and in-person diagnosis by a dermatologist; however, data were too scarce to draw firm conclusions. For the detection of invasive melanoma or atypical intraepidermal melanocytic variants both sensitivities and specificities were more variable. Sensitivities ranged from 59% (95% CI 42% to 74%) to 100% (95% CI 48% to 100%) and specificities from 30% (95% CI 22% to 40%) to 100% (95% CI 93% to 100%), with reported diagnostic thresholds including the correct diagnosis of melanoma, classification of lesions as 'atypical' or 'typical, and the decision to refer or to excise a lesion.Referral accuracy data comparing teledermatology against a face-to-face reference standard suggested good agreement for lesions considered to require some positive action by face-to-face assessment (sensitivities of over 90%). For lesions considered of less concern when assessed face-to-face (e.g. for lesions not recommended for excision or referral), agreement was more variable with teledermatology specificities ranging from 57% (95% CI 39% to 73%) to 100% (95% CI 86% to 100%), suggesting that remote assessment is more likely recommend excision, referral or follow-up compared to in-person decisions., Authors' Conclusions: Studies were generally small and heterogeneous and methodological quality was difficult to judge due to poor reporting. Bearing in mind concerns regarding the applicability of study participants and of lesion image acquisition in specialist settings, our results suggest that teledermatology can correctly identify the majority of malignant lesions. Using a more widely defined threshold to identify 'possibly' malignant cases or lesions that should be considered for excision is likely to appropriately triage those lesions requiring face-to-face assessment by a specialist. Despite the increasing use of teledermatology on an international level, the evidence base to support its ability to accurately diagnose lesions and to triage lesions from primary to secondary care is lacking and further prospective and pragmatic evaluation is needed.

Background: Early, accurate detection of all skin cancer types is essential to guide appropriate management and to improve morbidity and survival. Melanoma and squamous cell carcinoma (SCC) are high-risk skin cancers with the potential to metastasise and ultimately lead to death, whereas basal cell carcinoma (BCC) is usually localised, with potential to infiltrate and damage surrounding tissue. Anxiety around missing early curable cases needs to be balanced against inappropriate referral and unnecessary excision of benign lesions. Ultrasound is a non-invasive imaging technique that relies on the measurement of sound wave reflections from the tissues of the body. At lower frequencies, the deeper structures of the body such as the internal organs can be visualised, while high-frequency ultrasound (HFUS) with transducer frequencies of 20 MHz or more has a much lower depth of tissue penetration but produces a higher resolution image of tissues and structures closer to the skin surface. Used in conjunction with clinical and/or dermoscopic examination of suspected skin cancer, HFUS may offer additional diagnostic information compared to other technologies., Objectives: To assess the diagnostic accuracy of HFUS to assist in the diagnosis of a) cutaneous invasive melanoma and atypical intraepidermal melanocytic variants, b) cutaneous squamous cell carcinoma (cSCC), and c) basal cell carcinoma (BCC) in adults., Search Methods: We undertook a comprehensive search of the following databases from inception up to August 2016: Cochrane Central Register of Controlled Trials; MEDLINE; Embase; CINAHL; CPCI; Zetoc; Science Citation Index; US National Institutes of Health Ongoing Trials Register; NIHR Clinical Research Network Portfolio Database; and the World Health Organization International Clinical Trials Registry Platform. We studied reference lists as well as published systematic review articles., Selection Criteria: Studies evaluating HFUS (20 MHz or more) in adults with lesions suspicious for melanoma, cSCC or BCC versus a reference standard of histological confirmation or clinical follow-up., Data Collection and Analysis: Two review authors independently extracted all data using a standardised data extraction and quality assessment form (based on QUADAS-2). Due to scarcity of data and the poor quality of studies, we did not undertake a meta-analysis for this review. For illustrative purposes, we plot estimates of sensitivity and specificity on coupled forest plots., Main Results: We included six studies, providing 29 datasets: 20 for diagnosis of melanoma (1125 lesions and 242 melanomas) and 9 for diagnosis of BCC (993 lesions and 119 BCCs). We did not identify any data relating to the diagnosis of cSCC.Studies were generally poorly reported, limiting judgements of methodological quality. Half the studies did not set out to establish test accuracy, and all should be considered preliminary evaluations of the potential usefulness of HFUS. There were particularly high concerns for applicability of findings due to selective study populations and data-driven thresholds for test positivity. Studies reporting qualitative assessments of HFUS images excluded up to 22% of lesions (including some melanomas) due to lack of visualisation in the test.Derived sensitivities for qualitative HFUS characteristics were at least 83% (95% CI 75% to 90%) for the detection of melanoma; the combination of three features (lesions appearing hypoechoic, homogenous and well defined) demonstrating 100% sensitivity in two studies (lower limits of the 95% CIs were 94% and 82%), with variable corresponding specificities of 33% (95% CI 20% to 48%) and 73% (95% CI 57% to 85%), respectively. Quantitative measurement of HFUS outputs in two studies enabled decision thresholds to be set to achieve 100% sensitivity; specificities were 93% (95% CI 77% to 99%) and 65% (95% CI 51% to 76%). It was not possible to make summary statements regarding HFUS accuracy for the diagnosis of BCC due to highly variable sensitivities and specificities., Authors' Conclusions: Insufficient data are available on the potential value of HFUS in the diagnosis of melanoma or BCC. Given the between-study heterogeneity, unclear to low methodological quality and limited volume of evidence, we cannot draw any implications for practice. The main value of the preliminary studies included may be in providing guidance on the possible components of new diagnostic rules for diagnosis of melanoma or BCC using HFUS that will require future evaluation. A prospective evaluation of HFUS added to visual inspection and dermoscopy alone in a standard healthcare setting, with a clearly defined and representative population of participants, would be required for a full and proper evaluation of accuracy.

