title: Viral load of episomal and integrated forms of human papillomavirus type 33 in high-grade squamous intraepithelial lesions of the uterine cervix.
abstract: The association between total and integrated HPV-33 DNA loads and high-grade squamous intraepithelial lesions (HSIL) of the uterine cervix was investigated. Of 5,347 women recruited in 4 studies, 89 (64 without SIL, 7 low-grade SIL (LSIL), 15 HSIL, 3 unknown grade) were infected by HPV-33. HPV-33 E6, HPV-33 E2 and beta-globin DNA were measured with real-time PCR that allowed to assess total (E6), episomal (E2) and integrated (E6-E2) HPV-33 viral loads. HPV-33 E6/E2 ratios >/=>/=2.0 suggesting the presence of integrated HPV-33 were obtained for 28.6% (n = 18) of women without SIL and 21.4% (n = 3) of women with HSIL (p = 0.74). Although median viral loads were similar, there was a trend toward having a greater proportion of women with HSIL in the fourth quartile (>/=>/=10(6.69) copies/mug DNA) of total HPV-33 viral loads compared to normal women. Controlling for age, site, ethnicity and LCR polymorphism by logistic regression, HPV-33 total loads in the fourth quartile {odds ratio (OR) 4.5 [95% confidence interval (CI) 1.2-17.3]; p = 0.03} and episomal loads in the fourth quartile (>/=>/=10(6.64) copies/mug DNA) [OR 3.9 (95% CI 1.1-13.2); p = 0.05] but not integrated HPV-33 load in the fourth quartile [OR 1.0 (95% CI 0.3-3.3); p = 0.50] were associated with HSIL. Controlling for age, study site and SIL grade, HPV-33 episomal load [OR 0.2 (95% CI 0.1-0.5), p = 0.0004] was associated with the presence of HPV-33 integration. High episomal loads in HSIL and the presence of integration in women without SIL are likely to weaken the usefulness of HPV load of integrated forms in clinical practice.
authors: Laboratoire de Virologie Moléculaire du Centre de Recherche, Centre Hospitalier de l'Université de Montréal, Université de Montréal, Québec, Canada.
authors: Soraya
authors: S
authors: Khouadri
authors: Luisa L
authors: LL
authors: Villa
authors: Simon
authors: S
authors: Gagnon
authors: Anita
authors: A
authors: Koushik
authors: Harriet
authors: H
authors: Richardson
authors: Greg
authors: G
authors: Matlashewski
authors: Michel
authors: M
authors: Roger
authors: Alex S
authors: AS
authors: Ferenczy
authors: Eduardo L
authors: EL
authors: Franco
authors: François
authors: F
authors: Coutlée
mesh_terms: D000328:Adult; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000821:virology*; D016022:Case-Control Studies; D015331:Cohort Studies; D003588:Cytopathogenic Effect, Viral; D015344:DNA Probes, HPV; D004279:DNA, Viral; D005260:Female; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D016017:Odds Ratio; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000150:complications* / Q000821:virology; D010957:Plasmids; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D014412:Tumor Virus Infections / Q000150:complications* / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000473:pathology / Q000821:virology*; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000821:virology*; D014759:Viral Envelope Proteins / Q000378:metabolism; D019562:Viral Load
chemical_list: D015344:DNA Probes, HPV; D004279:DNA, Viral; C524476:E2 protein, HPV-33; C524477:E6 protein, HPV-33; D014759:Viral Envelope Proteins