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   HPV (Human papillomavirus) is a large group of viruses with double-stranded DNA. HPV usually infects the epidermal cells of the skin and mucosa. The genome of HPV is about 8 kb in size and typically has 8 genes. HPV is classified based on the nucleotide sequence of the gene encoding the viral capsid L1 protein. Different types of HPV have at least 10% differences in nucleotide sequences of the L1 gene. Up to 2016 August, 210 different types of HPV have been cloned, sequenced and officially labeled by International HPV Reference Center. (

Genital warts or condyloma accuminata are a common STD caused by HPV infection. The most common type of HPV causing warts is HPV6 of the genus Alphapapillomavirus. A small percentage of genital warts cases have had negative results in HPV test. According to Wal Boomer and Meijer (1997), besides true negative cases, the cases of false negatives can be explained as follows:

  • Inappropriate sampling
  • Methods are not sensitive enough and new types of HPV cannot be detected by the method used. In one study in southern Sweden, it was found that 96.3% of genital warts had a positive HPV test result, and a few reported negative HPV test results even when used broadband HPV PCR priming system.

The metagenomic sequencing method can help increase the sensitivity of the HPV detection process and determine the apperance of DNA in the samples. In a study published in August 2015, Arroyo and colleagues from Karolinska Institute and Lund University of Sweden used deep sequencing techniques, focusing on analyzing patterns. Genital warts have previously had a negative HPV test result in search of a more sensitive virus detection method and found new types of HPV. The results showed that 37/40 samples (92.5%) in the study, contained HPV sequences representing a total of 75 types of HPV in the genus Alpha, Beta and Gamma. Among these, there are 27 officially recognized HPV types (including 3 newly discovered and officially recognized types from this study). In addition, there are 5 known HPV types and at least 43 previously unknown HPV sequences were found. The presumptive types of HPV previously described have a part of the gene bank that has been registered but has not yet been given an official number because they have not been cloned, fully sequenced and unregistered at the international reference center for HPV. Thus, in this study, a total of 46 new hypothetical HPV types were detected. Three of them were cloned, sequenced and sent to the International Reference Information Center on HPV. The center has sequenced and officially recognized 3 new types of HPV and named as HPV200, HPV201 and HPV202.

Some of the 40 study samples contained types of HPV that were well-known to cause genital warts, especially HPV6, although previous PCR methods were not detected. It is thought that this may be due to changes in the target sequence of the primer or the probe used. Deep sequencing solves this problem by detecting HPV types without having to know the sequence in advance, regardless of PCR.

Clinically differentiation between genital warts and mollusca is not easy. There has been the simultaneous existence of molluscum contagiosum virus with HPV. In this study, the presence of molluscum contagiosum was detected in 24/40 samples of genital warts and 22 of those 24 samples also contained HPV. There is only one sample of genital warts that did not detect the presence of HPV as well as the molluscum contagiosum virus.

Conventional methods may not detect HPV in a certain percentage of genital warts specimens. The more advanced method of “deep sequencing” has a high sensitivity that can improve this problem. Results of the study by Arroyo et al. Suggest that genital warts with a negative HPV test result may be explained by the following causes: inadequate diagnosis, existence of virus variants, low viral load or the existence of previously unknown virus types.

Author: PhD Trần Dụ Chi
Publisher: Social Work Department