Evolution and Taxonomic Classification of Human Papillomavirus 16 (HPV16)-Related Variant Genomes: HPV31, HPV33, HPV35, HPV52, HPV58 and HPV67

Chen, Zigui; Schiffman, Mark; Herrero, Rolando; DeSalle, Rob; Anastos, Kathryn; Segondy, Michel; Sahasrabuddhe, Vikrant V.; Gravitt, Patti E.; Hsing, Ann W.; Burk, Robert D.

doi:10.1371/journal.pone.0020183

Cited by 154 publications

(266 citation statements)

References 60 publications

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“…SI) similar to that based on phylogenetic analysis performed using whole genome sequences. 22 Second, we tested only one sample per woman for most study subjects rather than all positive samples for variant characterization. If a change of the variants overtime is common, the risk estimates might be distorted.…”

Section: Discussionmentioning

confidence: 99%

“…To assess the appropriateness of our classification, we compared the lineages classified based on sequences of our targeted region to those previously reported based on the whole genome of 22 HPV31 variants. 22 A phylogenetic tree was reconstructed using a Bayesian Markov chain Monte Carlo (MCMC) method implemented in BEAST v1.62. 26 The HKY model of nucleotide substitution was employed assuming a molecular clock 27 .…”

Section: Characterization Of Hpv31 Variantsmentioning

confidence: 99%

“…1 Clinical relevance of HPV31 variants has been rarely described, [13][14][15] although the intratypic variations in the L1, E6, E7 and long control region were recognized. [14][15][16][17][18][19][20][21] A recent study by Chen et al 22 has defined HPV31 variants as A, B and C lineages based on the whole genome analyses. This provides a basis to view the variant as a distinct phylogenetic entity and better understand the variant-related pathogenesis of cervical lesion.…”

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confidence: 99%

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Association of human papillomavirus type 31 variants with risk of cervical intraepithelial neoplasia grades 2–3

Schiffman

Koutsky

et al. 2012

Intl Journal of Cancer

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Although the lineages of human papillomavirus type 31 (HPV31) variants are recognized, their clinical relevance is unknown. The purpose of our study was to examine risk of cervical intraepithelial neoplasia Grades 2-3 (CIN2/3) by HPV31 variants. Study subjects were women who participated in the atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion Triage Study and who had HPV31 infections detected at one or more visits. They were followed semi-annually over 2 years for detection of HPV DNA and cervical lesion. HPV31 isolates were characterized by DNA sequencing and assigned into 1 of 3 variant lineages. CIN2/3 was histologically confirmed in 127 (27.0%) of the 470 HPV31-positive women, 83 diagnosed at the first HPV31-positive visit and 44 thereafter. The odds ratio for the association of 2-year cumulative risk of CIN2/3 was 1.7 (95% CI: 1.0-2.9) for infections with A variants and 2.2 (95% CI: 1.2-3.9) for infections with B variants as compared to those with C variants. Among women without CIN2/3 at the first HPV31-positive visit, the risk of subsequent CIN2/3 was 2.2-fold greater for those with A variants (95% CI: 1.0-4.8) and 2.0-fold greater for those with B variants (95% CI: 0.9-4.9) as compared to those with C variants. Similar associations were observed when CIN3 was used as the endpoint. The findings from our study help to tag HPV31 variants that differ in risk of CIN2/3 and to explain in part why some HPV31 infections regress spontaneously and others lead to disease progression.Cervical infection with human papillomavirus (HPV) types is a necessary cause of cervical cancer and its precursor, cervical intraepithelial neoplasia Grades 2-3 (CIN2/3). 1-3 To date, >150 papillomavirus types have been fully characterized and classified, from the higher to lower taxon, as genera, species and type. 4,5 HPV types are known to differ in their tropisms and oncogenic potentials. Studies of the intratypic variation, i.e., the variant, a level below the taxon of type, have focused mainly on HPV16 and HPV18, showing that some variants were more aggressive than others. [6][7][8][9][10][11][12] HPV31 is one of the oncogenic types, most closely related to HPV16. Prevalence of some HPV types may vary geographically. Results from a recent meta-analysis (including 215 studies worldwide) have shown that on average prevalence of HPV31 infection ranks fourth, after types 16, 18 and 45, in cases of cervical cancer and second, only after type 16, in women with high-grade squamous intraepithelial lesion (referring both to cytologically detected high-grade lesions and histologically diagnosed CIN2/3 or carcinoma in situ in this analysis). 1 Clinical relevance of HPV31 variants has been rarely described, 13-15 although the intratypic variations in the L1, E6, E7 and long control region were recognized. 14-21 A recent study by Chen et al. 22 has defined HPV31 variants as A, B and C lineages based on the whole genome analyses. This provides a basis to view the variant as a distinct phylogenet...

