Human papillomavirus 16 non-european variants are preferentially associated with high-grade cervical lesions

Luciana Bueno Freitas, Zigui Chen, Elaine Freire Muqui, Neide Aparecida Tosato Boldrini, Angélica Espinosa Miranda, Liliana Cruz Spano, Robert D. Burk

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

HPV16 accounts for 50-70% of cervical cancer cases worldwide. Characterization of HPV16 variants previously indicated that they differ in risks for viral persistence, progression to cervical precancer and malignant cancer. The aim of this study was to examine the association of severity of disease with HPV16 variants identified in specimens (n = 281) obtained from a Cervical Pathology and Colposcopy outpatient clinic in the University Hospital of Espírito Santo State, Southeastern Brazil, from April 2010 to November 2011. All cytologic and histologic diagnoses were determined prior to definitive treatment. The DNA was isolated using QIAamp DNA Mini Kit and HPV was detected by amplification with PGMY09/11 primers and positive samples were genotyped by RFLP analyses and reverse line blot. The genomes of the HPV16 positive samples were sequenced, from which variant lineages were determined. Chi2 statistics was performed to test the association of HPV16 variants between case and control groups. The prevalence of HR-HPV types in <CIN1, CIN2 and CIN3+ were 33.7%, 84.4% and 91.6%, respectively. Thirty-eight of 49 (78%) HPV16 positive samples yielded HPV16 sequence information; of which, 32 complete genomes were sequenced and an additional 6 samples were partially sequenced. Phylogenetic analysis and patterns of variations identified 65.8% (n = 25) as HPV16 European (E) and 34.2% (n = 13) as non-European (NE) variants. Classification of disease into CIN3+ vs. <CIN3 indicated that NE types were associated with high-grade disease with an OR = 4.6 (1.07-20.2, p = 0.05). The association of HPV16 NE variants with an increased risk of CIN3+ is consistent with an HPV16 genetically determined enhanced oncogenicity. The prevalence of genetic variants of HPV16 is distributed across different geographical areas and with recent population admixture, only empiric data will provide information on the highest risk HPV16 variants within a given population.

Original languageEnglish (US)
Article numbere100746
JournalPLoS One
Volume9
Issue number7
DOIs
StatePublished - Jul 1 2014

Fingerprint

Human papillomavirus 16
Genes
Genome
Colposcopy
DNA
colposcopy
Pathology
Ambulatory Care Facilities
sampling
Uterine Cervical Neoplasms
Restriction Fragment Length Polymorphisms
Population
carcinogenicity
uterine cervical neoplasms
Amplification
Brazil
genome
Statistics
disease severity
restriction fragment length polymorphism

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Freitas, L. B., Chen, Z., Muqui, E. F., Boldrini, N. A. T., Miranda, A. E., Spano, L. C., & Burk, R. D. (2014). Human papillomavirus 16 non-european variants are preferentially associated with high-grade cervical lesions. PLoS One, 9(7), [e100746]. https://doi.org/10.1371/journal.pone.0100746

Human papillomavirus 16 non-european variants are preferentially associated with high-grade cervical lesions. / Freitas, Luciana Bueno; Chen, Zigui; Muqui, Elaine Freire; Boldrini, Neide Aparecida Tosato; Miranda, Angélica Espinosa; Spano, Liliana Cruz; Burk, Robert D.

In: PLoS One, Vol. 9, No. 7, e100746, 01.07.2014.

Research output: Contribution to journalArticle

Freitas, Luciana Bueno ; Chen, Zigui ; Muqui, Elaine Freire ; Boldrini, Neide Aparecida Tosato ; Miranda, Angélica Espinosa ; Spano, Liliana Cruz ; Burk, Robert D. / Human papillomavirus 16 non-european variants are preferentially associated with high-grade cervical lesions. In: PLoS One. 2014 ; Vol. 9, No. 7.
@article{3193e11521ed48c785df189f4d11943f,
title = "Human papillomavirus 16 non-european variants are preferentially associated with high-grade cervical lesions",
abstract = "HPV16 accounts for 50-70{\%} of cervical cancer cases worldwide. Characterization of HPV16 variants previously indicated that they differ in risks for viral persistence, progression to cervical precancer and malignant cancer. The aim of this study was to examine the association of severity of disease with HPV16 variants identified in specimens (n = 281) obtained from a Cervical Pathology and Colposcopy outpatient clinic in the University Hospital of Esp{\'i}rito Santo State, Southeastern Brazil, from April 2010 to November 2011. All cytologic and histologic diagnoses were determined prior to definitive treatment. The DNA was isolated using QIAamp DNA Mini Kit and HPV was detected by amplification with PGMY09/11 primers and positive samples were genotyped by RFLP analyses and reverse line blot. The genomes of the HPV16 positive samples were sequenced, from which variant lineages were determined. Chi2 statistics was performed to test the association of HPV16 variants between case and control groups. The prevalence of HR-HPV types in <CIN1, CIN2 and CIN3+ were 33.7{\%}, 84.4{\%} and 91.6{\%}, respectively. Thirty-eight of 49 (78{\%}) HPV16 positive samples yielded HPV16 sequence information; of which, 32 complete genomes were sequenced and an additional 6 samples were partially sequenced. Phylogenetic analysis and patterns of variations identified 65.8{\%} (n = 25) as HPV16 European (E) and 34.2{\%} (n = 13) as non-European (NE) variants. Classification of disease into CIN3+ vs. <CIN3 indicated that NE types were associated with high-grade disease with an OR = 4.6 (1.07-20.2, p = 0.05). The association of HPV16 NE variants with an increased risk of CIN3+ is consistent with an HPV16 genetically determined enhanced oncogenicity. The prevalence of genetic variants of HPV16 is distributed across different geographical areas and with recent population admixture, only empiric data will provide information on the highest risk HPV16 variants within a given population.",
author = "Freitas, {Luciana Bueno} and Zigui Chen and Muqui, {Elaine Freire} and Boldrini, {Neide Aparecida Tosato} and Miranda, {Ang{\'e}lica Espinosa} and Spano, {Liliana Cruz} and Burk, {Robert D.}",
year = "2014",
month = "7",
day = "1",
doi = "10.1371/journal.pone.0100746",
language = "English (US)",
volume = "9",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "7",

