Merkel Cell Polyomavirus and HPV-17 Associated With Cutaneous Squamous Cell Carcinoma Arising in a Patient With Melanoma Treated With the BRAF Inhibitor Dabrafenib

Abstract

Background Approximately 10–25% of patients treated with BRAF inhibitors develop cutaneous squamous cell carcinoma (SCC), but the mechanism responsible has not yet been determined. We report the first case in which Merkel cell polyomavirus (MCPyV) and HPV-17 are associated with cutaneous SCC which developed during treatment with BRAF inhibitor GSK2118436. Observations A 62 year-old woman with V600E BRAF-mutant metastatic melanoma enrolled on a phase I trial of GSK2118436, a selective inhibitor of V600-mutant BRAF kinase. During the first six weeks of treatment, the patient developed multiple skin lesions, including a 6-mm crusted papule on the left eyebrow, which was resected and revealed SCC. DNA extracted from paraffin-embedded tissue was amplified by polymerase chain reaction (PCR) for detection of MCPyV and epidermodysplasia verruciformis HPV (EV-HPV) types. Analysis of the cloned and sequenced PCR products revealed the presence of MCPyV and HPV-17 DNA. Other EV-HPV subtypes were not detected. Conclusions To our knowledge, this is the first report demonstrating the co-existence of MCPyV and HPV-17 in cutaneous SCC. Because both viruses have known oncogenic potential, the role of these viruses in the etiology of BRAF inhibitor-related SCC merits further investigation.

Cutaneous Epithelial Tumors Induced by Vemurafenib Involve the MAPK and Pi3KCA Pathways but Not HPV nor HPyV Viral Infection

“…In addition, HRAS H27H polymorphism was statistically associated with the risk of developing various cancers (gastric, thyroid, bladder, and oral squamous cell carcinoma) and was detected both in tumor and in blood samples [24]–[28]. In addition, it has been reported in a SCC lesion of one patient treated with dabrafenib [8]. In contrast to other HRAS mutations, this polymorphism may only reflect cancer susceptibility.…”

Vemurafenib Cooperates with HPV to Promote Initiation of Cutaneous Tumors

“…The majority of nonmelanocytic lesions occurring in vemurafenibtreated patients include several benign skin lesions with strong associations with HPV, including venereal warts and verrucous papillomas (5), which strongly implicates a role for HPV. Although the frequency is low, expression of HPV capsid protein has been observed in one cSCC from a patient treated with the RAF inhibitor dabrafenib (22), and HPV DNA was observed in a separate case study (23).…”

Presence of Human Polyomavirus 6 in Mutation-Specific BRAF Inhibitor–Induced Epithelial Proliferations

“…Notably, a recent case report identified HPV and Merkel cell polyomavirus (MCPyV) DNA in a cutaneous SCC that developed after BRAF inhibitor therapy. 14 In the present study, we tested for the presence of HPV and human polyomaviruses (HPyVs), ie, MCPyV and trichodysplasia spinulosa-associated polyomavirus (TSPyV), as well as HPyV-6, HPyV-7, HPyV-9, and HPyV-10, in a series of BRAF inhibitor-associated epithelial proliferations.…”