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Section: Discussionmentioning

confidence: 99%

Section: Characterization Of Hpv31 Variantsmentioning

confidence: 99%

mentioning

confidence: 99%

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Association of human papillomavirus type 31 variants with risk of cervical intraepithelial neoplasia grades 2–3

Schiffman

Koutsky

et al. 2012

Intl Journal of Cancer

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“…18 A cross-neutralizing monoclonal anti-L2 antibody, K4L2 [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38] , highly potent at neutralizing HPV 16 and other high-risk HPV pseudovirions (PSV), fails to neutralize HPV 31. Vice versa, an anti-HPV 31 L2 neutralizing antibody (K3L2 [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38] ) is not able to neutralize HPV 16 PSV. Also, anti-HPV 16 L2 polyclonal sera neutralize HPV 31 pseudovirions with a low efficiency (Seitz et al, unpublished data).…”

Section: Resultsmentioning

confidence: 99%

“…Of the 24 sequences analyzed, two contained previously described nonsilent exchanges, 28 one being an D ! N exchange at position 31 (D31N) and the other a P34T exchange (Fig.…”

Section: In Silico Analysis Of Natural L2 Variantsmentioning

confidence: 99%

Natural variants in the major neutralizing epitope of human papillomavirus minor capsid protein L2

Seitz

Schmitt

Böhmer³

et al. 2012

Intl Journal of Cancer

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The amino terminus of the human papillomavirus minor capsid protein L2 contains a major cross-neutralizing epitope that provides the basis for the development of a broadly protective HPV vaccine. This attainable broad protection would eliminate one of the major drawbacks of the commercial L1-based prophylactic vaccines. In this study, we asked whether there are natural variants of the L2 cross-neutralizing epitope and if these variants provide means for immune escape from vaccineinduced anti-L2 antibodies. For this, we isolated in silico and in vitro, a total of 477 L2 sequences of HPV types 16, 18, 31, 45, 51, 52 and 58. We identified natural L2 epitope variants for HPV 18, 31, 45 and 51. To determine whether these variants escape L2-directed neutralization, we generated pseudovirions encompassing the natural variants and tested these in an in vitro neutralization assay using monoclonal and polyclonal antibodies. Our results indicate that natural variants of the L2 major neutralizing epitope are frequent among two different study populations from Germany and Mongolia and in the GenBank database. Of two identified HPV 31 L2 single amino acid variants, one could be neutralized well, while the other variant was neutralized very poorly. We also observed that single amino acid variants of HPV 18 and 45 are neutralized well while a HPV 18 double variant was neutralized at significantly lower rates, indicating that L2 variants have to be accounted for when developing HPV L2-based prophylactic vaccines.Human papillomaviruses (HPVs) are the causative agents for the development of cervical cancer. Close to 100% of tumors from the uterine cervix harbor sequences of HPVs; at least 15 different types are linked to cancer, and these are termed as ''oncogenic HPV types.'' 1 Worldwide, the 10 most frequently isolated HPV types in cervical cancer are HPV 16,18,33, 45,31, 58, 52,35, 59 and 56. 2 In general, however, infection with genital HPV is common in adults, and most infections are cleared by the immune system. The most frequent HPV types isolated in women with normal cytology are, in order of prevalence, HPV 16, 42, 58,31,18, 56, 81,35,33, 45 and 52. 3 Although other factors contribute to the malignant transformation process, it is generally accepted that HPV infection is an absolute requirement. 4,5 Built on the recognition of HPV infection in the etiology of cervical cancer, two commercial vaccines, Gardasil V R and Cervarix V R , have been licensed in 2006 and 2007, respectively. 6,7 Both vaccines are based on the L1 major capsid protein and are highly effective in preventing HPV infection and HPV-induced cervical lesions. 8,9 It is expected that both vaccines will reduce the cervical cancer rate in vaccinated women by 70-80%.Both L1-based vaccines have some limitations including costly production, invasive administration and limited protection against nonvaccine HPV types. The latter is due to the fact that neutralizing anti-L1 binds to surface loops on the viral capsids, which are highly heterogeneous among the dif...

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Detection of human papillomavirus 67 single infection in high‐grade cervical lesions: Case report and review of literature

Schandevyl

Coorevits

Boelens

et al. 2018

Diagnostic Cytopathology

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Evolution and Taxonomic Classification of Human Papillomavirus 16 (HPV16)-Related Variant Genomes: HPV31, HPV33, HPV35, HPV52, HPV58 and HPV67

Cited by 154 publications

References 60 publications

Association of human papillomavirus type 31 variants with risk of cervical intraepithelial neoplasia grades 2–3

Association of human papillomavirus type 31 variants with risk of cervical intraepithelial neoplasia grades 2–3

Natural variants in the major neutralizing epitope of human papillomavirus minor capsid protein L2

Detection of human papillomavirus 67 single infection in high‐grade cervical lesions: Case report and review of literature

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