Tumor‐specific and gender‐specific pre‐vaccination distribution of human papillomavirus types 6 and 11 in anogenital warts and laryngeal papillomas: A study on 574 tissue specimens

Komloš, Kristina Fujs; Kocjan, Boštjan J.; Košorok, Pavle; Luzar, Boštjan; Meglič, Leon; Potočnik, Marko; Boltežar, Irena Hočevar; Gale, Nina; Seme, Katja; Poljak, Mario

doi:10.1002/jmv.23318

Cited by 61 publications

(53 citation statements)

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“…We present the first study of the global genomic diversity of HPV11, an etiological agent of the two most frequent benign tumors in the anogenital region and upper respiratory tract: anogenital warts and laryngeal papillomas, respectively (2,5,6). For the purpose of this study, a total of 207 HPV11 isolates were collected from 14 countries covering six continents, and four genomic regions, including the E5a, E5b, and L1 ORFs and the noncoding region URR were sequenced.…”

Section: Discussionmentioning

confidence: 99%

“…uman papillomavirus 11 (HPV11), which belongs to species 10 of the Alphapapillomavirus genus (Alpha-PV), is etiologically associated with approximately 20% of anogenital warts and 30 to 40% of laryngeal papillomas (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11). HPV11 is generally considered a low-risk HPV type due to its rare presence in HPVrelated cancers in humans, especially cervical cancer (9).…”

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confidence: 99%

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Global Genomic Diversity of Human Papillomavirus 11 Based on 433 Isolates and 78 Complete Genome Sequences

Jelen

Chen

Kocjan

et al. 2016

J Virol

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Human papillomavirus 11 (HPV11) is an etiological agent of anogenital warts and laryngeal papillomas and is included in the 4-valent and 9-valent prophylactic HPV vaccines. We established the largest collection of globally circulating HPV11 isolates to date and examined the genomic diversity of 433 isolates and 78 complete genomes (CGs) from six continents. The genomic variation within the 2,800-bp E5a-E5b-L1-upstream regulatory region was initially studied in 181/207 (87.4%) HPV11 isolates collected for this study. Of these, the CGs of 30 HPV11 variants containing unique single nucleotide polymorphisms (SNPs), indels (insertions or deletions), or amino acid changes were fully sequenced. A maximum likelihood tree based on the global alignment of 78 HPV11 CGs (30 CGs from our study and 48 CGs from GenBank) revealed two HPV11 lineages (lineages A and B) and four sublineages (sublineages A1, A2, A3, and A4). HPV11 (sub)lineage-specific SNPs within the CG were identified, as well as the 208-bp representative region for CG-based phylogenetic clustering within the partial E2 open reading frame and noncoding region 2. Globally, sublineage A2 was the most prevalent, followed by sublineages A1, A3, and A4 and lineage B. IMPORTANCEThis collaborative international study defined the global heterogeneity of HPV11 and established the largest collection of globally circulating HPV11 genomic variants to date. Thirty novel complete HPV11 genomes were determined and submitted to the available sequence repositories. Global phylogenetic analysis revealed two HPV11 variant lineages and four sublineages. The HPV11 (sub)lineage-specific SNPs and the representative region identified within the partial genomic region E2/noncoding region 2 (NCR2) will enable the simpler identification and comparison of HPV11 variants worldwide. This study provides an important knowledge base for HPV11 for future studies in HPV epidemiology, evolution, pathogenicity, prevention, and molecular assay development. Human papillomavirus 11 (HPV11), which belongs to species 10 of the Alphapapillomavirus genus (Alpha-PV), is etiologically associated with approximately 20% of anogenital warts and 30 to 40% of laryngeal papillomas (1-11). HPV11 is generally considered a low-risk HPV type due to its rare presence in HPVrelated cancers in humans, especially cervical cancer (9). HPV11 is present in 0.5% of samples from HPV-positive women with a normal cytology worldwide and causes 2.3% of cervical low-grade squamous cell intraepithelial lesions (12, 13). However, rare case reports of HPV11-positive cases of cervical and anal squamous cell carcinomas, malignantly transformed laryngeal papillomas, and sinonasal inverted papillomas associated with squamous cell carcinoma can be found in the literature (14-21). Due to its clinical significance, HPV11 has been included in the current quadrivalent and nonavalent prophylactic HPV vaccines (22,23).The genetic diversity of HPV11 was studied for the first time in 1995, when Heinzel et al. sequenced the noncoding upstre...

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Global Genomic Diversity of Human Papillomavirus 11 Based on 433 Isolates and 78 Complete Genome Sequences

Jelen

Chen

Kocjan

et al. 2016

J Virol

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“…The HPV genome is a short, circular, double-stranded DNA molecule that typically codes up to eight proteins, ranging in function from genomic regulation (E1 and E2) to capsid proteins (L1 and L2), and viral oncoproteins (E6 and E7) [3]. To date, over 170 different HPV types have been completely characterized and officially recognized, with HPV types 6 and 11 being found in a vast majority of the RRP patients [4,5].…”

Section: Introductionmentioning

confidence: 99%

Human papilloma virus vaccination in patients with an aggressive course of recurrent respiratory papillomatosis