Background: Early accurate detection of all skin cancer types is essential to guide appropriate management and to improve morbidity and survival. Melanoma and squamous cell carcinoma (SCC) are high-risk skin cancers, which have the potential to metastasise and ultimately lead to death, whereas basal cell carcinoma (BCC) is usually localised, with potential to infiltrate and damage surrounding tissue. Anxiety around missing early cases needs to be balanced against inappropriate referral and unnecessary excision of benign lesions. Optical coherence tomography (OCT) is a microscopic imaging technique, which magnifies the surface of a skin lesion using near-infrared light. Used in conjunction with clinical or dermoscopic examination of suspected skin cancer, or both, OCT may offer additional diagnostic information compared to other technologies., Objectives: To determine the diagnostic accuracy of OCT for the detection of cutaneous invasive melanoma and atypical intraepidermal melanocytic variants, basal cell carcinoma (BCC), or cutaneous squamous cell carcinoma (cSCC) in adults., Search Methods: We undertook a comprehensive search of the following databases from inception up to August 2016: Cochrane Central Register of Controlled Trials; MEDLINE; Embase; CINAHL; CPCI; Zetoc; Science Citation Index; US National Institutes of Health Ongoing Trials Register; NIHR Clinical Research Network Portfolio Database; and the World Health Organization International Clinical Trials Registry Platform. We studied reference lists and published systematic review articles., Selection Criteria: We included studies of any design evaluating OCT in adults with lesions suspicious for invasive melanoma and atypical intraepidermal melanocytic variants, BCC or cSCC, compared with a reference standard of histological confirmation or clinical follow-up., Data Collection and Analysis: Two review authors independently extracted data using a standardised data extraction and quality assessment form (based on QUADAS-2). Our unit of analysis was lesions. Where possible, we estimated summary sensitivities and specificities using the bivariate hierarchical model., Main Results: We included five studies with 529 cutaneous lesions (282 malignant lesions) providing nine datasets for OCT, two for visual inspection alone, and two for visual inspection plus dermoscopy. Studies were of moderate to unclear quality, using data-driven thresholds for test positivity and giving poor accounts of reference standard interpretation and blinding. Studies may not have been representative of populations eligible for OCT in practice, for example due to high disease prevalence in study populations, and may not have reflected how OCT is used in practice, for example by using previously acquired OCT images.It was not possible to make summary statements regarding accuracy of detection of melanoma or of cSCC because of the paucity of studies, small sample sizes, and for melanoma differences in the OCT technologies used (high-definition versus conventional resolution OCT), and differences in the degree of testing performed prior to OCT (i.e. visual inspection alone or visual inspection plus dermoscopy).Pooled data from two studies using conventional swept-source OCT alongside visual inspection and dermoscopy for the detection of BCC estimated the sensitivity of OCT as 95% (95% confidence interval (CI) 91% to 97%) and specificity of 77% (95% CI 69% to 83%).When applied to a hypothetical population of 1000 lesions at the mean observed BCC prevalence of 60%, OCT would miss 31 BCCs (91 fewer than would be missed by visual inspection alone and 53 fewer than would be missed by visual inspection plus dermoscopy), and OCT would lead to 93 false-positive results for BCC (a reduction in unnecessary excisions of 159 compared to using visual inspection alone and of 87 compared to visual inspection plus dermoscopy)., Authors' Conclusions: Insufficient data are available on the use of OCT for the detection of melanoma or cSCC. Initial data suggest conventional OCT may have a role for the diagnosis of BCC in clinically challenging lesions, with our meta-analysis showing a higher sensitivity and higher specificity when compared to visual inspection plus dermoscopy. However, the small number of studies and varying methodological quality means implications to guide practice cannot currently be drawn.Appropriately designed prospective comparative studies are required, given the paucity of data comparing OCT with dermoscopy and other similar diagnostic aids such as reflectance confocal microscopy.