}

TY - JOUR

T1 - Human papillomavirus 16 non-european variants are preferentially associated with high-grade cervical lesions

AU - Freitas, Luciana Bueno

AU - Chen, Zigui

AU - Muqui, Elaine Freire

AU - Boldrini, Neide Aparecida Tosato

AU - Miranda, Angélica Espinosa

AU - Spano, Liliana Cruz

AU - Burk, Robert D.

PY - 2014/7/1

Y1 - 2014/7/1

N2 - HPV16 accounts for 50-70% of cervical cancer cases worldwide. Characterization of HPV16 variants previously indicated that they differ in risks for viral persistence, progression to cervical precancer and malignant cancer. The aim of this study was to examine the association of severity of disease with HPV16 variants identified in specimens (n = 281) obtained from a Cervical Pathology and Colposcopy outpatient clinic in the University Hospital of Espírito Santo State, Southeastern Brazil, from April 2010 to November 2011. All cytologic and histologic diagnoses were determined prior to definitive treatment. The DNA was isolated using QIAamp DNA Mini Kit and HPV was detected by amplification with PGMY09/11 primers and positive samples were genotyped by RFLP analyses and reverse line blot. The genomes of the HPV16 positive samples were sequenced, from which variant lineages were determined. Chi2 statistics was performed to test the association of HPV16 variants between case and control groups. The prevalence of HR-HPV types in <CIN1, CIN2 and CIN3+ were 33.7%, 84.4% and 91.6%, respectively. Thirty-eight of 49 (78%) HPV16 positive samples yielded HPV16 sequence information; of which, 32 complete genomes were sequenced and an additional 6 samples were partially sequenced. Phylogenetic analysis and patterns of variations identified 65.8% (n = 25) as HPV16 European (E) and 34.2% (n = 13) as non-European (NE) variants. Classification of disease into CIN3+ vs. <CIN3 indicated that NE types were associated with high-grade disease with an OR = 4.6 (1.07-20.2, p = 0.05). The association of HPV16 NE variants with an increased risk of CIN3+ is consistent with an HPV16 genetically determined enhanced oncogenicity. The prevalence of genetic variants of HPV16 is distributed across different geographical areas and with recent population admixture, only empiric data will provide information on the highest risk HPV16 variants within a given population.

AB - HPV16 accounts for 50-70% of cervical cancer cases worldwide. Characterization of HPV16 variants previously indicated that they differ in risks for viral persistence, progression to cervical precancer and malignant cancer. The aim of this study was to examine the association of severity of disease with HPV16 variants identified in specimens (n = 281) obtained from a Cervical Pathology and Colposcopy outpatient clinic in the University Hospital of Espírito Santo State, Southeastern Brazil, from April 2010 to November 2011. All cytologic and histologic diagnoses were determined prior to definitive treatment. The DNA was isolated using QIAamp DNA Mini Kit and HPV was detected by amplification with PGMY09/11 primers and positive samples were genotyped by RFLP analyses and reverse line blot. The genomes of the HPV16 positive samples were sequenced, from which variant lineages were determined. Chi2 statistics was performed to test the association of HPV16 variants between case and control groups. The prevalence of HR-HPV types in <CIN1, CIN2 and CIN3+ were 33.7%, 84.4% and 91.6%, respectively. Thirty-eight of 49 (78%) HPV16 positive samples yielded HPV16 sequence information; of which, 32 complete genomes were sequenced and an additional 6 samples were partially sequenced. Phylogenetic analysis and patterns of variations identified 65.8% (n = 25) as HPV16 European (E) and 34.2% (n = 13) as non-European (NE) variants. Classification of disease into CIN3+ vs. <CIN3 indicated that NE types were associated with high-grade disease with an OR = 4.6 (1.07-20.2, p = 0.05). The association of HPV16 NE variants with an increased risk of CIN3+ is consistent with an HPV16 genetically determined enhanced oncogenicity. The prevalence of genetic variants of HPV16 is distributed across different geographical areas and with recent population admixture, only empiric data will provide information on the highest risk HPV16 variants within a given population.

UR - http://www.scopus.com/inward/record.url?scp=84903690152&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84903690152&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0100746

DO - 10.1371/journal.pone.0100746

M3 - Article

C2 - 24983739

AN - SCOPUS:84903690152

VL - 9

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 7

M1 - e100746

ER -