Visual inspection and dermoscopy, alone or in combination, for diagnosing keratinocyte skin cancers in adults

Abstract

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. 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. 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. 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. 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. 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. 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. Does dermoscopy improve the accuracy of diagnosing basal cell or squamous cell skin cancer (BCC or cSCC) compared to using the naked eye alone? What is the aim of the review? We wanted to find out whether using a handheld illuminated microscope (dermatoscope or ‘dermoscopy’) is any better at diagnosing basal cell carcinoma (BCC) or cutaneous squamous cell carcinoma (cSCC) compared to just looking at the skin with the naked eye. We included 24 studies to answer this question. Why is improving diagnosis of BCC or cSCC important? There are a number of different types of skin cancer. BCC and cSCC are less serious than melanoma skin cancer, because they usually grow more slowly and BCC does not spread to other organs in the body. Making the correct diagnosis of BCC or cSCC is still important, because their treatment may differ. A missed BCC (known as a false negative result) can result in disfigurement and the need for more major surgery. A missed cSCC can spread to other parts of the body. Diagnosing BCC or cSCC when they are not actually present (a false positive result) may mean unnecessary treatment, e.g. surgical removal which may result in a disfiguring scar, and worry to patients if the lesion (a mole or area of skin with an unusual appearance in comparison with the surrounding skin) is benign (not a cancer), or may result in wrong treatment, e.g. a non‐surgical therapy, being used if the lesion is misdiagnosed. What was studied in the review? A dermatoscope is a handheld magnifier that includes a light source. Dermoscopy is often used by skin specialists to help diagnose skin cancer. It is also being used more by community doctors. As well as seeing whether dermoscopy added anything to visual inspection alone overall, we also wanted to find out whether dermoscopy accuracy was different when used in a face‐to‐face consultation or when used on images of skin lesions sent to specialists. We also tried to find out whether the accuracy of dermoscopy was improved by use of a checklist, or if it was better when used by a skin specialist compared to a non‐specialist. What are the main results of the review? The review included 24 studies reporting information for people with lesions suspected of skin cancer. Diagnosis of BCC with the patient present We found 11 relevant studies. Eight studies (including 7017 suspicious skin lesions) investigated the accuracy of visual inspection on its own and seven studies (with 4683 suspicious skin lesions) investigated the accuracy of dermoscopy added to visual inspection (four of which reported data for both visual inspection on its own and for dermoscopy added to visual inspection). The results suggest that dermoscopy is more accurate than visual inspection on its own, both for identifying BCC correctly and for excluding things that are not BCCs. The results can be illustrated using a group of 1000 lesions, of which 170 (17%) are BCC. In order to see how much better dermoscopy is in identifying BCC correctly when compared to just looking at the skin, we have to assume that both lead to the same number of lesions being falsely diagnosed as BCC (we assumed that 166 of the 830 lesions without BCC would have an incorrect diagnosis of BCC). In this fixed situation, adding dermoscopy to visual inspection would correctly identify an extra 24 BCCs (158 compared with 134) that would have been missed by just looking at the skin alone. In other words, more BCC cancers would be correctly identified. In order to see how much better dermoscopy is in deciding if a skin lesion is not a BCC when compared to just looking at the skin, we have to assume that both lead to the same number of BCCs being correctly diagnosed (in this case we assumed that 136 out of the 170 BCCs would be correctly diagnosed). In this situation, adding in dermoscopy to visual inspection would reduce the number of lesions being wrongly diagnosed as being BCC by 183 (a reduction from 191 in the visual inspection group to eight people in the dermoscopy group). In other words, more lesions that were not BCC would be correctly identified, and fewer people would end up being sent for surgery. Image‐based diagnosis of BCC Eleven studies concerning BCC diagnosis using either clinical photographs or magnified images from a dermatoscope were included. Four studies, (including 853 suspicious skin lesions) used visual inspection of photographs and nine studies (including 2271 suspicious lesions) used dermoscopic images (two studies reported data for diagnosis using both photographs and using dermoscopic images). Results were very similar to the in‐person studies. Value of checklists and observer expertise There was no evidence that use of a checklist to help visual inspection or dermoscopy interpretation improved diagnostic accuracy. There was not enough evidence to examine the effect of clinical expertise and training. Diagnosis of cSCC There was not enough evidence to reliably comment on the accuracy of either test for the detection of cSCCs. How reliable are the results of the studies of this review? Most of our studies made a reliable final diagnosis by lesion biopsy and by following people up over time to make sure the skin lesion remained negative for skin cancer. Some studies used expert diagnosis to confirm the absence of skin cancer, which is less reliable*. Poor reporting of what was done in the studies made it difficult for us to judge how reliable they were. Some studies excluded certain types of skin lesion and some did not describe how a positive test result to trigger referral to a specialist or treatment was defined. Who do the results of this review apply to? Eleven studies were done in Europe (46%), and the rest in North America (n = 3), Asia (n = 5), Oceania (n = 2), or multiple countries (n = 3). People included in the studies were on average between 30 and 74 years old. The percentage of people with BCC ranged between 1% and 61% for in‐person studies and between 2% and 63% in studies using images. Almost all studies were done with people referred from primary care to specialist skin clinics. Over half of studies considered the ability of dermoscopy and visual inspection to diagnose any skin cancer, including melanoma and BCC, while 10 (42%) focused on just BCC. Variation in the expertise of doctors doing the examinations and differences in the definitions used to decide when a test was positive make it unclear how dermoscopy should be carried out and what level of training is needed in order to achieve the accuracy observed in studies. What are the implications of this review? When used by specialists, dermoscopy may be a useful tool to help diagnose BCC correctly when compared with visual inspection alone. It is not clear whether dermoscopy should be used by general practitioners to correctly identify people with suspicious lesions who need to be seen by a specialist. Checklists to help interpret dermoscopy do not seem to help improve accuracy for BCC. Further research is needed, to see if dermoscopy is useful in primary care. How up‐to‐date is this review? The review authors searched for and used studies published up to August 2016. *In these studies biopsy, clinical follow‐up or specialist clinician diagnosis were the reference standards (means of establishing the final diagnosis).