Review of Literature to Determine Recommended Application of HPV-42 Molecular Testing for Digital Papillary...

Digital Papillary Adenocarcinoma (DPA) is a rare tumor that can cause metastasis and death. It can morphologically mimic benign sweat gland tumors. In 2022, the novel association of HPV-42 and DPA was discovered by means of DNA sequencing. In this scoping review, we aimed to systematically evaluate alternatives to HPV-42 molecular sequencing. Of 87 articles on DPA identified in a PUBMED meta-search, eight met the inclusion criteria. We found that DNA sequencing for HPV-42 is most sensitive (94%). Comparable tests included HPV-42 in situ hybridization (ISH), which had 82% sensitivity, and p16 immunohistochemistry, which had 70%-75% sensitivity. We further evaluated the performance of HPV-42 ISH and performed a stratified analysis of HPV-42 ISH-negative DPA cases. There was a statistically significant difference in HPV-42 positivity in patients younger than and older than 60 years old (p = 0.02). We recommend HPV-42 ISH for cases with equivocal morphology from patients aged over 60 years. Tumors with equivocal morphology from patients under the age of 60 years should be sequenced for HPV-42. For cases with classic morphology, p16 can be used to support the diagnosis, but molecular testing for HPV-42 is unnecessary.