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<article xmlns:xlink="http://www.w3.org/1999/xlink" article-type="letter" dtd-version="2.0">
  <front>
    <journal-meta>
      <journal-id journal-id-type="publisher-id">JDERM</journal-id>
      <journal-id journal-id-type="nlm-ta">JMIR Dermatol</journal-id>
      <journal-title>JMIR Dermatology</journal-title>
      <issn pub-type="epub">2562-0959</issn>
      <publisher>
        <publisher-name>JMIR Publications</publisher-name>
        <publisher-loc>Toronto, Canada</publisher-loc>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id">v7i1e41657</article-id>
      <article-id pub-id-type="pmid">38451581</article-id>
      <article-id pub-id-type="doi">10.2196/41657</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Research Letter</subject>
        </subj-group>
        <subj-group subj-group-type="article-type">
          <subject>Research Letter</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>From the Cochrane Library: Visual Inspection and Dermoscopy, Alone or in Combination, for Diagnosing Keratinocyte Skin Cancers in Adults</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="editor">
          <name>
            <surname>Chi</surname>
            <given-names>Ching-Chi</given-names>
          </name>
        </contrib>
      </contrib-group>
      <contrib-group>
        <contrib contrib-type="reviewer">
          <name>
            <surname>Shakshouk</surname>
            <given-names>Hadir</given-names>
          </name>
        </contrib>
        <contrib contrib-type="reviewer">
          <name>
            <surname>Sibbald</surname>
            <given-names>Cathryn</given-names>
          </name>
        </contrib>
        <contrib contrib-type="reviewer">
          <name>
            <surname>Solomon</surname>
            <given-names>James</given-names>
          </name>
        </contrib>
        <contrib contrib-type="reviewer">
          <name>
            <surname>Long</surname>
            <given-names>Valencia</given-names>
          </name>
        </contrib>
      </contrib-group>
      <contrib-group>
        <contrib id="contrib1" contrib-type="author">
          <name name-style="western">
            <surname>Klein</surname>
            <given-names>Colleen M</given-names>
          </name>
          <degrees>BA</degrees>
          <xref rid="aff1" ref-type="aff">1</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0009-0004-1447-2583</ext-link>
        </contrib>
        <contrib id="contrib2" contrib-type="author">
          <name name-style="western">
            <surname>Sivesind</surname>
            <given-names>Torunn E</given-names>
          </name>
          <degrees>MD</degrees>
          <xref rid="aff2" ref-type="aff">2</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0003-4805-0632</ext-link>
        </contrib>
        <contrib id="contrib3" contrib-type="author" corresp="yes">
          <name name-style="western">
            <surname>Dellavalle</surname>
            <given-names>Robert P</given-names>
          </name>
          <degrees>MSPH, MD, PhD</degrees>
          <xref rid="aff2" ref-type="aff">2</xref>
          <address>
            <institution>Department of Dermatology</institution>
            <institution>University of Colorado Anschutz Medical Campus</institution>
            <addr-line>Rocky Mountain Regional VA Medical Center</addr-line>
            <addr-line>1700 N Wheeling St, Rm E1-342</addr-line>
            <addr-line>Aurora, CO, 80045</addr-line>
            <country>United States</country>
            <phone>1 720 857 5562</phone>
            <email>robert.dellavalle@cuanschutz.edu</email>
          </address>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0001-8132-088X</ext-link>
        </contrib>
      </contrib-group>
      <aff id="aff1">
        <label>1</label>
        <institution>Austin Skin Physicians</institution>
        <addr-line>Austin, TX</addr-line>
        <country>United States</country>
      </aff>
      <aff id="aff2">
        <label>2</label>
        <institution>Department of Dermatology</institution>
        <institution>University of Colorado Anschutz Medical Campus</institution>
        <addr-line>Aurora, CO</addr-line>
        <country>United States</country>
      </aff>
      <author-notes>
        <corresp>Corresponding Author: Robert P Dellavalle <email>robert.dellavalle@cuanschutz.edu</email></corresp>
      </author-notes>
      <pub-date pub-type="collection">
        <year>2024</year>
      </pub-date>
      <pub-date pub-type="epub">