Background: Early accurate detection of all skin cancer types is essential to guide appropriate management, reduce morbidity and improve survival. Basal cell carcinoma (BCC) is usually localised to the skin but has potential to infiltrate and damage surrounding tissue, while cutaneous squamous cell carcinoma (cSCC) and melanoma have a much higher potential to metastasise and ultimately lead to death. Exfoliative cytology is a non-invasive test that uses the Tzanck smear technique to identify disease by examining the structure of cells obtained from scraped samples. This simple procedure is a less invasive diagnostic test than a skin biopsy, and for BCC it has the potential to provide an immediate diagnosis that avoids an additional clinic visit to receive skin biopsy results. This may benefit patients scheduled for either Mohs micrographic surgery or non-surgical treatments such as radiotherapy. A cytology scrape can never give the same information as a skin biopsy, however, so it is important to better understand in which skin cancer situations it may be helpful., Objectives: To determine the diagnostic accuracy of exfoliative cytology for detecting basal cell carcinoma (BCC) in adults, and to compare its accuracy with that of standard diagnostic practice (visual inspection with or without dermoscopy). Secondary objectives were: to determine the diagnostic accuracy of exfoliative cytology for detecting cSCC, invasive melanoma and atypical intraepidermal melanocytic variants, and any other skin cancer; and for each of these secondary conditions to compare the accuracy of exfoliative cytology with visual inspection with or without dermoscopy in direct test comparisons; and to determine the effect of observer experience., Search Methods: We undertook a comprehensive search of the following databases from inception up to August 2016: Cochrane Central Register of Controlled Trials; MEDLINE; Embase; CINAHL; CPCI; Zetoc; Science Citation Index; US National Institutes of Health Ongoing Trials Register; NIHR Clinical Research Network Portfolio Database; and the World Health Organization International Clinical Trials Registry Platform. We also studied the reference lists of published systematic review articles., Selection Criteria: Studies evaluating exfoliative cytology in adults with lesions suspicious for BCC, cSCC or melanoma, compared with a reference standard of histological confirmation., Data Collection and Analysis: Two review authors independently extracted all data using a standardised data extraction and quality assessment form (based on QUADAS-2). Where possible we estimated summary sensitivities and specificities using the bivariate hierarchical model., Main Results: We synthesised the results of nine studies contributing a total of 1655 lesions to our analysis, including 1120 BCCs (14 datasets), 41 cSCCs (amongst 401 lesions in 2 datasets), and 10 melanomas (amongst 200 lesions in 1 dataset). Three of these datasets (one each for BCC, melanoma and any malignant condition) were derived from one study that also performed a direct comparison with dermoscopy. Studies were of moderate to poor quality, providing inadequate descriptions of participant selection, thresholds used to make cytological and histological diagnoses, and blinding. Reporting of participants' prior referral pathways was particularly poor, as were descriptions of the cytodiagnostic criteria used to make diagnoses. No studies evaluated the use of exfoliative cytology as a primary diagnostic test for detecting BCC or other skin cancers in lesions suspicious for skin cancer. Pooled data from seven studies using standard cytomorphological criteria (but various stain methods) to detect BCC in participants with a high clinical suspicion of BCC estimated the sensitivity and specificity of exfoliative cytology as 97.5% (95% CI 94.5% to 98.9%) and 90.1% (95% CI 81.1% to 95.1%). respectively. When applied to a hypothetical population of 1000 clinically suspected BCC lesions with a median observed BCC prevalence of 86%, exfoliative cytology would miss 21 BCCs and would lead to 14 false positive diagnoses of BCC. No false positive cases were histologically confirmed to be melanoma. Insufficient data are available to make summary statements regarding the accuracy of exfoliative cytology to detect melanoma or cSCC, or its accuracy compared to dermoscopy., Authors' Conclusions: The utility of exfoliative cytology for the primary diagnosis of skin cancer is unknown, as all included studies focused on the use of this technique for confirming strongly suspected clinical diagnoses. For the confirmation of BCC in lesions with a high clinical suspicion, there is evidence of high sensitivity and specificity. Since decisions to treat low-risk BCCs are unlikely in practice to require diagnostic confirmation given that clinical suspicion is already high, exfoliative cytology might be most useful for cases of BCC where the treatments being contemplated require a tissue diagnosis (e.g. radiotherapy). The small number of included studies, poor reporting and varying methodological quality prevent us from drawing strong conclusions to guide clinical practice. Despite insufficient data on the use of cytology for cSCC or melanoma, it is unlikely that cytology would be useful in these scenarios since preservation of the architecture of the whole lesion that would be available from a biopsy provides crucial diagnostic information. Given the paucity of good quality data, appropriately designed prospective comparative studies may be required to evaluate both the diagnostic value of exfoliative cytology by comparison to dermoscopy, and its confirmatory value in adequately reported populations with a high probability of BCC scheduled for further treatment requiring a tissue diagnosis.

