Author's reply to: Human papillomavirus type 197 is not associated with skin tumors

Abstract

Dear editor,We previously reported on a new human papillomavirus (HPV) type (HPV197) that was detected by next-generation sequencing of a series of skin cancer specimens. 1 As sequencing of a specimen is not dependent on primer sequences, it can also detect viruses that do not have sufficient sequence similarity to be amplified by known broad general primer polymerase chain reaction (PCR) systems and indeed this was the case for HPV197. 1 We also designed a specific real-time PCR for HPV197 and found that essentially the same specimens that had been positive for HPV197 by sequencing were also positive by the specific PCR. 1 However, in a subsequent article also published in International Journal of Cancer, 2 we analyzed 62 nonmelanoma skin cancers (NMSCs) and 27 other cancers and only 1 NMSC was positive for HPV197, 2 much less than in the first series. 1 In the first paper, we performed HPV197 detection by two methods based on different principles, making technical error unlikely, and use of negative controls also made laboratory contamination unlikely. 1 Apart from that different specimen series may differ, we also raised the possibility of biological contamination (i.e., contamination already before the sample arrives at the lab). 2 This phenomenon was most clearly shown for an HPV88-positive skin cancer that contained >1 million viral copies/cell and where the tumor appeared to have contaminated the fingers on the other arm of the patient. 3 We have also pointed out that many skin cancers that are positive for low amounts of HPV DNA appear to lack any detectable viral transcription, 4 suggesting that their presence may not reflect an infection but rather be a deposition caused by the patient or at the dermatology clinic, arguing that studies on HPV infections of the skin should focus on detection of viral RNA transcripts. 4 References 1. Arroyo Muhr LS, Hultin E, Bzhalava D, et al. Human papillomavirus type 197 is commonly present in skin tumors.

De novo sequence assembly requires bioinformatic checking of chimeric sequences

“…Metagenomics studies of viral DNA have detected a broad number of HPVs in both healthy skin and skin tumor samples [21][22][23][24][25][26]. Studies based on HPV detection using specific PCRs are limited by the fact that HPV types with no homology to the sequences present in primers and probes might have escaped amplification [2,4].…”