        <day>7</day>
        <month>3</month>
        <year>2024</year>
      </pub-date>
      <volume>7</volume>
      <elocation-id>e41657</elocation-id>
      <history>
        <date date-type="received">
          <day>3</day>
          <month>8</month>
          <year>2022</year>
        </date>
        <date date-type="rev-request">
          <day>23</day>
          <month>2</month>
          <year>2023</year>
        </date>
        <date date-type="rev-recd">
          <day>18</day>
          <month>7</month>
          <year>2023</year>
        </date>
        <date date-type="accepted">
          <day>3</day>
          <month>2</month>
          <year>2024</year>
        </date>
      </history>
      <copyright-statement>©Colleen M Klein, Torunn E Sivesind, Robert P Dellavalle. Originally published in JMIR Dermatology (http://derma.jmir.org), 07.03.2024.</copyright-statement>
      <copyright-year>2024</copyright-year>
      <license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/">
        <p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIR Dermatology, is properly cited. The complete bibliographic information, a link to the original publication on http://derma.jmir.org, as well as this copyright and license information must be included.</p>
      </license>
      <self-uri xlink:href="https://derma.jmir.org/2024/1/e41657" xlink:type="simple"/>
      <kwd-group>
        <kwd>nonmelanoma skin cancer</kwd>
        <kwd>dermoscopy</kwd>
        <kwd>dermatoscopy</kwd>
        <kwd>teledermatology</kwd>
        <kwd>dermascopic</kwd>
        <kwd>dermatoscope</kwd>
        <kwd>oncology</kwd>
        <kwd>skin</kwd>
        <kwd>cancer</kwd>
        <kwd>basal cell carcinoma</kwd>
        <kwd>dermatology</kwd>
        <kwd>cutaneous squamous cell carcinoma</kwd>
        <kwd>diagnostic odds ratio</kwd>
        <kwd>skin</kwd>
        <kwd>lesion</kwd>
        <kwd>diagnostic</kwd>
        <kwd>diagnosis</kwd>
        <kwd>keratinocyte carcinoma</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec sec-type="introduction">
      <title>Introduction</title>
      <p>Given the prevalence of keratinocyte carcinomas (KCs), it is imperative to identify accurate diagnostic tools for evaluating suspicious skin lesions [<xref ref-type="bibr" rid="ref1">1</xref>,<xref ref-type="bibr" rid="ref2">2</xref>]. Misdiagnosis carries significant harms, including unnecessary scarring, anxiety, and increased cost [<xref ref-type="bibr" rid="ref3">3</xref>].</p>
    </sec>
    <sec sec-type="methods">
      <title>Methods</title>
      <p>A 2018 Cochrane review [<xref ref-type="bibr" rid="ref3">3</xref>] assessed dermoscopy as an adjunct to visual inspection (VI) for KC diagnosis among adults with skin lesions suspicious for malignancy or at risk of KC development [<xref ref-type="bibr" rid="ref3">3</xref>]. Diagnosis was verified by histology for all malignant lesions, while clinical follow-up or histologic diagnosis was required for at least 50% of participants with benign lesions to be included in the review [<xref ref-type="bibr" rid="ref3">3</xref>]. When these parameters were met, cancer registry and “expert opinion” were also allowed as reference standards, although this was considered less desirable [<xref ref-type="bibr" rid="ref3">3</xref>].</p>
    </sec>
    <sec sec-type="results">
      <title>Results</title>
      <p>The review [<xref ref-type="bibr" rid="ref3">3</xref>] included 24 studies conducted between 1987 and 2016, encompassing adult participants from North America, the Middle East, Europe, Oceania, and East Asia. <xref ref-type="table" rid="table1">Table 1</xref> presents further information about the included studies. Among the included studies, there were a total of 8805 visually inspected lesions and 6855 lesions inspected with dermoscopy and VI. Face-to-face and teledermatology settings were evaluated separately, although no clear difference was found between settings.</p>
      <p>For in-person basal cell carcinoma (BCC) diagnosis, the diagnostic odds ratio revealed dermoscopy and VI were 8.2 (95% CI 3.5-9.3) times more effective than VI alone (likelihood-ratio test <italic>P</italic>&#60;.001), supporting the predicted sensitivity difference of 14% (79% vs 93%) at a fixed specificity of 80% and predicted specificity difference of 22% (77% vs 99%) at a fixed sensitivity of 80%. The predicted values for sensitivity and specificity were estimated using summary receiver operating characteristic (SROC) curves, which were constructed based on data points derived from individual studies included in the review [<xref ref-type="bibr" rid="ref4">4</xref>]. It is crucial to note that secondary to substantial heterogeneity between studies, the reported differences in sensitivity and specificity are illustrative examples of the values that might be achieved based on the observed data and do not necessarily reflect how the tests might perform in specific settings.</p>