Background: Melanoma has one of the fastest rising incidence rates of any cancer. It accounts for a small percentage of skin cancer cases but is responsible for the majority of skin cancer deaths. History-taking and visual inspection of a suspicious lesion by a clinician is usually the first in a series of 'tests' to diagnose skin cancer. Establishing the accuracy of visual inspection alone is critical to understating the potential contribution of additional tests to assist in the diagnosis of melanoma., Objectives: To determine the diagnostic accuracy of visual inspection for the detection of cutaneous invasive melanoma and atypical intraepidermal melanocytic variants in adults with limited prior testing and in those referred for further evaluation of a suspicious lesion. Studies were separated according to whether the diagnosis was recorded face-to-face (in-person) or based on remote (image-based) assessment., Search Methods: We undertook a comprehensive search of the following databases from inception up to August 2016: CENTRAL; CINAHL; CPCI; Zetoc; Science Citation Index; US National Institutes of Health Ongoing Trials Register; NIHR Clinical Research Network Portfolio Database; and the World Health Organization International Clinical Trials Registry Platform. We studied reference lists and published systematic review articles., Selection Criteria: Test accuracy studies of any design that evaluated visual inspection in adults with lesions suspicious for melanoma, compared with a reference standard of either histological confirmation or clinical follow-up. We excluded studies reporting data for 'clinical diagnosis' where dermoscopy may or may not have been used., Data Collection and Analysis: Two review authors independently extracted all data using a standardised data extraction and quality assessment form (based on QUADAS-2). We contacted authors of included studies where information related to the target condition or diagnostic threshold were missing. We estimated summary sensitivities and specificities per algorithm and threshold using the bivariate hierarchical model. We investigated the impact of: in-person test interpretation; use of a purposely developed algorithm to assist diagnosis; and observer expertise., Main Results: We included 49 publications reporting on a total of 51 study cohorts with 34,351 lesions (including 2499 cases), providing 134 datasets for visual inspection. Across almost all study quality domains, the majority of study reports provided insufficient information to allow us to judge the risk of bias, while in three of four domains that we assessed we scored concerns regarding applicability of study findings as 'high'. Selective participant recruitment, lack of detail regarding the threshold for deciding on a positive test result, and lack of detail on observer expertise were particularly problematic.Attempts to analyse studies by degree of prior testing were hampered by a lack of relevant information and by the restricted inclusion of lesions selected for biopsy or excision. Accuracy was generally much higher for in-person diagnosis compared to image-based evaluations (relative diagnostic odds ratio of 8.54, 95% CI 2.89 to 25.3, P < 0.001). Meta-analysis of in-person evaluations that could be clearly placed on the clinical pathway showed a general trade-off between sensitivity and specificity, with the highest sensitivity (92.4%, 95% CI 26.2% to 99.8%) and lowest specificity (79.7%, 95% CI 73.7% to 84.7%) observed in participants with limited prior testing (n = 3 datasets). Summary sensitivities were lower for those referred for specialist assessment but with much higher specificities (e.g. sensitivity 76.7%, 95% CI 61.7% to 87.1%) and specificity 95.7%, 95% CI 89.7% to 98.3%) for lesions selected for excision, n = 8 datasets). These differences may be related to differences in the spectrum of included lesions, differences in the definition of a positive test result, or to variations in observer expertise. We did not find clear evidence that accuracy is improved by the use of any algorithm to assist diagnosis in all settings. Attempts to examine the effect of observer expertise in melanoma diagnosis were hindered due to poor reporting., Authors' Conclusions: Visual inspection is a fundamental component of the assessment of a suspicious skin lesion; however, the evidence suggests that melanomas will be missed if visual inspection is used on its own. The evidence to support its accuracy in the range of settings in which it is used is flawed and very poorly reported. Although published algorithms do not appear to improve accuracy, there is insufficient evidence to suggest that the 'no algorithm' approach should be preferred in all settings. Despite the volume of research evaluating visual inspection, further prospective evaluation of the potential added value of using established algorithms according to the prior testing or diagnostic difficulty of lesions may be warranted.

