No evidence for integrated viral DNA in the genome sequence of cutaneous squamous cell carcinoma

Cutaneous squamous cell carcinoma (cSCC) is the second most common type of nonmelanoma skin cancer and is dramatically increased in the setting of immunosuppression such as organ transplantation (Grulich et al., 2007; Hartevelt et al., 1990; Jensen et al., 1999; Lindelof et al., 2000). This magnitude of increase is similar to that seen in virusrelated cancers, such as human herpesvirus-8 mediated Kaposi's sarcoma and Epstein-Barr virus related lymphoma (Vajdic et al., 2006). There have been multiple attempts to define a viral etiology for cSCC and to link cSCC with human papillomavirus (HPV). There is a clear epidemiologic association between HPV and cSCC (Aldabagh et al., 2012), but detection has been limited to viral DNA. Two studies have demonstrated the absence of viral transcription in cSCC RNAseq data, confirming that direct viral transformation of keratinocytes is not required for maintenance of tumor (Arron et al., 2011; Ganzenmueller et al., 2012). These data suggest that, if there is a viral pathogen causing cSCC, the mechanism of carcinogenesis is not simply through expression of viral oncogenes.