      <p>Sources of heterogeneity were unclear due to poor reporting and lack of available data, although the authors suggest that observer experience, type of dermatoscope used, and the case mix of included lesions may have contributed. Risk of bias and concerns regarding applicability were generally high or unclear across most domains assessed, particularly in participant selection, flow, and timing. Although the strength of the conclusions was limited, the addition of dermoscopy to in-person evaluations increased diagnostic accuracy on average. To estimate the impact of the predicted differences in specificity and sensitivity derived from the SROC curve for lesions inspected in person with VI alone versus VI and dermoscopy for the detection of BCC, they were applied to a hypothetical cohort of 1000 lesions. At the median prevalence of 17%, an additional 24 BCC would be identified and 183 fewer non-BCC would be treated unnecessarily with the use of dermoscopy and VI. This information is further illustrated in <xref ref-type="table" rid="table2">Table 2</xref>. Insufficient data were available for thorough analysis of cutaneous squamous cell carcinoma detection, and it could not be determined whether evaluator expertise or use of a formal algorithm improved the accuracy of KC detection.</p>
      <table-wrap position="float" id="table1">
        <label>Table 1</label>
        <caption>
          <p>Quantity of evidence for target lesions.</p>
        </caption>
        <table width="1000" cellpadding="5" cellspacing="0" border="1" rules="groups" frame="hsides">
          <col width="30"/>
          <col width="30"/>
          <col width="420"/>
          <col width="260"/>
          <col width="260"/>
          <thead>
            <tr valign="top">
              <td colspan="3">Setting and test (number of studies)</td>
              <td>Total lesions, n</td>
              <td>Total cases, n</td>
            </tr>
          </thead>
          <tbody>
            <tr valign="top">
              <td colspan="5">
                <bold>Basal cell carcinoma quantity of evidence (n=21)</bold>
              </td>
            </tr>
            <tr valign="top">
              <td>
                <break/>
              </td>
              <td colspan="2">
                <bold>In person</bold>
              </td>
              <td>
                <break/>
              </td>
              <td>
                <break/>
              </td>
            </tr>
            <tr valign="top">
              <td>
                <break/>
              </td>
              <td>
                <break/>
              </td>
              <td>VI<sup>a</sup></td>
              <td>7017</td>
              <td>1586</td>
            </tr>
            <tr valign="top">
              <td>
                <break/>
              </td>
              <td>
                <break/>
              </td>
              <td>VI + D<sup>b</sup></td>
              <td>4683</td>
              <td>363</td>
            </tr>
            <tr valign="top">
              <td>
                <break/>
              </td>
              <td colspan="2">
                <bold>Image based</bold>
              </td>
              <td colspan="2">
                <break/>
              </td>
            </tr>
            <tr valign="top">
              <td>
                <break/>
              </td>
              <td>
                <break/>
              </td>
              <td>VI</td>
              <td>853</td>
              <td>156</td>
            </tr>
            <tr valign="top">
              <td>
                <break/>
              </td>
              <td>
                <break/>
              </td>
              <td>VI + D</td>
              <td>2271</td>
              <td>737</td>
            </tr>
            <tr valign="top">
              <td colspan="5">
                <bold>Cutaneous squamous cell carcinoma quantity of evidence (n=4)</bold>
              </td>
            </tr>
            <tr valign="top">
              <td>
                <break/>
              </td>
              <td colspan="2">
                <bold>In person</bold>