Background: Early accurate detection of all skin cancer types is important to guide appropriate management, to reduce morbidity and to improve survival. Basal cell carcinoma (BCC) is almost always a localised skin cancer with potential to infiltrate and damage surrounding tissue, whereas a minority of cutaneous squamous cell carcinomas (cSCCs) and invasive melanomas are higher-risk skin cancers with the potential to metastasise and cause death. Dermoscopy has become an important tool to assist specialist clinicians in the diagnosis of melanoma, and is increasingly used in primary-care settings. Dermoscopy is a precision-built handheld illuminated magnifier that allows more detailed examination of the skin down to the level of the superficial dermis. Establishing the value of dermoscopy over and above visual inspection for the diagnosis of BCC or cSCC in primary- and secondary-care settings is critical to understanding its potential contribution to appropriate skin cancer triage, including referral of higher-risk cancers to secondary care, the identification of low-risk skin cancers that might be treated in primary care and to provide reassurance to those with benign skin lesions who can be safely discharged., Objectives: To determine the diagnostic accuracy of visual inspection and dermoscopy, alone or in combination, for the detection of (a) BCC and (b) cSCC, in adults. We separated studies according to whether the diagnosis was recorded face-to-face (in person) or based on remote (image-based) assessment., Search Methods: We undertook a comprehensive search of the following databases from inception up to August 2016: Cochrane Central Register of Controlled Trials; MEDLINE; Embase; CINAHL; CPCI; Zetoc; Science Citation Index; US National Institutes of Health Ongoing Trials Register; NIHR Clinical Research Network Portfolio Database; and the World Health Organization International Clinical Trials Registry Platform. We studied reference lists and published systematic review articles., Selection Criteria: Studies of any design that evaluated visual inspection or dermoscopy or both in adults with lesions suspicious for skin cancer, compared with a reference standard of either histological confirmation or clinical follow-up., Data Collection and Analysis: Two review authors independently extracted all data using a standardised data extraction and quality assessment form (based on QUADAS-2). We contacted authors of included studies where information related to the target condition or diagnostic thresholds were missing. We estimated accuracy using hierarchical summary ROC methods. We undertook analysis of studies allowing direct comparison between tests. To facilitate interpretation of results, we computed values of sensitivity at the point on the SROC curve with 80% fixed specificity and values of specificity with 80% fixed sensitivity. We investigated the impact of in-person test interpretation; use of a purposely-developed algorithm to assist diagnosis; and observer expertise., Main Results: We included 24 publications reporting on 24 study cohorts, providing 27 visual inspection datasets (8805 lesions; 2579 malignancies) and 33 dermoscopy datasets (6855 lesions; 1444 malignancies). The risk of bias was mainly low for the index test (for dermoscopy evaluations) and reference standard domains, particularly for in-person evaluations, and high or unclear for participant selection, application of the index test for visual inspection and for participant flow and timing. We scored concerns about the applicability of study findings as of 'high' or 'unclear' concern for almost all studies across all domains assessed. Selective participant recruitment, lack of reproducibility of diagnostic thresholds and lack of detail on observer expertise were particularly problematic.The detection of BCC was reported in 28 datasets; 15 on an in-person basis and 13 image-based. Analysis of studies by prior testing of participants and according to observer expertise was not possible due to lack of data. Studies were primarily conducted in participants referred for specialist assessment of lesions with available histological classification. We found no clear differences in accuracy between dermoscopy studies undertaken in person and those which evaluated images. The lack of effect observed may be due to other sources of heterogeneity, including variations in the types of skin lesion studied, in dermatoscopes used, or in the use of algorithms and varying thresholds for deciding on a positive test result.Meta-analysis found in-person evaluations of dermoscopy (7 evaluations; 4683 lesions and 363 BCCs) to be more accurate than visual inspection alone for the detection of BCC (8 evaluations; 7017 lesions and 1586 BCCs), with a relative diagnostic odds ratio (RDOR) of 8.2 (95% confidence interval (CI) 3.5 to 19.3; P < 0.001). This corresponds to predicted differences in sensitivity of 14% (93% versus 79%) at a fixed specificity of 80% and predicted differences in specificity of 22% (99% versus 77%) at a fixed sensitivity of 80%. We observed very similar results for the image-based evaluations.When applied to a hypothetical population of 1000 lesions, of which 170 are BCC (based on median BCC prevalence across studies), an increased sensitivity of 14% from dermoscopy would lead to 24 fewer BCCs missed, assuming 166 false positive results from both tests. A 22% increase in specificity from dermoscopy with sensitivity fixed at 80% would result in 183 fewer unnecessary excisions, assuming 34 BCCs missed for both tests. There was not enough evidence to assess the use of algorithms or structured checklists for either visual inspection or dermoscopy.Insufficient data were available to draw conclusions on the accuracy of either test for the detection of cSCCs., Authors' Conclusions: Dermoscopy may be a valuable tool for the diagnosis of BCC as an adjunct to visual inspection of a suspicious skin lesion following a thorough history-taking including assessment of risk factors for keratinocyte cancer. The evidence primarily comes from secondary-care (referred) populations and populations with pigmented lesions or mixed lesion types. There is no clear evidence supporting the use of currently-available formal algorithms to assist dermoscopy diagnosis.

