title: Epidemiological, clinical and viral determinants of the increased prevalence of high-risk human papillomavirus (HPV) infections in elderly women.
abstract: BACKGROUND
  Population-based studies have reported a second peak of human papillomavirus (HPV) prevalence among women > 55 years, but reasons for this U-shaped HPV prevalence curve are poorly understood.
  
  
  OBJECTIVE
  To analyse determinants of high-risk HPV (HR-HPV) infections among postmenopausal women.
  
  
  METHODS
  A cohort of 3,187 women was stratified into three age categories: i) youngest age group < 25 years (n = 1.103); ii) women between 26-55 years (n = 2.004), and iii) women > 55 years (n = 80), analysed for epidemiological, clinical and virological determinants of their HR-HPV infections. Real-time PCR was used for HPV genotyping, analysis of viral loads for HPV16, 18/45, 31, 33/52/58, 35 and 39, and load of integrated HPV16.
  
  
  RESULTS
  Age-standardised prevalence of HR-HPV infections showed a second peak among women > 55 years, with a perfect U-shaped curve (R2 = 0.966). The factors explaining this increased HR-HPV prevalence among older women include: i) cohort effect, ii) higher viral loads for HR-HPV types with cubic model curve (R2 = 0.714) for HPV 16, iii) distinct shift (p = 0.0001) from multiple-type infections to single HR-HPV types, iv) transition from episomal to integrated HPV16 (p = 0.009), v) higher load of integrated HPV16 (p = 0.009), and, vi) higher proportion of incident infections, higher rate of viral persistence, and lower rate of HR-HPV clearance.
  
  
  CONCLUSIONS
  These data suggest that in women who fail to eradicate their HR-HPV infection until menopause, selection of integrated viral clone has taken place, driving the process towards progressing disease. Consequent to this, most of the HR-HPV infections in women > 55 years were associated with high-grade CIN or invasive carcinoma.
authors.affiliation: Department of Oncology and Radiotherapy, Turku University Hospital, Turku, Finland. kari.syrjanen@tyks.fi
authors.forename: K
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authors.lastname: Syrjänen
authors.forename: S M
authors.initials: SM
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authors.lastname: Petrovichev
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authors.lastname: Zakharova
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authors.lastname: Pajanidi
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authors.lastname: Podistov
authors.forename: G
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authors.lastname: Chemeris
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authors.initials: L
authors.lastname: Sozaeva
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authors.lastname: Lipova
authors.forename: I
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authors.lastname: Tsidaeva
authors.forename: O
authors.initials: O
authors.lastname: Ivanchenko
authors.forename: A
authors.initials: A
authors.lastname: Pshepurko
authors.forename: S
authors.initials: S
authors.lastname: Zakharenko
authors.forename: R
authors.initials: R
authors.lastname: Nerovjna
authors.forename: L
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authors.lastname: Kljukina
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authors.initials: O
authors.lastname: Erokhina
authors.forename: M
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authors.lastname: Branovskaja
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authors.lastname: Nikitina
authors.forename: V
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authors.lastname: Grunjberga
authors.forename: A
authors.initials: A
authors.lastname: Grunjberg
authors.forename: A
authors.initials: A
authors.lastname: Juschenko
authors.forename: R
authors.initials: R
authors.lastname: Santopietro
authors.forename: M
authors.initials: M
authors.lastname: Cintorino
authors.forename: P
authors.initials: P
authors.lastname: Tosi
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authors.lastname: Syrjänen
mesh_terms: D000328:Adult; D052685:Alphapapillomavirus / Q000145:classification / Q000235:genetics / Q000472:pathogenicity*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D015344:DNA Probes, HPV; D005260:Female; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000453:epidemiology* / Q000473:pathology; D017698:Postmenopause; D015995:Prevalence; D012426:Russia / Q000453:epidemiology; D012725:Sexual Behavior; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology* / Q000473:pathology / Q000821:virology; D014626:Vaginal Smears; D019562:Viral Load; D002578:Uterine Cervical Dysplasia / Q000453:epidemiology* / Q000473:pathology / Q000821:virology
chemical_list: D015344:DNA Probes, HPV