              </td>
              <td>
                <break/>
              </td>
              <td>
                <break/>
              </td>
            </tr>
            <tr valign="top">
              <td>
                <break/>
              </td>
              <td>
                <break/>
              </td>
              <td>VI</td>
              <td>2684</td>
              <td>538</td>
            </tr>
            <tr valign="top">
              <td>
                <break/>
              </td>
              <td>
                <break/>
              </td>
              <td>VI + D</td>
              <td>—<sup>c</sup></td>
              <td>—</td>
            </tr>
            <tr valign="top">
              <td>
                <break/>
              </td>
              <td colspan="2">
                <bold>Image based</bold>
              </td>
              <td>
                <break/>
              </td>
              <td>
                <break/>
              </td>
            </tr>
            <tr valign="top">
              <td>
                <break/>
              </td>
              <td>
                <break/>
              </td>
              <td>VI</td>
              <td>—</td>
              <td>—</td>
            </tr>
            <tr valign="top">
              <td>
                <break/>
              </td>
              <td>
                <break/>
              </td>
              <td>VI + D</td>
              <td>717</td>
              <td>119</td>
            </tr>
            <tr valign="top">
              <td colspan="5">
                <bold>Any skin cancer quantity of evidence (n=11)</bold>
              </td>
            </tr>
            <tr valign="top">
              <td>
                <break/>
              </td>
              <td colspan="2">
                <bold>In person</bold>
              </td>
              <td>
                <break/>
              </td>
              <td>
                <break/>
              </td>
            </tr>
            <tr valign="top">
              <td>
                <break/>
              </td>
              <td>
                <break/>
              </td>
              <td>VI</td>
              <td>3618</td>
              <td>2021</td>
            </tr>
            <tr valign="top">
              <td>
                <break/>
              </td>
              <td>
                <break/>
              </td>
              <td>VI + D</td>
              <td>277</td>
              <td>85</td>
            </tr>
            <tr valign="top">
              <td>
                <break/>
              </td>
              <td colspan="2">
                <bold>Image based</bold>
              </td>
              <td>
                <break/>
              </td>
              <td>
                <break/>
              </td>
            </tr>
            <tr valign="top">
              <td>
                <break/>
              </td>
              <td>
                <break/>
              </td>
              <td>VI</td>
              <td>517</td>
              <td>124</td>
            </tr>
            <tr valign="top">
              <td>
                <break/>
              </td>
              <td>
                <break/>
              </td>
              <td>VI + D</td>
              <td>1526</td>
              <td>847</td>
            </tr>
          </tbody>
        </table>
        <table-wrap-foot>
          <fn id="table1fn1">
            <p><sup>a</sup>VI: visual inspection.</p>
          </fn>
          <fn id="table1fn2">
            <p><sup>b</sup>VI + D: visual inspection and dermoscopy.</p>
          </fn>
          <fn id="table1fn3">
            <p><sup>c</sup>Not applicable.</p>
          </fn>
        </table-wrap-foot>
      </table-wrap>
      <table-wrap position="float" id="table2">
        <label>Table 2</label>
        <caption>
          <p>Extrapolation of estimated sensitivity and specificity differences applied to a hypothetical cohort of 1000 lesions<sup>a</sup>.</p>
        </caption>
        <table width="1000" cellpadding="5" cellspacing="0" border="1" rules="groups" frame="hsides">
          <col width="30"/>
          <col width="170"/>
          <col width="100"/>
          <col width="100"/>
          <col width="0"/>
          <col width="100"/>
          <col width="100"/>
          <col width="0"/>
          <col width="100"/>
          <col width="100"/>
          <col width="0"/>
          <col width="100"/>
          <col width="100"/>
          <thead>
            <tr valign="top">