Background: Melanoma has one of the fastest rising incidence rates of any cancer. It accounts for a small percentage of skin cancer cases but is responsible for the majority of skin cancer deaths. Although history-taking and visual inspection of a suspicious lesion by a clinician are usually the first in a series of 'tests' to diagnose skin cancer, dermoscopy has become an important tool to assist diagnosis by specialist clinicians and is increasingly used in primary care settings. Dermoscopy is a magnification technique using visible light that allows more detailed examination of the skin compared to examination by the naked eye alone. Establishing the additive value of dermoscopy over and above visual inspection alone across a range of observers and settings is critical to understanding its contribution for the diagnosis of melanoma and to future understanding of the potential role of the growing number of other high-resolution image analysis techniques., Objectives: To determine the diagnostic accuracy of dermoscopy alone, or when added to visual inspection of a skin lesion, for the detection of cutaneous invasive melanoma and atypical intraepidermal melanocytic variants in adults. We separated studies according to whether the diagnosis was recorded face-to-face (in-person), or based on remote (image-based), assessment., Search Methods: We undertook a comprehensive search of the following databases from inception up to August 2016: CENTRAL; MEDLINE; Embase; CINAHL; CPCI; Zetoc; Science Citation Index; US National Institutes of Health Ongoing Trials Register; NIHR Clinical Research Network Portfolio Database; and the World Health Organization International Clinical Trials Registry Platform. We studied reference lists and published systematic review articles., Selection Criteria: Studies of any design that evaluated dermoscopy in adults with lesions suspicious for melanoma, compared with a reference standard of either histological confirmation or clinical follow-up. Data on the accuracy of visual inspection, to allow comparisons of tests, was included only if reported in the included studies of dermoscopy., Data Collection and Analysis: Two review authors independently extracted all data using a standardised data extraction and quality assessment form (based on QUADAS-2). We contacted authors of included studies where information related to the target condition or diagnostic threshold were missing. We estimated accuracy using hierarchical summary receiver operating characteristic (SROC),methods. Analysis of studies allowing direct comparison between tests was undertaken. To facilitate interpretation of results, we computed values of sensitivity at the point on the SROC curve with 80% fixed specificity and values of specificity with 80% fixed sensitivity. We investigated the impact of in-person test interpretation; use of a purposely developed algorithm to assist diagnosis; observer expertise; and dermoscopy training., Main Results: We included a total of 104 study publications reporting on 103 study cohorts with 42,788 lesions (including 5700 cases), providing 354 datasets for dermoscopy. The risk of bias was mainly low for the index test and reference standard domains and mainly high or unclear for participant selection and participant flow. Concerns regarding the applicability of study findings were largely scored as 'high' concern in three of four domains assessed. Selective participant recruitment, lack of reproducibility of diagnostic thresholds and lack of detail on observer expertise were particularly problematic.The accuracy of dermoscopy for the detection of invasive melanoma or atypical intraepidermal melanocytic variants was reported in 86 datasets; 26 for evaluations conducted in person (dermoscopy added to visual inspection), and 60 for image-based evaluations (diagnosis based on interpretation of dermoscopic images). Analyses of studies by prior testing revealed no obvious effect on accuracy; analyses were hampered by the lack of studies in primary care, lack of relevant information and the restricted inclusion of lesions selected for biopsy or excision. Accuracy was higher for in-person diagnosis compared to image-based evaluations (relative diagnostic odds ratio (RDOR) 4.6, 95% confidence interval (CI) 2.4 to 9.0; P < 0.001).We compared accuracy for (a), in-person evaluations of dermoscopy (26 evaluations; 23,169 lesions and 1664 melanomas),versus visual inspection alone (13 evaluations; 6740 lesions and 459 melanomas), and for (b), image-based evaluations of dermoscopy (60 evaluations; 13,475 lesions and 2851 melanomas),versus image-based visual inspection (11 evaluations; 1740 lesions and 305 melanomas). For both comparisons, meta-analysis found dermoscopy to be more accurate than visual inspection alone, with RDORs of (a), 4.7 (95% CI 3.0 to 7.5; P < 0.001), and (b), 5.6 (95% CI 3.7 to 8.5; P < 0.001). For a), the predicted difference in sensitivity at a fixed specificity of 80% was 16% (95% CI 8% to 23%; 92% for dermoscopy + visual inspection versus 76% for visual inspection), and predicted difference in specificity at a fixed sensitivity of 80% was 20% (95% CI 7% to 33%; 95% for dermoscopy + visual inspection versus 75% for visual inspection). For b) the predicted differences in sensitivity was 34% (95% CI 24% to 46%; 81% for dermoscopy versus 47% for visual inspection), at a fixed specificity of 80%, and predicted difference in specificity was 40% (95% CI 27% to 57%; 82% for dermoscopy versus 42% for visual inspection), at a fixed sensitivity of 80%.Using the median prevalence of disease in each set of studies ((a), 12% for in-person and (b), 24% for image-based), for a hypothetical population of 1000 lesions, an increase in sensitivity of (a), 16% (in-person), and (b), 34% (image-based), from using dermoscopy at a fixed specificity of 80% equates to a reduction in the number of melanomas missed of (a), 19 and (b), 81 with (a), 176 and (b), 152 false positive results. An increase in specificity of (a), 20% (in-person), and (b), 40% (image-based), at a fixed sensitivity of 80% equates to a reduction in the number of unnecessary excisions from using dermoscopy of (a), 176 and (b), 304 with (a), 24 and (b), 48 melanomas missed.The use of a named or published algorithm to assist dermoscopy interpretation (as opposed to no reported algorithm or reported use of pattern analysis), had no significant impact on accuracy either for in-person (RDOR 1.4, 95% CI 0.34 to 5.6; P = 0.17), or image-based (RDOR 1.4, 95% CI 0.60 to 3.3; P = 0.22), evaluations. This result was supported by subgroup analysis according to algorithm used. We observed higher accuracy for observers reported as having high experience and for those classed as 'expert consultants' in comparison to those considered to have less experience in dermoscopy, particularly for image-based evaluations. Evidence for the effect of dermoscopy training on test accuracy was very limited but suggested associated improvements in sensitivity., Authors' Conclusions: Despite the observed limitations in the evidence base, dermoscopy is a valuable tool to support the visual inspection of a suspicious skin lesion for the detection of melanoma and atypical intraepidermal melanocytic variants, particularly in referred populations and in the hands of experienced users. Data to support its use in primary care are limited, however, it may assist in triaging suspicious lesions for urgent referral when employed by suitably trained clinicians. Formal algorithms may be of most use for dermoscopy training purposes and for less expert observers, however reliable data comparing approaches using dermoscopy in person are lacking.