Boltežar

Matičič

Šereg-Bahar

et al. 2014

Eur Arch Otorhinolaryngol

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In the case of an aggressive course of recurrent respiratory papillomatosis (RRP), adjuvant therapy can be used besides surgery. The aim of the study was to investigate the influence of vaccination with a quadrivalent vaccine against human papilloma viruses (HPV) types 6, 11, 16 and 18 on the course of RRP. Eleven subjects aged 13-46 years with a rapid growth of laryngeal papillomas were included in the study. They were vaccinated with three doses of the quadrivalent prophylactic HPV vaccine (Silgard(®), MSD) and followed up for 12-52 months. The intervals between the successive surgical procedures, the extension of the disease (Derkay score) at each surgery, and the number of surgical procedures per year before vaccination and after its completion were compared. The mean interval between the surgical procedures was 271.2 days before the vaccination and 537.4 days after it (p = 0.034). The mean number of surgeries per year was 2.16 before the vaccination and 0.93 after it (p = 0.022). The Derkay score did not change significantly after vaccination. Complete remission of the disease was observed in one patient, partial response to the vaccination was observed in seven patients and no response was observed in three patients. In conclusion, vaccination with the quadrivalent HPV vaccine can favorably influence the course of RRP in patients with the rapid growth of the papillomas. It significantly prolongs the intervals between the surgical procedures and reduces the number of procedures needed in the majority of patients. The present investigation can serve as a pilot study for further research. For a final conclusion a longer follow-up and studies on more patients are necessary.

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“…HPV6 is considered a low-risk HPV, since it is rarely detected in invasive cervical cancer and other HPV-related anogenital cancers. It is the major etiological agent of anogenital warts and laryngeal papillomas, the most frequent benign tumors of the anogenital region and upper respiratory tract (2)(3)(4)(5). In addition, HPV6 has been associated with Buschke-Löwenstein tumor (6) and with sporadic cases of anal (7), vulvar (8), penile (9), and head and neck (10) cancers, and it is the most prevalent low-risk type in HPV-positive women with normal cytology, with a global prevalence of 0.8% (11).…”

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Global Genomic Diversity of Human Papillomavirus 6 Based on 724 Isolates and 190 Complete Genome Sequences

Jelen

Chen

Kocjan

et al. 2014

J Virol

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Human papillomavirus type 6 (HPV6) is the major etiological agent of anogenital warts and laryngeal papillomas and has been included in both the quadrivalent and nonavalent prophylactic HPV vaccines. This study investigated the global genomic diversity of HPV6, using 724 isolates and 190 complete genomes from six continents, and the association of HPV6 genomic variants with geographical location, anatomical site of infection/disease, and gender. Initially, a 2,800-bp E5a-E5b-L1-LCR fragment was sequenced from 492/530 (92.8%) HPV6-positive samples collected for this study. Among them, 130 exhibited at least one single nucleotide polymorphism (SNP), indel, or amino acid change in the E5a-E5b-L1-LCR fragment and were sequenced in full. A global alignment and maximum likelihood tree of 190 complete HPV6 genomes (130 fully sequenced in this study and 60 obtained from sequence repositories) revealed two variant lineages, A and B, and five B sublineages: B1, B2, B3, B4, and B5. HPV6 (sub)lineage-specific SNPs and a 960-bp representative region for whole-genome-based phylogenetic clustering within the L2 open reading frame were identified. Multivariate logistic regression analysis revealed that lineage B predominated globally. Sublineage B3 was more common in Africa and North and South America, and lineage A was more common in Asia. Sublineages B1 and B3 were associated with anogenital infections, indicating a potential lesion-specific predilection of some HPV6 sublineages. Females had higher odds for infection with sublineage B3 than males. In conclusion, a global HPV6 phylogenetic analysis revealed the existence of two variant lineages and five sublineages, showing some degree of ethnogeographic, gender, and/or disease predilection in their distribution. IMPORTANCEThis study established the largest database of globally circulating HPV6 genomic variants and contributed a total of 130 new, complete HPV6 genome sequences to available sequence repositories. Two HPV6 variant lineages and five sublineages were identified and showed some degree of association with geographical location, anatomical site of infection/disease, and/or gender. We additionally identified several HPV6 lineage-and sublineage-specific SNPs to facilitate the identification of HPV6 variants and determined a representative region within the L2 gene that is suitable for HPV6 whole-genome-based phylogenetic analysis. This study complements and significantly expands the current knowledge of HPV6 genetic diversity and forms a comprehensive basis for future epidemiological, evolutionary, functional, pathogenicity, vaccination, and molecular assay development studies.

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Tumor‐specific and gender‐specific pre‐vaccination distribution of human papillomavirus types 6 and 11 in anogenital warts and laryngeal papillomas: A study on 574 tissue specimens

Cited by 61 publications

References 65 publications

Global Genomic Diversity of Human Papillomavirus 11 Based on 433 Isolates and 78 Complete Genome Sequences

Global Genomic Diversity of Human Papillomavirus 11 Based on 433 Isolates and 78 Complete Genome Sequences

Human papilloma virus vaccination in patients with an aggressive course of recurrent respiratory papillomatosis

Global Genomic Diversity of Human Papillomavirus 6 Based on 724 Isolates and 190 Complete Genome Sequences

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