              <td colspan="2">
                <break/>
              </td>
              <td colspan="3">Sensitivity<sup>a</sup></td>
              <td colspan="3">Fixed specificity<sup>b</sup></td>
              <td colspan="3">Fixed sensitivity<sup>b</sup></td>
              <td colspan="2">Specificity<sup>c</sup></td>
            </tr>
            <tr valign="top">
              <td colspan="2">
                <break/>
              </td>
              <td>True positive, n</td>
              <td>False negative, n</td>
              <td colspan="2">False positive, n</td>
              <td>True negative, n</td>
              <td colspan="2">True positive, n</td>
              <td>False negative, n</td>
              <td colspan="2">False positive, n</td>
              <td>True negative, n</td>
            </tr>
          </thead>
          <tbody>
            <tr valign="top">
              <td colspan="2">
                <bold>10% prevalence</bold>
              </td>
              <td>—<sup>d</sup></td>
              <td>—</td>
              <td colspan="2">180</td>
              <td>720</td>
              <td colspan="2">80</td>
              <td>20</td>
              <td colspan="2">—</td>
              <td>—</td>
            </tr>
            <tr valign="top">
              <td>
                <break/>
              </td>
              <td>VI<sup>e</sup></td>
              <td>79</td>
              <td>21</td>
              <td colspan="2">—</td>
              <td>—</td>
              <td colspan="2">—</td>
              <td>—</td>
              <td colspan="2">207</td>
              <td>693</td>
            </tr>
            <tr valign="top">
              <td>
                <break/>
              </td>
              <td>VI + D<sup>f</sup></td>
              <td>93</td>
              <td>7</td>
              <td colspan="2">—</td>
              <td>—</td>
              <td colspan="2">—</td>
              <td>—</td>
              <td colspan="2">9</td>
              <td>891</td>
            </tr>
            <tr valign="top">
              <td colspan="2">
                <bold>17% prevalence</bold>
              </td>
              <td>—</td>
              <td>—</td>
              <td colspan="2">166</td>
              <td>664</td>
              <td colspan="2">136</td>
              <td>34</td>
              <td colspan="2">—</td>
              <td>—</td>
            </tr>
            <tr valign="top">
              <td>
                <break/>
              </td>
              <td>VI</td>
              <td>134</td>
              <td>36</td>
              <td colspan="2">—</td>
              <td>—</td>
              <td colspan="2">—</td>
              <td>—</td>
              <td colspan="2">191</td>
              <td>639</td>
            </tr>
            <tr valign="top">
              <td>
                <break/>
              </td>
              <td>VI + D</td>
              <td>158</td>
              <td>12</td>
              <td colspan="2">—</td>
              <td>—</td>
              <td colspan="2">—</td>
              <td>—</td>
              <td colspan="2">8</td>
              <td>822</td>
            </tr>
            <tr valign="top">
              <td colspan="2">
                <bold>53% prevalence</bold>
              </td>
              <td>—</td>
              <td>—</td>
              <td colspan="2">94</td>
              <td>376</td>
              <td colspan="2">424</td>
              <td>106</td>
              <td colspan="2">—</td>
              <td>—</td>
            </tr>
            <tr valign="top">
              <td>
                <break/>
              </td>
              <td>VI</td>
              <td>419</td>
              <td>111</td>
              <td colspan="2">—</td>
              <td>—</td>
              <td colspan="2">—</td>
              <td>—</td>
              <td colspan="2">108</td>
              <td>362</td>
            </tr>
            <tr valign="top">
              <td>
                <break/>
              </td>
              <td>VI + D</td>
              <td>493</td>
              <td>37</td>
              <td colspan="2">—</td>
              <td>—</td>
              <td colspan="2">—</td>
              <td>—</td>
              <td colspan="2">5</td>
              <td>465</td>
            </tr>
          </tbody>
        </table>
        <table-wrap-foot>
          <fn id="table2fn1">
            <p><sup>a</sup>The dermoscopy test had a sensitivity of 79%, and the visual inspection and dermoscopy test had a sensitivity of 93%.</p>