Background: Early accurate detection of all skin cancer types is important to guide appropriate management and improve morbidity and survival. Basal cell carcinoma (BCC) is usually a localised skin cancer but with potential to infiltrate and damage surrounding tissue, whereas cutaneous squamous cell carcinoma (cSCC) and melanoma are higher risk skin cancers with the potential to metastasise and ultimately lead to death. When used in conjunction with clinical or dermoscopic suspicion of malignancy, or both, reflectance confocal microscopy (RCM) may help to identify cancers eligible for non-surgical treatment without the need for a diagnostic biopsy, particularly in people with suspected BCC. Any potential benefit must be balanced against the risk of any misdiagnoses., Objectives: To determine the diagnostic accuracy of RCM for the detection of BCC, cSCC, or any skin cancer in adults with any suspicious lesion and lesions that are difficult to diagnose (equivocal); and to compare its accuracy with that of usual practice (visual inspection or dermoscopy, or both)., Search Methods: We undertook a comprehensive search of the following databases from inception to August 2016: Cochrane Central Register of Controlled Trials; MEDLINE; Embase; CINAHL; CPCI; Zetoc; Science Citation Index; US National Institutes of Health Ongoing Trials Register; NIHR Clinical Research Network Portfolio Database; and the World Health Organization International Clinical Trials Registry Platform. We studied reference lists and published systematic review articles., Selection Criteria: Studies of any design that evaluated the accuracy of RCM alone, or RCM in comparison to visual inspection or dermoscopy, or both, in adults with lesions suspicious for skin cancer compared with a reference standard of either histological confirmation or clinical follow-up, or both., Data Collection and Analysis: Two review authors independently extracted data using a standardised data extraction and quality assessment form (based on QUADAS-2). We contacted authors of included studies where information related to the target condition or diagnostic threshold were missing. We estimated summary sensitivities and specificities using the bivariate hierarchical model. For computation of likely numbers of true-positive, false-positive, false-negative, and true-negative findings in the 'Summary of findings' tables, we applied summary sensitivity and specificity estimates to lower quartile, median and upper quartiles of the prevalence observed in the study groups. We also investigated the impact of observer experience., Main Results: The review included 10 studies reporting on 11 study cohorts. All 11 cohorts reported data for the detection of BCC, including 2037 lesions (464 with BCC); and four cohorts reported data for the detection of cSCC, including 834 lesions (71 with cSCC). Only one study also reported data for the detection of BCC or cSCC using dermoscopy, limiting comparisons between RCM and dermoscopy. Studies were at high or unclear risk of bias across almost all methodological quality domains, and were of high or unclear concern regarding applicability of the evidence. Selective participant recruitment, unclear blinding of the reference test, and exclusions due to image quality or technical difficulties were observed. It was unclear whether studies were representative of populations eligible for testing with RCM, and test interpretation was often undertaken using images, remotely from the participant and the interpreter blinded to clinical information that would normally be available in practice.Meta-analysis found RCM to be more sensitive but less specific for the detection of BCC in studies of participants with equivocal lesions (sensitivity 94%, 95% confidence interval (CI) 79% to 98%; specificity 85%, 95% CI 72% to 92%; 3 studies) compared to studies that included any suspicious lesion (sensitivity 76%, 95% CI 45% to 92%; specificity 95%, 95% CI 66% to 99%; 4 studies), although CIs were wide. At the median prevalence of disease of 12.5% observed in studies including any suspicious lesion, applying these results to a hypothetical population of 1000 lesions results in 30 BCCs missed with 44 false-positive results (lesions misdiagnosed as BCCs). At the median prevalence of disease of 15% observed in studies of equivocal lesions, nine BCCs would be missed with 128 false-positive results in a population of 1000 lesions. Across both sets of studies, up to 15% of these false-positive lesions were observed to be melanomas mistaken for BCCs. There was some suggestion of higher sensitivities in studies with more experienced observers. Summary sensitivity and specificity could not be estimated for the detection of cSCC due to paucity of data., Authors' Conclusions: There is insufficient evidence for the use of RCM for the diagnosis of BCC or cSCC in either population group. A possible role for RCM in clinical practice is as a tool to avoid diagnostic biopsies in lesions with a relatively high clinical suspicion of BCC. The potential for, and consequences of, misclassification of other skin cancers such as melanoma as BCCs requires further research. Importantly, data are lacking that compare RCM to standard clinical practice (with or without dermoscopy).

