Transcriptome Sequencing Demonstrates that Human Papillomavirus Is Not Active in Cutaneous Squamous Cell Carcinoma

Abstract

Beta-papillomavirus (β-HPV) DNA is present in some cutaneous squamous cell carcinomas (cuSCC), but no mechanism of carcinogenesis has been determined. We used ultra-high throughput sequencing of the cancer transcriptome to assess whether papillomavirus transcripts are present in these cancers. Sixty-seven cuSCC samples were assayed for β-HPV DNA by PCR, and viral loads were measured with type-specific qPCR. Thirty-one SCCs were selected for whole transcriptome sequencing. Transcriptome libraries were prepared in parallel from the HPV18 positive HeLa cervical cancer cell line and HPV16 positive primary cervical and periungual SCC. Thirty percent (20/67) of the tumors were positive for β-HPV DNA, but there was no difference in β-HPV viral load between tumor and normal tissue (p=0.310). Immunosuppression and age were significantly associated with higher viral load (p=0.016 for immunosuppression; p=0.0004 for age). Transcriptome sequencing failed to identify papillomavirus expression in any of the skin tumors. In contrast, HPV 16 and 18 mRNA transcripts were readily identified in primary cervical and periungual cancers and HeLa cells. These data demonstrate that papillomavirus mRNA expression is not a factor in the maintenance of cuSCC.

Mapping of Betapapillomavirus Human Papillomavirus 5 Transcription and Characterization of Viral-Genome Replication Function

“…Transcriptome sequencing from cutaneous SCCs has also demonstrated low viral copy numbers for betaHPVs and a lack of transcripts potentially encoding oncogenic proteins, in contrast to alphaHPVs, which exhibit much higher viral copy numbers per cell (61). It is possible that unlike alphaHPVs, the betaHPV genome is generally not as strongly amplified during the last step of infection due to weaker enhancers in the LCR and the absence of important transcription factor recognition sites, such as SP-1 and TEF-1.…”

MicroRNA expression differs in cutaneous squamous cell carcinomas and healthy skin of immunocompetent individuals

“…HPV is supposedly a risk factor for cSCC development. However, only half of cSCCs reveal HPV-DNA (6,26,27), whereas no HPV activity could be detected (28). Evidences show that HPV effects are boosted during actinic keratosis (29).…”

A Review of Cutaneous Squamous Cell Carcinoma Epidemiology, Diagnosis, and Management

“…While some studies have reported an increased risk of CSCC in immunocompetent individuals with HPV infection (32)(33)(34), other studies have failed to show a relationship between HPV and CSCC risk (35)(36)(37) with the exception of anogenital CSCC (38).…”