          </fn>
          <fn id="table2fn2">
            <p><sup>b</sup>Both tests had a fixed specificity and fixed sensitivity of 80%.</p>
          </fn>
          <fn id="table2fn3">
            <p><sup>c</sup>The dermoscopy test had a specificity of 77%, and the visual inspection and dermoscopy test had a specificity of 99%.</p>
          </fn>
          <fn id="table2fn4">
            <p><sup>d</sup>Not applicable.</p>
          </fn>
          <fn id="table2fn5">
            <p><sup>e</sup>VI: visual inspection.</p>
          </fn>
          <fn id="table2fn6">
            <p><sup>f</sup>VI + D: visual inspection and dermoscopy.</p>
          </fn>
        </table-wrap-foot>
      </table-wrap>
    </sec>
    <sec sec-type="discussion">
      <title>Discussion</title>
      <p>Recent advancements in learning algorithms using dermoscopic images, particularly deep learning techniques like convolutional neural networks (CNNs), have shown promise in improving diagnostic accuracy. In a systematic review [<xref ref-type="bibr" rid="ref5">5</xref>] of 19 studies conducted between 2017 and 2021, CNNs demonstrated comparable or improved diagnostic accuracy compared to dermatologists. However, it is important to note that these studies primarily focused on melanoma due to its significant risk, leaving a gap in research specifically targeting KCs. Further research dedicated to KC diagnosis is crucial for a comprehensive evaluation of these conditions.</p>
      <p>The authors of the review [<xref ref-type="bibr" rid="ref3">3</xref>] postulated that adjunctive dermoscopy may aid specialists in identifying BCC. However, the results should be considered suggestive rather than conclusive, given the marked heterogeneity and concerns about the methodological quality of the included studies. Further investigation is required to determine any definitive benefit of dermoscopy for BCC diagnosis. Clear identification of evaluator expertise is essential to ensure meaningful results. Moreover, additional evaluation of the use of formal algorithms may benefit clinicians in varying levels of care. The ubiquity of KCs and risks of misdiagnosis underscore the need for transparent reporting of future studies to optimize diagnostic tools and improve outcomes for patients with suspicious skin lesions.</p>
    </sec>
  </body>
  <back>
    <app-group/>
    <glossary>
      <title>Abbreviations</title>
      <def-list>
        <def-item>
          <term id="abb1">BCC</term>
          <def>
            <p>basal cell carcinoma</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb2">CNN</term>
          <def>
            <p>convolutional neural network</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb3">KC</term>
          <def>
            <p>keratinocyte carcinoma</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb4">SROC</term>
          <def>
            <p>summary receiver operating characteristic</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb5">VI</term>
          <def>
            <p>visual inspection</p>
          </def>
        </def-item>
      </def-list>
    </glossary>
    <fn-group>
      <fn fn-type="conflict">
        <p>RPD is a joint coordinating editor for <italic>Cochrane Skin</italic>, a dermatology section editor for <italic>UpToDate</italic>, a social media editor for the <italic>Journal of the American Academy of Dermatology</italic> (JAAD), and a podcast editor for the <italic>Journal of Investigative Dermatology</italic> (JID). He is a coordinating editor representative on the Cochrane Council. He is editor in chief of <italic>JMIR Dermatology</italic>. TES is an editorial board member at large for <italic>JMIR Dermatology</italic>. RPD receives editorial stipends (JAAD and JID), royalties (<italic>UpToDate</italic>), and expense reimbursement from <italic>Cochrane Skin</italic>.</p>
      </fn>
      <fn fn-type="other">
        <p>
          <bold>Editorial Notice</bold>
        </p>
        <p>The views expressed in this paper are those of the author(s) and in no way represent the Cochrane Library or Wiley. This article is based on a Cochrane Review previously published in the Cochrane Database of Systematic Reviews 2018, Issue 12, DOI: 10.1002/14651858.CD011901.pub2 (see www.cochranelibrary.com for information). Cochrane Reviews are regularly updated as new evidence emerges and in response to feedback, and Cochrane Database of Systematic Reviews should be consulted for the most recent version of the review.</p>
      </fn>
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