Does human papillomavirus-negative condylomata exist?

Condylomata acuminata is caused by human papillomavirus (HPV). PCR with consensus primers will typically detect HPV in >96% of condylomata. Metagenomic sequencing has found that some "HPV-negative" condylomata do indeed contain HPV. We wished to perform a renewed evaluation of the "HPV-negative" condylomata using deeper metagenomics sequencing. Sequencing of whole genome amplified DNA from 40 apparently "HPV-negative" condylomata detected HPV in 37/40 specimens. We found 75 different HPV types, out of which 43 represented novel putative HPV types. Three types were cloned and established as HPV types 200, 201 and 202. Molluscum contagiosum virus was detected in 24 of the 40 samples. In summary, deep sequencing enables detection of HPV in almost all condylomata. "HPV-negative" condylomata might largely be explained by clinical misdiagnosis or the presence of viral variants, distantly related HPV types and/or low viral loads.