Background: Early accurate detection of all skin cancer types is essential to guide appropriate management and to improve morbidity and survival. Melanoma and cutaneous squamous cell carcinoma (cSCC) are high-risk skin cancers which have the potential to metastasise and ultimately lead to death, whereas basal cell carcinoma (BCC) is usually localised with potential to infiltrate and damage surrounding tissue. Anxiety around missing early curable cases needs to be balanced against inappropriate referral and unnecessary excision of benign lesions. Computer-assisted diagnosis (CAD) systems use artificial intelligence to analyse lesion data and arrive at a diagnosis of skin cancer. When used in unreferred settings ('primary care'), CAD may assist general practitioners (GPs) or other clinicians to more appropriately triage high-risk lesions to secondary care. Used alongside clinical and dermoscopic suspicion of malignancy, CAD may reduce unnecessary excisions without missing melanoma cases., Objectives: To determine the accuracy of CAD systems for diagnosing cutaneous invasive melanoma and atypical intraepidermal melanocytic variants, BCC or cSCC in adults, and to compare its accuracy with that of dermoscopy., Search Methods: We undertook a comprehensive search of the following databases from inception up to August 2016: Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; Embase; CINAHL; CPCI; Zetoc; Science Citation Index; US National Institutes of Health Ongoing Trials Register; NIHR Clinical Research Network Portfolio Database; and the World Health Organization International Clinical Trials Registry Platform. We studied reference lists and published systematic review articles., Selection Criteria: Studies of any design that evaluated CAD alone, or in comparison with dermoscopy, in adults with lesions suspicious for melanoma or BCC or cSCC, and compared with a reference standard of either histological confirmation or clinical follow-up., Data Collection and Analysis: Two review authors independently extracted all data using a standardised data extraction and quality assessment form (based on QUADAS-2). We contacted authors of included studies where information related to the target condition or diagnostic threshold were missing. We estimated summary sensitivities and specificities separately by type of CAD system, using the bivariate hierarchical model. We compared CAD with dermoscopy using (a) all available CAD data (indirect comparisons), and (b) studies providing paired data for both tests (direct comparisons). We tested the contribution of human decision-making to the accuracy of CAD diagnoses in a sensitivity analysis by removing studies that gave CAD results to clinicians to guide diagnostic decision-making., Main Results: We included 42 studies, 24 evaluating digital dermoscopy-based CAD systems (Derm-CAD) in 23 study cohorts with 9602 lesions (1220 melanomas, at least 83 BCCs, 9 cSCCs), providing 32 datasets for Derm-CAD and seven for dermoscopy. Eighteen studies evaluated spectroscopy-based CAD (Spectro-CAD) in 16 study cohorts with 6336 lesions (934 melanomas, 163 BCC, 49 cSCCs), providing 32 datasets for Spectro-CAD and six for dermoscopy. These consisted of 15 studies using multispectral imaging (MSI), two studies using electrical impedance spectroscopy (EIS) and one study using diffuse-reflectance spectroscopy. Studies were incompletely reported and at unclear to high risk of bias across all domains. Included studies inadequately address the review question, due to an abundance of low-quality studies, poor reporting, and recruitment of highly selected groups of participants.Across all CAD systems, we found considerable variation in the hardware and software technologies used, the types of classification algorithm employed, methods used to train the algorithms, and which lesion morphological features were extracted and analysed across all CAD systems, and even between studies evaluating CAD systems. Meta-analysis found CAD systems had high sensitivity for correct identification of cutaneous invasive melanoma and atypical intraepidermal melanocytic variants in highly selected populations, but with low and very variable specificity, particularly for Spectro-CAD systems. Pooled data from 22 studies estimated the sensitivity of Derm-CAD for the detection of melanoma as 90.1% (95% confidence interval (CI) 84.0% to 94.0%) and specificity as 74.3% (95% CI 63.6% to 82.7%). Pooled data from eight studies estimated the sensitivity of multispectral imaging CAD (MSI-CAD) as 92.9% (95% CI 83.7% to 97.1%) and specificity as 43.6% (95% CI 24.8% to 64.5%). When applied to a hypothetical population of 1000 lesions at the mean observed melanoma prevalence of 20%, Derm-CAD would miss 20 melanomas and would lead to 206 false-positive results for melanoma. MSI-CAD would miss 14 melanomas and would lead to 451 false diagnoses for melanoma. Preliminary findings suggest CAD systems are at least as sensitive as assessment of dermoscopic images for the diagnosis of invasive melanoma and atypical intraepidermal melanocytic variants. We are unable to make summary statements about the use of CAD in unreferred populations, or its accuracy in detecting keratinocyte cancers, or its use in any setting as a diagnostic aid, because of the paucity of studies., Authors' Conclusions: In highly selected patient populations all CAD types demonstrate high sensitivity, and could prove useful as a back-up for specialist diagnosis to assist in minimising the risk of missing melanomas. However, the evidence base is currently too poor to understand whether CAD system outputs translate to different clinical decision-making in practice. Insufficient data are available on the use of CAD in community settings, or for the detection of keratinocyte cancers. The evidence base for individual systems is too limited to draw conclusions on which might be preferred for practice. Prospective comparative studies are required that evaluate the use of already evaluated CAD systems as diagnostic aids, by comparison to face-to-face dermoscopy, and in participant populations that are representative of those in which the test would be used in practice.